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Conserved domains on  [gi|1938958509|ref|NP_446360|]
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tyrosine-protein phosphatase non-receptor type 6 [Rattus norvegicus]

Protein Classification

dual specificity protein phosphatase family protein; protein-tyrosine phosphatase family protein( domain architecture ID 12969958)

dual specificity protein phosphatase family protein such as dual specificity phosphatases, which dephosphorylate phosphotyrosine, phosphoserine, and phosphothreonine residues, as well as tyrosine-specific protein phosphatases; protein-tyrosine phosphatase family protein, similar to Saccharomyces cerevisiae OCA6 that is required for replication of Brome mosaic virus, but may be inactive as a protein-tyrosine phosphatase as it lacks the CxxxxxR catalytic motif

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTPc-N6 cd14606
catalytic domain of tyrosine-protein phosphatase non-receptor type 6; Tyrosine-protein ...
 255-520 0e+00

catalytic domain of tyrosine-protein phosphatase non-receptor type 6; Tyrosine-protein phosphatase non-receptor type 6 (PTPN6), also called SH2 domain-containing protein-tyrosine phosphatase 1 (SHP1 or SHP-1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN6 expression is restricted mainly to hematopoietic and epithelial cells. It is an important regulator of hematopoietic cells, downregulating pathways that promote cell growth, survival, adhesion, and activation. It regulates glucose homeostasis by modulating insulin signalling in the liver and muscle, and it also negatively regulates bone resorption, affecting both the formation and the function of osteoclasts. PTPN6 contains two tandem SH2 domains, a catalytic PTP domain, and a C-terminal tail with regulatory properties.


:

Pssm-ID: 350454 [Multi-domain]  Cd Length: 266  Bit Score: 559.88  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 255 KQEVKNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKNQLLGPDENSKTYIASQGCLDATV 334
Cdd:cd14606     1 KQEVKNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKNQLLGPDENAKTYIASQGCLEATV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 335 NDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDLVREIWHY 414
Cdd:cd14606    81 NDFWQMAWQENSRVIVMTTREVEKGRNKCVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGELIREIWHY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 415 QYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCDIDIQKTIQMVR 494
Cdd:cd14606   161 QYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMENISTKGLDCDIDIQKTIQMVR 240

                         250       260
                  ....*....|....*....|....*.
gi 1938958509 495 AQRSGMVQTEAQYKFIYVAIAQFIET 520
Cdd:cd14606   241 AQRSGMVQTEAQYKFIYVAIAQFIET 266
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 6-103 2.08e-57

N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198203  Cd Length: 99  Bit Score: 187.61  E-value: 2.08e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYYTQQQ 85
Cdd:cd10340     2 WFHPVISGIEAENLLKTRGVDGSFLARPSKSNPGDFTLSVRRGDEVTHIKIQNTGDYYDLYGGEKFATLSELVQYYMEQH 81

                          90
                  ....*....|....*...
gi 1938958509  86 GILQDRDGTIIHLKYPLN 103
Cdd:cd10340    82 GQLREKNGDVIELKYPLN 99
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 111-217 2.60e-55

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


:

Pssm-ID: 198185  Cd Length: 99  Bit Score: 182.09  E-value: 2.60e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 111 RWYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQPKagpgsplrVTHIKVMCEGGRYTVGGSETFDSLT 190
Cdd:cd09931     1 RWFHGHLSGKEAEKLLLEKGKPGSFLVRESQSKPGDFVLSVRTDDDK--------VTHIMIRCQGGKYDVGGGEEFDSLT 72

                          90       100
                  ....*....|....*....|....*..
gi 1938958509 191 DLVEHFKKTGIEEASGAFVYLRQPYYA 217
Cdd:cd09931    73 DLVEHYKKNPMVETSGTVVHLKQPLNA 99
 
Name Accession Description Interval E-value
PTPc-N6 cd14606
catalytic domain of tyrosine-protein phosphatase non-receptor type 6; Tyrosine-protein ...
 255-520 0e+00

catalytic domain of tyrosine-protein phosphatase non-receptor type 6; Tyrosine-protein phosphatase non-receptor type 6 (PTPN6), also called SH2 domain-containing protein-tyrosine phosphatase 1 (SHP1 or SHP-1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN6 expression is restricted mainly to hematopoietic and epithelial cells. It is an important regulator of hematopoietic cells, downregulating pathways that promote cell growth, survival, adhesion, and activation. It regulates glucose homeostasis by modulating insulin signalling in the liver and muscle, and it also negatively regulates bone resorption, affecting both the formation and the function of osteoclasts. PTPN6 contains two tandem SH2 domains, a catalytic PTP domain, and a C-terminal tail with regulatory properties.


Pssm-ID: 350454 [Multi-domain]  Cd Length: 266  Bit Score: 559.88  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 255 KQEVKNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKNQLLGPDENSKTYIASQGCLDATV 334
Cdd:cd14606     1 KQEVKNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKNQLLGPDENAKTYIASQGCLEATV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 335 NDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDLVREIWHY 414
Cdd:cd14606    81 NDFWQMAWQENSRVIVMTTREVEKGRNKCVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGELIREIWHY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 415 QYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCDIDIQKTIQMVR 494
Cdd:cd14606   161 QYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMENISTKGLDCDIDIQKTIQMVR 240

                         250       260
                  ....*....|....*....|....*.
gi 1938958509 495 AQRSGMVQTEAQYKFIYVAIAQFIET 520
Cdd:cd14606   241 AQRSGMVQTEAQYKFIYVAIAQFIET 266
PTPc smart00194
Protein tyrosine phosphatase, catalytic domain;
245-516 3.72e-116

Protein tyrosine phosphatase, catalytic domain;


Pssm-ID: 214550 [Multi-domain]  Cd Length: 259  Bit Score: 345.80  E-value: 3.72e-116
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509  245 GFWEEFESLQKQEVKNLHQRlEGQRPENKSKNRYKNILPFDHSRVILQGRDSniPGSDYINANYVKnqllGPDENsKTYI 324
Cdd:smart00194   1 GLEEEFEKLDRLKPDDESCT-VAAFPENRDKNRYKDVLPYDHTRVKLKPPPG--EGSDYINASYID----GPNGP-KAYI 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509  325 ASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWP-EVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLD 403
Cdd:smart00194  73 ATQGPLPSTVEDFWRMVWEQKVTVIVMLTELVEKGREKCAQYWPdEEGEPLTYGDITVTLKSVEKVDDYTIRTLEVTNTG 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509  404 NGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLphAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGldcD 483
Cdd:smart00194 153 CSE-TRTVTHYHYTNWPDHGVPESPESILDLIRAVRKSQSTS--TGPIVVHCSAGVGRTGTFIAIDILLQQLEAGK---E 226

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1938958509  484 IDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQ 516
Cdd:smart00194 227 VDIFEIVKELRSQRPGMVQTEEQYIFLYRAILE 259
Y_phosphatase pfam00102
Protein-tyrosine phosphatase;
272-516 2.79e-105

Protein-tyrosine phosphatase;


Pssm-ID: 459674 [Multi-domain]  Cd Length: 234  Bit Score: 316.88  E-value: 2.79e-105
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 272 NKSKNRYKNILPFDHSRVILQGRDSNipgSDYINANYVKnqllGPDeNSKTYIASQGCLDATVNDFWQMAWQENTRVIVM 351
Cdd:pfam00102   1 NLEKNRYKDVLPYDHTRVKLTGDPGP---SDYINASYID----GYK-KPKKYIATQGPLPNTVEDFWRMVWEEKVTIIVM 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 352 TTREVEKGRNKCVPYWPE-VGTQRVYGLYSVTNCKEH-DTAEYKLRTLQISpLDNGDLVREIWHYQYLSWPDHGVPSEPG 429
Cdd:pfam00102  73 LTELEEKGREKCAQYWPEeEGESLEYGDFTVTLKKEKeDEKDYTVRTLEVS-NGGSEETRTVKHFHYTGWPDHGVPESPN 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 430 GVLSFLDQINQRQESlPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKF 509
Cdd:pfam00102 152 SLLDLLRKVRKSSLD-GRSGPIVVHCSAGIGRTGTFIAIDIALQQLEAEG---EVDIFQIVKELRSQRPGMVQTLEQYIF 227


                  ....*..
gi 1938958509 510 IYVAIAQ 516
Cdd:pfam00102 228 LYDAILE 234
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 6-103 2.08e-57

N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198203  Cd Length: 99  Bit Score: 187.61  E-value: 2.08e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYYTQQQ 85
Cdd:cd10340     2 WFHPVISGIEAENLLKTRGVDGSFLARPSKSNPGDFTLSVRRGDEVTHIKIQNTGDYYDLYGGEKFATLSELVQYYMEQH 81

                          90
                  ....*....|....*...
gi 1938958509  86 GILQDRDGTIIHLKYPLN 103
Cdd:cd10340    82 GQLREKNGDVIELKYPLN 99
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 111-217 2.60e-55

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 182.09  E-value: 2.60e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 111 RWYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQPKagpgsplrVTHIKVMCEGGRYTVGGSETFDSLT 190
Cdd:cd09931     1 RWFHGHLSGKEAEKLLLEKGKPGSFLVRESQSKPGDFVLSVRTDDDK--------VTHIMIRCQGGKYDVGGGEEFDSLT 72

                          90       100
                  ....*....|....*....|....*..
gi 1938958509 191 DLVEHFKKTGIEEASGAFVYLRQPYYA 217
Cdd:cd09931    73 DLVEHYKKNPMVETSGTVVHLKQPLNA 99
PHA02742 PHA02742
protein tyrosine phosphatase; Provisional
 271-517 1.01e-49

protein tyrosine phosphatase; Provisional


Pssm-ID: 165109 [Multi-domain]  Cd Length: 303  Bit Score: 174.42  E-value: 1.01e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 271 ENKSKNRYKNILPFDHSRVILQGRDSnipGSDYINANYVKNQllgpdeNSK-TYIASQGCLDATVNDFWQMAWQENTRVI 349
Cdd:PHA02742   51 KNMKKCRYPDAPCFDRNRVILKIEDG---GDDFINASYVDGH------NAKgRFICTQAPLEETALDFWQAIFQDQVRVI 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 350 VMTTREVEKGRNKCVPYW-PEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGdLVREIWHYQYLSWPDHGVPSEP 428
Cdd:PHA02742  122 VMITKIMEDGKEACYPYWmPHERGKATHGEFKIKTKKIKSFRNYAVTNLCLTDTNTG-ASLDIKHFAYEDWPHGGLPRDP 200

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 429 GGVLSFLDQINQRQ---------ESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSG 499
Cdd:PHA02742  201 NKFLDFVLAVREADlkadvdikgENIVKEPPILVHCSAGLDRAGAFCAIDICISKYNERAI---IPLLSIVRDLRKQRHN 277

                         250
                  ....*....|....*...
gi 1938958509 500 MVQTEAQYKFIYVAIAQF 517
Cdd:PHA02742  278 CLSLPQQYIFCYFIVLIF 295
COG5599 COG5599
Protein tyrosine phosphatase [Signal transduction mechanisms];
248-516 1.76e-44

Protein tyrosine phosphatase [Signal transduction mechanisms];


Pssm-ID: 444335 [Multi-domain]  Cd Length: 282  Bit Score: 159.49  E-value: 1.76e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 248 EEFESLQKQEVKNLHQrlegQRPENKSKNRYKNILPFDHSRVilqgrDSNIPgsdYINANYVKnqllGPDENskTYIASQ 327
Cdd:COG5599    22 TLTNELAPSHNDPQYL----QNINGSPLNRFRDIQPYKETAL-----RANLG---YLNANYIQ----VIGNH--RYIATQ 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 328 GCLDATVNDFWQMAWQENTRVIVMTTREVE--KGRNKCVPYWPEVGTqrvYGLYSVTNcKEHDTAEYK----LRTLQISP 401
Cdd:COG5599    84 YPLEEQLEDFFQMLFDNNTPVLVVLASDDEisKPKVKMPVYFRQDGE---YGKYEVSS-ELTESIQLRdgieARTYVLTI 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 402 LDNGDLVREIWHYQYLSWPDHGVPSePGGVLSFLDQINQRQE-SLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKgL 480
Cdd:COG5599   160 KGTGQKKIEIPVLHVKNWPDHGAIS-AEALKNLADLIDKKEKiKDPDKLLPVVHCRAGVGRTGTLIACLALSKSINAL-V 237

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 1938958509 481 DCDIDIQKTIQMVRAQR-SGMVQTEAQYKFIyVAIAQ 516
Cdd:COG5599   238 QITLSVEEIVIDMRTSRnGGMVQTSEQLDVL-VKLAE 273
SH2 pfam00017
SH2 domain;
6-81 4.56e-28

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 107.30  E-value: 4.56e-28
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDF-YDLYGGEKFATLTELVEYY 81
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNGgYYISGGVKFSSLAELVEHY 77
SH2 pfam00017
SH2 domain;
112-196 7.69e-26

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 100.75  E-value: 7.69e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMC-EGGRYTVGGSETFDSLT 190
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPDGTFLVRESESTPGGYTLSVRDDG---------KVKHYKIQStDNGGYYISGGVKFSSLA 71


                  ....*.
gi 1938958509 191 DLVEHF 196
Cdd:pfam00017  72 ELVEHY 77
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 6-84 1.91e-24

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 97.30  E-value: 1.91e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509    6 WFHRDLSGPDAETLLKGRGvPGSFLARPSRKNQGDFSLSVRVDDQVTHIRI-QNSGDFYDLYGGEKFATLTELVEYYTQQ 84
Cdd:smart00252   3 WYHGFISREEAEKLLKNEG-DGDFLVRDSESSPGDYVLSVRVKGKVKHYRIrRNEDGKFYLEGGRKFPSLVELVEHYQKN 81
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 110-201 1.25e-22

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 91.91  E-value: 1.25e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509  110 ERWYHGHMSGGQAESLLQAKGePWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMC-EGGRYTVGGSETFDS 188
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEG-DGDFLVRDSESSPGDYVLSVRVKG---------KVKHYRIRRnEDGKFYLEGGRKFPS 70

                           90
                   ....*....|...
gi 1938958509  189 LTDLVEHFKKTGI 201
Cdd:smart00252  71 LVELVEHYQKNSL 83
 
Name Accession Description Interval E-value
PTPc-N6 cd14606
catalytic domain of tyrosine-protein phosphatase non-receptor type 6; Tyrosine-protein ...
 255-520 0e+00

catalytic domain of tyrosine-protein phosphatase non-receptor type 6; Tyrosine-protein phosphatase non-receptor type 6 (PTPN6), also called SH2 domain-containing protein-tyrosine phosphatase 1 (SHP1 or SHP-1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN6 expression is restricted mainly to hematopoietic and epithelial cells. It is an important regulator of hematopoietic cells, downregulating pathways that promote cell growth, survival, adhesion, and activation. It regulates glucose homeostasis by modulating insulin signalling in the liver and muscle, and it also negatively regulates bone resorption, affecting both the formation and the function of osteoclasts. PTPN6 contains two tandem SH2 domains, a catalytic PTP domain, and a C-terminal tail with regulatory properties.


Pssm-ID: 350454 [Multi-domain]  Cd Length: 266  Bit Score: 559.88  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 255 KQEVKNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKNQLLGPDENSKTYIASQGCLDATV 334
Cdd:cd14606     1 KQEVKNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKNQLLGPDENAKTYIASQGCLEATV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 335 NDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDLVREIWHY 414
Cdd:cd14606    81 NDFWQMAWQENSRVIVMTTREVEKGRNKCVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGELIREIWHY 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 415 QYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCDIDIQKTIQMVR 494
Cdd:cd14606   161 QYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMENISTKGLDCDIDIQKTIQMVR 240

                         250       260
                  ....*....|....*....|....*.
gi 1938958509 495 AQRSGMVQTEAQYKFIYVAIAQFIET 520
Cdd:cd14606   241 AQRSGMVQTEAQYKFIYVAIAQFIET 266
PTPc-N11_6 cd14544
catalytic domain of tyrosine-protein phosphatase non-receptor type 11 and type 6; ...
 272-520 1.02e-172

catalytic domain of tyrosine-protein phosphatase non-receptor type 11 and type 6; Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) and type 6 (PTPN6) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN11 and PTPN6, are also called SH2 domain-containing tyrosine phosphatase 2 (SHP2) and 1 (SHP1), respectively. They contain two tandem SH2 domains: a catalytic PTP domain, and a C-terminal tail with regulatory properties. Although structurally similar, they have different localization and different roles in signal transduction. PTPN11/SHP2 is expressed ubiquitously and plays a positive role in cell signaling, leading to cell activation, while PTPN6/SHP1 expression is restricted mainly to hematopoietic and epithelial cells and functions as a negative regulator of signaling events.


Pssm-ID: 350392 [Multi-domain]  Cd Length: 251  Bit Score: 489.67  E-value: 1.02e-172
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 272 NKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKNQLLGP--DENSKTYIASQGCLDATVNDFWQMAWQENTRVI 349
Cdd:cd14544     1 NKGKNRYKNILPFDHTRVILKDRDPNVPGSDYINANYIRNENEGPttDENAKTYIATQGCLENTVSDFWSMVWQENSRVI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 350 VMTTREVEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDLVREIWHYQYLSWPDHGVPSEPG 429
Cdd:cd14544    81 VMTTKEVERGKNKCVRYWPDEGMQKQYGPYRVQNVSEHDTTDYTLRELQVSKLDQGDPIREIWHYQYLSWPDHGVPSDPG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 430 GVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKF 509
Cdd:cd14544   161 GVLNFLEDVNQRQESLPHAGPIVVHCSAGIGRTGTFIVIDMLLDQIKRKGLDCDIDIQKTIQMVRSQRSGMVQTEAQYKF 240

                         250
                  ....*....|.
gi 1938958509 510 IYVAIAQFIET 520
Cdd:cd14544   241 IYVAVAQYIET 251
PTPc-N11 cd14605
catalytic domain of tyrosine-protein phosphatase non-receptor type 11; Tyrosine-protein ...
 271-520 5.08e-128

catalytic domain of tyrosine-protein phosphatase non-receptor type 11; Tyrosine-protein phosphatase non-receptor type 11 (PTPN11), also called SH2 domain-containing tyrosine phosphatase 2 (SHP-2 or SHP2), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN11 promotes the activation of the RAS/Mitogen-Activated Protein Kinases (MAPK) Extracellular-Regulated Kinases 1/2 (ERK1/2) pathway, a canonical signaling cascade that plays key roles in various cellular processes, including proliferation, survival, differentiation, migration, or metabolism. It also regulates the phosphoinositide 3-kinase (PI3K)/AKT pathway, a fundamental cascade that functions in cell survival, proliferation, migration, morphogenesis, and metabolism. PTPN11 dysregulation is associated with several developmental diseases and malignancies, such as Noonan syndrome and juvenile myelomonocytic leukemia. It contains two tandem SH2 domains, a catalytic PTP domain, and a C-terminal tail with regulatory properties.


Pssm-ID: 350453 [Multi-domain]  Cd Length: 253  Bit Score: 376.28  E-value: 5.08e-128
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 271 ENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKNQLLGPDENSK---TYIASQGCLDATVNDFWQMAWQENTR 347
Cdd:cd14605     1 ENKNKNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMPEFETKCNNSKpkkSYIATQGCLQNTVNDFWRMVFQENSR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 348 VIVMTTREVEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDLVREIWHYQYLSWPDHGVPSE 427
Cdd:cd14605    81 VIVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYILRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSD 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 428 PGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQY 507
Cdd:cd14605   161 PGGVLDFLEEVHHKQESIMDAGPVVVHCSAGIGRTGTFIVIDILIDIIREKGVDCDIDVPKTIQMVRSQRSGMVQTEAQY 240

                         250
                  ....*....|...
gi 1938958509 508 KFIYVAIAQFIET 520
Cdd:cd14605   241 RFIYMAVQHYIET 253
PTPc smart00194
Protein tyrosine phosphatase, catalytic domain;
245-516 3.72e-116

Protein tyrosine phosphatase, catalytic domain;


Pssm-ID: 214550 [Multi-domain]  Cd Length: 259  Bit Score: 345.80  E-value: 3.72e-116
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509  245 GFWEEFESLQKQEVKNLHQRlEGQRPENKSKNRYKNILPFDHSRVILQGRDSniPGSDYINANYVKnqllGPDENsKTYI 324
Cdd:smart00194   1 GLEEEFEKLDRLKPDDESCT-VAAFPENRDKNRYKDVLPYDHTRVKLKPPPG--EGSDYINASYID----GPNGP-KAYI 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509  325 ASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWP-EVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLD 403
Cdd:smart00194  73 ATQGPLPSTVEDFWRMVWEQKVTVIVMLTELVEKGREKCAQYWPdEEGEPLTYGDITVTLKSVEKVDDYTIRTLEVTNTG 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509  404 NGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLphAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGldcD 483
Cdd:smart00194 153 CSE-TRTVTHYHYTNWPDHGVPESPESILDLIRAVRKSQSTS--TGPIVVHCSAGVGRTGTFIAIDILLQQLEAGK---E 226

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1938958509  484 IDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQ 516
Cdd:smart00194 227 VDIFEIVKELRSQRPGMVQTEEQYIFLYRAILE 259
Y_phosphatase pfam00102
Protein-tyrosine phosphatase;
272-516 2.79e-105

Protein-tyrosine phosphatase;


Pssm-ID: 459674 [Multi-domain]  Cd Length: 234  Bit Score: 316.88  E-value: 2.79e-105
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 272 NKSKNRYKNILPFDHSRVILQGRDSNipgSDYINANYVKnqllGPDeNSKTYIASQGCLDATVNDFWQMAWQENTRVIVM 351
Cdd:pfam00102   1 NLEKNRYKDVLPYDHTRVKLTGDPGP---SDYINASYID----GYK-KPKKYIATQGPLPNTVEDFWRMVWEEKVTIIVM 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 352 TTREVEKGRNKCVPYWPE-VGTQRVYGLYSVTNCKEH-DTAEYKLRTLQISpLDNGDLVREIWHYQYLSWPDHGVPSEPG 429
Cdd:pfam00102  73 LTELEEKGREKCAQYWPEeEGESLEYGDFTVTLKKEKeDEKDYTVRTLEVS-NGGSEETRTVKHFHYTGWPDHGVPESPN 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 430 GVLSFLDQINQRQESlPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKF 509
Cdd:pfam00102 152 SLLDLLRKVRKSSLD-GRSGPIVVHCSAGIGRTGTFIAIDIALQQLEAEG---EVDIFQIVKELRSQRPGMVQTLEQYIF 227


                  ....*..
gi 1938958509 510 IYVAIAQ 516
Cdd:pfam00102 228 LYDAILE 234
PTPc cd00047
catalytic domain of protein tyrosine phosphatases; Protein tyrosine phosphatases (PTP, EC 3.1. ...
 303-511 5.67e-89

catalytic domain of protein tyrosine phosphatases; Protein tyrosine phosphatases (PTP, EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr (pTyr) residues, instead of pSer or pThr. This family has a distinctive active site signature motif, HCSAGxGRxG, and are characterized as either transmembrane, receptor-like or non-transmembrane (soluble) PTPs. Receptor-like PTP domains tend to occur in two copies in the cytoplasmic region of the transmembrane proteins, only one copy may be active.


Pssm-ID: 350343 [Multi-domain]  Cd Length: 200  Bit Score: 273.78  E-value: 5.67e-89
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKnqllGPDEnSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWP-EVGTQRVYGLYSV 381
Cdd:cd00047     1 YINASYID----GYRG-PKEYIATQGPLPNTVEDFWRMVWEQKVSVIVMLTNLVEKGREKCERYWPeEGGKPLEYGDITV 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 382 TNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQInqRQESLPHAGPIIVHCSAGIGR 461
Cdd:cd00047    76 TLVSEEELSDYTIRTLELSPKGCSE-SREVTHLHYTGWPDHGVPSSPEDLLALVRRV--RKEARKPNGPIVVHCSAGVGR 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1938958509 462 TGTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd00047   153 TGTFIAIDILLERLEAEG---EVDVFEIVKALRKQRPGMVQTLEQYEFIY 199
R-PTPc-LAR-1 cd14553
catalytic domain of LAR family receptor-type tyrosine-protein phosphatases, repeat 1; The LAR ...
 272-514 7.19e-84

catalytic domain of LAR family receptor-type tyrosine-protein phosphatases, repeat 1; The LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs) include three vertebrate members: LAR (or PTPRF), R-PTP-delta (or PTPRD), and R-PTP-sigma (or PTPRS). They belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. LAR-RPTPs are synaptic adhesion molecules; they bind to distinct synaptic membrane proteins and are physiologically responsible for mediating presynaptic development by shaping various synaptic adhesion pathways. They play roles in various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. LAR-RPTPs contain an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the catalytic PTP domain (repeat 1).


Pssm-ID: 350401 [Multi-domain]  Cd Length: 238  Bit Score: 261.95  E-value: 7.19e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 272 NKSKNRYKNILPFDHSRVILQGRDSnIPGSDYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVM 351
Cdd:cd14553     3 NKPKNRYANVIAYDHSRVILQPIEG-VPGSDYINANYCDGY-----RKQNAYIATQGPLPETFGDFWRMVWEQRSATIVM 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 352 TTREVEKGRNKCVPYWPEVGTQrVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGV 431
Cdd:cd14553    77 MTKLEERSRVKCDQYWPTRGTE-TYGLIQVTLLDTVELATYTVRTFALHKNGSSE-KREVRQFQFTAWPDHGVPEHPTPF 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 432 LSFLDQInqRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTkglDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14553   155 LAFLRRV--KACNPPDAGPIVVHCSAGVGRTGCFIVIDSMLERIKH---EKTVDIYGHVTCLRAQRNYMVQTEDQYIFIH 229


                  ...
gi 1938958509 512 VAI 514
Cdd:cd14553   230 DAL 232
PTPc-N9 cd14543
catalytic domain of tyrosine-protein phosphatase non-receptor type 9; Tyrosine-protein ...
 243-511 1.05e-74

catalytic domain of tyrosine-protein phosphatase non-receptor type 9; Tyrosine-protein phosphatase non-receptor type 9 (PTPN9), also called protein-tyrosine phosphatase MEG2, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN9 plays an important role in promoting intracellular secretary vesicle fusion in hematopoietic cells and promotes the dephosphorylation of ErbB2 and EGFR in breast cancer cells, leading to impaired activation of STAT5 and STAT3. It also directly dephosphorylates STAT3 at the Tyr705 residue, resulting in its inactivation. PTPN9 has been found to be dysregulated in various human cancers, including breast, colorectal, and gastric cancer.


Pssm-ID: 350391 [Multi-domain]  Cd Length: 271  Bit Score: 239.57  E-value: 1.05e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 243 KAGFWEEFESLQKQEVKNLHQRleGQRPENKSKNRYKNILPFDHSRVILQGRDSNiPGSDYINANYVKNQllgpdENSKT 322
Cdd:cd14543     2 KRGIYEEYEDIRREPPAGTFLC--SLAPANQEKNRYGDVLCLDQSRVKLPKRNGD-ERTDYINANFMDGY-----KQKNA 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 323 YIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWP-EVGTQRVYGLYSVTN----CKEHdtaeYKLRTL 397
Cdd:cd14543    74 YIATQGPLPKTYSDFWRMVWEQKVLVIVMTTRVVERGRVKCGQYWPlEEGSSLRYGDLTVTNlsveNKEH----YKKTTL 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 398 QIsplDN--GDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESL-----------PHAGPIIVHCSAGIGRTGT 464
Cdd:cd14543   150 EI---HNteTDESRQVTHFQFTSWPDFGVPSSAAALLDFLGEVRQQQALAvkamgdrwkghPPGPPIVVHCSAGIGRTGT 226

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 1938958509 465 IIVIDML---MESVSTkgldcdIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14543   227 FCTLDIClsqLEDVGT------LNVMQTVRRMRTQRAFSIQTPDQYYFCY 270
PTPc-N18 cd14603
catalytic domain of tyrosine-protein phosphatase non-receptor type 18; Tyrosine-protein ...
 267-516 4.15e-74

catalytic domain of tyrosine-protein phosphatase non-receptor type 18; Tyrosine-protein phosphatase non-receptor type 18 (PTPN18), also called brain-derived phosphatase, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination states. The N-terminal catalytic PTP domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation, and its C-terminal PEST domain promotes K48-linked HER2 ubiquitination and its destruction via the proteasome pathway.


Pssm-ID: 350451 [Multi-domain]  Cd Length: 266  Bit Score: 237.80  E-value: 4.15e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 267 GQRPENKSKNRYKNILPFDHSRVILQGRDSNiPGSDYINANYVKnqllGPDeNSKTYIASQGCLDATVNDFWQMAWQENT 346
Cdd:cd14603    25 GGRKENVKKNRYKDILPYDQTRVILSLLQEE-GHSDYINANFIK----GVD-GSRAYIATQGPLSHTVLDFWRMIWQYGV 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 347 RVIVMTTREVEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHD-TAEYKLRTLQISPLDNGdlvREIWHYQYLSWPDHGVP 425
Cdd:cd14603    99 KVILMACREIEMGKKKCERYWAQEQEPLQTGPFTITLVKEKRlNEEVILRTLKVTFQKES---RSVSHFQYMAWPDHGIP 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 426 SEPGGVLSFLDQINQRQESLPHagPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCDIDIQKTIQMVRAQRSGMVQTEA 505
Cdd:cd14603   176 DSPDCMLAMIELARRLQGSGPE--PLCVHCSAGCGRTGVICTVDYVRQLLLTQRIPPDFSIFDVVLEMRKQRPAAVQTEE 253

                         250
                  ....*....|.
gi 1938958509 506 QYKFIYVAIAQ 516
Cdd:cd14603   254 QYEFLYHTVAQ 264
R3-PTPc cd14548
catalytic domain of R3 subfamily receptor-type tyrosine-protein phosphatases and similar ...
 277-511 7.21e-74

catalytic domain of R3 subfamily receptor-type tyrosine-protein phosphatases and similar proteins; R3 subfamily receptor-type phosphotyrosine phosphatases (RPTP) are characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. Vertebrate members include receptor-type tyrosine-protein phosphatase-like O (PTPRO), J (PTPRJ), Q (PTPRQ), B (PTPRB), V (PTPRV) and H (PTPRH). They belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Most members are PTPs, except for PTPRQ, which dephosphorylates phosphatidylinositide substrates. PTPRV is characterized only in rodents; its function has been lost in humans. Both vertebrate and invertebrate R3 subfamily RPTPs are involved in the control of a variety of cellular processes, including cell growth, differentiation, mitotic cycle and oncogenic transformation.


Pssm-ID: 350396 [Multi-domain]  Cd Length: 222  Bit Score: 235.33  E-value: 7.21e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 277 RYKNILPFDHSRVILQGRDSNiPGSDYINANYVknqllgPDENS-KTYIASQGCLDATVNDFWQMAWQENTRVIVMTTRE 355
Cdd:cd14548     1 RYTNILPYDHSRVKLIPINEE-EGSDYINANYI------PGYNSpREFIATQGPLPGTKDDFWRMVWEQNSHTIVMLTQC 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 356 VEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISpldNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFL 435
Cdd:cd14548    74 MEKGRVKCDHYWPFDQDPVYYGDITVTMLSESVLPDWTIREFKLE---RGDEVRSVRQFHFTAWPDHGVPEAPDSLLRFV 150

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1938958509 436 DQInqRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14548   151 RLV--RDYIKQEKGPTIVHCSAGVGRTGTFIALDRLLQQIESEDY---VDIFGIVYDLRKHRPLMVQTEAQYIFLH 221
PTPc-KIM cd14547
catalytic domain of the kinase interaction motif (KIM) family of protein-tyrosine phosphatases; ...
 276-511 6.83e-73

catalytic domain of the kinase interaction motif (KIM) family of protein-tyrosine phosphatases; The kinase interaction motif (KIM) family of protein-tyrosine phosphatases (PTPs) includes tyrosine-protein phosphatases non-receptor type 7 (PTPN7) and non-receptor type 5 (PTPN5), and protein-tyrosine phosphatase receptor type R (PTPRR). PTPN7 is also called hematopoietic protein-tyrosine phosphatase (HePTP) while PTPN5 is also called striatal-enriched protein-tyrosine phosphatase (STEP). They belong to the family of classical tyrosine-specific PTPs (EC 3.1.3.48) that catalyze the dephosphorylation of phosphotyrosine peptides. KIM-PTPs are characterized by the presence of a 16-amino-acid KIM that binds specifically to members of the MAPK (mitogen-activated protein kinase) family. They are highly specific to the MAPKs ERK1/2 (extracellular-signal-regulated kinase 1/2) and p38, over JNK (c-Jun N-terminal kinase); they dephosphorylate these kinases and thereby critically modulate cell proliferation and differentiation.


Pssm-ID: 350395 [Multi-domain]  Cd Length: 224  Bit Score: 233.06  E-value: 6.83e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 276 NRYKNILPFDHSRVILqGRDSNIPGSDYINANYVKnqllGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTRE 355
Cdd:cd14547     1 NRYKTILPNEHSRVCL-PSVDDDPLSSYINANYIR----GYDGEEKAYIATQGPLPNTVADFWRMVWQEKTPIIVMITNL 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 356 VEKgRNKCVPYWP-EVGTQrvYGLYSVT--NCKEHDtaEYKLRTLQispLDNGDLVREIWHYQYLSWPDHGVPSEPGGVL 432
Cdd:cd14547    76 TEA-KEKCAQYWPeEENET--YGDFEVTvqSVKETD--GYTVRKLT---LKYGGEKRYLKHYWYTSWPDHKTPEAAQPLL 147

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509 433 SFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14547   148 SLVQEVEEARQTEPHRGPIVVHCSAGIGRTGCFIATSIGCQQLREEG---VVDVLGIVCQLRLDRGGMVQTAEQYEFVH 223
PTP_fungal cd18533
fungal protein tyrosine phosphatases; This subfamily contains Saccharomyces cerevisiae ...
 303-511 2.66e-71

fungal protein tyrosine phosphatases; This subfamily contains Saccharomyces cerevisiae protein-tyrosine phosphatases 1 (PTP1) and 2 (PTP2), Schizosaccharomyces pombe PTP1, PTP2, and PTP3, and similar fungal proteins. PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. PTP2, together with PTP3, is the major phosphatase that dephosphorylates and inactivates the MAP kinase HOG1 and also modulates its subcellular localization.


Pssm-ID: 350509 [Multi-domain]  Cd Length: 212  Bit Score: 228.29  E-value: 2.66e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKnqlLGPDENsKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRVYGLYSVT 382
Cdd:cd18533     1 YINASYIT---LPGTSS-KRYIATQGPLPATIGDFWKMIWQNNVGVIVMLTPLVENGREKCDQYWPSGEYEGEYGDLTVE 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEH--DTAEYKLRTLQISPldNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIG 460
Cdd:cd18533    77 LVSEEenDDGGFIVREFELSK--EDGKVKKVYHIQYKSWPDFGVPDSPEDLLTLIKLKRELNDSASLDPPIIVHCSAGVG 154

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1938958509 461 RTGTIIVIDMLM---ESVSTKGLDCDID---IQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd18533   155 RTGTFIALDSLLdelKRGLSDSQDLEDSedpVYEIVNQLRKQRMSMVQTLRQYIFLY 211
R-PTPc-F-1 cd14626
catalytic domain of receptor-type tyrosine-protein phosphatase F, repeat 1; Receptor-type ...
 246-516 4.92e-69

catalytic domain of receptor-type tyrosine-protein phosphatase F, repeat 1; Receptor-type tyrosine-protein phosphatase F (PTPRF), also known as leukocyte common antigen related (LAR), is the prototypical member of the LAR family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRF/LAR plays a role for LAR in cadherin complexes where it associates with and dephosphorylates beta-catenin, a pathway which may be critical for cadherin complex stability and cell-cell association. It also regulates focal adhesions through cyclin-dependent kinase-1 and is involved in axon guidance in the developing nervous system. It also functions in regulating insulin signaling. PTPRF contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the catalytic PTP domain (repeat 1).


Pssm-ID: 350474 [Multi-domain]  Cd Length: 276  Bit Score: 224.91  E-value: 4.92e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 246 FWEEFESLQK-QEVKNLHQRLEgqrpENKSKNRYKNILPFDHSRVILQGRDSnIPGSDYINANYVKNQllgpdENSKTYI 324
Cdd:cd14626    18 FSQEYESIDPgQQFTWENSNLE----VNKPKNRYANVIAYDHSRVILTSVDG-VPGSDYINANYIDGY-----RKQNAYI 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 325 ASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQrVYGLYSVTNCKEHDTAEYKLRTLQISPlDN 404
Cdd:cd14626    88 ATQGPLPETLSDFWRMVWEQRTATIVMMTRLEEKSRVKCDQYWPIRGTE-TYGMIQVTLLDTVELATYSVRTFALYK-NG 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 405 GDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQInqRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVStkgLDCDI 484
Cdd:cd14626   166 SSEKREVRQFQFMAWPDHGVPEYPTPILAFLRRV--KACNPPDAGPMVVHCSAGVGRTGCFIVIDAMLERMK---HEKTV 240

                         250       260       270
                  ....*....|....*....|....*....|..
gi 1938958509 485 DIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQ 516
Cdd:cd14626   241 DIYGHVTCMRSQRNYMVQTEDQYIFIHEALLE 272
PTPc-N13 cd14597
catalytic domain of tyrosine-protein phosphatase non-receptor type 13; Tyrosine-protein ...
 271-514 1.05e-67

catalytic domain of tyrosine-protein phosphatase non-receptor type 13; Tyrosine-protein phosphatase non-receptor type 13 (PTPN13, also known as PTPL1) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Human PTPN13 is an important regulator of tumor aggressiveness. It regulates breast cancer cell aggressiveness through direct inactivation of Src kinase. In hepatocellular carcinoma, PTPN13 is a tumor suppressor. PTPN13 contains a FERM domain, five PDZ domains, and a C-terminal catalytic PTP domain. With its PDZ domains, PTPN13 has numerous interacting partners that can actively participate in the regulation of its phosphatase activity or can permit direct or indirect recruitment of tyrosine phosphorylated substrates. Its FERM domain is necessary for localization to the membrane.


Pssm-ID: 350445 [Multi-domain]  Cd Length: 234  Bit Score: 219.70  E-value: 1.05e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 271 ENKSKNRYKNILPFDHSRVILqGRDSnipgsDYINANYVKnqlLGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVIV 350
Cdd:cd14597     2 ENRKKNRYKNILPYDTTRVPL-GDEG-----GYINASFIK---MPVGDEEFVYIACQGPLPTTVADFWQMVWEQKSTVIA 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 351 MTTREVEKGRNKCVPYWPEV--GTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEP 428
Cdd:cd14597    73 MMTQEVEGGKIKCQRYWPEIlgKTTMVDNRLQLTLVRMQQLKNFVIRVLELEDIQTRE-VRHITHLNFTAWPDHDTPSQP 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 429 GGVLSFLDQINQRQESlphaGPIIVHCSAGIGRTGTIIVIDMLMESVSTkglDCDIDIQKTIQMVRAQRSGMVQTEAQYK 508
Cdd:cd14597   152 EQLLTFISYMRHIHKS----GPIITHCSAGIGRSGTLICIDVVLGLISK---DLDFDISDIVRTMRLQRHGMVQTEDQYI 224


                  ....*.
gi 1938958509 509 FIYVAI 514
Cdd:cd14597   225 FCYQVI 230
R5-PTPc-1 cd14549
catalytic domain of R5 subfamily receptor-type tyrosine-protein phosphatases, repeat 1; The R5 ...
 303-511 5.18e-67

catalytic domain of R5 subfamily receptor-type tyrosine-protein phosphatases, repeat 1; The R5 subfamily of receptor-type phosphotyrosine phosphatases (RPTP) is composed of receptor-type tyrosine-protein phosphatase Z (PTPRZ) and G (PTPRG). They belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. They are type 1 integral membrane proteins consisting of an extracellular region with a carbonic anhydrase-like (CAH) and a fibronectin type III (FN3) domains, and an intracellular region with a catalytic PTP domain (repeat 1) proximal to the membrane, and a catalytically inactive PTP-fold domain (repeat 2) distal to the membrane. This model represents the catalytic PTP domain (repeat 1).


Pssm-ID: 350397 [Multi-domain]  Cd Length: 204  Bit Score: 216.83  E-value: 5.18e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRvYGLYSVT 382
Cdd:cd14549     1 YINANYVDGY-----NKARAYIATQGPLPSTFDDFWRMVWEQNSAIIVMITNLVERGRRKCDQYWPKEGTET-YGNIQVT 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEHDTAEYKLRTLQISPL-----DNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLdqinqRQESL---PHAGPIIVH 454
Cdd:cd14549    75 LLSTEVLATYTVRTFSLKNLklkkvKGRSSERVVYQYHYTQWPDHGVPDYTLPVLSFV-----RKSSAanpPGAGPIVVH 149

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1938958509 455 CSAGIGRTGTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14549   150 CSAGVGRTGTYIVIDSMLQQIQDKG---TVNVFGFLKHIRTQRNYLVQTEEQYIFIH 203
R-PTPc-T-1 cd14630
catalytic domain of receptor-type tyrosine-protein phosphatase T, repeat 1; Receptor-type ...
 271-516 5.54e-66

catalytic domain of receptor-type tyrosine-protein phosphatase T, repeat 1; Receptor-type tyrosine-protein phosphatase T (PTPRT), also known as receptor-type tyrosine-protein phosphatase rho (RPTP-rho or PTPrho), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRT is highly expressed in the nervous system and it plays a critical role in regulation of synaptic formation and neuronal development. It dephosphorylates a specific tyrosine residue in syntaxin-binding protein 1, a key component of synaptic vesicle fusion machinery, and regulates its binding to syntaxin 1. PTPRT has been identified as a potential candidate gene for autism spectrum disorder (ASD) susceptibility. It contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the first (repeat 1) PTP domain.


Pssm-ID: 350478 [Multi-domain]  Cd Length: 237  Bit Score: 215.27  E-value: 5.54e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 271 ENKSKNRYKNILPFDHSRVILQGRDSNiPGSDYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIV 350
Cdd:cd14630     2 ENRNKNRYGNIISYDHSRVRLQLLDGD-PHSDYINANYIDGY-----HRPRHYIATQGPMQETVKDFWRMIWQENSASVV 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 351 MTTREVEKGRNKCVPYWPEvgTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGG 430
Cdd:cd14630    76 MVTNLVEVGRVKCVRYWPD--DTEVYGDIKVTLIETEPLAEYVIRTFTVQKKGYHE-IREIRQFHFTSWPDHGVPCYATG 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 431 VLSFLDQInqRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFI 510
Cdd:cd14630   153 LLGFVRQV--KFLNPPDAGPIVVHCSAGAGRTGCFIAIDIMLDMAENEGV---VDIFNCVRELRAQRVNMVQTEEQYVFV 227


                  ....*.
gi 1938958509 511 YVAIAQ 516
Cdd:cd14630   228 HDAILE 233
R-PTP-LAR-2 cd14554
PTP-like domain of the LAR family receptor-type tyrosine-protein phosphatases, repeat 2; The ...
 270-513 7.26e-65

PTP-like domain of the LAR family receptor-type tyrosine-protein phosphatases, repeat 2; The LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs) include three vertebrate members: LAR (or PTPRF), R-PTP-delta (or PTPRD), and R-PTP-sigma (or PTPRS). They belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. LAR-RPTPs are synaptic adhesion molecules; they bind to distinct synaptic membrane proteins and are physiologically responsible for mediating presynaptic development by shaping various synaptic adhesion pathways. They play roles in various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. LAR-RPTPs contain an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the non-catalytic PTP-like domain (repeat 2).


Pssm-ID: 350402 [Multi-domain]  Cd Length: 238  Bit Score: 212.38  E-value: 7.26e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 270 PENKSKNRYKNILPFDHSRVILQ---GRDsnipGSDYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENT 346
Cdd:cd14554     4 PCNKFKNRLVNILPYESTRVCLQpirGVE----GSDYINASFIDGY-----RQRGAYIATQGPLAETTEDFWRMLWEHNS 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 347 RVIVMTTREVEKGRNKCVPYWPEVGTQRvYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPS 426
Cdd:cd14554    75 TIIVMLTKLREMGREKCHQYWPAERSAR-YQYFVVDPMAEYNMPQYILREFKVTDARDGQ-SRTVRQFQFTDWPEQGVPK 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 427 EPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQ 506
Cdd:cd14554   153 SGEGFIDFIGQVHKTKEQFGQEGPITVHCSAGVGRTGVFITLSIVLERMRYEGV---VDVFQTVKLLRTQRPAMVQTEDQ 229


                  ....*..
gi 1938958509 507 YKFIYVA 513
Cdd:cd14554   230 YQFCYRA 236
R-PTPc-B cd14617
catalytic domain of receptor-type tyrosine-protein phosphatase B; Receptor-type ...
 276-511 2.64e-64

catalytic domain of receptor-type tyrosine-protein phosphatase B; Receptor-type tyrosine-protein phosphatase B (PTPRB), also known as receptor-type tyrosine-protein phosphatase beta (R-PTP-beta) or vascular endothelial protein tyrosine phosphatase(VE-PTP), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRB/VE-PTP is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It is expressed specifically in vascular endothelial cells and it plays an important role in blood vessel remodeling and angiogenesis.


Pssm-ID: 350465 [Multi-domain]  Cd Length: 228  Bit Score: 210.55  E-value: 2.64e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 276 NRYKNILPFDHSRVILQGRDSNiPGSDYINANYVknqllgPDEN-SKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTR 354
Cdd:cd14617     1 NRYNNILPYDSTRVKLSNVDDD-PCSDYINASYI------PGNNfRREYIATQGPLPGTKDDFWKMVWEQNVHNIVMVTQ 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 355 EVEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDLVREIWHYQYLSWPDHGVPSEPGGVLSF 434
Cdd:cd14617    74 CVEKGRVKCDHYWPADQDSLYYGDLIVQMLSESVLPEWTIREFKICSEEQLDAPRLVRHFHYTVWPDHGVPETTQSLIQF 153

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1938958509 435 LDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKgldCDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14617   154 VRTVRDYINRTPGSGPTVVHCSAGVGRTGTFIALDRILQQLDSK---DSVDIYGAVHDLRLHRVHMVQTECQYVYLH 227
R-PTPc-G-1 cd17667
catalytic domain of receptor-type tyrosine-protein phosphatase G, repeat 1; Receptor-type ...
 246-518 4.12e-63

catalytic domain of receptor-type tyrosine-protein phosphatase G, repeat 1; Receptor-type tyrosine-protein phosphatase G (PTPRG), also called protein-tyrosine phosphatase gamma (R-PTP-gamma), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRG is an important tumor suppressor gene in multiple human cancers such as lung, ovarian, and breast cancers. It is widely expressed in many tissues, including the central nervous system, where it plays a role during neuroinflammation processes. It can dephosphorylate platelet-derived growth factor receptor beta (PDGFRB) and may play a role in PDGFRB-related infantile myofibromatosis. PTPRG has four splicing isoforms: three transmembrane isoforms, PTPRG-A, B, and C, and one secretory isoform, PTPRG-S, which are expressed in many tissues including the brain. PTPRG is a type 1 integral membrane protein consisting of an extracellular region with a carbonic anhydrase-like (CAH) and a fibronectin type III (FN3) domains, and an intracellular region with a catalytic PTP domain (repeat 1) proximal to the membrane, and a catalytically inactive PTP-fold domain (repeat 2) distal to the membrane. This model represents the catalytic PTP domain (repeat 1).


Pssm-ID: 350505 [Multi-domain]  Cd Length: 274  Bit Score: 209.12  E-value: 4.12e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 246 FWEEFESLQKQEVKNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQ---GRDSNipGSDYINANYVKNQllgpdENSKT 322
Cdd:cd17667     1 FSEDFEEVQRCTADMNITAEHSNHPDNKHKNRYINILAYDHSRVKLRplpGKDSK--HSDYINANYVDGY-----NKAKA 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 323 YIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRvYGLYSVTNCKEHDTAEYKLRTLQI--S 400
Cdd:cd17667    74 YIATQGPLKSTFEDFWRMIWEQNTGIIVMITNLVEKGRRKCDQYWPTENSEE-YGNIIVTLKSTKIHACYTVRRFSIrnT 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 401 PLDNGDL--------VREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQesLPHAGPIIVHCSAGIGRTGTIIVIDMLM 472
Cdd:cd17667   153 KVKKGQKgnpkgrqnERTVIQYHYTQWPDMGVPEYALPVLTFVRRSSAAR--TPEMGPVLVHCSAGVGRTGTYIVIDSML 230

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 1938958509 473 ESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFI 518
Cdd:cd17667   231 QQIKDKS---TVNVLGFLKHIRTQRNYLVQTEEQYIFIHDALLEAI 273
PTPc-N12 cd14604
catalytic domain of tyrosine-protein phosphatase non-receptor type 12; Tyrosine-protein ...
 236-519 6.79e-63

catalytic domain of tyrosine-protein phosphatase non-receptor type 12; Tyrosine-protein phosphatase non-receptor type 12 (PTPN12), also called PTP-PEST or protein-tyrosine phosphatase G1 (PTPG1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN12 is characterized as a tumor suppressor and a pivotal regulator of EGFR/HER2 signaling. It regulates various physiological processes, including cell migration, immune response, and neuronal activity, by dephosphorylating multiple substrates including HER2, FAK, PYK2, PSTPIP, WASP, p130Cas, paxillin, Shc, catenin, c-Abl, ArgBP2, p190RhoGAP, RhoGDI, cell adhesion kinase beta, and Rho GTPase.


Pssm-ID: 350452 [Multi-domain]  Cd Length: 297  Bit Score: 209.40  E-value: 6.79e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 236 QESEDTAKAG---FWEEFESLQKQEVK----NLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRDSNIPgSDYINANY 308
Cdd:cd14604    14 QAMKSTDHNGednFASDFMRLRRLSTKyrteKIYPTATGEKEENVKKNRYKDILPFDHSRVKLTLKTSSQD-SDYINANF 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 309 VKNqLLGPdensKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRV-YGLYSVTNCKEH 387
Cdd:cd14604    93 IKG-VYGP----KAYIATQGPLANTVIDFWRMIWEYNVAIIVMACREFEMGRKKCERYWPLYGEEPMtFGPFRISCEAEQ 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 388 DTAEYKLRTLQISpLDNGdlVREIWHYQYLSWPDHGVPSEpggVLSFLDQINQRQESLPHAG-PIIVHCSAGIGRTGTII 466
Cdd:cd14604   168 ARTDYFIRTLLLE-FQNE--TRRLYQFHYVNWPDHDVPSS---FDSILDMISLMRKYQEHEDvPICIHCSAGCGRTGAIC 241

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1938958509 467 VIDMLMESVSTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIE 519
Cdd:cd14604   242 AIDYTWNLLKAGKIPEEFNVFNLIQEMRTQRHSAVQTKEQYELVHRAIAQLFE 294
PTPc-N7 cd14612
catalytic domain of tyrosine-protein phosphatase non-receptor type 7; Tyrosine-protein ...
 270-517 6.99e-63

catalytic domain of tyrosine-protein phosphatase non-receptor type 7; Tyrosine-protein phosphatase non-receptor type 7 (PTPN7), also called hematopoietic protein-tyrosine phosphatase (HePTP) or LC-PTP. belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN7/HePTP is a kinase interaction motif (KIM)-PTP, characterized by the presence of a 16-amino-acid KIM that binds specifically to members of the MAPK (mitogen-activated protein kinase) family. PTPN7/HePTP is found exclusively in the white blood cells in bone marrow, thymus, spleen, lymph nodes and all myeloid and lymphoid cell lines. It negatively regulates T-cell activation and proliferation, and is often dysregulated in the preleukemic disorder myelodysplastic syndrome, as well as in acute myelogenous leukemia.


Pssm-ID: 350460 [Multi-domain]  Cd Length: 247  Bit Score: 207.77  E-value: 6.99e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 270 PENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKnqllGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVI 349
Cdd:cd14612    13 PGHASKDRYKTILPNPQSRVCLRRAGSQEEEGSYINANYIR----GYDGKEKAYIATQGPMLNTVSDFWEMVWQEECPII 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 350 VMTTREVEKgRNKCVPYWPEvgTQRVYGLYSVTNCKEHDTAEYKLRTLQISpldNGDLVREIWHYQYLSWPDHGVPSEPG 429
Cdd:cd14612    89 VMITKLKEK-KEKCVHYWPE--KEGTYGRFEIRVQDMKECDGYTIRDLTIQ---LEEESRSVKHYWFSSWPDHQTPESAG 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 430 GVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKF 509
Cdd:cd14612   163 PLLRLVAEVEESRQTAASPGPIVVHCSAGIGRTGCFIATSIGCQQLKDTG---KVDILGIVCQLRLDRGGMIQTSEQYQF 239


                  ....*...
gi 1938958509 510 IYVAIAQF 517
Cdd:cd14612   240 LHHTLALY 247
PTPc-N22 cd14602
catalytic domain of tyrosine-protein phosphatase non-receptor type 22; Tyrosine-protein ...
 275-514 8.92e-63

catalytic domain of tyrosine-protein phosphatase non-receptor type 22; Tyrosine-protein phosphatase non-receptor type 22 (PTPN22), also called lymphoid phosphatase (LyP), PEST-domain phosphatase (PEP), or hematopoietic cell protein-tyrosine phosphatase 70Z-PEP, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN22 is expressed in hematopoietic cells and it functions as a key regulator of immune homeostasis by inhibiting T-cell receptor signaling through the direct dephosphorylation of Src family kinases (Lck and Fyn), ITAMs of the TCRz/CD3 complex, and other signaling molecules. Mutations in the PTPN22 gene are associated with multiple connective tissue and autoimmune diseases including type 1 diabetes mellitus, rheumatoid arthritis, and systemic lupus erythematosus. PTPN22 contains an N-terminal catalytic PTP domain and four proline-rich regions at the C-terminus.


Pssm-ID: 350450 [Multi-domain]  Cd Length: 234  Bit Score: 207.00  E-value: 8.92e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 275 KNRYKNILPFDHSRVILQGRDSNiPGSDYINANYVKNqLLGPdensKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTR 354
Cdd:cd14602     1 KNRYKDILPYDHSRVELSLITSD-EDSDYINANFIKG-VYGP----RAYIATQGPLSTTLLDFWRMIWEYSVLIIVMACM 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 355 EVEKGRNKCVPYWPEVGTQRV-YGLYSVTNCKEHDTAEYKLRTLQISpldNGDLVREIWHYQYLSWPDHGVPSEPGGVLS 433
Cdd:cd14602    75 EFEMGKKKCERYWAEPGEMQLeFGPFSVTCEAEKRKSDYIIRTLKVK---FNSETRTIYQFHYKNWPDHDVPSSIDPILE 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 434 FLDQINQRQESlpHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVA 513
Cdd:cd14602   152 LIWDVRCYQED--DSVPICIHCSAGCGRTGVICAIDYTWMLLKDGIIPENFSVFSLIQEMRTQRPSLVQTKEQYELVYNA 229


                  .
gi 1938958509 514 I 514
Cdd:cd14602   230 V 230
R-PTPc-S-1 cd14625
catalytic domain of receptor-type tyrosine-protein phosphatase S, repeat 1; Receptor-type ...
 227-518 9.58e-63

catalytic domain of receptor-type tyrosine-protein phosphatase S, repeat 1; Receptor-type tyrosine-protein phosphatase S (PTPRS), also known as receptor-type tyrosine-protein phosphatase sigma (R-PTP-sigma), belongs to the LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRS is a receptor for glycosaminoglycans, including heparan sulfate proteoglycan and neural chondroitin sulfate proteoglycans (CSPGs), which present a barrier to axon regeneration. It also plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. PTPRS contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the catalytic PTP domain (repeat 1).


Pssm-ID: 350473 [Multi-domain]  Cd Length: 282  Bit Score: 208.41  E-value: 9.58e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 227 NRVLELNKKQESEDTAKAGFWEefeslqkqevknlHQRLEgqrpENKSKNRYKNILPFDHSRVILQGRDSnIPGSDYINA 306
Cdd:cd14625    19 NDNLKLSQEYESIDPGQQFTWE-------------HSNLE----VNKPKNRYANVIAYDHSRVILQPIEG-IMGSDYINA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 307 NYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQrVYGLYSVTNCKE 386
Cdd:cd14625    81 NYIDGY-----RKQNAYIATQGPLPETFGDFWRMVWEQRSATVVMMTKLEEKSRIKCDQYWPSRGTE-TYGMIQVTLLDT 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 387 HDTAEYKLRTLQISPlDNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQInqRQESLPHAGPIIVHCSAGIGRTGTII 466
Cdd:cd14625   155 IELATFCVRTFSLHK-NGSSEKREVRQFQFTAWPDHGVPEYPTPFLAFLRRV--KTCNPPDAGPIVVHCSAGVGRTGCFI 231

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1938958509 467 VIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFI 518
Cdd:cd14625   232 VIDAMLERIKHEK---TVDIYGHVTLMRSQRNYMVQTEDQYSFIHDALLEAV 280
R-PTPc-D-1 cd14624
catalytic domain of receptor-type tyrosine-protein phosphatase D, repeat 1; Receptor-type ...
 246-518 1.12e-62

catalytic domain of receptor-type tyrosine-protein phosphatase D, repeat 1; Receptor-type tyrosine-protein phosphatase D (PTPRD), also known as receptor-type tyrosine-protein phosphatase delta (R-PTP-delta), belongs to the LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. LAR-RPTPs are synaptic adhesion molecules that play roles in various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. PTPRD is involved in pre-synaptic differentiation through interaction with SLITRK2. It contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the catalytic PTP domain (repeat 1).


Pssm-ID: 350472 [Multi-domain]  Cd Length: 284  Bit Score: 208.43  E-value: 1.12e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 246 FWEEFESLQK-QEVKNLHQRLEgqrpENKSKNRYKNILPFDHSRVILQGRDSnIPGSDYINANYVKNQllgpdENSKTYI 324
Cdd:cd14624    24 FSQEYESIDPgQQFTWEHSNLE----VNKPKNRYANVIAYDHSRVLLSAIEG-IPGSDYINANYIDGY-----RKQNAYI 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 325 ASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQrVYGLYSVTNCKEHDTAEYKLRTLQISPlDN 404
Cdd:cd14624    94 ATQGALPETFGDFWRMIWEQRSATVVMMTKLEERSRVKCDQYWPSRGTE-TYGLIQVTLLDTVELATYCVRTFALYK-NG 171

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 405 GDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQInqRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGldcDI 484
Cdd:cd14624   172 SSEKREVRQFQFTAWPDHGVPEHPTPFLAFLRRV--KTCNPPDAGPMVVHCSAGVGRTGCFIVIDAMLERIKHEK---TV 246

                         250       260       270
                  ....*....|....*....|....*....|....
gi 1938958509 485 DIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFI 518
Cdd:cd14624   247 DIYGHVTLMRAQRNYMVQTEDQYIFIHDALLEAV 280
PTPc-N1_2 cd14545
catalytic domain of tyrosine-protein phosphatase non-receptor type 1 and type 2; ...
 275-511 1.85e-62

catalytic domain of tyrosine-protein phosphatase non-receptor type 1 and type 2; Tyrosine-protein phosphatase non-receptor type 1 (PTPN1) type 2 (PTPN2) belong to the family of classical tyrosine-specific protein tyrosine phosphatases, (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN1 (or PTP-1B) is the first PTP to be purified and characterized and is the prototypical intracellular PTP found in a wide variety of human tissues. It dephosphorylates and regulates the activity of a number of receptor tyrosine kinases, including the insulin receptor, the EGF receptor, and the PDGF receptor. PTPN2 (or TCPTP), a tumor suppressor, dephosphorylates and inactivates EGFRs, Src family kinases, Janus-activated kinases (JAKs)-1 and -3, and signal transducer and activators of transcription (STATs)-1, -3 and -5, in a cell type and context-dependent manner.


Pssm-ID: 350393 [Multi-domain]  Cd Length: 231  Bit Score: 205.70  E-value: 1.85e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 275 KNRYKNILPFDHSRVILQGRDSnipGSDYINANYVKNQLLGpdensKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTR 354
Cdd:cd14545     1 LNRYRDRDPYDHDRSRVKLKQG---DNDYINASLVEVEEAK-----RSYILTQGPLPNTSGHFWQMVWEQNSKAVIMLNK 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 355 EVEKGRNKCVPYWP---EVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLdNGDLVREIWHYQYLSWPDHGVPSEPGGV 431
Cdd:cd14545    73 LMEKGQIKCAQYWPqgeGNAMIFEDTGLKVTLLSEEDKSYYTVRTLELENL-KTQETREVLHFHYTTWPDFGVPESPAAF 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 432 LSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDcDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14545   152 LNFLQKVRESGSLSSDVGPPVVHCSAGIGRSGTFCLVDTCLVLIEKGNPS-SVDVKKVLLEMRKYRMGLIQTPDQLRFSY 230
R-PTPc-O cd14614
catalytic domain of receptor-type tyrosine-protein phosphatase O; Receptor-type ...
 270-511 2.88e-62

catalytic domain of receptor-type tyrosine-protein phosphatase O; Receptor-type tyrosine-protein phosphatase O (PTPRO or R-PTP-O), also known as glomerular epithelial protein 1 or protein tyrosine phosphatase U2 (PTP-U2), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRO is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It is essential for sustaining the structure and function of foot processes by regulating tyrosine phosphorylation of podocyte proteins. It has been identified as a synaptic cell adhesion molecule (CAM) that serves as a potent initiator of synapse formation. It is also a tumor suppressor in several types of cancer, such as hepatocellular carcinoma, lung cancer, and breast cancer.


Pssm-ID: 350462 [Multi-domain]  Cd Length: 245  Bit Score: 205.89  E-value: 2.88e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 270 PENKSKNRYKNILPFDHSRVILQGRDSNiPGSDYINANYVknqllgPDENS-KTYIASQGCLDATVNDFWQMAWQENTRV 348
Cdd:cd14614    10 PVNRCKNRYTNILPYDFSRVKLVSMHEE-EGSDYINANYI------PGYNSpQEYIATQGPLPETRNDFWKMVLQQKSQI 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 349 IVMTTREVEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISpldNGDLVREIWHYQYLSWPDHGVPSEP 428
Cdd:cd14614    83 IVMLTQCNEKRRVKCDHYWPFTEEPVAYGDITVEMLSEEEQPDWAIREFRVS---YADEVQDVMHFNYTAWPDHGVPTAN 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 429 GG--VLSFLDQInqRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQ 506
Cdd:cd14614   160 AAesILQFVQMV--RQQAVKSKGPMIIHCSAGVGRTGTFIALDRLLQHIRDHEF---VDILGLVSEMRSYRMSMVQTEEQ 234


                  ....*
gi 1938958509 507 YKFIY 511
Cdd:cd14614   235 YIFIH 239
PTPc-N3 cd14600
catalytic domain of tyrosine-protein phosphatase non-receptor type 3; Tyrosine-protein ...
 270-514 5.71e-62

catalytic domain of tyrosine-protein phosphatase non-receptor type 3; Tyrosine-protein phosphatase non-receptor type 3 (PTPN3), also called protein-tyrosine phosphatase H1 (PTP-H1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN3 interacts with mitogen-activated protein kinase p38gamma and serves as its specific phosphatase. PTPN3 and p38gamma cooperate to promote Ras-induced oncogenesis. PTPN3 is a large modular protein containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain. Its PDZ domain binds with the PDZ-binding motif of p38gamma and enables efficient tyrosine dephosphorylation.


Pssm-ID: 350448 [Multi-domain]  Cd Length: 274  Bit Score: 206.24  E-value: 5.71e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 270 PENKSKNRYKNILPFDHSRVILQGRDsnipgsDYINANYVKNQLLGPDENSKtYIASQGCLDATVNDFWQMAWQENTRVI 349
Cdd:cd14600    38 PQNMDKNRYKDVLPYDATRVVLQGNE------DYINASYVNMEIPSANIVNK-YIATQGPLPHTCAQFWQVVWEQKLSLI 110

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 350 VMTTREVEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPG 429
Cdd:cd14600   111 VMLTTLTERGRTKCHQYWPDPPDVMEYGGFRVQCHSEDCTIAYVFREMLLTNTQTGE-ERTVTHLQYVAWPDHGVPDDSS 189

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 430 GVLSFLDQINQ-RQESLphagPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCDIDIqktIQMVRAQRSGMVQTEAQYK 508
Cdd:cd14600   190 DFLEFVNYVRSkRVENE----PVLVHCSAGIGRTGVLVTMETAMCLTERNQPVYPLDI---VRKMRDQRAMMVQTSSQYK 262


                  ....*.
gi 1938958509 509 FIYVAI 514
Cdd:cd14600   263 FVCEAI 268
R-PTPc-J cd14615
catalytic domain of receptor-type tyrosine-protein phosphatase J; Receptor-type ...
 276-510 6.84e-62

catalytic domain of receptor-type tyrosine-protein phosphatase J; Receptor-type tyrosine-protein phosphatase J (PTPRJ or R-PTP-J), also known as receptor-type tyrosine-protein phosphatase eta (R-PTP-eta) or density-enhanced phosphatase 1 (DEP-1) OR CD148, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRJ is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats (eight in PTPRJ) and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It is expressed in various cell types including epithelial, hematopoietic, and endothelial cells. It plays a role in cell adhesion, migration, proliferation and differentiation. It dephosphorylates or contributes to the dephosphorylation of various substrates including protein kinases such as FLT3, PDGFRB, MET, RET (variant MEN2A), VEGFR-2, LYN, SRC, MAPK1, MAPK3, and EGFR, as well as PIK3R1 and PIK3R2.


Pssm-ID: 350463 [Multi-domain]  Cd Length: 229  Bit Score: 204.28  E-value: 6.84e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 276 NRYKNILPFDHSRVILQgrDSNIPGSDYINANYVknqllgPDENS-KTYIASQGCLDATVNDFWQMAWQENTRVIVMTTR 354
Cdd:cd14615     1 NRYNNVLPYDISRVKLS--VQSHSTDDYINANYM------PGYNSkKEFIAAQGPLPNTVKDFWRMVWEKNVYAIVMLTK 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 355 EVEKGRNKCVPYWPEVGTQRvYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSF 434
Cdd:cd14615    73 CVEQGRTKCEEYWPSKQKKD-YGDITVTMTSEIVLPEWTIRDFTVKNAQTNE-SRTVRHFHFTSWPDHGVPETTDLLINF 150

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1938958509 435 LDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFI 510
Cdd:cd14615   151 RHLVREYMKQNPPNSPILVHCSAGVGRTGTFIAIDRLIYQIENENV---VDVYGIVYDLRMHRPLMVQTEDQYVFL 223
PTPc-N20_13 cd14538
catalytic domain of tyrosine-protein phosphatase non-receptor type 20 and type 13; ...
 303-516 5.47e-61

catalytic domain of tyrosine-protein phosphatase non-receptor type 20 and type 13; Tyrosine-protein phosphatase non-receptor type 20 (PTPN20) and type 13 (PTPN13, also known as PTPL1) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Human PTPN20 is a widely expressed phosphatase with a dynamic subcellular distribution that is targeted to sites of actin polymerization. Human PTPN13 is an important regulator of tumor aggressiveness.


Pssm-ID: 350386 [Multi-domain]  Cd Length: 207  Bit Score: 201.06  E-value: 5.47e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQLlgpDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEV--GTQRVYGLYS 380
Cdd:cd14538     1 YINASHIRIPV---GGDTYHYIACQGPLPNTTGDFWQMVWEQKSEVIAMVTQDVEGGKVKCHRYWPDSlnKPLICGGRLE 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 381 VTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQInqrqESLPHAGPIIVHCSAGIG 460
Cdd:cd14538    78 VSLEKYQSLQDFVIRRISLRDKETGE-VHHITHLNFTTWPDHGTPQSADPLLRFIRYM----RRIHNSGPIVVHCSAGIG 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1938958509 461 RTGTIIVIDMLMESVSTkglDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQ 516
Cdd:cd14538   153 RTGVLITIDVALGLIER---DLPFDIQDIVKDLREQRQGMIQTKDQYIFCYKACLE 205
R-PTPc-H cd14619
catalytic domain of receptor-type tyrosine-protein phosphatase H; Receptor-type ...
 276-518 1.55e-60

catalytic domain of receptor-type tyrosine-protein phosphatase H; Receptor-type tyrosine-protein phosphatase H (PTPRH or R-PTP-H), also known as stomach cancer-associated protein tyrosine phosphatase 1 (SAP-1), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRH is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It is localized specifically at microvilli of the brush border in gastrointestinal epithelial cells. It plays a role in intestinal immunity by regulating CEACAM20 through tyrosine dephosphorylation. It is also a negative regulator of integrin-mediated signaling and may contribute to contact inhibition of cell growth and motility.


Pssm-ID: 350467 [Multi-domain]  Cd Length: 233  Bit Score: 200.89  E-value: 1.55e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 276 NRYKNILPFDHSRVILQGRDSNiPGSDYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTRE 355
Cdd:cd14619     1 NRFRNVLPYDWSRVPLKPIHEE-PGSDYINANYMPGY-----WSSQEFIATQGPLPQTVGDFWRMIWEQQSSTIVMLTNC 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 356 VEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSFL 435
Cdd:cd14619    75 MEAGRVKCEHYWPLDYTPCTYGHLRVTVVSEEVMENWTVREFLLKQVEEQK-TLSVRHFHFTAWPDHGVPSSTDTLLAFR 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 436 DQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIA 515
Cdd:cd14619   154 RLLRQWLDQTMSGGPTVVHCSAGVGRTGTLIALDVLLQQLQSEGL---LGPFSFVQKMRENRPLMVQTESQYVFLHQCIL 230


                  ...
gi 1938958509 516 QFI 518
Cdd:cd14619   231 DFL 233
PTPc-N1 cd14608
catalytic domain of tyrosine-protein phosphatase non-receptor type 1; Tyrosine-protein ...
 270-518 2.22e-60

catalytic domain of tyrosine-protein phosphatase non-receptor type 1; Tyrosine-protein phosphatase non-receptor type 1 (PTPN1), also called protein-tyrosine phosphatase 1B (PTP-1B), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN1/PTP-1B is the first PTP to be purified and characterized and is the prototypical intracellular PTP found in a wide variety of human tissues. It contains an N-terminal catalytic PTP domain, followed by two tandem proline-rich motifs that mediate interaction with SH3-domain-containing proteins, and a small hydrophobic stretch that localizes the enzyme to the endoplasmic reticulum (ER). It dephosphorylates and regulates the activity of a number of receptor tyrosine kinases, including the insulin receptor, the EGF receptor, and the PDGF receptor.


Pssm-ID: 350456 [Multi-domain]  Cd Length: 277  Bit Score: 202.18  E-value: 2.22e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 270 PENKSKNRYKNILPFDHSRVILQGRDSnipgsDYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVI 349
Cdd:cd14608    23 PKNKNRNRYRDVSPFDHSRIKLHQEDN-----DYINASLIKME-----EAQRSYILTQGPLPNTCGHFWEMVWEQKSRGV 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 350 VMTTREVEKGRNKCVPYWPEVGTQRVygLYSVTNCK-----EHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGV 424
Cdd:cd14608    93 VMLNRVMEKGSLKCAQYWPQKEEKEM--IFEDTNLKltlisEDIKSYYTVRQLELENLTTQE-TREILHFHYTTWPDFGV 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 425 PSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCDIDIQKTIQMVRAQRSGMVQTE 504
Cdd:cd14608   170 PESPASFLNFLFKVRESGSLSPEHGPVVVHCSAGIGRSGTFCLADTCLLLMDKRKDPSSVDIKKVLLEMRKFRMGLIQTA 249

                         250
                  ....*....|....*..
gi 1938958509 505 AQYKFIYVAI---AQFI 518
Cdd:cd14608   250 DQLRFSYLAViegAKFI 266
PTPc-N3_4 cd14541
catalytic domain of tyrosine-protein phosphatase non-receptor type 21 and type 14; ...
 302-514 2.65e-60

catalytic domain of tyrosine-protein phosphatase non-receptor type 21 and type 14; Tyrosine-protein phosphatase non-receptor type 3 (PTPN3) and type 4 (PTPN4) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN3 and PTPN4 are large modular proteins containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain. PTPN3 interacts with mitogen-activated protein kinase p38gamma and serves as its specific phosphatase. PTPN4 functions in TCR cell signaling, apoptosis, cerebellar synaptic plasticity, and innate immune responses.


Pssm-ID: 350389 [Multi-domain]  Cd Length: 212  Bit Score: 199.48  E-value: 2.65e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 302 DYINANYVKNQLLGPDENSKtYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRVYGLYSV 381
Cdd:cd14541     1 DYINANYVNMEIPGSGIVNR-YIAAQGPLPNTCADFWQMVWEQKSTLIVMLTTLVERGRVKCHQYWPDLGETMQFGNLQI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 382 TNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLphAGPIIVHCSAGIGR 461
Cdd:cd14541    80 TCVSEEVTPSFAFREFILTNTNTGE-ERHITQMQYLAWPDHGVPDDSSDFLDFVKRVRQNRVGM--VEPTVVHCSAGIGR 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509 462 TGTIIVIDMLM------ESVSTkgldcdIDIQKTIqmvRAQRSGMVQTEAQYKFIYVAI 514
Cdd:cd14541   157 TGVLITMETAMclieanEPVYP------LDIVRTM---RDQRAMLIQTPSQYRFVCEAI 206
R-PTPc-R cd14611
catalytic domain of receptor-type tyrosine-protein phosphatase R; Receptor-type ...
 274-511 1.34e-59

catalytic domain of receptor-type tyrosine-protein phosphatase R; Receptor-type tyrosine-protein phosphatase-like R (PTPRR or R-PTP-R), also called protein-tyrosine phosphatase PCPTP1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRR is a kinase interaction motif (KIM)-PTP, characterized by the presence of a 16-amino-acid KIM that binds specifically to members of the MAPK (mitogen-activated protein kinase) family. The human and mouse PTPRR gene produces multiple neuronal protein isoforms of varying sizes (in human, PTPPBS-alpha, beta, gamma and delta). All isoforms contain the KIM motif and the catalytic PTP domain. PTPRR-deficient mice show significant defects in fine motor coordination and balance skills that are reminiscent of a mild ataxia.


Pssm-ID: 350459 [Multi-domain]  Cd Length: 226  Bit Score: 198.22  E-value: 1.34e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 274 SKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKnqllGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTT 353
Cdd:cd14611     1 TKNRYKTILPNPHSRVCLKPKNSNDSLSTYINANYIR----GYGGKEKAFIATQGPMINTVNDFWQMVWQEDSPVIVMIT 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 354 REVEKGRnKCVPYWPEvgTQRVYGLYSVTNCKEHDTAEYKLRTLQispLDNGDLVREIWHYQYLSWPDHGVPSEPGGVLS 433
Cdd:cd14611    77 KLKEKNE-KCVLYWPE--KRGIYGKVEVLVNSVKECDNYTIRNLT---LKQGSQSRSVKHYWYTSWPDHKTPDSAQPLLQ 150

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1938958509 434 FLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14611   151 LMLDVEEDRLASPGRGPVVVHCSAGIGRTGCFIATTIGCQQLKEEGV---VDVLSIVCQLRVDRGGMVQTSEQYEFVH 225
R-PTP-N2 cd14610
PTP-like domain of receptor-type tyrosine-protein phosphatase N2; Receptor-type ...
 267-516 2.02e-59

PTP-like domain of receptor-type tyrosine-protein phosphatase N2; Receptor-type tyrosine-protein phosphatase N2 (PTPRN2 or R-PTP-N2), also called islet cell autoantigen-related protein (IAR), ICAAR, phogrin, or IA-2beta, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). It consists of a large ectodomain that contains a RESP18HD (regulated endocrine-specific protein 18 homology domain), followed by a transmembrane segment, and a single, catalytically-impaired, PTP domain. It is mainly expressed in neuropeptidergic neurons and peptide-secreting endocrine cells, including insulin-producing pancreatic beta-cells. It may function as a phosphatidylinositol phosphatase to regulate insulin secretion. It is also required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain.


Pssm-ID: 350458 [Multi-domain]  Cd Length: 283  Bit Score: 199.90  E-value: 2.02e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 267 GQRPENKSKNRYKNILPFDHSRVILQGRDSNiPGSDYINANYVKNQllgpDENSKTYIASQGCLDATVNDFWQMAWQENT 346
Cdd:cd14610    39 AQREENVQKNRSLAVLPYDHSRIILKAENSH-SHSDYINASPIMDH----DPRNPAYIATQGPLPATVADFWQMVWESGC 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 347 RVIVMTTREVEKGRNKCVPYWPEVGTQrVYGLYSVTNCKEHDTAE-YKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVP 425
Cdd:cd14610   114 VVIVMLTPLAENGVKQCYHYWPDEGSN-LYHIYEVNLVSEHIWCEdFLVRSFYLKNLQTNE-TRTVTQFHFLSWNDQGVP 191

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 426 SEPGGVLSFLDQINQ--RQESLphagPIIVHCSAGIGRTGTIIVIDMLMESVStKGLDcDIDIQKTIQMVRAQRSGMVQT 503
Cdd:cd14610   192 ASTRSLLDFRRKVNKcyRGRSC----PIIVHCSDGAGRSGTYILIDMVLNKMA-KGAK-EIDIAATLEHLRDQRPGMVQT 265

                         250
                  ....*....|...
gi 1938958509 504 EAQYKFIYVAIAQ 516
Cdd:cd14610   266 KEQFEFALTAVAE 278
PTPc-N2 cd14607
catalytic domain of tyrosine-protein phosphatase non-receptor type 2; Tyrosine-protein ...
 270-514 2.15e-59

catalytic domain of tyrosine-protein phosphatase non-receptor type 2; Tyrosine-protein phosphatase non-receptor type 2 (PTPN2), also called T-cell protein-tyrosine phosphatase (TCPTP), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN2, a tumor suppressor, dephosphorylates and inactivates EGFRs, Src family kinases, Janus-activated kinases (JAKs)-1 and -3, and signal transducer and activators of transcription (STATs)-1, -3 and -5, in a cell type and context-dependent manner. It is deleted in 6% of all T-cell acute lymphoblastic leukemias and is associated with constitutive JAK1/STAT5 signaling and tumorigenesis.


Pssm-ID: 350455 [Multi-domain]  Cd Length: 257  Bit Score: 198.65  E-value: 2.15e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 270 PENKSKNRYKNILPFDHSRVILQGRDSnipgsDYINANyvknqLLGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVI 349
Cdd:cd14607    22 PENRNRNRYRDVSPYDHSRVKLQNTEN-----DYINAS-----LVVIEEAQRSYILTQGPLPNTCCHFWLMVWQQKTKAV 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 350 VMTTREVEKGRNKCVPYWP----EVGTQRVYGlYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVP 425
Cdd:cd14607    92 VMLNRIVEKDSVKCAQYWPtdeeEVLSFKETG-FSVKLLSEDVKSYYTVHLLQLENINSGE-TRTISHFHYTTWPDFGVP 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 426 SEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVID---MLMEsvstKGLDCDIDIQKTIQMVRAQRSGMVQ 502
Cdd:cd14607   170 ESPASFLNFLFKVRESGSLSPEHGPAVVHCSAGIGRSGTFSLVDtclVLME----KKDPDSVDIKQVLLDMRKYRMGLIQ 245

                         250
                  ....*....|..
gi 1938958509 503 TEAQYKFIYVAI 514
Cdd:cd14607   246 TPDQLRFSYMAV 257
R-PTPc-M-1 cd14633
catalytic domain of receptor-type tyrosine-protein phosphatase M, repeat 1; Receptor-type ...
 245-516 2.46e-59

catalytic domain of receptor-type tyrosine-protein phosphatase M, repeat 1; Receptor-type tyrosine-protein phosphatase M (PTPRM), also known as protein-tyrosine phosphatase mu (R-PTP-mu or PTPmu), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRM/PTPmu is a homophilic cell adhesion molecule expressed in CNS neurons and glia. It is required for E-, N-, and R-cadherin-dependent neurite outgrowth. Loss of PTPmu contributes to tumor cell migration and dispersal of human glioblastomas. PTPRM contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the first (repeat 1) PTP domain.


Pssm-ID: 350481 [Multi-domain]  Cd Length: 273  Bit Score: 199.11  E-value: 2.46e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 245 GFWEEFESLQKQEVKNLHQrleGQRPENKSKNRYKNILPFDHSRVILQGRDSNiPGSDYINANYVKNQllgpdENSKTYI 324
Cdd:cd14633    16 GFKEEYESFFEGQSAPWDS---AKKDENRMKNRYGNIIAYDHSRVRLQPIEGE-TSSDYINGNYIDGY-----HRPNHYI 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 325 ASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEvgTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDN 404
Cdd:cd14633    87 ATQGPMQETIYDFWRMVWHENTASIIMVTNLVEVGRVKCCKYWPD--DTEIYKDIKVTLIETELLAEYVIRTFAVEKRGV 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 405 GDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQInqRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdI 484
Cdd:cd14633   165 HE-IREIRQFHFTGWPDHGVPYHATGLLGFVRQV--KSKSPPNAGPLVVHCSAGAGRTGCFIVIDIMLDMAEREGV---V 238

                         250       260       270
                  ....*....|....*....|....*....|..
gi 1938958509 485 DIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQ 516
Cdd:cd14633   239 DIYNCVRELRSRRVNMVQTEEQYVFIHDAILE 270
PTPc-N5 cd14613
catalytic domain of tyrosine-protein phosphatase non-receptor type 5; Tyrosine-protein ...
 275-517 3.65e-59

catalytic domain of tyrosine-protein phosphatase non-receptor type 5; Tyrosine-protein phosphatase non-receptor type 5 (PTPN5), also called striatum-enriched protein-tyrosine phosphatase (STEP) or neural-specific PTP, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN5/STEP is a kinase interaction motif (KIM)-PTP, characterized by the presence of a 16-amino-acid KIM that binds specifically to members of the MAPK (mitogen-activated protein kinase) family. It is a CNS-enriched protein that regulates key signaling proteins required for synaptic strengthening, as well as NMDA and AMPA receptor trafficking. PTPN5 is implicated in multiple neurologic and neuropsychiatric disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, and fragile X syndrome.


Pssm-ID: 350461 [Multi-domain]  Cd Length: 258  Bit Score: 198.16  E-value: 3.65e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 275 KNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKnqllGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTr 354
Cdd:cd14613    28 KNRYKTILPNPHSRVCLTSPDQDDPLSSYINANYIR----GYGGEEKVYIATQGPTVNTVGDFWRMVWQERSPIIVMIT- 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 355 EVEKGRNKCVPYWPEvgTQRVYGLYSVTNCKEHDTAEYKLRTLQispLDNGDLVREIWHYQYLSWPDHGVPSEPGGVLSF 434
Cdd:cd14613   103 NIEEMNEKCTEYWPE--EQVTYEGIEITVKQVIHADDYRLRLIT---LKSGGEERGLKHYWYTSWPDQKTPDNAPPLLQL 177

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 435 LDQINQ-RQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYVA 513
Cdd:cd14613   178 VQEVEEaRQQAEPNCGPVIVHCSAGIGRTGCFIATSICCKQLRNEGV---VDILRTTCQLRLDRGGMIQTCEQYQFVHHV 254


                  ....
gi 1938958509 514 IAQF 517
Cdd:cd14613   255 LSLY 258
R-PTP-D-2 cd14628
PTP-like domain of receptor-type tyrosine-protein phosphatase D, repeat 2; Receptor-type ...
 218-518 1.05e-58

PTP-like domain of receptor-type tyrosine-protein phosphatase D, repeat 2; Receptor-type tyrosine-protein phosphatase-like D (PTPRD), also known as receptor-type tyrosine-protein phosphatase delta (R-PTP-delta), belongs to the LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. LAR-RPTPs are synaptic adhesion molecules that play roles in various aspects of neuronal development, including axon guidance, neurite extension, and synapse formation and function. PTPRD is involved in pre-synaptic differentiation through interaction with SLITRK2. It contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the non-catalytic PTP-like domain (repeat 2). Although described as non-catalytic, this domain contains the catalytic cysteine and the active site signature motif, HCSAGxGRxG.


Pssm-ID: 350476 [Multi-domain]  Cd Length: 292  Bit Score: 198.03  E-value: 1.05e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 218 TRVNAADIENRVLELNKKQESEDTAkaGFWEEFESLQKQEVkNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRdSN 297
Cdd:cd14628     1 TEVPARNLYAYIQKLTQIETGENVT--GMELEFKRLASSKA-HTSRFISANLPCNKFKNRLVNIMPYESTRVCLQPI-RG 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 298 IPGSDYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRvYG 377
Cdd:cd14628    77 VEGSDYINASFIDGY-----RQQKAYIATQGPLAETTEDFWRMLWEHNSTIVVMLTKLREMGREKCHQYWPAERSAR-YQ 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 378 LYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSA 457
Cdd:cd14628   151 YFVVDPMAEYNMPQYILREFKVTDARDGQ-SRTVRQFQFTDWPEQGVPKSGEGFIDFIGQVHKTKEQFGQDGPISVHCSA 229

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1938958509 458 GIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFI 518
Cdd:cd14628   230 GVGRTGVFITLSIVLERMRYEGV---VDIFQTVKMLRTQRPAMVQTEDQYQFCYRAALEYL 287
R-PTPc-E-1 cd14620
catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 1; Receptor-type ...
 278-514 1.20e-58

catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 1; Receptor-type tyrosine-protein phosphatase E (PTPRE), also known as receptor-type tyrosine-protein phosphatase epsilon (R-PTP-epsilon), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. The PTPRE gene contains two distinct promoters that generate the two major isoforms: transmembrane (receptor type RPTPe or PTPeM) and cytoplasmic (cyt-PTPe or PTPeC). Receptor type RPTPe plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells, and may also play a role in osteoclast formation and function. It also negatively regulates PDGFRbeta-mediated signaling pathways that are crucial for the pathogenesis of atherosclerosis. cyt-PTPe acts as a negative regulator of insulin receptor signaling in skeletal muscle. It regulates insulin-induced phosphorylation of proteins downstream of the insulin receptor. Receptor type RPTPe contains a small extracellular region, a single transmembrane segment, and an intracellular region two tandem catalytic PTP domains. This model represents the first PTP domain (repeat 1).


Pssm-ID: 350468 [Multi-domain]  Cd Length: 229  Bit Score: 195.93  E-value: 1.20e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 278 YKNILPFDHSRVILQGRDSNiPGSDYINANYVKnqllGPDENSKtYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVE 357
Cdd:cd14620     1 YPNILPYDHSRVILSQLDGI-PCSDYINASYID----GYKEKNK-FIAAQGPKQETVNDFWRMVWEQKSATIVMLTNLKE 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 358 KGRNKCVPYWPEVGTQrVYGlySVTNCKEHDT--AEYKLRTLQISPL--DNGDLVREIWHYQYLSWPDHGVPSEPGGVLS 433
Cdd:cd14620    75 RKEEKCYQYWPDQGCW-TYG--NIRVAVEDCVvlVDYTIRKFCIQPQlpDGCKAPRLVTQLHFTSWPDFGVPFTPIGMLK 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 434 FLDQINQRQESlpHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVA 513
Cdd:cd14620   152 FLKKVKSVNPV--HAGPIVVHCSAGVGRTGTFIVIDAMIDMMHAEQ---KVDVFEFVSRIRNQRPQMVQTDMQYSFIYQA 226


                  .
gi 1938958509 514 I 514
Cdd:cd14620   227 L 227
PTPc-N21_14 cd14540
catalytic domain of tyrosine-protein phosphatase non-receptor type 21 and type 14; ...
 303-518 3.00e-58

catalytic domain of tyrosine-protein phosphatase non-receptor type 21 and type 14; Tyrosine-protein phosphatase non-receptor type 21 (PTPN21) and type 14 (PTPN14) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Both PTPN21 and PTPN14 contain an N-terminal FERM domain and a C-terminal catalytic PTP domain, separated by a long intervening sequence.


Pssm-ID: 350388 [Multi-domain]  Cd Length: 219  Bit Score: 194.21  E-value: 3.00e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQLLGpdeNSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQR---VYGLY 379
Cdd:cd14540     1 YINASHITATVGG---KQRFYIAAQGPLQNTVGDFWQMVWEQGVYLVVMVTAEEEGGREKCFRYWPTLGGEHdalTFGEY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 380 SVTNCKEHDTAEYKLRTLQISPLdNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQ-----RQESLPHA--GPII 452
Cdd:cd14540    78 KVSTKFSVSSGCYTTTGLRVKHT-LSGQSRTVWHLQYTDWPDHGCPEDVSGFLDFLEEINSvrrhtNQDVAGHNrnPPTL 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1938958509 453 VHCSAGIGRTGTIIVIDMLMESVSTkglDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFI 518
Cdd:cd14540   157 VHCSAGVGRTGVVILADLMLYCLDH---NEELDIPRVLALLRHQRMLLVQTLAQYKFVYNVLIQYL 219
R-PTP-S-2 cd14627
PTP-like domain of receptor-type tyrosine-protein phosphatase S, repeat 2; Receptor-type ...
 270-518 5.71e-58

PTP-like domain of receptor-type tyrosine-protein phosphatase S, repeat 2; Receptor-type tyrosine-protein phosphatase S (PTPRS), also known as receptor-type tyrosine-protein phosphatase sigma (R-PTP-sigma), belongs to the LAR (leukocyte common antigen-related) family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRS is a receptor for glycosaminoglycans, including heparan sulfate proteoglycan and neural chondroitin sulfate proteoglycans (CSPGs), which present a barrier to axon regeneration. It also plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. PTPRS contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the non-catalytic PTP-like domain (repeat 2). Although described as non-catalytic, this domain contains the catalytic cysteine and the active site signature motif, HCSAGxGRxG.


Pssm-ID: 350475 [Multi-domain]  Cd Length: 290  Bit Score: 196.11  E-value: 5.71e-58
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 270 PENKSKNRYKNILPFDHSRVILQGRdSNIPGSDYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVI 349
Cdd:cd14627    51 PCNKFKNRLVNIMPYETTRVCLQPI-RGVEGSDYINASFIDGY-----RQQKAYIATQGPLAETTEDFWRMLWENNSTIV 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 350 VMTTREVEKGRNKCVPYWPEVGTQRvYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPG 429
Cdd:cd14627   125 VMLTKLREMGREKCHQYWPAERSAR-YQYFVVDPMAEYNMPQYILREFKVTDARDGQ-SRTVRQFQFTDWPEQGVPKSGE 202

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 430 GVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKF 509
Cdd:cd14627   203 GFIDFIGQVHKTKEQFGQDGPISVHCSAGVGRTGVFITLSIVLERMRYEGV---VDIFQTVKMLRTQRPAMVQTEDEYQF 279


                  ....*....
gi 1938958509 510 IYVAIAQFI 518
Cdd:cd14627   280 CYQAALEYL 288
R-PTPc-A-1 cd14621
catalytic domain of receptor-type tyrosine-protein phosphatase A, repeat 1; Receptor-type ...
 231-516 1.39e-57

catalytic domain of receptor-type tyrosine-protein phosphatase A, repeat 1; Receptor-type tyrosine-protein phosphatase A (PTPRA), also known as receptor-type tyrosine-protein phosphatase alpha (R-PTP-alpha), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRA is a positive regulator of Src and Src family kinases via dephosphorylation of the Src-inhibitory tyrosine 527. Thus, it affects transformation and tumorigenesis, inhibition of proliferation, cell cycle arrest, integrin signaling, neuronal differentiation and outgrowth, and ion channel activity. It is also involved in interleukin-1 signaling in fibroblasts through its interaction with the focal adhesion targeting domain of focal adhesion kinase. PTPRA comprises a small extracellular domain, a transmembrane segment, and an intracellular region containing two tandem catalytic PTP domains. This model represents the first catalytic PTP domain (repeat 1).


Pssm-ID: 350469 [Multi-domain]  Cd Length: 296  Bit Score: 195.24  E-value: 1.39e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 231 ELNKKQESEDTAkagFWEEFESLQKQEVKNLHQrlEGQRPENKSKNRYKNILPFDHSRVILQGRDSnIPGSDYINANYVK 310
Cdd:cd14621    16 EINRRMADDNKL---FREEFNALPACPIQATCE--AASKEENKEKNRYVNILPYDHSRVHLTPVEG-VPDSDYINASFIN 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 311 nqllGPDENSKtYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQrVYGLYSVTNCKEHDTA 390
Cdd:cd14621    90 ----GYQEKNK-FIAAQGPKEETVNDFWRMIWEQNTATIVMVTNLKERKECKCAQYWPDQGCW-TYGNIRVSVEDVTVLV 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 391 EYKLRTL---QISPLDNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESlpHAGPIIVHCSAGIGRTGTIIV 467
Cdd:cd14621   164 DYTVRKFciqQVGDVTNKKPQRLITQFHFTSWPDFGVPFTPIGMLKFLKKVKNCNPQ--YAGAIVVHCSAGVGRTGTFIV 241

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 1938958509 468 IDMLMESVstkGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQ 516
Cdd:cd14621   242 IDAMLDMM---HAERKVDVYGFVSRIRAQRCQMVQTDMQYVFIYQALLE 287
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 6-103 2.08e-57

N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198203  Cd Length: 99  Bit Score: 187.61  E-value: 2.08e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYYTQQQ 85
Cdd:cd10340     2 WFHPVISGIEAENLLKTRGVDGSFLARPSKSNPGDFTLSVRRGDEVTHIKIQNTGDYYDLYGGEKFATLSELVQYYMEQH 81

                          90
                  ....*....|....*...
gi 1938958509  86 GILQDRDGTIIHLKYPLN 103
Cdd:cd10340    82 GQLREKNGDVIELKYPLN 99
PTPc-N14 cd14599
catalytic domain of tyrosine-protein phosphatase non-receptor type 14; Tyrosine-protein ...
 270-519 7.04e-57

catalytic domain of tyrosine-protein phosphatase non-receptor type 14; Tyrosine-protein phosphatase non-receptor type 14 (PTPN14), also called protein-tyrosine phosphatase pez, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN14 is a potential tumor suppressor and plays a regulatory role in the Hippo and Wnt/beta-catenin signaling pathways. It contains an N-terminal FERM domain and a C-terminal catalytic PTP domain, separated by a long intervening sequence.


Pssm-ID: 350447 [Multi-domain]  Cd Length: 287  Bit Score: 193.29  E-value: 7.04e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 270 PENKSKNRYKNILPFDHSRVILQGRDSNIPGsdYINANYVKNQLLGPDENsktYIASQGCLDATVNDFWQMAWQENTRVI 349
Cdd:cd14599    36 PENAERNRIREVVPYEENRVELVPTKENNTG--YINASHIKVTVGGEEWH---YIATQGPLPHTCHDFWQMVWEQGVNVI 110

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 350 VMTTREVEKGRNKCVPYWPEVGTQR---VYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPS 426
Cdd:cd14599   111 AMVTAEEEGGRSKSHRYWPKLGSKHssaTYGKFKVTTKFRTDSGCYATTGLKVKHLLSGQ-ERTVWHLQYTDWPDHGCPE 189

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 427 EPGGVLSFLDQINQ-RQESLPHAG-------PIIVHCSAGIGRTGTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRS 498
Cdd:cd14599   190 EVQGFLSYLEEIQSvRRHTNSMLDstkncnpPIVVHCSAGVGRTGVVILTELMIGCLEHNE---KVEVPVMLRHLREQRM 266

                         250       260
                  ....*....|....*....|.
gi 1938958509 499 GMVQTEAQYKFIYVAIAQFIE 519
Cdd:cd14599   267 FMIQTIAQYKFVYQVLIQFLK 287
R-PTPc-typeIIb-1 cd14555
catalytic domain of type IIb (or R2B) subfamily receptor-type tyrosine-protein phosphatases, ...
 303-514 4.55e-56

catalytic domain of type IIb (or R2B) subfamily receptor-type tyrosine-protein phosphatases, repeat 1; The type II (or R2B) subfamily of receptor protein tyrosine phosphatases (RPTPs) include the prototypical member PTPmu (or PTPRM), PCP-2 (or PTPRU), PTPrho (or PTPRT), and PTPkappa (or PTPRK). They belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Type IIb RPTPs mediate cell-cell adhesion though homophilic interactions; their ligand is an identical molecule on an adjacent cell. No heterophilic interactions between the subfamily members have been observed. They also commonly function as tumor suppressors. They contain an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the first (repeat 1) PTP domain.


Pssm-ID: 350403 [Multi-domain]  Cd Length: 204  Bit Score: 188.20  E-value: 4.55e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEvgTQRVYGLYSVT 382
Cdd:cd14555     1 YINANYIDGY-----HRPNHYIATQGPMQETVYDFWRMVWQENSASIVMVTNLVEVGRVKCSRYWPD--DTEVYGDIKVT 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQInqRQESLPHAGPIIVHCSAGIGRT 462
Cdd:cd14555    74 LVETEPLAEYVVRTFALERRGYHE-IREVRQFHFTGWPDHGVPYHATGLLGFIRRV--KASNPPSAGPIVVHCSAGAGRT 150

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1938958509 463 GTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAI 514
Cdd:cd14555   151 GCYIVIDIMLDMAEREGV---VDIYNCVKELRSRRVNMVQTEEQYIFIHDAI 199
R-PTPc-K-1 cd14631
catalytic domain of receptor-type tyrosine-protein phosphatase K, repeat 1; Receptor-type ...
 288-516 7.12e-56

catalytic domain of receptor-type tyrosine-protein phosphatase K, repeat 1; Receptor-type tyrosine-protein phosphatase K (PTPRK), also known as receptor-type tyrosine-protein phosphatase kappa (RPTP-kappa or PTPkappa), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRK is widely expressed and has been shown to stimulate cell motility and neurite outgrowth. It is required for anti-proliferative and pro-migratory effects of TGF-beta, suggesting a role in regulation, maintenance, and restoration of cell adhesion. It is a potential tumour suppressor in primary central nervous system lymphomas, colorectal cancer, and breast cancer. It contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the first (repeat 1) PTP domain.


Pssm-ID: 350479 [Multi-domain]  Cd Length: 218  Bit Score: 187.92  E-value: 7.12e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 288 RVILQGRDSNiPGSDYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYW 367
Cdd:cd14631     1 RVILQPVEDD-PSSDYINANYIDGY-----QRPSHYIATQGPVHETVYDFWRMIWQEQSACIVMVTNLVEVGRVKCYKYW 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 368 PEvgTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQInqRQESLPH 447
Cdd:cd14631    75 PD--DTEVYGDFKVTCVEMEPLAEYVVRTFTLERRGYNE-IREVKQFHFTGWPDHGVPYHATGLLSFIRRV--KLSNPPS 149

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509 448 AGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQ 516
Cdd:cd14631   150 AGPIVVHCSAGAGRTGCYIVIDIMLDMAEREGV---VDIYNCVKALRSRRINMVQTEEQYIFIHDAILE 215
R-PTP-F-2 cd14629
PTP-like domain of receptor-type tyrosine-protein phosphatase F, repeat 2; Receptor-type ...
 270-518 1.06e-55

PTP-like domain of receptor-type tyrosine-protein phosphatase F, repeat 2; Receptor-type tyrosine-protein phosphatase F (PTPRF), also known as leukocyte common antigen related (LAR), is the prototypical member of the LAR family of receptor-type tyrosine-protein phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRF/LAR plays a role for LAR in cadherin complexes where it associates with and dephosphorylates beta-catenin, a pathway which may be critical for cadherin complex stability and cell-cell association. It also regulates focal adhesions through cyclin-dependent kinase-1 and is involved in axon guidance in the developing nervous system. It also functions in regulating insulin signaling. PTPRF contains an extracellular region with three immunoglobulin-like (Ig) domains and four to eight fibronectin type III (FN3) repeats (determined by alternative splicing), a single transmembrane domain, followed by an intracellular region with a membrane-proximal catalytic PTP domain (repeat 1, also called D1) and a membrane-distal non-catalytic PTP-like domain (repeat 2, also called D2). This model represents the non-catalytic PTP-like domain (repeat 2). Although described as non-catalytic, this domain contains the catalytic cysteine and the active site signature motif, HCSAGxGRxG.


Pssm-ID: 350477 [Multi-domain]  Cd Length: 291  Bit Score: 190.32  E-value: 1.06e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 270 PENKSKNRYKNILPFDHSRVILQGRdSNIPGSDYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVI 349
Cdd:cd14629    51 PCNKFKNRLVNIMPYELTRVCLQPI-RGVEGSDYINASFIDGY-----RQQKAYIATQGPLAETTEDFWRMLWEHNSTIV 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 350 VMTTREVEKGRNKCVPYWPEVGTQRvYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPG 429
Cdd:cd14629   125 VMLTKLREMGREKCHQYWPAERSAR-YQYFVVDPMAEYNMPQYILREFKVTDARDGQ-SRTIRQFQFTDWPEQGVPKTGE 202

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 430 GVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKF 509
Cdd:cd14629   203 GFIDFIGQVHKTKEQFGQDGPITVHCSAGVGRTGVFITLSIVLERMRYEGV---VDMFQTVKTLRTQRPAMVQTEDQYQL 279


                  ....*....
gi 1938958509 510 IYVAIAQFI 518
Cdd:cd14629   280 CYRAALEYL 288
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 111-217 2.60e-55

C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [SIVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198185  Cd Length: 99  Bit Score: 182.09  E-value: 2.60e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 111 RWYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQPKagpgsplrVTHIKVMCEGGRYTVGGSETFDSLT 190
Cdd:cd09931     1 RWFHGHLSGKEAEKLLLEKGKPGSFLVRESQSKPGDFVLSVRTDDDK--------VTHIMIRCQGGKYDVGGGEEFDSLT 72

                          90       100
                  ....*....|....*....|....*..
gi 1938958509 191 DLVEHFKKTGIEEASGAFVYLRQPYYA 217
Cdd:cd09931    73 DLVEHYKKNPMVETSGTVVHLKQPLNA 99
R-PTP-N cd14609
PTP-like domain of receptor-type tyrosine-protein phosphatase N; Receptor-type ...
 267-516 2.77e-55

PTP-like domain of receptor-type tyrosine-protein phosphatase N; Receptor-type tyrosine-protein phosphatase-like N (PTPRN or R-PTP-N), also called islet cell antigen 512 (ICA512) or PTP IA-2, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). It consists of a large ectodomain that contains a RESP18HD (regulated endocrine-specific protein 18 homology domain), followed by a transmembrane segment, and a single, catalytically-impaired, PTP domain. PTPRN is located in secretory granules of neuroendocrine cells and is involved in the generation, cargo storage, traffic, exocytosis and recycling of insulin secretory granules, as well as in beta-cell proliferation. It is a major autoantigen in type 1 diabetes and is involved in the regulation of insulin secretion.


Pssm-ID: 350457 [Multi-domain]  Cd Length: 281  Bit Score: 188.71  E-value: 2.77e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 267 GQRPENKSKNRYKNILPFDHSRVILQGrDSNIPGSDYINANYVKNQllgpDENSKTYIASQGCLDATVNDFWQMAWQENT 346
Cdd:cd14609    37 AQGEANVKKNRNPDFVPYDHARIKLKA-ESNPSRSDYINASPIIEH----DPRMPAYIATQGPLSHTIADFWQMVWENGC 111

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 347 RVIVMTTREVEKGRNKCVPYWPEVGTQrVYGLYSVTNCKEHDTAE-YKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVP 425
Cdd:cd14609   112 TVIVMLTPLVEDGVKQCDRYWPDEGSS-LYHIYEVNLVSEHIWCEdFLVRSFYLKNVQTQE-TRTLTQFHFLSWPAEGIP 189

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 426 SEPGGVLSFLDQINQ--RQESLphagPIIVHCSAGIGRTGTIIVIDMLMESVStKGLDcDIDIQKTIQMVRAQRSGMVQT 503
Cdd:cd14609   190 SSTRPLLDFRRKVNKcyRGRSC----PIIVHCSDGAGRTGTYILIDMVLNRMA-KGVK-EIDIAATLEHVRDQRPGMVRT 263

                         250
                  ....*....|...
gi 1938958509 504 EAQYKFIYVAIAQ 516
Cdd:cd14609   264 KDQFEFALTAVAE 276
PTPc-N22_18_12 cd14542
catalytic domain of tyrosine-protein phosphatase non-receptor type 22, type 18 and type 12; ...
 303-511 6.22e-55

catalytic domain of tyrosine-protein phosphatase non-receptor type 22, type 18 and type 12; Tyrosine-protein phosphatase non-receptor type 22 (PTPN22), type 18 (PTPN18) and type 12 (PTPN12) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN22 is expressed in hematopoietic cells and it functions as a key regulator of immune homeostasis by inhibiting T-cell receptor signaling through the direct dephosphorylation of Src family kinases (Lck and Fyn), ITAMs of the TCRz/CD3 complex, and other signaling molecules. TPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination states. PTPN12 is characterized as a tumor suppressor and a pivotal regulator of EGFR/HER2 signaling.


Pssm-ID: 350390 [Multi-domain]  Cd Length: 202  Bit Score: 184.93  E-value: 6.22e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKnqllGPDeNSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVG-TQRVYGLYSV 381
Cdd:cd14542     1 YINANFIK----GVS-GSKAYIATQGPLPNTVLDFWRMIWEYNVQVIVMACREFEMGKKKCERYWPEEGeEQLQFGPFKI 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 382 TNCKEHD-TAEYKLRTLQispLDNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESlpHAGPIIVHCSAGIG 460
Cdd:cd14542    76 SLEKEKRvGPDFLIRTLK---VTFQKESRTVYQFHYTAWPDHGVPSSVDPILDLVRLVRDYQGS--EDVPICVHCSAGCG 150

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1938958509 461 RTGTIIVIDMLMESVSTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14542   151 RTGTICAIDYVWNLLKTGKIPEEFSLFDLVREMRKQRPAMVQTKEQYELVY 201
PTPc_plant_PTP1 cd17658
protein tyrosine phosphatase 1 from Arabidopsis thaliana and similar plant PTPs; Arabidopsis ...
 303-511 9.76e-55

protein tyrosine phosphatase 1 from Arabidopsis thaliana and similar plant PTPs; Arabidopsis thaliana protein tyrosine phosphatase 1 (AtPTP1) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. AtPTP1 dephosphorylates and inhibits MAP kinase 6 (MPK6) in non-oxidative stress conditions. Together with MAP kinase phosphatase 1 (MKP1) it expresses salicylic acid (SA) and camalexin biosynthesis, and therefore, modulating defense response.


Pssm-ID: 350496 [Multi-domain]  Cd Length: 206  Bit Score: 184.59  E-value: 9.76e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNqllgPD-ENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGR-NKCVPYWP-EVGTQRVYGLY 379
Cdd:cd17658     1 YINASLVET----PAsESLPKFIATQGPLPHTFEDFWEMVIQQRCPVIIMLTRLVDNYStAKCADYFPaEENESREFGRI 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 380 SVTNCKE-HDTAEYKLRTLQISPLDNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQeslPHAGPIIVHCSAG 458
Cdd:cd17658    77 SVTNKKLkHSQHSITLRVLEVQYIESEEPPLSVLHIQYPEWPDHGVPKDTRSVRELLKRLYGIP---PSAGPIVVHCSAG 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1938958509 459 IGRTGTIIVIDMLMESVsTKGLDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd17658   154 IGRTGAYCTIHNTIRRI-LEGDMSAVDLSKTVRKFRSQRIGMVQTQDQYIFCY 205
R-PTPc-V cd14618
catalytic domain of receptor-type tyrosine-protein phosphatase V; Receptor-type ...
 276-514 1.91e-53

catalytic domain of receptor-type tyrosine-protein phosphatase V; Receptor-type tyrosine-protein phosphatase V (PTPRV or R-PTP-V), also known as embryonic stem cell protein-tyrosine phosphatase (ES cell phosphatase) or osteotesticular protein-tyrosine phosphatase (OST-PTP), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRV is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. In rodents, it may play a role in the maintenance of pluripotency and may function in signaling pathways during bone remodeling. It is the only PTP whose function has been lost between rodent and human. The human OST-PTP gene is a pseudogene.


Pssm-ID: 350466 [Multi-domain]  Cd Length: 230  Bit Score: 182.06  E-value: 1.91e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 276 NRYKNILPFDHSRVILQgRDSNIPGSDYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTRE 355
Cdd:cd14618     1 NRYPHVLPYDHSRVRLS-QLGGEPHSDYINANFIPGY-----TSPQEFIATQGPLKKTIEDFWRLVWEQQVCNIIMLTVG 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 356 VEKGRNKCVPYWPEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQispLDNGDL--VREIWHYQYLSWPDHGVPSEPGGVLS 433
Cdd:cd14618    75 MENGRVLCDHYWPSESTPVSYGHITVHLLAQSSEDEWTRREFK---LWHEDLrkERRVKHLHYTAWPDHGIPESTSSLMA 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 434 FLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYVA 513
Cdd:cd14618   152 FRELVREHVQATKGKGPTLVHCSAGVGRSGTFIALDRLLRQLKEEKV---VDVFNTVYILRMHRYLMIQTLSQYIFLHSC 228


                  .
gi 1938958509 514 I 514
Cdd:cd14618   229 I 229
R-PTP-N-N2 cd14546
PTP-like domain of receptor-type tyrosine-protein phosphatase-like N and N2; Receptor-type ...
 303-516 3.08e-53

PTP-like domain of receptor-type tyrosine-protein phosphatase-like N and N2; Receptor-type tyrosine-protein phosphatase-like N (PTPRN) and N2 (PTPRN2) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). They consist of a large ectodomain that contains a RESP18HD (regulated endocrine-specific protein 18 homology domain), followed by a transmembrane segment, and a single, catalytically-impaired, PTP domain. They are mainly expressed in neuropeptidergic neurons and peptide-secreting endocrine cells, including insulin-producing pancreatic beta-cells, and are involved in involved in the generation, cargo storage, traffic, exocytosis and recycling of insulin secretory granules, as well as in beta-cell proliferation. They also are major autoantigens in type 1 diabetes and are involved in the regulation of insulin secretion.


Pssm-ID: 350394 [Multi-domain]  Cd Length: 208  Bit Score: 180.72  E-value: 3.08e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQllgpDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQrVYGLYSVT 382
Cdd:cd14546     1 YINASTIYDH----DPRNPAYIATQGPLPHTIADFWQMIWEQGCVVIVMLTRLQENGVKQCARYWPEEGSE-VYHIYEVH 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEHD-TAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLphAGPIIVHCSAGIGR 461
Cdd:cd14546    76 LVSEHIwCDDYLVRSFYLKNLQTSE-TRTVTQFHFLSWPDEGIPASAKPLLEFRRKVNKSYRGR--SCPIVVHCSDGAGR 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1938958509 462 TGTIIVIDMLMESVsTKGLDcDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQ 516
Cdd:cd14546   153 TGTYILIDMVLNRM-AKGAK-EIDIAATLEHLRDQRPGMVKTKDQFEFVLTAVAE 205
R-PTPc-C-1 cd14557
catalytic domain of receptor-type tyrosine-protein phosphatase C, repeat 1; Receptor-type ...
 303-511 7.55e-53

catalytic domain of receptor-type tyrosine-protein phosphatase C, repeat 1; Receptor-type tyrosine-protein phosphatase C (PTPRC), also known as CD45, leukocyte common antigen (LCA) or GP180, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRC/CD45 is found in all nucleated hematopoietic cells and is an essential regulator of T- and B-cell antigen receptor signaling. It controls immune response, both positively and negatively, by dephosphorylating a number of signaling molecules such as the Src family kinases, the CD3zeta chain of TCY, and ZAP-70 kinase. Mutations in the human PTPRC/CD45 gene are associated with severe combined immunodeficiency (SCID) and multiple sclerosis. PTPRC/CD45 contains an extracellular receptor-like region with fibronectin type III (FN3) repeats, a short transmembrane segment, and a cytoplasmic region comprising of a membrane proximal catalytically active PTP domain (repeat 1 or D1) and a membrane distal catalytically impaired PTP-like domain (repeat 2, or D2). This model represents repeat 1.


Pssm-ID: 350405 [Multi-domain]  Cd Length: 201  Bit Score: 179.25  E-value: 7.55e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGT-QRVYGLYSV 381
Cdd:cd14557     1 YINASYIDGF-----KEPRKYIAAQGPKDETVDDFWRMIWEQKSTVIVMVTRCEEGNRNKCAQYWPSMEEgSRAFGDVVV 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 382 TNCKEHDTAEYKLRTLQISPLDNGDLVREIWHYQYLSWPDHGVPSEPggvlSFLDQINQRQESLPHA--GPIIVHCSAGI 459
Cdd:cd14557    76 KINEEKICPDYIIRKLNINNKKEKGSGREVTHIQFTSWPDHGVPEDP----HLLLKLRRRVNAFNNFfsGPIVVHCSAGV 151

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1938958509 460 GRTGTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14557   152 GRTGTYIGIDAMLEGLEAEG---RVDVYGYVVKLRRQRCLMVQVEAQYILIH 200
PTPc-N4 cd14601
catalytic domain of tyrosine-protein phosphatase non-receptor type 4; Tyrosine-protein ...
 302-519 3.66e-52

catalytic domain of tyrosine-protein phosphatase non-receptor type 4; Tyrosine-protein phosphatase non-receptor type 4 (PTPN4), also called protein-tyrosine phosphatase MEG1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN4 functions in TCR cell signaling, apoptosis, cerebellar synaptic plasticity, and innate immune responses. It specifically inhibits the TRIF-dependent TLR4 pathway by suppressing tyrosine phosphorylation of TRAM. It is a large modular protein containing an N-terminal FERM domain, a PDZ domain and a C-terminal catalytic PTP domain; the PDZ domain regulates the catalytic activity of PTPN4.


Pssm-ID: 350449 [Multi-domain]  Cd Length: 212  Bit Score: 177.83  E-value: 3.66e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 302 DYINANYVKNQLLGPDENSKtYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRVYGLYSV 381
Cdd:cd14601     1 DYINANYINMEIPSSSIINR-YIACQGPLPNTCSDFWQMTWEQGSSMVVMLTTQVERGRVKCHQYWPEPSGSSSYGGFQV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 382 TNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQInqRQESLPHAGPIIVHCSAGIGR 461
Cdd:cd14601    80 TCHSEEGNPAYVFREMTLTNLEKNE-SRPLTQIQYIAWPDHGVPDDSSDFLDFVCLV--RNKRAGKDEPVVVHCSAGIGR 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1938958509 462 TGTIIVIDMLMESVSTKGLDCDIDIQKTIqmvRAQRSGMVQTEAQYKFIYVAIAQFIE 519
Cdd:cd14601   157 TGVLITMETAMCLIECNQPVYPLDIVRTM---RDQRAMMIQTPSQYRFVCEAILKVYE 211
R-PTPc-U-1 cd14632
catalytic domain of receptor-type tyrosine-protein phosphatase U, repeat 1; Receptor-type ...
 303-516 9.73e-52

catalytic domain of receptor-type tyrosine-protein phosphatase U, repeat 1; Receptor-type tyrosine-protein phosphatase U (PTPRU), also known as pancreatic carcinoma phosphatase 2 (PCP-2), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRU/PCP-2 is the most distant member of the type IIb subfamily and may have a distinct biological function other than cell-cell aggregation. It localizes to the adherens junctions and directly binds and dephosphorylates beta-catenin, and regulates the balance between signaling and adhesive beta-catenin. It plays an important role in the maintenance of epithelial integrity. PTPRU contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the first (repeat 1) PTP domain.


Pssm-ID: 350480 [Multi-domain]  Cd Length: 205  Bit Score: 176.78  E-value: 9.73e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEvgTQRVYGLYSVT 382
Cdd:cd14632     1 YINANYIDGY-----HRSNHFIATQGPKQEMVYDFWRMVWQEHCSSIVMITKLVEVGRVKCSKYWPD--DSDTYGDIKIT 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEHDTAEYKLRTLQISplDNGDLVR-EIWHYQYLSWPDHGVPSEPGGVLSFLDQInqRQESLPHAGPIIVHCSAGIGR 461
Cdd:cd14632    74 LLKTETLAEYSVRTFALE--RRGYSARhEVKQFHFTSWPEHGVPYHATGLLAFIRRV--KASTPPDAGPVVVHCSAGAGR 149

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1938958509 462 TGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQ 516
Cdd:cd14632   150 TGCYIVLDVMLDMAECEGV---VDIYNCVKTLCSRRINMIQTEEQYIFIHDAILE 201
PTPc-N21 cd14598
catalytic domain of tyrosine-protein phosphatase non-receptor type 21; Tyrosine-protein ...
 303-519 2.24e-51

catalytic domain of tyrosine-protein phosphatase non-receptor type 21; Tyrosine-protein phosphatase non-receptor type 21 (PTPN21), also called protein-tyrosine phosphatase D1, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPN21 is a component of a multivalent scaffold complex nucleated by focal adhesion kinase (FAK) at specific intracellular sites. It promotes cytoskeleton events that induce cell adhesion and migration by modulating Src-FAK signaling. It can also selectively associate with and stimulate Tec family kinases and modulate Stat3 activation. Human PTPN21 may also play a pathologic role in gastrointestinal tract tumorigenesis. PTPN21 contains an N-terminal FERM domain and a C-terminal catalytic PTP domain, separated by a long intervening sequence.


Pssm-ID: 350446 [Multi-domain]  Cd Length: 220  Bit Score: 176.32  E-value: 2.24e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQLLGPDENsktYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQR---VYGLY 379
Cdd:cd14598     1 YINASHIKVTVGGKEWD---YIATQGPLQNTCQDFWQMVWEQGVAIIAMVTAEEEGGREKSFRYWPRLGSRHntvTYGRF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 380 SVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQI-------NQRQESLPHAGPII 452
Cdd:cd14598    78 KITTRFRTDSGCYATTGLKIKHLLTGQ-ERTVWHLQYTDWPEHGCPEDLKGFLSYLEEIqsvrrhtNSTIDPKSPNPPVL 156

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1938958509 453 VHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIE 519
Cdd:cd14598   157 VHCSAGVGRTGVVILSEIMIACLEHNEM---LDIPRVLDMLRQQRMMMVQTLSQYTFVYKVLIQFLK 220
R-PTPc-A-E-1 cd14551
catalytic domain of receptor-type tyrosine-protein phosphatase A and E, repeat 1; ...
 303-511 9.47e-51

catalytic domain of receptor-type tyrosine-protein phosphatase A and E, repeat 1; Receptor-type tyrosine-protein phosphatase A (PTPRA) and E (PTPRE) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRA and PTPRE share several functions including regulation of Src family kinases and voltage-gated potassium (Kv) channels. They both contain a small extracellular domain, a transmembrane segment, and an intracellular region containing two tandem catalytic PTP domains. This model represents the first catalytic PTP domain (repeat 1).


Pssm-ID: 350399 [Multi-domain]  Cd Length: 202  Bit Score: 173.95  E-value: 9.47e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKnqllGPDENSKtYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGtQRVYGlySVT 382
Cdd:cd14551     1 YINASYID----GYQEKNK-FIAAQGPKDETVNDFWRMIWEQGSATIVMVTNLKERKEKKCSQYWPDQG-CWTYG--NLR 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEHDT--AEYKLRTLQISPLDNG---DLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQInqRQESLPHAGPIIVHCSA 457
Cdd:cd14551    73 VRVEDTVvlVDYTTRKFCIQKVNRGigeKRVRLVTQFHFTSWPDFGVPFTPIGMLKFLKKV--KSANPPRAGPIVVHCSA 150

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1938958509 458 GIGRTGTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14551   151 GVGRTGTFIVIDAMLDMMHAEG---KVDVFGFVSRIRQQRSQMVQTDMQYVFIY 201
R-PTPc-Q cd14616
catalytic domain of receptor-type tyrosine-protein phosphatase Q; Receptor-type ...
 276-511 2.02e-50

catalytic domain of receptor-type tyrosine-protein phosphatase Q; Receptor-type tyrosine-protein phosphatase Q (PTPRQ or R-PTP-Q), also called phosphatidylinositol phosphatase PTPRQ, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRQ is a member of the R3 subfamily of receptor-type phosphotyrosine phosphatases (RPTP), characterized by a unique modular composition consisting of multiple extracellular fibronectin type III (FN3) repeats (18 in PTPRQ) and a single (most RPTP subtypes have two) cytoplasmic catalytic PTP domain. It displays low tyrosine-protein phosphatase activity; rather, it functions as a phosphatidylinositol phosphatase required for auditory processes. It regulates the levels of phosphatidylinositol 4,5-bisphosphate (PIP2) in the basal region of hair bundles. It can dephosphorylate a broad range of phosphatidylinositol phosphates, including phosphatidylinositol 3,4,5-trisphosphate and most phosphatidylinositol monophosphates and diphosphates.


Pssm-ID: 350464 [Multi-domain]  Cd Length: 224  Bit Score: 173.55  E-value: 2.02e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 276 NRYKNILPFDHSRVILQGrDSNIPGSDYINANYVKNQLLgPDEnsktYIASQGCLDATVNDFWQMAWQENTRVIVMTTRE 355
Cdd:cd14616     1 NRFPNIKPYNNNRVKLIA-DAGVPGSDYINASYISGYLC-PNE----FIATQGPLPGTVGDFWRMVWETRAKTIVMLTQC 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 356 VEKGRNKCVPYWPEVGTQ-RVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDLVReiwHYQYLSWPDHGVPSEPGGVLSF 434
Cdd:cd14616    75 FEKGRIRCHQYWPEDNKPvTVFGDIVITKLMEDVQIDWTIRDLKIERHGDYMMVR---QCNFTSWPEHGVPESSAPLIHF 151

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1938958509 435 LDQInqRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVStkglDCD-IDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14616   152 VKLV--RASRAHDNTPMIVHCSAGVGRTGVFIALDHLTQHIN----DHDfVDIYGLVAELRSERMCMVQNLAQYIFLH 223
PHA02742 PHA02742
protein tyrosine phosphatase; Provisional
 271-517 1.01e-49

protein tyrosine phosphatase; Provisional


Pssm-ID: 165109 [Multi-domain]  Cd Length: 303  Bit Score: 174.42  E-value: 1.01e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 271 ENKSKNRYKNILPFDHSRVILQGRDSnipGSDYINANYVKNQllgpdeNSK-TYIASQGCLDATVNDFWQMAWQENTRVI 349
Cdd:PHA02742   51 KNMKKCRYPDAPCFDRNRVILKIEDG---GDDFINASYVDGH------NAKgRFICTQAPLEETALDFWQAIFQDQVRVI 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 350 VMTTREVEKGRNKCVPYW-PEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGdLVREIWHYQYLSWPDHGVPSEP 428
Cdd:PHA02742  122 VMITKIMEDGKEACYPYWmPHERGKATHGEFKIKTKKIKSFRNYAVTNLCLTDTNTG-ASLDIKHFAYEDWPHGGLPRDP 200

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 429 GGVLSFLDQINQRQ---------ESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSG 499
Cdd:PHA02742  201 NKFLDFVLAVREADlkadvdikgENIVKEPPILVHCSAGLDRAGAFCAIDICISKYNERAI---IPLLSIVRDLRKQRHN 277

                         250
                  ....*....|....*...
gi 1938958509 500 MVQTEAQYKFIYVAIAQF 517
Cdd:PHA02742  278 CLSLPQQYIFCYFIVLIF 295
R-PTPc-Z-1 cd17668
catalytic domain of receptor-type tyrosine-protein phosphatase Z, repeat 1; Receptor-type ...
 303-514 1.55e-49

catalytic domain of receptor-type tyrosine-protein phosphatase Z, repeat 1; Receptor-type tyrosine-protein phosphatase Z (PTPRZ), also called receptor-type tyrosine-protein phosphatase zeta (R-PTP-zeta), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Three isoforms are generated by alternative splicing from a single PTPRZ gene: two transmembrane isoforms, PTPRZ-A and PTPRZ-B, and one secretory isoform, PTPRZ-S (also known as phosphacan); all are preferentially expressed in the central nervous system (CNS) as chondroitin sulfate (CS) proteoglycans. PTPRZ isoforms play important roles in maintaining oligodendrocyte precursor cells in an undifferentiated state. PTPRZ is a type 1 integral membrane protein consisting of an extracellular region with a carbonic anhydrase-like (CAH) and a fibronectin type III (FN3) domains, and an intracellular region with a catalytic PTP domain (repeat 1) proximal to the membrane, and a catalytically inactive PTP-fold domain (repeat 2) distal to the membrane. This model represents the catalytic PTP domain (repeat 1).


Pssm-ID: 350506 [Multi-domain]  Cd Length: 209  Bit Score: 170.93  E-value: 1.55e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRvYGLYSVT 382
Cdd:cd17668     1 YINANYVDGY-----NKPKAYIAAQGPLKSTAEDFWRMIWEHNVEVIVMITNLVEKGRRKCDQYWPADGSEE-YGNFLVT 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEHDTAEYKLR--TLQISPLDNGDLV-----REIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESlpHAGPIIVHC 455
Cdd:cd17668    75 QKSVQVLAYYTVRnfTLRNTKIKKGSQKgrpsgRVVTQYHYTQWPDMGVPEYTLPVLTFVRKASYAKRH--AVGPVVVHC 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509 456 SAGIGRTGTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAI 514
Cdd:cd17668   153 SAGVGRTGTYIVLDSMLQQIQHEG---TVNIFGFLKHIRSQRNYLVQTEEQYVFIHDAL 208
PHA02738 PHA02738
hypothetical protein; Provisional
 262-527 2.63e-48

hypothetical protein; Provisional


Pssm-ID: 222923 [Multi-domain]  Cd Length: 320  Bit Score: 171.26  E-value: 2.63e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 262 HQRLEGQRPE--------NKSKNRYKNILPFDHSRVILQGRDSNipgSDYINANYVKNQllgpdENSKTYIASQGCLDAT 333
Cdd:PHA02738   31 HQKVISEKVDgtfnaekkNRKLNRYLDAVCFDHSRVILPAERNR---GDYINANYVDGF-----EYKKKFICGQAPTRQT 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 334 VNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEV-GTQRVYGLYSVTNCKEHDTAEYKLRTLQISplDNGDLVREIW 412
Cdd:PHA02738  103 CYDFYRMLWMEHVQIIVMLCKKKENGREKCFPYWSDVeQGSIRFGKFKITTTQVETHPHYVKSTLLLT--DGTSATQTVT 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 413 HYQYLSWPDHGVPSEPGGVLSFLDQINQRQESL-----------PHAGPIIVHCSAGIGRTGTIIVIDMlmeSVSTKGLD 481
Cdd:PHA02738  181 HFNFTAWPDHDVPKNTSEFLNFVLEVRQCQKELaqeslqighnrLQPPPIVVHCNAGLGRTPCYCVVDI---SISRFDAC 257

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 1938958509 482 CDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQFIETTKKKLEI 527
Cdd:PHA02738  258 ATVSIPSIVSSIRNQRYYSLFIPFQYFFCYRAVKRYVNLTVNKVSK 303
R-PTPc-A-E-2 cd14552
catalytic domain of receptor-type tyrosine-protein phosphatase A and E, repeat 2; ...
 303-514 9.93e-48

catalytic domain of receptor-type tyrosine-protein phosphatase A and E, repeat 2; Receptor-type tyrosine-protein phosphatase A (PTPRA) and E (PTPRE) belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRA and PTPRE share several functions including regulation of Src family kinases and voltage-gated potassium (Kv) channels. They both contain a small extracellular domain, a transmembrane segment, and an intracellular region containing two tandem catalytic PTP domains. This model represents the second PTP domain (repeat 2).


Pssm-ID: 350400 [Multi-domain]  Cd Length: 202  Bit Score: 165.91  E-value: 9.93e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRvYGLYSVT 382
Cdd:cd14552     1 YINASFIDGY-----RQKDAYIATQGPLDHTVEDFWRMIWEWKSCSIVMLTEIKERSQNKCAQYWPEDGSVS-SGDITVE 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEHDTAEYKLRTLQISpLDNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQInQRQESLPHAGPIIVHCSAGIGRT 462
Cdd:cd14552    75 LKDQTDYEDYTLRDFLVT-KGKGGSTRTVRQFHFHGWPEVGIPDNGKGMIDLIAAV-QKQQQQSGNHPITVHCSAGAGRT 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1938958509 463 GTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAI 514
Cdd:cd14552   153 GTFCALSTVLERVKAEGV---LDVFQVVKSLRLQRPHMVQTLEQYEFCYKVV 201
COG5599 COG5599
Protein tyrosine phosphatase [Signal transduction mechanisms];
248-516 1.76e-44

Protein tyrosine phosphatase [Signal transduction mechanisms];


Pssm-ID: 444335 [Multi-domain]  Cd Length: 282  Bit Score: 159.49  E-value: 1.76e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 248 EEFESLQKQEVKNLHQrlegQRPENKSKNRYKNILPFDHSRVilqgrDSNIPgsdYINANYVKnqllGPDENskTYIASQ 327
Cdd:COG5599    22 TLTNELAPSHNDPQYL----QNINGSPLNRFRDIQPYKETAL-----RANLG---YLNANYIQ----VIGNH--RYIATQ 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 328 GCLDATVNDFWQMAWQENTRVIVMTTREVE--KGRNKCVPYWPEVGTqrvYGLYSVTNcKEHDTAEYK----LRTLQISP 401
Cdd:COG5599    84 YPLEEQLEDFFQMLFDNNTPVLVVLASDDEisKPKVKMPVYFRQDGE---YGKYEVSS-ELTESIQLRdgieARTYVLTI 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 402 LDNGDLVREIWHYQYLSWPDHGVPSePGGVLSFLDQINQRQE-SLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKgL 480
Cdd:COG5599   160 KGTGQKKIEIPVLHVKNWPDHGAIS-AEALKNLADLIDKKEKiKDPDKLLPVVHCRAGVGRTGTLIACLALSKSINAL-V 237

                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 1938958509 481 DCDIDIQKTIQMVRAQR-SGMVQTEAQYKFIyVAIAQ 516
Cdd:COG5599   238 QITLSVEEIVIDMRTSRnGGMVQTSEQLDVL-VKLAE 273
PTPc-N20 cd14596
catalytic domain of tyrosine-protein phosphatase non-receptor type 20; Tyrosine-protein ...
 303-511 7.92e-44

catalytic domain of tyrosine-protein phosphatase non-receptor type 20; Tyrosine-protein phosphatase non-receptor type 20 (PTPN20) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Human PTPN20 is a widely expressed phosphatase with a dynamic subcellular distribution that is targeted to sites of actin polymerization.


Pssm-ID: 350444 [Multi-domain]  Cd Length: 207  Bit Score: 155.29  E-value: 7.92e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQLlgpDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQRV-YGLYSV 381
Cdd:cd14596     1 YINASYITMPV---GEEELFYIATQGPLPSTIDDFWQMVWENRSDVIAMMTREVERGKVKCHRYWPETLQEPMeLENYQL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 382 TNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESlphaGPIIVHCSAGIGR 461
Cdd:cd14596    78 RLENYQALQYFIIRIIKLVEKETGE-NRLIKHLQFTTWPDHGTPQSSDQLVKFICYMRKVHNT----GPIVVHCSAGIGR 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1938958509 462 TGTIIVIDMLMESVSTkglDCDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14596   153 AGVLICVDVLLSLIEK---DLSFNIKDIVREMRQQRYGMIQTKDQYLFCY 199
PHA02746 PHA02746
protein tyrosine phosphatase; Provisional
 239-524 1.61e-42

protein tyrosine phosphatase; Provisional


Pssm-ID: 165113 [Multi-domain]  Cd Length: 323  Bit Score: 155.57  E-value: 1.61e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 239 EDTAKAGFWEeFESLQKQEVKNLHQR---LEGQRPENKSKNRYKNILPFDHSRVILQGRDSNI----------------- 298
Cdd:PHA02746   16 DKTNHAKFCE-FVLLEHAEVMDIPIRgttNHFLKKENLKKNRFHDIPCWDHSRVVINAHESLKmfdvgdsdgkkievtse 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 299 -PGSDYINANYVKnqllGPDENSKtYIASQGCLDATVNDFWQMAWQENTRVIVMTTrEVEKGRNKCVPYW-PEVGTQRVY 376
Cdd:PHA02746   95 dNAENYIHANFVD----GFKEANK-FICAQGPKEDTSEDFFKLISEHESQVIVSLT-DIDDDDEKCFELWtKEEDSELAF 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 377 GLYSVTNCKEHDTAEYKLRTLQISPLDNgDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESL--------PHA 448
Cdd:PHA02746  169 GRFVAKILDIIEELSFTKTRLMITDKIS-DTSREIHHFWFPDWPDNGIPTGMAEFLELINKVNEEQAELikqadndpQTL 247

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1938958509 449 GPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLDCdidIQKTIQMVRAQRSGMVQTEAQYKFIYVAIA-QFIETTKKK 524
Cdd:PHA02746  248 GPIVVHCSAGIGRAGTFCAIDNALEQLEKEKEVC---LGEIVLKIRKQRHSSVFLPEQYAFCYKALKyAIIEEAKKK 321
R-PTPc-A-2 cd14623
catalytic domain of receptor-type tyrosine-protein phosphatase A, repeat 2; Receptor-type ...
 277-516 1.94e-42

catalytic domain of receptor-type tyrosine-protein phosphatase A, repeat 2; Receptor-type tyrosine-protein phosphatase A (PTPRA), also known as receptor-type tyrosine-protein phosphatase alpha (R-PTP-alpha), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRA is a positive regulator of Src and Src family kinases via dephosphorylation of the Src-inhibitory tyrosine 527. Thus, it affects transformation and tumorigenesis, inhibition of proliferation, cell cycle arrest, integrin signaling, neuronal differentiation and outgrowth, and ion channel activity. It is also involved in interleukin-1 signaling in fibroblasts through its interaction with the focal adhesion targeting domain of focal adhesion kinase. PTPRA comprises a small extracellular domain, a transmembrane segment, and an intracellular region containing two tandem catalytic PTP domains. This model represents the second PTP domain (repeat 2).


Pssm-ID: 350471 [Multi-domain]  Cd Length: 228  Bit Score: 152.51  E-value: 1.94e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 277 RYKNILPFDHSRVILQGRDSNiPGSDYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREV 356
Cdd:cd14623     1 RVLQIIPYEFNRVIIPVKRGE-ENTDYVNASFIDGY-----RQKDSYIASQGPLQHTIEDFWRMIWEWKSCSIVMLTELE 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 357 EKGRNKCVPYWPEVGTQrVYGLYSVTNCKEHDTAEYKLRTLQISPlDNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLD 436
Cdd:cd14623    75 ERGQEKCAQYWPSDGSV-SYGDITIELKKEEECESYTVRDLLVTN-TRENKSRQIRQFHFHGWPEVGIPSDGKGMINIIA 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 437 QIN-QRQESLPHagPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIA 515
Cdd:cd14623   153 AVQkQQQQSGNH--PITVHCSAGAGRTGTFCALSTVLERVKAEGI---LDVFQTVKSLRLQRPHMVQTLEQYEFCYKVVQ 227


                  .
gi 1938958509 516 Q 516
Cdd:cd14623   228 E 228
R-PTP-C-2 cd14558
PTP-like domain of receptor-type tyrosine-protein phosphatase C, repeat 2; Receptor-type ...
 303-511 2.96e-42

PTP-like domain of receptor-type tyrosine-protein phosphatase C, repeat 2; Receptor-type tyrosine-protein phosphatase C (PTPRC), also known as CD45, leukocyte common antigen (LCA) or GP180, belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRC/CD45 is found in all nucleated hematopoietic cells and is an essential regulator of T- and B-cell antigen receptor signaling. It controls immune response, both positively and negatively, by dephosphorylating a number of signaling molecules such as the Src family kinases, the CD3zeta chain of TCY, and ZAP-70 kinase. Mutations in the human PTPRC/CD45 gene are associated with severe combined immunodeficiency (SCID) and multiple sclerosis. PTPRC/CD45 contains an extracellular receptor-like region with fibronectin type III (FN3) repeats, a short transmembrane segment, and a cytoplasmic region comprising of a membrane proximal catalytically active PTP domain (repeat 1 or D1) and a membrane distal catalytically impaired PTP-like domain (repeat 2, or D2). This model represents repeat 2.


Pssm-ID: 350406 [Multi-domain]  Cd Length: 203  Bit Score: 151.01  E-value: 2.96e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVkNQLLGPdensKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTqrVYGLYSVT 382
Cdd:cd14558     1 YINASFI-DGYWGP----KSLIATQGPLPDTIADFWQMIFQKKVKVIVMLTELKEGDQEQCAQYWGDEKK--TYGDIEVE 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAG----PIIVHCSAG 458
Cdd:cd14558    74 LKDTEKSPTYTVRVFEITHLKRKD-SRTVYQYQYHKWKGEELPEKPKDLVDMIKSIKQKLPYKNSKHgrsvPIVVHCSDG 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1938958509 459 IGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14558   153 SSRTGIFCALWNLLESAETEKV---VDVFQVVKALRKQRPGMVSTLEQYQFLY 202
PTP-N23 cd14539
PTP-like domain of tyrosine-protein phosphatase non-receptor type 23; Tyrosine-protein ...
 303-511 1.69e-41

PTP-like domain of tyrosine-protein phosphatase non-receptor type 23; Tyrosine-protein phosphatase non-receptor type 23 (PTPN23), also called His domain-containing protein tyrosine phosphatase (HD-PTP) or protein tyrosine phosphatase TD14 (PTP-TD14), is a catalytically inactive member of the tyrosine-specific protein tyrosine phosphatase (PTP) family. Human PTPN23 may be involved in the regulation of small nuclear ribonucleoprotein assembly and pre-mRNA splicing by modifying the survival motor neuron (SMN) complex. It plays a role in ciliogenesis and is part of endosomal sorting complex required for transport (ESCRT) pathways. PTPN23 contains five domains: a BRO1-like domain that plays a role in endosomal sorting; a V-domain that interacts with Lys63-linked polyubiquitinated substrates; a central proline-rich region that might recruit SH3-containing proteins; a PTP-like domain; and a proteolytic degradation-targeting motif, also known as a PEST sequence.


Pssm-ID: 350387 [Multi-domain]  Cd Length: 205  Bit Score: 149.07  E-value: 1.69e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNqlLGPdeNSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWP-EVGTQRVYGLYSV 381
Cdd:cd14539     1 YINASLIED--LTP--YCPRFIATQAPLPGTAADFWLMVYEQQVSVIVMLVSEQENEKQKVHRYWPtERGQALVYGAITV 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 382 TNCKEHDTAEYKLRTLQISPLDNgDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQIN---QRQESLPHagPIIVHCSAG 458
Cdd:cd14539    77 SLQSVRTTPTHVERIISIQHKDT-RLSRSVVHLQFTTWPELGLPDSPNPLLRFIEEVHshyLQQRSLQT--PIVVHCSSG 153

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1938958509 459 IGRTGTI-IVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14539   154 VGRTGAFcLLYAAVQEIEAGNGI---PDLPQLVRKMRQQRKYMLQEKEHLKFCY 204
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
410-516 3.96e-41

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 144.42  E-value: 3.96e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509  410 EIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKglDCDIDIQKT 489
Cdd:smart00404   1 TVKHYHYTGWPDHGVPESPDSILELLRAVKKNLNQSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAE--AGEVDIFDT 78

                           90       100
                   ....*....|....*....|....*..
gi 1938958509  490 IQMVRAQRSGMVQTEAQYKFIYVAIAQ 516
Cdd:smart00404  79 VKELRSQRPGMVQTEEQYLFLYRALLE 105
PTPc_DSPc smart00012
Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine ...
 410-516 3.96e-41

Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine phosphatases. Homologues detected by this profile and not by those of "PTPc" or "DSPc" are predicted to be protein phosphatases with a similar fold to DSPs and PTPs, yet with unpredicted specificities.


Pssm-ID: 214469 [Multi-domain]  Cd Length: 105  Bit Score: 144.42  E-value: 3.96e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509  410 EIWHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKglDCDIDIQKT 489
Cdd:smart00012   1 TVKHYHYTGWPDHGVPESPDSILELLRAVKKNLNQSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAE--AGEVDIFDT 78

                           90       100
                   ....*....|....*....|....*..
gi 1938958509  490 IQMVRAQRSGMVQTEAQYKFIYVAIAQ 516
Cdd:smart00012  79 VKELRSQRPGMVQTEEQYLFLYRALLE 105
PHA02747 PHA02747
protein tyrosine phosphatase; Provisional
 268-510 1.06e-40

protein tyrosine phosphatase; Provisional


Pssm-ID: 165114 [Multi-domain]  Cd Length: 312  Bit Score: 150.15  E-value: 1.06e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 268 QRPENKSKNRYKNILPFDHSRVILQGRDSNIpgSDYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTR 347
Cdd:PHA02747   47 EKPENQPKNRYWDIPCWDHNRVILDSGGGST--SDYIHANWIDGF-----EDDKKFIATQGPFAETCADFWKAVWQEHCS 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 348 VIVM-TTREVEKGRNKCVPYW-PEVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISPLDNGDlVREIWHYQYLSWPDHGVP 425
Cdd:PHA02747  120 IIVMlTPTKGTNGEEKCYQYWcLNEDGNIDMEDFRIETLKTSVRAKYILTLIEITDKILKD-SRKISHFQCSEWFEDETP 198

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 426 SEPGGVLSFLDQINQ-RQESLPHAG-------PIIVHCSAGIGRTGTIIVIDM-LMESVSTKGldcdIDIQKTIQMVRAQ 496
Cdd:PHA02747  199 SDHPDFIKFIKIIDInRKKSGKLFNpkdallcPIVVHCSDGVGKTGIFCAVDIcLNQLVKRKA----ICLAKTAEKIREQ 274

                         250
                  ....*....|....
gi 1938958509 497 RSGMVQTEAQYKFI 510
Cdd:PHA02747  275 RHAGIMNFDDYLFI 288
R-PTPc-E-2 cd14622
catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 2; Receptor-type ...
 302-517 1.20e-38

catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 2; Receptor-type tyrosine-protein phosphatase E (PTPRE), also known as receptor-type tyrosine-protein phosphatase epsilon (R-PTP-epsilon), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. The PTPRE gene contains two distinct promoters that generate the two major isoforms: transmembrane (receptor type RPTPe or PTPeM) and cytoplasmic (cyt-PTPe or PTPeC). Receptor type RPTPe plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells, and may also play a role in osteoclast formation and function. It also negatively regulates PDGFRbeta-mediated signaling pathways that are crucial for the pathogenesis of atherosclerosis. cyt-PTPe acts as a negative regulator of insulin receptor signaling in skeletal muscle. It regulates insulin-induced phosphorylation of proteins downstream of the insulin receptor. Receptor type RPTPe contains a small extracellular region, a single transmembrane segment, and an intracellular region two tandem catalytic PTP domains. This model represents the second PTP domain (repeat 2).


Pssm-ID: 350470 [Multi-domain]  Cd Length: 205  Bit Score: 141.30  E-value: 1.20e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 302 DYINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTQrVYGLYSV 381
Cdd:cd14622     1 DYINASFIDGY-----RQKDYFIATQGPLAHTVEDFWRMVWEWKCHTIVMLTELQEREQEKCVQYWPSEGSV-THGEITI 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 382 TNCKEHDTAEYKLRTLQISpLDNGDLVREIWHYQYLSWPDHGVPSEPGGVLSFLDQInQRQESLPHAGPIIVHCSAGIGR 461
Cdd:cd14622    75 EIKNDTLLETISIRDFLVT-YNQEKQTRLVRQFHFHGWPEIGIPAEGKGMIDLIAAV-QKQQQQTGNHPIVVHCSAGAGR 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1938958509 462 TGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAIAQF 517
Cdd:cd14622   153 TGTFIALSNILERVKAEGL---LDVFQTVKSLRLQRPHMVQTLEQYEFCYRVVQDF 205
R-PTPc-typeIIb-2 cd14556
PTP domain of type IIb (or R2B) subfamily receptor-type tyrosine-protein phosphatases, repeat ...
 303-512 3.13e-31

PTP domain of type IIb (or R2B) subfamily receptor-type tyrosine-protein phosphatases, repeat 2; The type IIb (or R2B) subfamily of receptor protein tyrosine phosphatases (RPTPs) include the prototypical member PTPmu (or PTPRM), PCP-2 (or PTPRU), PTPrho (or PTPRT), and PTPkappa (or PTPRK). They belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Type IIb RPTPs mediate cell-cell adhesion though homophilic interactions; their ligand is an identical molecule on an adjacent cell. No heterophilic interactions between the subfamily members have been observed. They also commonly function as tumor suppressors. They contain an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the second (repeat 2) PTP domain.


Pssm-ID: 350404 [Multi-domain]  Cd Length: 201  Bit Score: 120.59  E-value: 3.13e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTrEVEKGRNKCVPYWPEVGTQRvYGLYSVT 382
Cdd:cd14556     1 YINAALLDSY-----KQPAAFIVTQHPLPNTVTDFWRLVYDYGCTSIVMLN-QLDPKDQSCPQYWPDEGSGT-YGPIQVE 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEHDTAEYKLRTLQIS----PLDNGDLVReiwHYQYLSWPDHG-VPSEPGGVLSFLDQINQRQESlPHAGPIIVHCSA 457
Cdd:cd14556    74 FVSTTIDEDVISRIFRLQnttrPQEGYRMVQ---QFQFLGWPRDRdTPPSKRALLKLLSEVEKWQEQ-SGEGPIVVHCLN 149

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1938958509 458 GIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYV 512
Cdd:cd14556   150 GVGRSGVFCAISSVCERIKVENV---VDVFQAVKTLRNHRPNMVETEEQYKFCYD 201
SH2 pfam00017
SH2 domain;
6-81 4.56e-28

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 107.30  E-value: 4.56e-28
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDF-YDLYGGEKFATLTELVEYY 81
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNGgYYISGGVKFSSLAELVEHY 77
SH2 pfam00017
SH2 domain;
112-196 7.69e-26

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 100.75  E-value: 7.69e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMC-EGGRYTVGGSETFDSLT 190
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPDGTFLVRESESTPGGYTLSVRDDG---------KVKHYKIQStDNGGYYISGGVKFSSLA 71


                  ....*.
gi 1938958509 191 DLVEHF 196
Cdd:pfam00017  72 ELVEHY 77
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 6-84 1.91e-24

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 97.30  E-value: 1.91e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509    6 WFHRDLSGPDAETLLKGRGvPGSFLARPSRKNQGDFSLSVRVDDQVTHIRI-QNSGDFYDLYGGEKFATLTELVEYYTQQ 84
Cdd:smart00252   3 WYHGFISREEAEKLLKNEG-DGDFLVRDSESSPGDYVLSVRVKGKVKHYRIrRNEDGKFYLEGGRKFPSLVELVEHYQKN 81
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 110-201 1.25e-22

Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides via 2 surface pockets. Specificity is provided via interaction with residues that are distinct from the phosphotyrosine. Only a single occurrence of a SH2 domain has been found in S. cerevisiae.


Pssm-ID: 214585 [Multi-domain]  Cd Length: 84  Bit Score: 91.91  E-value: 1.25e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509  110 ERWYHGHMSGGQAESLLQAKGePWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMC-EGGRYTVGGSETFDS 188
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEG-DGDFLVRDSESSPGDYVLSVRVKG---------KVKHYRIRRnEDGKFYLEGGRKFPS 70

                           90
                   ....*....|...
gi 1938958509  189 LTDLVEHFKKTGI 201
Cdd:smart00252  71 LVELVEHYQKNSL 83
R-PTP-Z-2 cd17669
catalytic domain of receptor-type tyrosine-protein phosphatase Z, repeat 2; Receptor-type ...
 303-514 1.07e-20

catalytic domain of receptor-type tyrosine-protein phosphatase Z, repeat 2; Receptor-type tyrosine-protein phosphatase Z (PTPRZ), also called receptor-type tyrosine-protein phosphatase zeta (R-PTP-zeta), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Three isoforms are generated by alternative splicing from a single PTPRZ gene: two transmembrane isoforms, PTPRZ-A and PTPRZ-B, and one secretory isoform, PTPRZ-S (also known as phosphacan); all are preferentially expressed in the central nervous system (CNS) as chondroitin sulfate (CS) proteoglycans. PTPRZ isoforms play important roles in maintaining oligodendrocyte precursor cells in an undifferentiated state. PTPRZ is a type 1 integral membrane protein consisting of an extracellular region with a carbonic anhydrase-like (CAH) and a fibronectin type III (FN3) domains, and an intracellular region with a catalytic PTP domain (repeat 1) proximal to the membrane, and a catalytically inactive PTP-fold domain (repeat 2) distal to the membrane. This model represents the inactive PTP-like domain (repeat 2).


Pssm-ID: 350507 [Multi-domain]  Cd Length: 204  Bit Score: 90.44  E-value: 1.07e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVpYWPEVGTQRVYGLYSVT 382
Cdd:cd17669     1 YINASYIMGY-----YQSNEFIITQHPLLHTIKDFWRMIWDHNAQLIVMLPDGQNMAEDEFV-YWPNKDEPINCETFKVT 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEHDTAEYKLRTLQISPL----DNGDLVREIWHYQYLSWPDhgvPSEPggVLSFLDQINQ-RQESLPHAGPIIVHCSA 457
Cdd:cd17669    75 LIAEEHKCLSNEEKLIIQDFileaTQDDYVLEVRHFQCPKWPN---PDSP--ISKTFELISIiKEEAANRDGPMIVHDEH 149

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1938958509 458 GIGRTGTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAI 514
Cdd:cd17669   150 GGVTAGTFCALTTLMHQLEKEN---SVDVYQVAKMINLMRPGVFTDIEQYQFLYKAI 203
R-PTPc-T-2 cd14634
PTP domain of receptor-type tyrosine-protein phosphatase T, repeat 2; Receptor-type ...
 303-511 1.54e-20

PTP domain of receptor-type tyrosine-protein phosphatase T, repeat 2; Receptor-type tyrosine-protein phosphatase T (PTPRT), also known as receptor-type tyrosine-protein phosphatase rho (RPTP-rho or PTPrho), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRT is highly expressed in the nervous system and it plays a critical role in regulation of synaptic formation and neuronal development. It dephosphorylates a specific tyrosine residue in syntaxin-binding protein 1, a key component of synaptic vesicle fusion machinery, and regulates its binding to syntaxin 1. PTPRT has been identified as a potential candidate gene for autism spectrum disorder (ASD) susceptibility. It contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the second (repeat 2) PTP domain.


Pssm-ID: 350482 [Multi-domain]  Cd Length: 206  Bit Score: 90.08  E-value: 1.54e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINAnyvknQLLGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTrEVEKGRnKCVPYWPEvGTQRVYGLYSVT 382
Cdd:cd14634     1 YINA-----ALMDSHKQPAAFIVTQHPLPNTVADFWRLVFDYNCSSVVMLN-EMDAAQ-LCMQYWPE-KTSCCYGPIQVE 72

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEHDTAEYKLRTLQISPLDN-GDLVREIWHYQYLSWPDH-GVPSEPGGVLSFLDQINQRQESLP-HAGPIIVHCSAGI 459
Cdd:cd14634    73 FVSADIDEDIISRIFRICNMARpQDGYRIVQHLQYIGWPAYrDTPPSKRSILKVVRRLEKWQEQYDgREGRTVVHCLNGG 152

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1938958509 460 GRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14634   153 GRSGTFCAICSVCEMIQQQNI---IDVFHTVKTLRNNKSNMVETLEQYKFVY 201
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 111-196 6.95e-20

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 84.04  E-value: 6.95e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 111 RWYHGHMSGGQAESLLQAKgEPWTFLVRESLSQPGDFVLSVLNDQPkagpgsplRVTHIKVMCEGGRYTVGGSE--TFDS 188
Cdd:cd00173     1 PWFHGSISREEAERLLRGK-PDGTFLVRESSSEPGDYVLSVRSGDG--------KVKHYLIERNEGGYYLLGGSgrTFPS 71


                  ....*...
gi 1938958509 189 LTDLVEHF 196
Cdd:cd00173    72 LPELVEHY 79
R-PTPc-U-2 cd14637
PTP domain of receptor-type tyrosine-protein phosphatase U, repeat 2; Receptor-type ...
 303-511 1.72e-19

PTP domain of receptor-type tyrosine-protein phosphatase U, repeat 2; Receptor-type tyrosine-protein phosphatase U (PTPRU), also known as pancreatic carcinoma phosphatase 2 (PCP-2), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRU/PCP-2 is the most distant member of the type IIb subfamily and may have a distinct biological function other than cell-cell aggregation. It localizes to the adherens junctions and directly binds and dephosphorylates beta-catenin, and regulates the balance between signaling and adhesive beta-catenin. It plays an important role in the maintenance of epithelial integrity. PTPRU contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the second (repeat 2) PTP domain.


Pssm-ID: 350485 [Multi-domain]  Cd Length: 207  Bit Score: 87.27  E-value: 1.72e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINAnyvknQLLGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRN-KCVPYWPEVGTQRvYGLYSV 381
Cdd:cd14637     1 YINA-----ALTDSYTRSAAFIVTLHPLQNTTTDFWRLVYDYGCTSVVMLNQLNQSNSAwPCLQYWPEPGLQQ-YGPMEV 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 382 ---TNCKEHDTAEYKLRTLQISPLDNGDLVreIWHYQYLSW-PDHGVPSEPGGVLSFLDQINQRQESlPHAGPIIVHCSA 457
Cdd:cd14637    75 efvSGSADEDIVTRLFRVQNITRLQEGHLM--VRHFQFLRWsAYRDTPDSKKAFLHLLASVEKWQRE-SGEGRTVVHCLN 151

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1938958509 458 GIGRTGTIIVIDMLMESVSTKgldCDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14637   152 GGGRSGTYCASAMILEMIRCH---NIVDVFYAVKTLRNYKPNMVETLEQYRFCY 202
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 6-81 1.54e-18

Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they bind pTyr-containing polypeptide ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites. They are present in a wide array of proteins including: adaptor proteins (Nck1, Crk, Grb2), scaffolds (Slp76, Shc, Dapp1), kinases (Src, Syk, Fps, Tec), phosphatases (Shp-1, Shp-2), transcription factors (STAT1), Ras signaling molecules (Ras-Gap), ubiquitination factors (c-Cbl), cytoskeleton regulators (Tensin), signal regulators (SAP), and phospholipid second messengers (PLCgamma), amongst others.


Pssm-ID: 198173 [Multi-domain]  Cd Length: 79  Bit Score: 80.19  E-value: 1.54e-18
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509   6 WFHRDLSGPDAETLLKGRgVPGSFLARPSRKNQGDFSLSVRVD-DQVTHIRIQNSGDFYDLYGGEK--FATLTELVEYY 81
Cdd:cd00173     2 WFHGSISREEAERLLRGK-PDGTFLVRESSSEPGDYVLSVRSGdGKVKHYLIERNEGGYYLLGGSGrtFPSLPELVEHY 79
R-PTPc-K-2 cd14636
PTP domain of receptor-type tyrosine-protein phosphatase K, repeat 2; Receptor-type ...
 308-511 1.66e-18

PTP domain of receptor-type tyrosine-protein phosphatase K, repeat 2; Receptor-type tyrosine-protein phosphatase K (PTPRK), also known as receptor-type tyrosine-protein phosphatase kappa (RPTP-kappa or PTPkappa), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRK is widely expressed and has been shown to stimulate cell motility and neurite outgrowth. It is required for anti-proliferative and pro-migratory effects of TGF-beta, suggesting a role in regulation, maintenance, and restoration of cell adhesion. It is a potential tumour suppressor in primary central nervous system lymphomas, colorectal cancer, and breast cancer. It contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the second (repeat 2) PTP domain.


Pssm-ID: 350484 [Multi-domain]  Cd Length: 206  Bit Score: 84.31  E-value: 1.66e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 308 YVKNQLLGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTrEVEKGRNkCVPYWPEVGTQRvYGLYSV--TNCK 385
Cdd:cd14636     1 YINAALMDSYRQPAAFIVTQHPLPNTVKDFWRLVYDYGCTSIVMLN-EVDLAQG-CPQYWPEEGMLR-YGPIQVecMSCS 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 386 -EHDTAEYKLRTLQISPLDNGDLVreIWHYQYLSWPDH-GVPSEPGGVLSFLDQINQRQESLPHA-GPIIVHCSAGIGRT 462
Cdd:cd14636    78 mDCDVISRIFRICNLTRPQEGYLM--VQQFQYLGWASHrEVPGSKRSFLKLILQVEKWQEECDEGeGRTIIHCLNGGGRS 155

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1938958509 463 GTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14636   156 GMFCAISIVCEMIKRQNV---VDVFHAVKTLRNSKPNMVETPEQYRFCY 201
PHA02740 PHA02740
protein tyrosine phosphatase; Provisional
 263-521 2.89e-18

protein tyrosine phosphatase; Provisional


Pssm-ID: 165107 [Multi-domain]  Cd Length: 298  Bit Score: 85.79  E-value: 2.89e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 263 QRLEGQRPENKSKNRYKN------ILPFDHSRVILQGRDSnipgsdYINANYVKnqllGPDENSKTYIASQGCLDATvND 336
Cdd:PHA02740   38 HEDEANKACAQAENKAKDenlalhITRLLHRRIKLFNDEK------VLDARFVD----GYDFEQKFICIINLCEDAC-DK 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 337 FWQMAWQENTRVIVMTTREVEKgrNKCVPYWP-EVGTQRVYGLYSVTNCKEHDTAEYKLRTLQISplDNGDLVREIWHYQ 415
Cdd:PHA02740  107 FLQALSDNKVQIIVLISRHADK--KCFNQFWSlKEGCVITSDKFQIETLEIIIKPHFNLTLLSLT--DKFGQAQKISHFQ 182

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 416 YLSWPDHGVPSEPGGVLSFLDQIN------QRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKT 489
Cdd:PHA02740  183 YTAWPADGFSHDPDAFIDFFCNIDdlcadlEKHKADGKIAPIIIDCIDGISSSAVFCVFDICATEFDKTGM---LSIANA 259

                         250       260       270
                  ....*....|....*....|....*....|..
gi 1938958509 490 IQMVRAQRSGMVQTEAQYKFIYVAIAQFIETT 521
Cdd:PHA02740  260 LKKVRQKKYGCMNCLDDYVFCYHLIAAYLKEK 291
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
 111-214 1.84e-17

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 77.72  E-value: 1.84e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 111 RWYHGHMSGGQAESLLQAKgEPWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMCEGGRYTVGGSETFDSLT 190
Cdd:cd09937     4 PWFHGKISREEAERLLQPP-EDGLFLVRESTNYPGDYTLCVSFEG---------KVEHYRVIYRNGKLTIDEEEYFENLI 73

                          90       100
                  ....*....|....*....|....
gi 1938958509 191 DLVEHFKKtgieEASGAFVYLRQP 214
Cdd:cd09937    74 QLVEHYTK----DADGLCTRLVKP 93
R5-PTP-2 cd14550
PTP-like domain of R5 subfamily receptor-type tyrosine-protein phosphatases, repeat 2; The R5 ...
 303-511 2.18e-17

PTP-like domain of R5 subfamily receptor-type tyrosine-protein phosphatases, repeat 2; The R5 subfamily of receptor-type phosphotyrosine phosphatases (RPTP) is composed of receptor-type tyrosine-protein phosphatase Z (PTPRZ) and G (PTPRG). They belong to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. They are type 1 integral membrane proteins consisting of an extracellular region with a carbonic anhydrase-like (CAH) and a fibronectin type III (FN3) domains, and an intracellular region with a catalytic PTP domain (repeat 1) proximal to the membrane, and a catalytically inactive PTP-fold domain (repeat 2) distal to the membrane. This model represents the inactive PTP-like domain (repeat 2).


Pssm-ID: 350398 [Multi-domain]  Cd Length: 200  Bit Score: 80.83  E-value: 2.18e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQllgpdENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCvpYWPEVGTQRVYGLYSVT 382
Cdd:cd14550     1 YINASYLQGY-----RRSNEFIITQHPLEHTIKDFWQMIWDHNSQTIVMLTDNELNEDEPI--YWPTKEKPLECETFKVT 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 NCKEH---DTAEYKLRT----LQiSPLDngDLVREIWHYQYLSWPDHGVPSEpggvlSFLDQINQRQE-SLPHAGPIIVH 454
Cdd:cd14550    74 LSGEDhscLSNEIRLIVrdfiLE-STQD--DYVLEVRQFQCPSWPNPCSPIH-----TVFELINTVQEwAQQRDGPIVVH 145

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1938958509 455 -----CSAGIGRTGTIIVIDMLMESVstkgldcdIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14550   146 dryggVQAATFCALTTLHQQLEHESS--------VDVYQVAKLYHLMRPGVFTSKEDYQFLY 199
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 111-216 3.22e-16

N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The SH2 domain phosphatases (SHP-1, SHP-2/Syp, Drosophila corkscrew (csw), and Caenorhabditis elegans Protein Tyrosine Phosphatase (Ptp-2)) are cytoplasmic signaling enzymes. They are both targeted and regulated by interactions of their SH2 domains with phosphotyrosine docking sites. These proteins contain two SH2 domains (N-SH2, C-SH2) followed by a tyrosine phosphatase (PTP) domain, and a C-terminal extension. Shp1 and Shp2 have two tyrosyl phosphorylation sites in their C-tails, which are phosphorylated differentially by receptor and nonreceptor PTKs. Csw retains the proximal tyrosine and Ptp-2 lacks both sites. Shp-binding proteins include receptors, scaffolding adapters, and inhibitory receptors. Some of these bind both Shp1 and Shp2 while others bind only one. Most proteins that bind a Shp SH2 domain contain one or more immuno-receptor tyrosine-based inhibitory motifs (ITIMs): [IVL]xpYxx[IVL]. Shp1 N-SH2 domain blocks the catalytic domain and keeps the enzyme in the inactive conformation, and is thus believed to regulate the phosphatase activity of SHP-1. Its C-SH2 domain is thought to be involved in searching for phosphotyrosine activators. The SHP2 N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. The C-SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. Csw SH2 domain function is essential, but either SH2 domain can fulfill this requirement. The role of the csw SH2 domains during Sevenless receptor tyrosine kinase (SEV) signaling is to bind Daughter of Sevenless rather than activated SEV. Ptp-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote major sperm protein (MSP)-induced MAP Kinase (MPK-1) phosphorylation. Ptp-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. It is thought that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation and that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198203  Cd Length: 99  Bit Score: 74.36  E-value: 3.22e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 111 RWYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVL-NDQpkagpgsplrVTHIKVMCEGGRYTVGGSETFDSL 189
Cdd:cd10340     1 RWFHPVISGIEAENLLKTRGVDGSFLARPSKSNPGDFTLSVRrGDE----------VTHIKIQNTGDYYDLYGGEKFATL 70

                          90       100
                  ....*....|....*....|....*....
gi 1938958509 190 TDLVEHF--KKTGIEEASGAFVYLRQPYY 216
Cdd:cd10340    71 SELVQYYmeQHGQLREKNGDVIELKYPLN 99
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 6-81 4.28e-16

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198217  Cd Length: 77  Bit Score: 73.23  E-value: 4.28e-16
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYY 81
Cdd:cd10354     2 WFHGKISREEAYNMLVKVGGPGSFLVRESDNTPGDYSLSFRVNEGIKHFKIIPTGNNQFMMGGRYFSSLDDVIDRY 77
R-PTP-G-2 cd17670
PTP-like domain of receptor-type tyrosine-protein phosphatase G, repeat 2; Receptor-type ...
 303-514 4.44e-16

PTP-like domain of receptor-type tyrosine-protein phosphatase G, repeat 2; Receptor-type tyrosine-protein phosphatase G (PTPRG), also called protein-tyrosine phosphatase gamma (R-PTP-gamma), belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRG is an important tumor suppressor gene in multiple human cancers such as lung, ovarian, and breast cancers. It is widely expressed in many tissues, including the central nervous system, where it plays a role during neuroinflammation processes. It can dephosphorylate platelet-derived growth factor receptor beta (PDGFRB) and may play a role in PDGFRB-related infantile myofibromatosis. PTPRG is a type 1 integral membrane protein consisting of an extracellular region with a carbonic anhydrase-like (CAH) and a fibronectin type III (FN3) domains, and an intracellular region with a catalytic PTP domain (repeat 1) proximal to the membrane, and a catalytically inactive PTP-fold domain (repeat 2) distal to the membrane. This model represents the inactive PTP-like domain (repeat 2).


Pssm-ID: 350508 [Multi-domain]  Cd Length: 205  Bit Score: 77.03  E-value: 4.44e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 303 YINANYVKNQLlgpdeNSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVpYWPEVGTQRVYGLYSVT 382
Cdd:cd17670     1 YINASYIMGYY-----RSNEFIITQHPLPHTTKDFWRMIWDHNAQIIVMLPDNQGLAEDEFV-YWPSREESMNCEAFTVT 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 383 ----------NCKEHDTAEYKLRTLQIspldngDLVREIWHYQYLSWPDhgvPSEPggVLSFLDQINQ-RQESLPHAGPI 451
Cdd:cd17670    75 liskdrlclsNEEQIIIHDFILEATQD------DYVLEVRHFQCPKWPN---PDAP--ISSTFELINViKEEALTRDGPT 143

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1938958509 452 IVHCSAGIGRTGTIIVIDMLMESVSTKGLdcdIDIQKTIQMVRAQRSGMVQTEAQYKFIYVAI 514
Cdd:cd17670   144 IVHDEFGAVSAGTLCALTTLSQQLENENA---VDVYQVAKMINLMRPGVFTDIEQYQFLYKAM 203
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
 109-199 1.56e-15

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 72.23  E-value: 1.56e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKGEP-WTFLVRESLSQPGDFVLSVLNDQPKAGPgsplRVTH--IKVMcEGGRYTVGGSET 185
Cdd:cd09933     2 AEEWFFGKIKRKDAEKLLLAPGNPrGTFLIRESETTPGAYSLSVRDGDDARGD----TVKHyrIRKL-DNGGYYITTRAT 76

                          90
                  ....*....|....
gi 1938958509 186 FDSLTDLVEHFKKT 199
Cdd:cd09933    77 FPTLQELVQHYSKD 90
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
 6-84 2.54e-15

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 71.53  E-value: 2.54e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRI--QNSGDFYdLYgGEKFATLTELVEYYTQ 83
Cdd:cd09941     5 WFHGKISRAEAEEILMNQRPDGAFLIRESESSPGDFSLSVKFGNDVQHFKVlrDGAGKYF-LW-VVKFNSLNELVDYHRT 82


                  .
gi 1938958509  84 Q 84
Cdd:cd09941    83 T 83
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
 105-210 6.32e-15

Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is part of a growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases, including Sos1 and 2, GRF1 and 2, CalDAG-GEF/GRP1-4, C3G, cAMP-GEF/Epac 1 and 2, PDZ-GEFs, MR-GEF, RalGDS family members, RalGPS, RasGEF, Smg GDS, and phospholipase C(epsilon). 12102558 21262352 BCAR3 binds to the carboxy-terminus of BCAR1/p130Cas, a focal adhesion adapter protein. Over expression of BCAR1 (p130Cas) and BCAR3 induces estrogen independent growth in normally estrogen-dependent cell lines. They have been linked to resistance to anti-estrogens in breast cancer, Rac activation, and cell motility, though the BCAR3/p130Cas complex is not required for this activity in BCAR3. Many BCAR3-mediated signaling events in epithelial and mesenchymal cells are independent of p130Cas association. Structurally these proteins contain a single SH2 domain upstream of their RasGEF domain, which is responsible for the ability of BCAR3 to enhance p130Cas over-expression-induced migration. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198200 [Multi-domain]  Cd Length: 136  Bit Score: 71.98  E-value: 6.32e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 105 SDPTSERWYHGHMSGGQAESLLQAKGEpwtFLVRESLSQPGDFVLSVlndQPKagpGSPLRVTHIKVMCEGGR-YTVG-- 181
Cdd:cd10337     1 EDLRSHAWYHGRIPRQVAESLVQREGD---FLVRDSLSSPGDYVLTC---RWK---GQPLHFKINRVVLRPSEaYTRVqy 71

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1938958509 182 --GSETFDSLTDLVEHFKKTG--IEEASGAFVY 210
Cdd:cd10337    72 qfEDEQFDSIPALVHFYVGNRrpISQASGAIIS 104
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
 6-101 8.14e-15

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 70.11  E-value: 8.14e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLkGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQ-NSGDFYDLYGGEKFATLTELVEYYTQQ 84
Cdd:cd09935     5 WYHGPISRNAAEYLL-SSGINGSFLVRESESSPGQYSISLRYDGRVYHYRISeDSDGKVYVTQEHRFNTLAELVHHHSKN 83

                          90
                  ....*....|....*..
gi 1938958509  85 QgilqdrDGTIIHLKYP 101
Cdd:cd09935    84 A------DGLITTLRYP 94
R-PTPc-M-2 cd14635
PTP domain of receptor-type tyrosine-protein phosphatase M, repeat 2; Receptor-type ...
 308-511 9.70e-15

PTP domain of receptor-type tyrosine-protein phosphatase M, repeat 2; Receptor-type tyrosine-protein phosphatase M (PTPRM), also known as protein-tyrosine phosphatase mu (R-PTP-mu or PTPmu), belongs to the type IIb subfamily of receptor protein tyrosine phosphatases (RPTPs), which belong to the larger family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. PTPRM/PTPmu is a homophilic cell adhesion molecule expressed in CNS neurons and glia. It is required for E-, N-, and R-cadherin-dependent neurite outgrowth. Loss of PTPmu contributes to tumor cell migration and dispersal of human glioblastomas. PTPRM contains an extracellular region with an Meprin-A5 (neuropilin)-mu (MAM) domain, an immunoglobulin (Ig) domain, and four fibronectin type III (FN3) repeats, a transmembrane domain, and an intracellular segment with a juxtamembrane domain similar to the cytoplasmic domain of classical cadherins and two tandem PTP domains. This model represents the second (repeat 2) PTP domain.


Pssm-ID: 350483 [Multi-domain]  Cd Length: 206  Bit Score: 73.18  E-value: 9.70e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 308 YVKNQLLGPDENSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTrEVEKGRnKCVPYWPEVGTQRvYGLYSVTNCK-- 385
Cdd:cd14635     1 YINAALMDSYKQPSAFIVTQHPLPNTVKDFWRLVLDYHCTSIVMLN-DVDPAQ-LCPQYWPENGVHR-HGPIQVEFVSad 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 386 -EHDTAEYKLRTLQISPLDNGdlVREIWHYQYLSWPDH-GVPSEPGGVLSFLDQINQRQESLPHA-GPIIVHCSAGIGRT 462
Cdd:cd14635    78 lEEDIISRIFRIYNAARPQDG--YRMVQQFQFLGWPMYrDTPVSKRSFLKLIRQVDKWQEEYNGGeGRTVVHCLNGGGRS 155

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1938958509 463 GTIIVIDMLMESVSTKGldcDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14635   156 GTFCAISIVCEMLRHQR---AVDVFHAVKTLRNNKPNMVDLLDQYKFCY 201
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 2-103 1.84e-14

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 69.60  E-value: 1.84e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   2 LSRGWFHRDLSGPDAETLLKGrgVP--GSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLyGGEKFATLTELVE 79
Cdd:cd09932     2 ESKEWFHANLTREQAEEMLMR--VPrdGAFLVRPSETDPNSFAISFRAEGKIKHCRIKQEGRLFVI-GTSQFESLVELVS 78

                          90       100
                  ....*....|....*....|....
gi 1938958509  80 YYTQQQgiLQDRdgtiIHLKYPLN 103
Cdd:cd09932    79 YYEKHP--LYRK----IKLRYPVN 96
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
 5-84 8.11e-14

Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( DAPP1)/B lymphocyte adaptor molecule of 32 kDa (Bam32)-like proteins; DAPP1/Bam32 contains a putative myristoylation site at its N-terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C-terminus. DAPP1 could potentially be recruited to the cell membrane by any of these domains. Its putative myristoylation site could facilitate the interaction of DAPP1 with the lipid bilayer. Its SH2 domain may also interact with phosphotyrosine residues on membrane-associated proteins such as activated tyrosine kinase receptors. And finally its PH domain exhibits a high-affinity interaction with the PtdIns(3,4,5)P(3) PtdIns(3,4)P(2) second messengers produced at the cell membrane following the activation of PI 3-kinases. DAPP1 is thought to interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and therefore may play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). This protein is likely to play an important role in triggering signal transduction pathways that lie downstream from receptor tyrosine kinases and PI 3-kinase. It is likely that DAPP1 functions as an adaptor to recruit other proteins to the plasma membrane in response to extracellular signals. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198218  Cd Length: 92  Bit Score: 67.12  E-value: 8.11e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   5 GWFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDlYGGEKFATLTELVEYYTQQ 84
Cdd:cd10355     7 GWYHGNLTRHAAEALLLSNGVDGSYLLRNSNEGTGLFSLSVRAKDSVKHFHVEYTGYSFK-FGFNEFSSLQDFVKHFANQ 85
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 112-196 2.47e-13

C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198217  Cd Length: 77  Bit Score: 65.52  E-value: 2.47e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSV-LNDQpkagpgsplrVTHIKVMC-EGGRYTVGGsETFDSL 189
Cdd:cd10354     2 WFHGKISREEAYNMLVKVGGPGSFLVRESDNTPGDYSLSFrVNEG----------IKHFKIIPtGNNQFMMGG-RYFSSL 70


                  ....*..
gi 1938958509 190 TDLVEHF 196
Cdd:cd10354    71 DDVIDRY 77
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
 6-82 5.64e-13

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198196  Cd Length: 93  Bit Score: 64.84  E-value: 5.64e-13
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLyGGEKFATLTELVEYYT 82
Cdd:cd09943     3 WYYGRITRHQAETLLNEHGHEGDFLIRDSESNPGDYSVSLKAPGRNKHFKVQVVDNVYCI-GQRKFHTMDELVEHYK 78
CDC14 COG2453
Protein-tyrosine phosphatase [Signal transduction mechanisms];
412-511 5.75e-13

Protein-tyrosine phosphatase [Signal transduction mechanisms];


Pssm-ID: 441989 [Multi-domain]  Cd Length: 140  Bit Score: 66.15  E-value: 5.75e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 412 WHYQYLSWPDHGVPSEPGgVLSFLDQINQRqesLPHAGPIIVHCSAGIGRTGTIIVIDMLMESVStkgldcdidIQKTIQ 491
Cdd:COG2453    48 LEYLHLPIPDFGAPDDEQ-LQEAVDFIDEA---LREGKKVLVHCRGGIGRTGTVAAAYLVLLGLS---------AEEALA 114

                          90       100
                  ....*....|....*....|
gi 1938958509 492 MVRAQRSGMVQTEAQYKFIY 511
Cdd:COG2453   115 RVRAARPGAVETPAQRAFLE 134
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
 112-201 8.33e-13

Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198196  Cd Length: 93  Bit Score: 64.46  E-value: 8.33e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVlndqpkAGPGsplRVTHIKVMCEGGRYTVgGSETFDSLTD 191
Cdd:cd09943     3 WYYGRITRHQAETLLNEHGHEGDFLIRDSESNPGDYSVSL------KAPG---RNKHFKVQVVDNVYCI-GQRKFHTMDE 72

                          90
                  ....*....|
gi 1938958509 192 LVEHFKKTGI 201
Cdd:cd09943    73 LVEHYKKAPI 82
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
 6-84 8.62e-13

Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src family kinases are nonreceptor tyrosine kinases that have been implicated in pathways regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. It is thought that transforming ability of Src is linked to its ability to activate key signaling molecules in these pathways, rather than through direct activity. As such blocking Src activation has been a target for drug companies. Src family members can be divided into 3 groups based on their expression pattern: 1) Src, Fyn, and Yes; 2) Blk, Fgr, Hck, Lck, and Lyn; and 3) Frk-related kinases Frk/Rak and Iyk/Bsk Of these, cellular c-Src is the best studied and most frequently implicated in oncogenesis. The c-Src contains five distinct regions: a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Src exists in both active and inactive conformations. Negative regulation occurs through phosphorylation of Tyr, resulting in an intramolecular association between phosphorylated Tyr and the SH2 domain of SRC, which locks the protein in a closed conformation. Further stabilization of the inactive state occurs through interactions between the SH3 domain and a proline-rich stretch of residues within the kinase domain. Conversely, dephosphorylation of Tyr allows SRC to assume an open conformation. Full activity requires additional autophosphorylation of a Tyr residue within the catalytic domain. Loss of the negative-regulatory C-terminal segment has been shown to result in increased activity and transforming potential. Phosphorylation of the C-terminal Tyr residue by C-terminal Src kinase (Csk) and Csk homology kinase results in increased intramolecular interactions and consequent Src inactivation. Specific phosphatases, protein tyrosine phosphatase a (PTPa) and the SH-containing phosphatases SHP1/SHP2, have also been shown to take a part in Src activation. Src is also activated by direct binding of focal adhesion kinase (Fak) and Crk-associated substrate (Cas) to the SH2 domain. SRC activity can also be regulated by numerous receptor tyrosine kinases (RTKs), such as Her2, epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199827  Cd Length: 101  Bit Score: 64.53  E-value: 8.62e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVP-GSFLARPSRKNQGDFSLSVRVDDQ-----VTHIRIQN--SGDFYdLYGGEKFATLTEL 77
Cdd:cd09933     5 WFFGKIKRKDAEKLLLAPGNPrGTFLIRESETTPGAYSLSVRDGDDargdtVKHYRIRKldNGGYY-ITTRATFPTLQEL 83


                  ....*..
gi 1938958509  78 VEYYTQQ 84
Cdd:cd09933    84 VQHYSKD 90
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
 112-208 1.21e-12

Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins; The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199828  Cd Length: 95  Bit Score: 63.83  E-value: 1.21e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMCEG-GRYTVgGSETFDSLT 190
Cdd:cd09941     5 WFHGKISRAEAEEILMNQRPDGAFLIRESESSPGDFSLSVKFGN---------DVQHFKVLRDGaGKYFL-WVVKFNSLN 74

                          90
                  ....*....|....*...
gi 1938958509 191 DLVEHFKKTGIEEASGAF 208
Cdd:cd09941    75 ELVDYHRTTSVSRNQQIF 92
SH2_Nterm_RasGAP cd10353
N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 105-196 3.50e-12

N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the N-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198216  Cd Length: 103  Bit Score: 62.93  E-value: 3.50e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 105 SDPTSERWYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLndqpkagpgSPLRVTHIKVMCEGGRYTVGGSE 184
Cdd:cd10353    14 TAPPTNQWYHGRLDRTIAEERLRQAGKLGSYLIRESDRRPGSFVLSFL---------SRTGVNHFRIIAMCGDYYIGGRR 84

                          90
                  ....*....|..
gi 1938958509 185 tFDSLTDLVEHF 196
Cdd:cd10353    85 -FSSLSDLIGYY 95
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 4-103 6.76e-12

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198184  Cd Length: 104  Bit Score: 62.05  E-value: 6.76e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   4 RGWFHRDLSGPDAETLLKGRgvP-GSFLARPSRKnQGDFSLSVRVDDQVTHIRIQNS------GDFYDLYGgekfaTLTE 76
Cdd:cd09930     6 RTWLVGDINRTQAEELLRGK--PdGTFLIRESST-QGCYACSVVCNGEVKHCVIYKTetgygfAEPYNLYE-----SLKE 77

                          90       100
                  ....*....|....*....|....*..
gi 1938958509  77 LVEYYtQQQGILQDRDGTIIHLKYPLN 103
Cdd:cd09930    78 LVLHY-AHNSLEQHNDSLTVTLAYPVL 103
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
 110-157 7.37e-12

Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide variety of pathways including regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. An adapter protein, SHC has been implicated in Ras activation following the stimulation of a number of different receptors, including growth factors [insulin, epidermal growth factor (EGF), nerve growth factor, and platelet derived growth factor (PDGF)], cytokines [interleukins 2, 3, and 5], erythropoietin, and granulocyte/macrophage colony-stimulating factor, and antigens [T-cell and B-cell receptors]. SHC has been shown to bind to tyrosine-phosphorylated receptors, and receptor stimulation leads to tyrosine phosphorylation of SHC. Upon phosphorylation, SHC interacts with another adapter protein, Grb2, which binds to the Ras GTP/GDP exchange factor mSOS which leads to Ras activation. SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198179  Cd Length: 104  Bit Score: 61.98  E-value: 7.37e-12
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1938958509 110 ERWYHGHMSGGQAESLLQAKGEpwtFLVRESLSQPGDFVLSVL-NDQPK 157
Cdd:cd09925     7 EPWYHGKMSRRDAESLLQTDGD---FLVRESTTTPGQYVLTGMqNGQPK 52
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
 3-101 1.23e-11

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 61.37  E-value: 1.23e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   3 SRGWFHRDLSGPDAET-LLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQ--NSGDFYdLYGGEKFATLTELVE 79
Cdd:cd10370     2 AEPWYFGKIKRIEAEKkLLLPENEHGAFLIRDSESRHNDYSLSVRDGDTVKHYRIRqlDEGGFF-IARRTTFRTLQELVE 80

                          90       100
                  ....*....|....*....|..
gi 1938958509  80 YYTqqqgilQDRDGTIIHLKYP 101
Cdd:cd10370    81 HYS------KDSDGLCVNLRKP 96
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 109-198 1.26e-11

C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198186  Cd Length: 104  Bit Score: 61.51  E-value: 1.26e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMCEGGRYTVGGSEtFDS 188
Cdd:cd09932     3 SKEWFHANLTREQAEEMLMRVPRDGAFLVRPSETDPNSFAISFRAEG---------KIKHCRIKQEGRLFVIGTSQ-FES 72

                          90
                  ....*....|
gi 1938958509 189 LTDLVEHFKK 198
Cdd:cd09932    73 LVELVSYYEK 82
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
 112-196 1.53e-11

Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( DAPP1)/B lymphocyte adaptor molecule of 32 kDa (Bam32)-like proteins; DAPP1/Bam32 contains a putative myristoylation site at its N-terminus, followed by a SH2 domain, and a pleckstrin homology (PH) domain at its C-terminus. DAPP1 could potentially be recruited to the cell membrane by any of these domains. Its putative myristoylation site could facilitate the interaction of DAPP1 with the lipid bilayer. Its SH2 domain may also interact with phosphotyrosine residues on membrane-associated proteins such as activated tyrosine kinase receptors. And finally its PH domain exhibits a high-affinity interaction with the PtdIns(3,4,5)P(3) PtdIns(3,4)P(2) second messengers produced at the cell membrane following the activation of PI 3-kinases. DAPP1 is thought to interact with both tyrosine phosphorylated proteins and 3-phosphoinositides and therefore may play a role in regulating the location and/or activity of such proteins(s) in response to agonists that elevate PtdIns(3,4,5)P(3) and PtdIns(3,4)P(2). This protein is likely to play an important role in triggering signal transduction pathways that lie downstream from receptor tyrosine kinases and PI 3-kinase. It is likely that DAPP1 functions as an adaptor to recruit other proteins to the plasma membrane in response to extracellular signals. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198218  Cd Length: 92  Bit Score: 60.95  E-value: 1.53e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQPkagpgsplrVTHIKVMCEGGRYTVGGSEtFDSLTD 191
Cdd:cd10355     8 WYHGNLTRHAAEALLLSNGVDGSYLLRNSNEGTGLFSLSVRAKDS---------VKHFHVEYTGYSFKFGFNE-FSSLQD 77


                  ....*
gi 1938958509 192 LVEHF 196
Cdd:cd10355    78 FVKHF 82
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
 6-106 2.82e-11

Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal Src kinase (CSK) and CSK-homologous kinase (CHK) are members of the CSK-family of protein tyrosine kinases. These proteins suppress activity of Src-family kinases (SFK) by selectively phosphorylating the conserved C-terminal tail regulatory tyrosine by a similar mechanism. CHK is also capable of inhibiting SFKs by a non-catalytic mechanism that involves binding of CHK to SFKs to form stable protein complexes. The unphosphorylated form of SFKs is inhibited by CSK and CHK by a two-step mechanism. The first step involves the formation of a complex of SFKs with CSK/CHK with the SFKs in the complex are inactive. The second step, involves the phosphorylation of the C-terminal tail tyrosine of SFKs, which then dissociates and adopt an inactive conformation. The structural basis of how the phosphorylated SFKs dissociate from CSK/CHK to adopt the inactive conformation is not known. The inactive conformation of SFKs is stabilized by two intramolecular inhibitory interactions: (a) the pYT:SH2 interaction in which the phosphorylated C-terminal tail tyrosine (YT) binds to the SH2 domain, and (b) the linker:SH3 interaction of which the SH2-kinase domain linker binds to the SH3 domain. SFKs are activated by multiple mechanisms including binding of the ligands to the SH2 and SH3 domains to displace the two inhibitory intramolecular interactions, autophosphorylation, and dephosphorylation of YT. By selective phosphorylation and the non-catalytic inhibitory mechanism CSK and CHK are able to inhibit the active forms of SFKs. CSK and CHK are regulated by phosphorylation and inter-domain interactions. They both contain SH3, SH2, and kinase domains separated by the SH3-SH2 connector and SH2 kinase linker, intervening segments separating the three domains. They lack a conserved tyrosine phosphorylation site in the kinase domain and the C-terminal tail regulatory tyrosine phosphorylation site. The CSK SH2 domain is crucial for stabilizing the kinase domain in the active conformation. A disulfide bond here regulates CSK kinase activity. The subcellular localization and activity of CSK are regulated by its SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198190  Cd Length: 98  Bit Score: 60.38  E-value: 2.82e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVpGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYYTqqq 85
Cdd:cd09937     5 WFHGKISREEAERLLQPPED-GLFLVRESTNYPGDYTLCVSFEGKVEHYRVIYRNGKLTIDEEEYFENLIQLVEHYT--- 80

                          90       100
                  ....*....|....*....|.
gi 1938958509  86 gilQDRDGTIIHLKYPLNCSD 106
Cdd:cd09937    81 ---KDADGLCTRLVKPKVKEG 98
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
 4-102 2.84e-11

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198272  Cd Length: 98  Bit Score: 60.43  E-value: 2.84e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   4 RGWFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLyGGEKFATLTELVEYYtQ 83
Cdd:cd10409     1 KEWYYGNVTRHQAECALNERGVEGDFLIRDSESSPSDFSVSLKAVGKNKHFKVQLVDNVYCI-GQRRFNSMDELVEHY-K 78

                          90
                  ....*....|....*....
gi 1938958509  84 QQGILQDRDGTIIHLKYPL 102
Cdd:cd10409    79 KAPIFTSEHGEKLYLVKAL 97
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 110-196 5.80e-11

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 58.93  E-value: 5.80e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 110 ERWYHGHMSGGQAESLLQAKG-EPWTFLVRESLSQPGDFVLSVL-NDQpkagpgsplrVTHIKVMCEGGR--YTVGGSET 185
Cdd:cd10347     1 LRWYHGKISREVAEALLLREGgRDGLFLVRESTSAPGDYVLSLLaQGE----------VLHYQIRRHGEDafFSDDGPLI 70

                          90
                  ....*....|.
gi 1938958509 186 FDSLTDLVEHF 196
Cdd:cd10347    71 FHGLDTLIEHY 81
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
 6-81 6.06e-11

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 59.23  E-value: 6.06e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVpGSFLARPSRKNQGDFSLSVRVDDQVTHIRI-QNSGDFYDLYGGEKFATLTELVEYY 81
Cdd:cd09940     7 WFVGEMERDTAENRLENRPD-GTYLVRVRPQGETQYALSIKYNGDVKHMKIeQRSDGLYYLSESRHFKSLVELVNYY 82
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
 6-81 7.72e-11

Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (srm); Srm is a nonreceptor protein kinase that has two SH2 domains, a SH3 domain, and a kinase domain with a tyrosine residue for autophosphorylation. However it lacks an N-terminal glycine for myristoylation and a C-terminal tyrosine which suppresses kinase activity when phosphorylated. Srm is most similar to members of the Tec family who other members include: Tec, Btk/Emb, and Itk/Tsk/Emt. However Srm differs in its N-terminal unique domain it being much smaller than in the Tec family and is closer to Src. Srm is thought to be a new family of nonreceptor tyrosine kinases that may be redundant in function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198223  Cd Length: 79  Bit Score: 58.43  E-value: 7.72e-11
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509   6 WFHRDLSGPDAETLL-KGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRI--QNSGDFYdLYGGEKFATLTELVEYY 81
Cdd:cd10360     2 WYFSGISRTQAQQLLlSPPNEPGAFLIRPSESSLGGYSLSVRAQAKVCHYRIcmAPSGSLY-LQKGRLFPGLEELLAYY 79
SH2_Vav1 cd10405
Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the ...
 6-90 7.90e-11

Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav1 plays a role in T-cell and B-cell development and activation. It has been identified as the specific binding partner of Nef proteins from HIV-1, resulting in morphological changes, cytoskeletal rearrangements, and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Vav1 has been shown to interact with Ku70, PLCG1, Lymphocyte cytosolic protein 2, Janus kinase 2, SIAH2, S100B, Abl gene, ARHGDIB, SHB, PIK3R1, PRKCQ, Grb2, MAPK1, Syk, Linker of activated T cells, Cbl gene and EZH2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198268  Cd Length: 103  Bit Score: 59.26  E-value: 7.90e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGvPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYYtqQQ 85
Cdd:cd10405     7 WYAGPMERAGAESILANRS-DGTYLVRQRVKDAAEFAISIKYNVEVKHIKIMTAEGLYRITEKKAFRGLTELVEFY--QQ 83


                  ....*
gi 1938958509  86 GILQD 90
Cdd:cd10405    84 NSLKD 88
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
 112-214 9.13e-11

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198271  Cd Length: 97  Bit Score: 58.89  E-value: 9.13e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSvLNDQPKAgpgsplrvTHIKVMCEGGRYTVgGSETFDSLTD 191
Cdd:cd10408     3 WYYGKVTRHQAEMALNERGNEGDFLIRDSESSPNDFSVS-LKAQGKN--------KHFKVQLKECVYCI-GQRKFSSMEE 72

                          90       100
                  ....*....|....*....|....
gi 1938958509 192 LVEHFKKTGI-EEASGAFVYLRQP 214
Cdd:cd10408    73 LVEHYKKAPIfTSEQGEKLYLIKA 96
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
 6-101 1.50e-10

Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav2 is a GEF for RhoA, RhoB and RhoG and may activate Rac1 and Cdc42. Vav2 has been shown to interact with CD19 and Grb2. Alternatively spliced transcript variants encoding different isoforms have been found for Vav2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198269  Cd Length: 103  Bit Score: 58.54  E-value: 1.50e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRgVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYYtQQQ 85
Cdd:cd10406     7 WFAGNMERQQTDNLLKSH-ASGTYLIRERPAEAERFAISIKFNDEVKHIKVVEKDNWIHITEAKKFESLLELVEYY-QCH 84

                          90
                  ....*....|....*.
gi 1938958509  86 GILQDRDGTIIHLKYP 101
Cdd:cd10406    85 SLKESFKQLDTTLKYP 100
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 109-199 1.62e-10

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199829  Cd Length: 99  Bit Score: 58.13  E-value: 1.62e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQ--AESLLQA--KGEPWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMC--EGG--RYTV 180
Cdd:cd10341     3 TEPWFHGKLGDGRdeAEKLLLEycEGGDGTFLVRESETFVGDYTLSFWRNG---------KVQHCRIRSrqENGekKYYL 73

                          90
                  ....*....|....*....
gi 1938958509 181 GGSETFDSLTDLVEHFKKT 199
Cdd:cd10341    74 TDNLVFDSLYELIDYYRQN 92
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
 112-214 1.69e-10

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198272  Cd Length: 98  Bit Score: 58.12  E-value: 1.69e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVlndqpKAGPgsplRVTHIKVMCEGGRYTVgGSETFDSLTD 191
Cdd:cd10409     3 WYYGNVTRHQAECALNERGVEGDFLIRDSESSPSDFSVSL-----KAVG----KNKHFKVQLVDNVYCI-GQRRFNSMDE 72

                          90       100
                  ....*....|....*....|....
gi 1938958509 192 LVEHFKKTGI-EEASGAFVYLRQP 214
Cdd:cd10409    73 LVEHYKKAPIfTSEHGEKLYLVKA 96
CDKN3-like cd14505
cyclin-dependent kinase inhibitor 3 and similar proteins; This family is composed of ...
 381-511 1.88e-10

cyclin-dependent kinase inhibitor 3 and similar proteins; This family is composed of eukaryotic cyclin-dependent kinase inhibitor 3 (CDKN3) and related archaeal and bacterial proteins. CDKN3 is also known as kinase-associated phosphatase (KAP), CDK2-associated dual-specificity phosphatase, cyclin-dependent kinase interactor 1 (CDI1), or cyclin-dependent kinase-interacting protein 2 (CIP2). It has been characterized as dual-specificity phosphatase, which function as a protein-serine/threonine phosphatase (EC 3.1.3.16) and protein-tyrosine-phosphatase (EC 3.1.3.48). It dephosphorylates CDK2 at a threonine residue in a cyclin-dependent manner, resulting in the inhibition of G1/S cell cycle progression. It also interacts with CDK1 and controls progression through mitosis by dephosphorylating CDC2. CDKN3 may also function as a tumor suppressor; its loss of function was found in a variety of cancers including glioblastoma and hepatocellular carcinoma. However, it has also been found over-expressed in many cancers such as breast, cervical, lung and prostate cancers, and may also have an oncogenic function.


Pssm-ID: 350355 [Multi-domain]  Cd Length: 163  Bit Score: 59.58  E-value: 1.88e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 381 VTNCKEHDTAEYKLRTLqispldnGDLVRE---IWHYqyLSWPDHGVPSEPGGVLSFLDQINQRqesLPHAGPIIVHCSA 457
Cdd:cd14505    48 VTLCTDGELEELGVPDL-------LEQYQQagiTWHH--LPIPDGGVPSDIAQWQELLEELLSA---LENGKKVLIHCKG 115

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1938958509 458 GIGRTGTIIVIDMLMESVstkgldcDIDIQKTIQMVRAQRSGMVQTEAQYKFIY 511
Cdd:cd14505   116 GLGRTGLIAACLLLELGD-------TLDPEQAIAAVRALRPGAIQTPKQENFLH 162
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 6-84 2.56e-10

N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a signaling molecule that is recruited to the C-terminal tail of the receptor upon autophosphorylation of a highly conserved tyrosine. PLCgamma is composed of a Pleckstrin homology (PH) domain followed by an elongation factor (EF) domain, 2 catalytic regions of PLC domains that flank 2 tandem SH2 domains (N-SH2, C-SH2), and ending with a SH3 domain and C2 domain. N-SH2 SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. Both N-SH2 and C-SH2 have a very similar binding affinity to pY. But in growth factor stimulated cells these domains bind to different target proteins. N-SH2 binds to pY containing sites in the C-terminal tails of tyrosine kinases and other receptors. Recently it has been shown that this interaction is mediated by phosphorylation-independent interactions between a secondary binding site found exclusively on the N-SH2 domain and a region of the FGFR1 tyrosine kinase domain. This secondary site on the SH2 cooperates with the canonical pY site to regulate selectivity in mediating a specific cellular process. C-SH2 binds to an intramolecular site on PLCgamma itself which allows it to hydrolyze phosphatidylinositol-4,5-bisphosphate into diacylglycerol and inositol triphosphate. These then activate protein kinase C and release calcium. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199829  Cd Length: 99  Bit Score: 57.36  E-value: 2.56e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSG--PDAETLLKG--RGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQ----NSGDFYDLYGGEKFATLTEL 77
Cdd:cd10341     6 WFHGKLGDgrDEAEKLLLEycEGGDGTFLVRESETFVGDYTLSFWRNGKVQHCRIRsrqeNGEKKYYLTDNLVFDSLYEL 85


                  ....*..
gi 1938958509  78 VEYYTQQ 84
Cdd:cd10341    86 IDYYRQN 92
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 6-83 2.72e-10

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 57.05  E-value: 2.72e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDA-ETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGD-FYDLYGGEKFATLTELVEYYTQ 83
Cdd:cd10348     2 WLHGALDRNEAvEILKQKADADGSFLVRYSRRRPGGYVLTLVYENHVYHFEIQNRDDkWFYIDDGPYFESLEHLIEHYTQ 81
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
 109-214 2.99e-10

Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the Src non-receptor type tyrosine kinase family of proteins. The integration of receptor tyrosine kinase-induced RAS and Src42 signals by Connector eNhancer of KSR (CNK) as a two-component input is essential for RAF activation in Drosophila. Src42 is present in a wide variety of organisms including: California sea hare, pea aphid, yellow fever mosquito, honey bee, Panamanian leafcutter ant, and sea urchin. Src42 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198233  Cd Length: 96  Bit Score: 57.13  E-value: 2.99e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAES-LLQAKGEPWTFLVRESLSQPGDFVLSVLNdqpkagpGSPLRVTHIKVMCEGGrYTVGGSETFD 187
Cdd:cd10370     2 AEPWYFGKIKRIEAEKkLLLPENEHGAFLIRDSESRHNDYSLSVRD-------GDTVKHYRIRQLDEGG-FFIARRTTFR 73

                          90       100
                  ....*....|....*....|....*..
gi 1938958509 188 SLTDLVEHFKKtgieEASGAFVYLRQP 214
Cdd:cd10370    74 TLQELVEHYSK----DSDGLCVNLRKP 96
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
 6-101 3.15e-10

Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. It is expressed in the brain, T-cells, and NK cells. The unique domain of Lck mediates its interaction with two T-cell surface molecules, CD4 and CD8. It associates with their cytoplasmic tails on CD4 T helper cells and CD8 cytotoxic T cells to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck phosphorylase the intracellular chains of the CD3 and zeta-chains of the TCR complex, allowing ZAP-70 to bind them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates Linker of Activated T cells (LAT), a transmembrane protein that serves as a docking site for proteins including: Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). The tyrosine phosphorylation cascade culminates in the intracellular mobilization of a calcium ions and activation of important signaling cascades within the lymphocyte, including the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-kappaB, and AP-1. These transcription factors regulate the production cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes. The N-terminal tail of Lck is myristoylated and palmitoylated and it tethers the protein to the plasma membrane of the cell. Lck also contains a SH3 domain, a SH2 domain, and a C-terminal tyrosine kinase domain. Lck has 2 phosphorylation sites, the first an autophosphorylation site that is linked to activation of the protein and the second which is phosphorylated by Csk, which inhibits it. Lck is also inhibited by SHP-1 dephosphorylation and by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198225  Cd Length: 101  Bit Score: 57.19  E-value: 3.15e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRG-VPGSFLARPSRKNQGDFSLSVRVDDQ-----VTHIRIQN--SGDFYdLYGGEKFATLTEL 77
Cdd:cd10362     5 WFFKNLSRNDAERQLLAPGnTHGSFLIRESETTAGSFSLSVRDFDQnqgevVKHYKIRNldNGGFY-ISPRITFPGLHEL 83

                          90       100
                  ....*....|....*....|....
gi 1938958509  78 VEYYTqqqgilQDRDGTIIHLKYP 101
Cdd:cd10362    84 VRHYT------NASDGLCTRLSRP 101
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
 6-102 4.26e-10

Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. There are two members known in this family: Nck1 (Nckalpha) and Nck2 (Nckbeta and Growth factor receptor-bound protein 4 (Grb4)). They are characterized by having 3 SH3 domains and a C-terminal SH2 domain. Nck1 and Nck2 have overlapping functions as determined by gene knockouts. Both bind receptor tyrosine kinases and other tyrosine-phosphorylated proteins through their SH2 domains. In addition they also bind distinct targets. Neuronal signaling proteins: EphrinB1, EphrinB2, and Disabled-1 (Dab-1) all bind to Nck-2 exclusively. And in the case of PDGFR, Tyr(P)751 binds to Nck1 while Tyr(P)1009 binds to Nck2. Nck1 and Nck2 have a role in the infection process of enteropathogenic Escherichia coli (EPEC). Their SH3 domains are involved in recruiting and activating the N-WASP/Arp2/3 complex inducing actin polymerization resulting in the production of pedestals, dynamic bacteria-presenting protrusions of the plasma membrane. A similar thing occurs in the vaccinia virus where motile plasma membrane projections are formed beneath the virus. Recently it has been shown that the SH2 domains of both Nck1 and Nck2 bind the G-protein coupled receptor kinase-interacting protein 1 (GIT1) in a phosphorylation-dependent manner. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198271  Cd Length: 97  Bit Score: 56.96  E-value: 4.26e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLyGGEKFATLTELVEYYtQQQ 85
Cdd:cd10408     3 WYYGKVTRHQAEMALNERGNEGDFLIRDSESSPNDFSVSLKAQGKNKHFKVQLKECVYCI-GQRKFSSMEELVEHY-KKA 80

                          90
                  ....*....|....*..
gi 1938958509  86 GILQDRDGTIIHLKYPL 102
Cdd:cd10408    81 PIFTSEQGEKLYLIKAL 97
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
 5-102 4.55e-10

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 57.07  E-value: 4.55e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   5 GWFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRI-QNSGDFYDLYGGE-----KFATLTELV 78
Cdd:cd10343     4 PWYHGNITRSKAEELLSKAGKDGSFLVRDSESVSGAYALCVLYQNCVHTYRIlPNAEDKLSVQASEgvpvrFFTTLPELI 83

                          90       100
                  ....*....|....*....|....
gi 1938958509  79 EYYtqqqgiLQDRDGTIIHLKYPL 102
Cdd:cd10343    84 EFY------QKENMGLVTHLLYPV 101
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 6-103 4.82e-10

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 57.02  E-value: 4.82e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVP-GSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNS-GDFYDLYGGEKFATLTELVEYYTq 83
Cdd:cd09938     3 FFYGSITREEAEEYLKLAGMSdGLFLLRQSLRSLGGYVLSVCHGRKFHHYTIERQlNGTYAIAGGKAHCGPAELCEYHS- 81

                          90       100
                  ....*....|....*....|
gi 1938958509  84 qqgilQDRDGTIIHLKYPLN 103
Cdd:cd09938    82 -----TDLDGLVCLLRKPCN 96
PTP_PTPDC1 cd14506
protein tyrosine phosphatase domain of PTP domain-containing protein 1; protein tyrosine ...
 409-510 6.77e-10

protein tyrosine phosphatase domain of PTP domain-containing protein 1; protein tyrosine phosphatase domain-containing protein 1 (PTPDC1) is an uncharacterized non-receptor class protein-tyrosine phosphatase (PTP). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. Small interfering RNA (siRNA) knockdown of the ptpdc1 gene is associated with elongated cilia.


Pssm-ID: 350356 [Multi-domain]  Cd Length: 206  Bit Score: 59.28  E-value: 6.77e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 409 REIWHYQYlSWPDHGVPSePGGVLsflDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLMEsvstkgldCDIDIQK 488
Cdd:cd14506    75 AGIYFYNF-GWKDYGVPS-LTTIL---DIVKVMAFALQEGGKVAVHCHAGLGRTGVLIACYLVYA--------LRMSADQ 141

                          90       100
                  ....*....|....*....|..
gi 1938958509 489 TIQMVRAQRSGMVQTEAQYKFI 510
Cdd:cd14506   142 AIRLVRSKRPNSIQTRGQVLCV 163
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
 6-101 9.36e-10

Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in hemopoietic cells. HCK is proposed to couple the Fc receptor to the activation of the respiratory burst. It may also play a role in neutrophil migration and in the degranulation of neutrophils. It has two different translational starts that have different subcellular localization. HCK has been shown to interact with BCR gene, ELMO1 Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. HCK has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198226  Cd Length: 104  Bit Score: 56.13  E-value: 9.36e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAE-TLLKGRGVPGSFLARPSRKNQGDFSLSVR-----VDDQVTH--IRIQNSGDFYdLYGGEKFATLTEL 77
Cdd:cd10363     5 WFFKGISRKDAErQLLAPGNMLGSFMIRDSETTKGSYSLSVRdydpqHGDTVKHykIRTLDNGGFY-ISPRSTFSTLQEL 83

                          90       100
                  ....*....|....*....|....
gi 1938958509  78 VEYYTQQQgilqdrDGTIIHLKYP 101
Cdd:cd10363    84 VDHYKKGN------DGLCQKLSVP 101
SH2_Nterm_RasGAP cd10353
N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 6-82 9.43e-10

N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP is part of the GAP1 family of GTPase-activating proteins. The protein is located in the cytoplasm and stimulates the GTPase activity of normal RAS p21, but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in RAS inactivation, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Alternative splicing results in two isoforms. The shorter isoform which lacks the N-terminal hydrophobic region, has the same activity, and is expressed in placental tissues. In general the longer isoform contains 2 SH2 domains, a SH3 domain, a pleckstrin homology (PH) domain, and a calcium-dependent phospholipid-binding C2 domain. The C-terminus contains the catalytic domain of RasGap which catalyzes the activation of Ras by hydrolyzing GTP-bound active Ras into an inactive GDP-bound form of Ras. This model contains the N-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198216  Cd Length: 103  Bit Score: 55.99  E-value: 9.43e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQN-SGDFYdlYGGEKFATLTELVEYYT 82
Cdd:cd10353    21 WYHGRLDRTIAEERLRQAGKLGSYLIRESDRRPGSFVLSFLSRTGVNHFRIIAmCGDYY--IGGRRFSSLSDLIGYYS 96
SH2_Vav1 cd10405
Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the ...
 112-203 1.17e-09

Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav1 plays a role in T-cell and B-cell development and activation. It has been identified as the specific binding partner of Nef proteins from HIV-1, resulting in morphological changes, cytoskeletal rearrangements, and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Vav1 has been shown to interact with Ku70, PLCG1, Lymphocyte cytosolic protein 2, Janus kinase 2, SIAH2, S100B, Abl gene, ARHGDIB, SHB, PIK3R1, PRKCQ, Grb2, MAPK1, Syk, Linker of activated T cells, Cbl gene and EZH2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198268  Cd Length: 103  Bit Score: 55.79  E-value: 1.17e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPwTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMCEGGRYTVGGSETFDSLTD 191
Cdd:cd10405     7 WYAGPMERAGAESILANRSDG-TYLVRQRVKDAAEFAISIKYNV---------EVKHIKIMTAEGLYRITEKKAFRGLTE 76

                          90
                  ....*....|..
gi 1938958509 192 LVEHFKKTGIEE 203
Cdd:cd10405    77 LVEFYQQNSLKD 88
PTP_DSP_cys cd14494
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
 431-511 1.45e-09

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.


Pssm-ID: 350344 [Multi-domain]  Cd Length: 113  Bit Score: 55.82  E-value: 1.45e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 431 VLSFLDQINQrQESLPHagPIIVHCSAGIGRTGTIIVIDMLMESvstkgldcDIDIQKTIQMVRAQR-SGMVQTEAQYKF 509
Cdd:cd14494    42 VDRFLEVLDQ-AEKPGE--PVLVHCKAGVGRTGTLVACYLVLLG--------GMSAEEAVRIVRLIRpGGIPQTIEQLDF 110


                  ..
gi 1938958509 510 IY 511
Cdd:cd14494   111 LI 112
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
 6-101 1.97e-09

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 54.88  E-value: 1.97e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAE-TLLKGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQ--NSGDFYdLYGGEKFATLTELVEYYT 82
Cdd:cd10369     5 WFFGAIKRADAEkQLLYSENQTGAFLIRESESQKGEFSLSVLDGGVVKHYRIRrlDEGGFF-LTRRKTFSTLNEFVNYYT 83

                          90
                  ....*....|....*....
gi 1938958509  83 QQQgilqdrDGTIIHLKYP 101
Cdd:cd10369    84 TTS------DGLCVKLGKP 96
SH2_SH2D4A cd10350
Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains ...
 6-84 3.41e-09

Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198213  Cd Length: 103  Bit Score: 54.55  E-value: 3.41e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLkGRGVPGSFLARPSRKNQGdFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKF--ATLTELVEYYTQ 83
Cdd:cd10350     9 WFHGILTLKKANELL-LSTMPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASADSYSFLGVDQLqhATLADLVEYHKE 86


                  .
gi 1938958509  84 Q 84
Cdd:cd10350    87 E 87
SH2_SH2D4B cd10351
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ...
 6-84 5.08e-09

Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198214  Cd Length: 103  Bit Score: 54.13  E-value: 5.08e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRgVPGSFLARPSRKNQGdFSLSVRVDDQVTHIRIQNSGDFYDLYGGE--KFATLTELVEYYTQ 83
Cdd:cd10351     9 WFHGIISREEAEALLMNA-TEGSFLVRVSEKIWG-YTLSYRLQSGFKHFLVDASGDFYSFLGVDpnRHATLTDLIDFHKE 86


                  .
gi 1938958509  84 Q 84
Cdd:cd10351    87 E 87
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 6-81 5.71e-09

N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in the carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198210  Cd Length: 81  Bit Score: 53.15  E-value: 5.71e-09
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509   6 WFHRDLSGPDAETLL-KGRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGD--FYDLYGGEKFATLTELVEYY 81
Cdd:cd10347     3 WYHGKISREVAEALLlREGGRDGLFLVRESTSAPGDYVLSLLAQGEVLHYQIRRHGEdaFFSDDGPLIFHGLDTLIEHY 81
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 2-88 8.94e-09

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 53.58  E-value: 8.94e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   2 LSRGWFHRDLSGPDAETLLKGRG-VPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGD----FYDLYGGE-KFATLT 75
Cdd:cd09944     3 RSQPWFHGGISRDEAARLIRQQGlVDGVFLVRESQSNPGAFVLSLKHGQKIKHYQIIPIEDegqwYFTLDDGVtKFYDLL 82

                          90
                  ....*....|...
gi 1938958509  76 ELVEYYTQQQGIL 88
Cdd:cd09944    83 QLVEFYQLNAGSL 95
DUSP23 cd14504
dual specificity phosphatase 23; Dual specificity phosphatase 23 (DUSP23), also known as ...
 414-510 9.17e-09

dual specificity phosphatase 23; Dual specificity phosphatase 23 (DUSP23), also known as VH1-like phosphatase Z (VHZ) or low molecular mass dual specificity phosphatase 3 (LDP-3), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP23 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It is able to enhance activation of JNK and p38 MAPK, and has been shown to dephosphorylate p44-ERK1 (MAPK3) in vitro. It has been associated with cell growth and human primary cancers. It has also been identified as a cell-cell adhesion regulatory protein; it promotes the dephosphorylation of beta-catenin at Tyr 142 and enhances the interaction between alpha- and beta-catenin.


Pssm-ID: 350354 [Multi-domain]  Cd Length: 142  Bit Score: 54.21  E-value: 9.17e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 414 YQYLSWPDHGVPSePGGVLSFLDQINQRQESlphAGPIIVHCSAGIGRTGTIIVIDMLMESVSTKgldcdidiQKTIQMV 493
Cdd:cd14504    52 YHHIPIEDYTPPT-LEQIDEFLDIVEEANAK---NEAVLVHCLAGKGRTGTMLACYLVKTGKISA--------VDAINEI 119

                          90
                  ....*....|....*..
gi 1938958509 494 RAQRSGMVQTEAQYKFI 510
Cdd:cd14504   120 RRIRPGSIETSEQEKFV 136
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
 5-81 1.20e-08

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198178  Cd Length: 81  Bit Score: 52.20  E-value: 1.20e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   5 GWFHRDLSGPDAETLLKGRGvPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYG----GEKFATLTELVEY 80
Cdd:cd09923     1 GWYWGGITRYEAEELLAGKP-EGTFLVRDSSDSRYLFSVSFRTYGRTLHARIEYSNGRFSFDSsdpsVPRFPCVVELIEH 79


                  .
gi 1938958509  81 Y 81
Cdd:cd09923    80 Y 80
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
 6-84 1.22e-08

Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in the hematopoietic cells, in neural tissues, liver, and adipose tissue. There are two alternatively spliced forms of Lyn. Lyn plays an inhibitory role in myeloid lineage proliferation. Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation, triggering a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phospholipase C2 (PLC2) and phosphatidyl inositol-3 kinase. These kinases play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FC RIIb1. Their ITIM phosphorylation subsequently leads to recruitment and activation of phosphatases such as SHIP-1 and SHP-1 which further down modulate signaling pathways, attenuate cell activation and can mediate tolerance. Lyn also plays a role in the insulin signaling pathway. Activated Lyn phosphorylates insulin receptor substrate 1 (IRS1) leading to an increase in translocation of Glut-4 to the cell membrane and increased glucose utilization. It is the primary Src family member involved in signaling downstream of the B cell receptor. Lyn plays an unusual, 2-fold role in B cell receptor signaling; it is essential for initiation of signaling but is also later involved in negative regulation of the signal. Lyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198227  Cd Length: 101  Bit Score: 52.68  E-value: 1.22e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAE-TLLKGRGVPGSFLARPSRKNQGDFSLSVR-VD----DQVTH--IRIQNSGDFYdLYGGEKFATLTEL 77
Cdd:cd10364     5 WFFKDITRKDAErQLLAPGNSAGAFLIRESETLKGSYSLSVRdYDpqhgDVIKHykIRSLDNGGYY-ISPRITFPCISDM 83


                  ....*..
gi 1938958509  78 VEYYTQQ 84
Cdd:cd10364    84 IKHYQKQ 90
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
 108-202 1.34e-08

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 52.14  E-value: 1.34e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 108 TSERWYHGHMSGGQAESLLQAKGEpwtFLVRESLSQPGD---FVLSVLNDQpkagpgsplRVTHIKVM-CEGGRYTVGGs 183
Cdd:cd10361     4 ENEPYYHGLLPREDAEELLKNDGD---FLVRKTEPKGGGkrkLVLSVRWDG---------KIRHFVINrDDGGKYYIEG- 70

                          90
                  ....*....|....*....
gi 1938958509 184 ETFDSLTDLVEHFKKTGIE 202
Cdd:cd10361    71 KSFKSISELINYYQKTKEP 89
SH2_Grb14 cd10414
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ...
 3-88 1.36e-08

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb14 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR) and weakly to the erbB2 receptor. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198277  Cd Length: 108  Bit Score: 53.01  E-value: 1.36e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   3 SRGWFHRDLSGPDAETLLKGRG-VPGSFLARPSRKNQGDFSLSVRVDDQVTHIRI----QNSGDFYDLYGGE-KFATLTE 76
Cdd:cd10414     4 SQPWFHHKISRDEAQRLIIQQGlVDGVFLVRDSQSNPRTFVLSMSHGQKIKHFQIipveDDGELFHTLDDGHtRFTDLIQ 83

                          90
                  ....*....|..
gi 1938958509  77 LVEYYTQQQGIL 88
Cdd:cd10414    84 LVEFYQLNKGVL 95
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
 101-196 1.37e-08

Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198207  Cd Length: 104  Bit Score: 52.88  E-value: 1.37e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 101 PLNCSDPTSERWYHGHMSGGQAESLLQAKG-EPWTFLVRESLSQPGDFVLSVLndqpKAGPGSPLRVTHIKVMC-EGGRY 178
Cdd:cd10344     1 PSNYVAKVYHGWLFEGLSREKAEELLMLPGnQVGSFLIRESETRRGCYSLSVR----HRGSQSRDSVKHYRIFRlDNGWF 76

                          90
                  ....*....|....*...
gi 1938958509 179 TVGGSETFDSLTDLVEHF 196
Cdd:cd10344    77 YISPRLTFQCLEDMVNHY 94
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
 112-196 1.75e-08

Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198198  Cd Length: 98  Bit Score: 52.43  E-value: 1.75e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPwTFLVRESLSQPGDFVLSVlndqpKAGPGsplrVTHIKVM-CEGGRYTVG-GSETFDSL 189
Cdd:cd09945     3 WYHGAITRIEAESLLRPCKEG-SYLVRNSESTKQDYSLSL-----KSAKG----FMHMRIQrNETGQYILGqFSRPFETI 72


                  ....*..
gi 1938958509 190 TDLVEHF 196
Cdd:cd09945    73 PEMIRHY 79
SH2_BLNK_SLP-76 cd09929
Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing ...
 112-199 1.81e-08

Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76); BLNK (also known as SLP-65 or BASH) is an important adaptor protein expressed in B-lineage cells. BLNK consists of a N-terminal sterile alpha motif (SAM) domain and a C-terminal SH2 domain. BLNK is a cytoplasmic protein, but a part of it is bound to the plasma membrane through an N-terminal leucine zipper motif and transiently bound to a cytoplasmic domain of Iga through its C-terminal SH2 domain upon B cell antigen receptor (BCR)-stimulation. A non-ITAM phosphotyrosine in Iga is necessary for the binding with the BLNK SH2 domain and/or for normal BLNK function in signaling and B cell activation. Upon phosphorylation BLNK binds Btk and PLCgamma2 through their SH2 domains and mediates PLCgamma2 activation by Btk. BLNK also binds other signaling molecules such as Vav, Grb2, Syk, and HPK1. BLNK has been shown to be necessary for BCR-mediated Ca2+ mobilization, for the activation of mitogen-activated protein kinases such as ERK, JNK, and p38 in a chicken B cell line DT40, and for activation of transcription factors such as NF-AT and NF-kappaB in human or mouse B cells. BLNK is involved in B cell development, B cell survival, activation, proliferation, and T-independent immune responses. BLNK is structurally homologous to SLP-76. SLP-76 and (linker for activation of T cells) LAT are adaptor/linker proteins in T cell antigen receptor activation and T cell development. BLNK interacts with many downstream signaling proteins that interact directly with both SLP-76 and LAT. New data suggest functional complementation of SLP-76 and LAT in T cell antigen receptor function with BLNK in BCR function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198183  Cd Length: 121  Bit Score: 53.09  E-value: 1.81e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRES----LSQPgdFVLSVLNDQpkagpgsplRVTHIKVMC--EGGRYTVG---- 181
Cdd:cd09929    13 WYAGNIDRKEAEEALRRSNKDGTFLVRDSsgkdSSQP--YTLMVLYND---------KVYNIQIRFleNTRQYALGtglr 81

                          90
                  ....*....|....*...
gi 1938958509 182 GSETFDSLTDLVEHFKKT 199
Cdd:cd09929    82 GEETFSSVAEIIEHHQKT 99
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
 112-198 2.46e-08

Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domain, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have coevolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198189  Cd Length: 94  Bit Score: 51.62  E-value: 2.46e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLqAKGEPWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMCE-GGRYTVGGSETFDSLT 190
Cdd:cd09935     5 WYHGPISRNAAEYLL-SSGINGSFLVRESESSPGQYSISLRYDG---------RVYHYRISEDsDGKVYVTQEHRFNTLA 74


                  ....*...
gi 1938958509 191 DLVEHFKK 198
Cdd:cd09935    75 ELVHHHSK 82
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 6-101 2.48e-08

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 52.23  E-value: 2.48e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAE-TLLKGRGVPGSFLARPsRKNQGDFSLSVRVDDQVTHIRI-QNSGDFYDLYGGEKFATLTELVEYYTQ 83
Cdd:cd10402    12 WYHGSIARDEAErRLYSGAQPDGKFLLRE-RKESGTYALSLVYGKTVYHYRIdQDKSGKYSIPEGTKFDTLWQLVEYLKL 90

                          90
                  ....*....|....*...
gi 1938958509  84 QQgilqdrDGTIIHLKYP 101
Cdd:cd10402    91 KP------DGLIFVLRES 102
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
 112-193 3.87e-08

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 51.63  E-value: 3.87e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESlSQPGDFVLSVLNdqpKAgPGSP-LRVTHIKVMCEGGRYtVGGSETFDSLT 190
Cdd:cd09934     8 WYVGDMSRQRAESLLKQEDKEGCFVVRNS-STKGLYTVSLFT---KV-PGSPhVKHYHIKQNARSEFY-LAEKHCFETIP 81


                  ...
gi 1938958509 191 DLV 193
Cdd:cd09934    82 ELI 84
SH2_SOCS7 cd10388
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 5-79 3.97e-08

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198251  Cd Length: 101  Bit Score: 51.20  E-value: 3.97e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509   5 GWFHRDLSGPDAETLLKGRgVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFA----TLTELVE 79
Cdd:cd10388    11 GWYWGPMSWEDAEKVLSNK-PDGSFLVRDSSDDRYIFSLSFRSQGSVHHTRIEQYQGTFSLGSRNKFVdrsqSLVEFIE 88
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
 109-214 4.50e-08

Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src non-receptor type tyrosine kinase family of proteins. The Frk subfamily is composed of Frk/Rak and Iyk/Bsk/Gst. It is expressed primarily epithelial cells. Frk is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. Unlike the other Src members it lacks a glycine at position 2 of SH4 which is important for addition of a myristic acid moiety that is involved in targeting Src PTKs to cellular membranes. FRK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where both induce PC12 cell differentiation and beta-cell proliferation. Under conditions that cause beta-cell degeneration these proteins augment beta-cell apoptosis. The FRK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Frk has been demonstrated to interact with retinoblastoma protein. Frk regulates PTEN protein stability by phosphorylating PTEN, which in turn prevents PTEN degradation. Frk also plays a role in regulation of embryonal pancreatic beta cell formation. Frk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its activation loop. The tryosine involved is at the same site as the tyrosine involved in the autophosphorylation of Src. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199831  Cd Length: 96  Bit Score: 51.03  E-value: 4.50e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAE-SLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQPkagpgsplrVTHIKV-MCEGGRYTVGGSETF 186
Cdd:cd10369     2 AEPWFFGAIKRADAEkQLLYSENQTGAFLIRESESQKGEFSLSVLDGGV---------VKHYRIrRLDEGGFFLTRRKTF 72

                          90       100
                  ....*....|....*....|....*...
gi 1938958509 187 DSLTDLVEHFKKTgieeASGAFVYLRQP 214
Cdd:cd10369    73 STLNEFVNYYTTT----SDGLCVKLGKP 96
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
 109-214 7.94e-08

Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src non-receptor type tyrosine kinase family of proteins. It is expressed in the brain, T-cells, and NK cells. The unique domain of Lck mediates its interaction with two T-cell surface molecules, CD4 and CD8. It associates with their cytoplasmic tails on CD4 T helper cells and CD8 cytotoxic T cells to assist signaling from the T cell receptor (TCR) complex. When the T cell receptor is engaged by the specific antigen presented by MHC, Lck phosphorylase the intracellular chains of the CD3 and zeta-chains of the TCR complex, allowing ZAP-70 to bind them. Lck then phosphorylates and activates ZAP-70, which in turn phosphorylates Linker of Activated T cells (LAT), a transmembrane protein that serves as a docking site for proteins including: Shc-Grb2-SOS, PI3K, and phospholipase C (PLC). The tyrosine phosphorylation cascade culminates in the intracellular mobilization of a calcium ions and activation of important signaling cascades within the lymphocyte, including the Ras-MEK-ERK pathway, which goes on to activate certain transcription factors such as NFAT, NF-kappaB, and AP-1. These transcription factors regulate the production cytokines such as Interleukin-2 that promote long-term proliferation and differentiation of the activated lymphocytes. The N-terminal tail of Lck is myristoylated and palmitoylated and it tethers the protein to the plasma membrane of the cell. Lck also contains a SH3 domain, a SH2 domain, and a C-terminal tyrosine kinase domain. Lck has 2 phosphorylation sites, the first an autophosphorylation site that is linked to activation of the protein and the second which is phosphorylated by Csk, which inhibits it. Lck is also inhibited by SHP-1 dephosphorylation and by Cbl ubiquitin ligase, which is part of the ubiquitin-mediated pathway. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198225  Cd Length: 101  Bit Score: 50.64  E-value: 7.94e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKGEPW-TFLVRESLSQPGDFVLSVLNDQPKAGPGsplrVTHIKV--MCEGGRYtVGGSET 185
Cdd:cd10362     2 PEPWFFKNLSRNDAERQLLAPGNTHgSFLIRESETTAGSFSLSVRDFDQNQGEV----VKHYKIrnLDNGGFY-ISPRIT 76

                          90       100
                  ....*....|....*....|....*....
gi 1938958509 186 FDSLTDLVEHFKKtgieEASGAFVYLRQP 214
Cdd:cd10362    77 FPGLHELVRHYTN----ASDGLCTRLSRP 101
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
 5-83 8.71e-08

Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of adapter proteins that negatively regulate cellular signaling initiated by tyrosine kinases. It has a myristylated N-terminus, SH3 and SH2 domains with high homology to Src family tyrosine kinases, and a unique C-terminal tail, which is important for c-Cbl binding. SLAP negatively regulates platelet-derived growth factor (PDGF)-induced mitogenesis in fibroblasts and regulates F-actin assembly for dorsal ruffles formation. c-Cbl mediated SLAP inhibition towards actin remodeling. Moreover, SLAP enhanced PDGF-induced c-Cbl phosphorylation by SFK. In contrast, SLAP mitogenic inhibition was not mediated by c-Cbl, but it rather involved a competitive mechanism with SFK for PDGF-receptor (PDGFR) association and mitogenic signaling. Accordingly, phosphorylation of the Src mitogenic substrates Stat3 and Shc were reduced by SLAP. Thus, we concluded that SLAP regulates PDGFR signaling by two independent mechanisms: a competitive mechanism for PDGF-induced Src mitogenic signaling and a non-competitive mechanism for dorsal ruffles formation mediated by c-Cbl. SLAP is a hematopoietic adaptor containing Src homology (SH)3 and SH2 motifs and a unique carboxy terminus. Unlike c-Src, SLAP lacks a tyrosine kinase domain. Unlike c-Src, SLAP does not impact resorptive function of mature osteoclasts but induces their early apoptosis. SLAP negatively regulates differentiation of osteoclasts and proliferation of their precursors. Conversely, SLAP decreases osteoclast death by inhibiting activation of caspase 3. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198207  Cd Length: 104  Bit Score: 50.57  E-value: 8.71e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   5 GWFHRDLSGPDAETLLKGRGV-PGSFLARPSRKNQGDFSLSVR-----VDDQVTHIRIQ--NSGDFYdLYGGEKFATLTE 76
Cdd:cd10344    11 GWLFEGLSREKAEELLMLPGNqVGSFLIRESETRRGCYSLSVRhrgsqSRDSVKHYRIFrlDNGWFY-ISPRLTFQCLED 89


                  ....*..
gi 1938958509  77 LVEYYTQ 83
Cdd:cd10344    90 MVNHYSE 96
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
 6-84 9.68e-08

Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav3 preferentially activates RhoA, RhoG and, to a lesser extent, Rac1. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. VAV3 has been shown to interact with Grb2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198270  Cd Length: 103  Bit Score: 50.39  E-value: 9.68e-08
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509   6 WFHRDLSGPDAETLLKGRgVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYYTQQ 84
Cdd:cd10407     7 WYAGAMERLQAETELINR-VNSTYLVRHRTKESGEYAISIKYNNEVKHIKILTRDGFFHIAENRKFKSLMELVEYYKHH 84
SH2_SHB_SHD_SHE_SHF_like cd09945
Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, ...
 4-82 1.23e-07

Src homology 2 domain found in SH2 domain-containing adapter proteins B, D, E, and F (SHB, SHD, SHE, SHF); SHB, SHD, SHE, and SHF are SH2 domain-containing proteins that play various roles throughout the cell. SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. SHE is expressed in heart, lung, brain, and skeletal muscle, while expression of SHD is restricted to the brain. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198198  Cd Length: 98  Bit Score: 49.73  E-value: 1.23e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   4 RGWFHRDLSGPDAETLLKGRGvPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYG--GEKFATLTELVEYY 81
Cdd:cd09945     1 QGWYHGAITRIEAESLLRPCK-EGSYLVRNSESTKQDYSLSLKSAKGFMHMRIQRNETGQYILGqfSRPFETIPEMIRHY 79


                  .
gi 1938958509  82 T 82
Cdd:cd09945    80 C 80
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
 105-197 1.31e-07

Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the CRK proteins. CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK. CRKs regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 domain of CRK associates with tyrosine-phosphorylated receptors or components of focal adhesions, such as p130Cas and paxillin. CRK transmits signals to small G proteins through effectors that bind its SH3 domain, such as C3G, the guanine-nucleotide exchange factor (GEF) for Rap1 and R-Ras, and DOCK180, the GEF for Rac6. The binding of p130Cas to the CRK-C3G complex activates Rap1, leading to regulation of cell adhesion, and activates R-Ras, leading to JNK-mediated activation of cell proliferation, whereas the binding of CRK DOCK180 induces Rac1-mediated activation of cellular migration. The activity of the different splicing isoforms varies greatly with CRKI displaying substantial transforming activity, CRKII less so, and phosphorylated CRKII with no biological activity whatsoever. CRKII has a linker region with a phosphorylated Tyr and an additional C-terminal SH3 domain. The phosphorylated Tyr creates a binding site for its SH2 domain which disrupts the association between CRK and its SH2 target proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198180 [Multi-domain]  Cd Length: 106  Bit Score: 50.16  E-value: 1.31e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 105 SDPTSerWYHGHMSGGQAESLLQAKGEPwTFLVRESLSQPGDFVLSVLNDQ-------PKAGPGSPLRVthikvmceggR 177
Cdd:cd09926     4 SDRSS--WYFGPMSRQEAQELLQGQRHG-VFLVRDSSTIPGDYVLSVSENSrvshyiiNSLGQPAPNQS----------R 70

                          90       100
                  ....*....|....*....|
gi 1938958509 178 YTVgGSETFDSLTDLVEHFK 197
Cdd:cd09926    71 YRI-GDQEFDDLPALLEFYK 89
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
 106-215 1.33e-07

Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, Vav2 and Vav3 are more ubiquitously expressed. The members here include insect and amphibian Vavs. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198193  Cd Length: 102  Bit Score: 49.98  E-value: 1.33e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 106 DPTSERWYHGHMSGGQAESLLqaKGEP-WTFLVRESLSQPGDFVLSV-LNDQpkagpgsplrVTHIKVMCE-GGRYTVGG 182
Cdd:cd09940     1 DLSEFLWFVGEMERDTAENRL--ENRPdGTYLVRVRPQGETQYALSIkYNGD----------VKHMKIEQRsDGLYYLSE 68

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1938958509 183 SETFDSLTDLVEHFKKTGIEEA-SGAFVYLRQPY 215
Cdd:cd09940    69 SRHFKSLVELVNYYERNSLGENfAGLDTTLKWPY 102
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
 109-198 1.41e-07

Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src non-receptor type tyrosine kinase family of proteins. Src is thought to play a role in the regulation of embryonic development and cell growth. Members here include v-Src and c-Src. v-Src lacks the C-terminal inhibitory phosphorylation site and is therefore constitutively active as opposed to normal cellular src (c-Src) which is only activated under certain circumstances where it is required (e.g. growth factor signaling). v-Src is an oncogene whereas c-Src is a proto-oncogene. c-Src consists of three domains, an N-terminal SH3 domain, a central SH2 domain and a tyrosine kinase domain. The SH2 and SH3 domains work together in the auto-inhibition of the kinase domain. The phosphorylation of an inhibitory tyrosine near the c-terminus of the protein produces a binding site for the SH2 domain which then facilitates binding of the SH3 domain to a polyproline site within the linker between the SH2 domain and the kinase domain. Binding of the SH3 domain inactivates the enzyme. This allows for multiple mechanisms for c-Src activation: dephosphorylation of the C-terminal tyrosine by a protein tyrosine phosphatase, binding of the SH2 domain by a competitive phospho-tyrosine residue, or competitive binding of a polyproline binding site to the SH3 domain. Unlike most other Src members Src lacks cysteine residues in the SH4 domain that undergo palmitylation. Serine and threonine phosphorylation sites have also been identified in the unique domains of Src and are believed to modulate protein-protein interactions or regulate catalytic activity. Alternatively spliced forms of Src, which contain 6- or 11-amino acid insertions in the SH3 domain, are expressed in CNS neurons. c-Src has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198228  Cd Length: 101  Bit Score: 49.66  E-value: 1.41e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKGEP-WTFLVRESLSQPGDFVLSVLNDQPKAGpgspLRVTHIKV--MCEGGRYTVGGSEt 185
Cdd:cd10365     2 AEEWYFGKITRRESERLLLNAENPrGTFLVRESETTKGAYCLSVSDFDNAKG----LNVKHYKIrkLDSGGFYITSRTQ- 76

                          90
                  ....*....|...
gi 1938958509 186 FDSLTDLVEHFKK 198
Cdd:cd10365    77 FNSLQQLVAYYSK 89
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
 6-85 1.47e-07

Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related (Fes/Fps/Fer) proteins; The Fps family consists of members Fps/Fes and Fer/Flk/Tyk3. They are cytoplasmic protein-tyrosine kinases implicated in signaling downstream from cytokines, growth factors and immune receptors. Fes/Fps/Fer contains three coiled-coil regions, an SH2 (Src-homology-2) and a TK (tyrosine kinase catalytic) domain signature. Members here include: Fps/Fes, Fer, Kin-31, and In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198224  Cd Length: 90  Bit Score: 49.45  E-value: 1.47e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGrgvPGSFLAR---PSRKNQGDFSLSVRVDDQVTHIRIQ-NSGDFYDLYGgEKFATLTELVEYY 81
Cdd:cd10361     8 YYHGLLPREDAEELLKN---DGDFLVRktePKGGGKRKLVLSVRWDGKIRHFVINrDDGGKYYIEG-KSFKSISELINYY 83


                  ....
gi 1938958509  82 TQQQ 85
Cdd:cd10361    84 QKTK 87
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
 106-215 2.48e-07

Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav2 is a GEF for RhoA, RhoB and RhoG and may activate Rac1 and Cdc42. Vav2 has been shown to interact with CD19 and Grb2. Alternatively spliced transcript variants encoding different isoforms have been found for Vav2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198269  Cd Length: 103  Bit Score: 49.30  E-value: 2.48e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 106 DPTSERWYHGHMSGGQAESLLQAKGEPwTFLVRESLSQPGDFVLSV-LNDQpkagpgsplrVTHIKVMCEGGRYTVGGSE 184
Cdd:cd10406     1 DYTAYPWFAGNMERQQTDNLLKSHASG-TYLIRERPAEAERFAISIkFNDE----------VKHIKVVEKDNWIHITEAK 69

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1938958509 185 TFDSLTDLVEHFKKTGIEEASGAF-VYLRQPY 215
Cdd:cd10406    70 KFESLLELVEYYQCHSLKESFKQLdTTLKYPY 101
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 111-214 2.49e-07

N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198191  Cd Length: 104  Bit Score: 49.31  E-value: 2.49e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 111 RWYHGHMSGGQAESLLQAKG-EPWTFLVRESLSQPGDFVLSVLNDqpkagpgspLRVTHIKVMCE-GGRYTVGGSETFDS 188
Cdd:cd09938     2 PFFYGSITREEAEEYLKLAGmSDGLFLLRQSLRSLGGYVLSVCHG---------RKFHHYTIERQlNGTYAIAGGKAHCG 72

                          90       100
                  ....*....|....*....|....*.
gi 1938958509 189 LTDLVEHFKKtgieEASGAFVYLRQP 214
Cdd:cd09938    73 PAELCEYHST----DLDGLVCLLRKP 94
PTP_YopH-like cd14559
YopH and related bacterial protein tyrosine phosphatases; Yersinia outer protein H (YopH) ...
 304-508 2.63e-07

YopH and related bacterial protein tyrosine phosphatases; Yersinia outer protein H (YopH) belongs to the family of classical tyrosine-specific protein tyrosine phosphatases (PTPs). PTPs (EC 3.1.3.48) catalyze the dephosphorylation of phosphotyrosine peptides. YopH is an essential virulence determinant of the pathogenic bacterium by dephosphorylating several focal adhesion proteins including p130Cas in human epithelial cells, resulting in the disruption of focal adhesions and cell detachment from the extracellular matrix. It contains an N-terminal domain that contains signals required for TTSS-mediated delivery of YopH into host cells and a C-terminal catalytic PTP domain.


Pssm-ID: 350407 [Multi-domain]  Cd Length: 227  Bit Score: 51.63  E-value: 2.63e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 304 INANYVKnqlLGpdeNSKTYIASQGCLDATVNDFWQMAWQENTRVIVMTTREVEKGRNKCVPYWPEVGTqrvYGLYSVTN 383
Cdd:cd14559    18 LNANRVQ---IG---NKNVAIACQYPKNEQLEDHLKMLADNRTPCLVVLASNKDIQRKGLPPYFRQSGT---YGSVTVKS 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 384 CKEH-----DTAEYKLRTLQISPlDNGDLVREIWHYQylSWPDHG-VPSE-----------------PGGVLSFLDQINQ 440
Cdd:cd14559    89 KKTGkdelvDGLKADMYNLKITD-GNKTITIPVVHVT--NWPDHTaISSEglkeladlvnksaeekrNFYKSKGSSAIND 165

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509 441 RQESLPhagpiIVHCSAGIGRTGTIIVIDMLMESVSTkgldcdIDIQKTIQMVRAQRSG-MVQTEAQYK 508
Cdd:cd14559   166 KNKLLP-----VIHCRAGVGRTGQLAAAMELNKSPNN------LSVEDIVSDMRTSRNGkMVQKDEQLD 223
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
 109-206 2.67e-07

Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198281  Cd Length: 101  Bit Score: 48.84  E-value: 2.67e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKGEP-WTFLVRESLSQPGDFVLSVLN-DQPKAGpgsplRVTHIKV-MCEGGRYTVGGSET 185
Cdd:cd10418     2 AEEWYFGKLGRKDAERQLLSFGNPrGTFLIRESETTKGAYSLSIRDwDDMKGD-----HVKHYKIrKLDNGGYYITTRAQ 76

                          90       100
                  ....*....|....*....|.
gi 1938958509 186 FDSLTDLVEHFkktgIEEASG 206
Cdd:cd10418    77 FETLQQLVQHY----SERAAG 93
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
 6-89 3.16e-07

Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src non-receptor type tyrosine kinase family of proteins. Blk is expressed in the B-cells. Unlike most other Src members Blk lacks cysteine residues in the SH4 domain that undergo palmitylation. Blk is required for the development of IL-17-producing gamma-delta T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. Blk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198234 [Multi-domain]  Cd Length: 100  Bit Score: 48.86  E-value: 3.16e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAE-TLLKGRGVPGSFLARPSRKNQGDFSLSVR-VDDQ---VTH--IRIQNSGDFYdLYGGEKFATLTELV 78
Cdd:cd10371     5 WFFRTISRKDAErQLLAPMNKAGSFLIRESESNKGAFSLSVKdVTTQgevVKHykIRSLDNGGYY-ISPRITFPTLQALV 83

                          90
                  ....*....|..
gi 1938958509  79 EYYTQQ-QGILQ 89
Cdd:cd10371    84 QHYSKKgDGLCQ 95
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
 109-196 3.72e-07

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 48.75  E-value: 3.72e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKGEPW-TFLVRESLSQPGDFVLSVLN-DQPKagpGSPLRVTHIKVMCEGGRYTVGGSEtF 186
Cdd:cd10367     2 AEEWYFGKIGRKDAERQLLSPGNPRgAFLIRESETTKGAYSLSIRDwDQNR---GDHVKHYKIRKLDTGGYYITTRAQ-F 77

                          90
                  ....*....|
gi 1938958509 187 DSLTDLVEHF 196
Cdd:cd10367    78 DTVQELVQHY 87
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
 109-200 3.72e-07

Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in hemopoietic cells. HCK is proposed to couple the Fc receptor to the activation of the respiratory burst. It may also play a role in neutrophil migration and in the degranulation of neutrophils. It has two different translational starts that have different subcellular localization. HCK has been shown to interact with BCR gene, ELMO1 Cbl gene, RAS p21 protein activator 1, RASA3, Granulocyte colony-stimulating factor receptor, ADAM15 and RAPGEF1. Like the other members of the Src family the SH2 domain in addition to binding the target, also plays an autoinhibitory role by binding to its C-terminal tail. In general SH2 domains are involved in signal transduction. HCK has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198226  Cd Length: 104  Bit Score: 48.81  E-value: 3.72e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKGEPW-TFLVRESLSQPGDFVLSVLNDQPKAGPgsplRVTH--IKVMCEGGRYtVGGSET 185
Cdd:cd10363     2 TEEWFFKGISRKDAERQLLAPGNMLgSFMIRDSETTKGSYSLSVRDYDPQHGD----TVKHykIRTLDNGGFY-ISPRST 76

                          90
                  ....*....|....*
gi 1938958509 186 FDSLTDLVEHFKKTG 200
Cdd:cd10363    77 FSTLQELVDHYKKGN 91
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
 110-200 5.19e-07

Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src non-receptor type tyrosine kinase family of proteins. Blk is expressed in the B-cells. Unlike most other Src members Blk lacks cysteine residues in the SH4 domain that undergo palmitylation. Blk is required for the development of IL-17-producing gamma-delta T cells. Furthermore, Blk is expressed in lymphoid precursors and, in this capacity, plays a role in regulating thymus cellularity during ontogeny. Blk has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198234 [Multi-domain]  Cd Length: 100  Bit Score: 48.09  E-value: 5.19e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 110 ERWYHGHMSGGQAE-SLLQAKGEPWTFLVRESLSQPGDFVLSVlNDQPKAGPgsplRVTHIKVMC--EGGrYTVGGSETF 186
Cdd:cd10371     3 EKWFFRTISRKDAErQLLAPMNKAGSFLIRESESNKGAFSLSV-KDVTTQGE----VVKHYKIRSldNGG-YYISPRITF 76

                          90
                  ....*....|....
gi 1938958509 187 DSLTDLVEHFKKTG 200
Cdd:cd10371    77 PTLQALVQHYSKKG 90
SH2_SHF cd10392
Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought ...
 6-102 7.64e-07

Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought to play a role in PDGF-receptor signaling and regulation of apoptosis. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198255  Cd Length: 98  Bit Score: 47.76  E-value: 7.64e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKgRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEK--FATLTELVEYYTQ 83
Cdd:cd10392     3 WYHGAISRTDAENLLR-LCKEASYLVRNSETSKNDFSLSLKSSQGFMHMKLSRTKEHKYVLGQNSppFSSVPEIIHHYAS 81

                          90
                  ....*....|....*....
gi 1938958509  84 QQgiLQDRDGTIIHLKYPL 102
Cdd:cd10392    82 RK--LPIKGAEHMSLLYPV 98
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
 6-101 7.74e-07

Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the founding member of a family that includes Btk, Itk, Bmx, and Txk. The members have a PH domain, a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is involved in B-cell receptor signaling with mutations in Btk responsible for X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Itk is involved in T-cell receptor signaling. Tec is expressed in both T and B cells, and is thought to function in activated and effector T lymphocytes to induce the expression of genes regulated by NFAT transcription factors. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198188  Cd Length: 104  Bit Score: 47.78  E-value: 7.74e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRKnQGDFSLSV----RVDDQVTH--IRIQNSGDFydlYGGEK--FATLTEL 77
Cdd:cd09934     8 WYVGDMSRQRAESLLKQEDKEGCFVVRNSST-KGLYTVSLftkvPGSPHVKHyhIKQNARSEF---YLAEKhcFETIPEL 83

                          90       100
                  ....*....|....*....|....
gi 1938958509  78 VEYYTQQQGilqdrdGTIIHLKYP 101
Cdd:cd09934    84 INYHQHNSG------GLATRLKYP 101
SH2_Src_Fyn_isoform_a_like cd10418
Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src ...
 6-84 8.19e-07

Src homology 2 (SH2) domain found in Fyn isoform a like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform a type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198281  Cd Length: 101  Bit Score: 47.69  E-value: 8.19e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVP-GSFLARPSRKNQGDFSLSVR-----VDDQVTHIRIQ--NSGDFYdLYGGEKFATLTEL 77
Cdd:cd10418     5 WYFGKLGRKDAERQLLSFGNPrGTFLIRESETTKGAYSLSIRdwddmKGDHVKHYKIRklDNGGYY-ITTRAQFETLQQL 83


                  ....*..
gi 1938958509  78 VEYYTQQ 84
Cdd:cd10418    84 VQHYSER 90
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
 7-78 8.48e-07

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 47.36  E-value: 8.48e-07
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1938958509   7 FHRDLSGPDAETLLKGRGvPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEK-FATLTELV 78
Cdd:cd10352     9 YHGLISREEAEQLLSGAS-DGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYYDGKNHYHYVGEKrFDTIHDLV 80
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
 112-197 1.03e-06

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198178  Cd Length: 81  Bit Score: 46.81  E-value: 1.03e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPwTFLVRESlSQPGD-FVLSVlndQPKAGPgsplrvTHIKVMCEGGRYTV----GGSETF 186
Cdd:cd09923     2 WYWGGITRYEAEELLAGKPEG-TFLVRDS-SDSRYlFSVSF---RTYGRT------LHARIEYSNGRFSFdssdPSVPRF 70

                          90
                  ....*....|.
gi 1938958509 187 DSLTDLVEHFK 197
Cdd:cd09923    71 PCVVELIEHYV 81
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
 6-82 1.03e-06

C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Syk. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198264  Cd Length: 99  Bit Score: 47.19  E-value: 1.03e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509   6 WFHRDLSGPDAET-LLKGRGVPGSFLARpSRKNQGDFSLSVRVDDQVTHIRI-QNSGDFYDLYGGEKFATLTELVEYYT 82
Cdd:cd10401     5 WFHGKISREESEQiLLIGSKTNGKFLIR-ERDNNGSYALCLLHDGKVLHYRIdKDKTGKLSIPDGKKFDTLWQLVEHYS 82
SH2_SH2B_family cd10346
Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein ...
 112-206 1.07e-06

Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein family has 3 members: SH2B1 (SH2-B, PSM), SH2B2 (APS), and SH2B3 (Lnk). SH2B family members contain a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198209  Cd Length: 97  Bit Score: 47.03  E-value: 1.07e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEP--WTFLVRESLSQPGDFVLSvLNDQPKAgpgSPLRVT-------HIKVMCeggrytvgg 182
Cdd:cd10346    10 WFHGTLSRSDAAQLVLHSGADghGVFLVRQSETRRGEFVLT-FNFQGRA---KHLRLTlnekgqcRVQHLW--------- 76

                          90       100
                  ....*....|....*....|....
gi 1938958509 183 setFDSLTDLVEHFKKTGIEEASG 206
Cdd:cd10346    77 ---FPSIFDMLEHFRQNPIPLESG 97
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
 109-198 1.44e-06

Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type tyrosine kinase family of proteins and is expressed in the hematopoietic cells, in neural tissues, liver, and adipose tissue. There are two alternatively spliced forms of Lyn. Lyn plays an inhibitory role in myeloid lineage proliferation. Following engagement of the B cell receptors, Lyn undergoes rapid phosphorylation and activation, triggering a cascade of signaling events mediated by Lyn phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based activation motifs (ITAM) of the receptor proteins, and subsequent recruitment and activation of other kinases including Syk, phospholipase C2 (PLC2) and phosphatidyl inositol-3 kinase. These kinases play critical roles in proliferation, Ca2+ mobilization and cell differentiation. Lyn plays an essential role in the transmission of inhibitory signals through phosphorylation of tyrosine residues within the immunoreceptor tyrosine-based inhibitory motifs (ITIM) in regulatory proteins such as CD22, PIR-B and FC RIIb1. Their ITIM phosphorylation subsequently leads to recruitment and activation of phosphatases such as SHIP-1 and SHP-1 which further down modulate signaling pathways, attenuate cell activation and can mediate tolerance. Lyn also plays a role in the insulin signaling pathway. Activated Lyn phosphorylates insulin receptor substrate 1 (IRS1) leading to an increase in translocation of Glut-4 to the cell membrane and increased glucose utilization. It is the primary Src family member involved in signaling downstream of the B cell receptor. Lyn plays an unusual, 2-fold role in B cell receptor signaling; it is essential for initiation of signaling but is also later involved in negative regulation of the signal. Lyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198227  Cd Length: 101  Bit Score: 46.90  E-value: 1.44e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKG-EPWTFLVRESLSQPGDFVLSVLNDQPKAGPGsplrVTHIKVMC-EGGRYTVGGSETF 186
Cdd:cd10364     2 TEEWFFKDITRKDAERQLLAPGnSAGAFLIRESETLKGSYSLSVRDYDPQHGDV----IKHYKIRSlDNGGYYISPRITF 77

                          90
                  ....*....|..
gi 1938958509 187 DSLTDLVEHFKK 198
Cdd:cd10364    78 PCISDMIKHYQK 89
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
 106-203 1.57e-06

Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding proteins. All vavs are activated by tyrosine phosphorylation leading to their activation. There are three Vav mammalian family members: Vav1 which is expressed in the hematopoietic system, and Vav2 and Vav3 are more ubiquitously expressed. Vav3 preferentially activates RhoA, RhoG and, to a lesser extent, Rac1. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. VAV3 has been shown to interact with Grb2. Vav proteins are involved in several processes that require cytoskeletal reorganization, such as the formation of the immunological synapse (IS), phagocytosis, platelet aggregation, spreading, and transformation. Vavs function as guanine nucleotide exchange factors (GEFs) for the Rho/Rac family of GTPases. Vav family members have several conserved motifs/domains including: a leucine-rich region, a leucine-zipper, a calponin homology (CH) domain, an acidic domain, a Dbl-homology (DH) domain, a pleckstrin homology (PH) domain, a cysteine-rich domain, 2 SH3 domains, a proline-rich region, and a SH2 domain. Vavs are the only known Rho GEFs that have both the DH/PH motifs and SH2/SH3 domains in the same protein. The leucine-rich helix-loop-helix (HLH) domain is thought to be involved in protein heterodimerization with other HLH proteins and it may function as a negative regulator by forming inactive heterodimers. The CH domain is usually involved in the association with filamentous actin, but in Vav it controls NFAT stimulation, Ca2+ mobilization, and its transforming activity. Acidic domains are involved in protein-protein interactions and contain regulatory tyrosines. The DH domain is a GDP-GTP exchange factor on Rho/Rac GTPases. The PH domain in involved in interactions with GTP-binding proteins, lipids and/or phosphorylated serine/threonine residues. The SH3 domain is involved in localization of proteins to specific sites within the cell interacting with protein with proline-rich sequences. The SH2 domain mediates a high affinity interaction with tyrosine phosphorylated proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198270  Cd Length: 103  Bit Score: 46.92  E-value: 1.57e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 106 DPTSERWYHGHMSGGQAESLLQAKgEPWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMCEGGRYTVGGSET 185
Cdd:cd10407     1 DYSCQPWYAGAMERLQAETELINR-VNSTYLVRHRTKESGEYAISIKYNN---------EVKHIKILTRDGFFHIAENRK 70

                          90
                  ....*....|....*...
gi 1938958509 186 FDSLTDLVEHFKKTGIEE 203
Cdd:cd10407    71 FKSLMELVEYYKHHSLKE 88
SH2_C-SH2_Zap70_Syk_like cd10345
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 6-80 1.66e-06

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins; ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198208  Cd Length: 95  Bit Score: 46.60  E-value: 1.66e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1938958509   6 WFHRDLSGPDAE-TLLKGRGVPGSFLARPsRKNQGDFSLSVRVDDQVTHIRI-QNSGDFYDLYGGEKFATLTELVEY 80
Cdd:cd10345     2 WFHGKISREESEqIVLIGSKTNGKFLIRA-RDNNGSYALCLLHEGKVLHYRIdKDKTGKLSIPEGKKFDTLWQLVEH 77
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
 6-83 2.04e-06

Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Fgr; Fgr is a member of the Src non-receptor type tyrosine kinase family of proteins. The protein contains N-terminal sites for myristoylation and palmitoylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. Fgr is expressed in B-cells and myeloid cells, localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Multiple alternatively spliced variants, encoding the same protein, have been identified Fgr has been shown to interact with Wiskott-Aldrich syndrome protein. Fgr has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198230  Cd Length: 101  Bit Score: 46.44  E-value: 2.04e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVP-GSFLARPSRKNQGDFSLSVRVDDQ-----VTHIRIQ--NSGDFYdLYGGEKFATLTEL 77
Cdd:cd10367     5 WYFGKIGRKDAERQLLSPGNPrGAFLIRESETTKGAYSLSIRDWDQnrgdhVKHYKIRklDTGGYY-ITTRAQFDTVQEL 83


                  ....*.
gi 1938958509  78 VEYYTQ 83
Cdd:cd10367    84 VQHYME 89
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
 6-84 2.15e-06

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 46.56  E-value: 2.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVP-GSFLARPSRKNQGDFSLSVR-----VDDQVTHIRIQ--NSGDFYdLYGGEKFATLTEL 77
Cdd:cd10368     5 WYFGKLGRKDAERQLLSFGNPrGTFLIRESETTKGAYSLSIRdwddmKGDHVKHYKIRklDNGGYY-ITTRAQFETLQQL 83


                  ....*..
gi 1938958509  78 VEYYTQQ 84
Cdd:cd10368    84 VQHYSET 90
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 112-196 2.37e-06

C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) proteins; These non-receptor protein-tyrosine kinases contain two SH2 domains, five ankyrin (ANK)-like repeats, and a potential tyrosine phosphorylation site in its carboxyl-terminal tail which resembles the phosphorylation site in members of the src family. Like, mammalian non-receptor protein-tyrosine kinases, ZAP-70 and syk proteins, they do not have SH3 domains. However, the presence of ANK makes these unique among protein-tyrosine kinases. Both tyrosine kinases and ANK repeats have been shown to transduce developmental signals, and SH2 domains are known to participate intimately in tyrosine kinase signaling. These tyrosine kinases are believed to be involved in epithelial cell polarity. The members of this family include the shark (SH2 domains, ANK, and kinase domain) gene in Drosophila and yellow fever mosquitos, as well as the hydra protein HTK16. Drosophila Shark is proposed to transduce intracellularly the Crumbs, a protein necessary for proper organization of ectodermal epithelia, intercellular signal. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198211  Cd Length: 86  Bit Score: 45.88  E-value: 2.37e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQA-ESLLQAKGEPWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMCEGGR-YTVGGSETFDSL 189
Cdd:cd10348     2 WLHGALDRNEAvEILKQKADADGSFLVRYSRRRPGGYVLTLVYEN---------HVYHFEIQNRDDKwFYIDDGPYFESL 72


                  ....*..
gi 1938958509 190 TDLVEHF 196
Cdd:cd10348    73 EHLIEHY 79
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
 109-199 2.72e-06

Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198231 [Multi-domain]  Cd Length: 101  Bit Score: 46.18  E-value: 2.72e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKGEP-WTFLVRESLSQPGDFVLSVLNDQPKAGPgsplRVTHIKV-MCEGGRYTVGGSETF 186
Cdd:cd10368     2 AEEWYFGKLGRKDAERQLLSFGNPrGTFLIRESETTKGAYSLSIRDWDDMKGD----HVKHYKIrKLDNGGYYITTRAQF 77

                          90
                  ....*....|...
gi 1938958509 187 DSLTDLVEHFKKT 199
Cdd:cd10368    78 ETLQQLVQHYSET 90
SH2_ShkA_ShkC cd10356
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC) ...
 1-87 6.65e-06

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkA and shkC. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198219  Cd Length: 113  Bit Score: 45.29  E-value: 6.65e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   1 MLSRGWFHRDLSGPDAETLLKGRGVpGSFLARPSRKNQGDFSLSVRVDD-QVTHIRIQNSGDFYDlYGGEKFATLTELVE 79
Cdd:cd10356     7 LMECAWFHGDISTSESENRLNGKPE-GTFLVRFSTSEPGAYTISKVSKNgGISHQRIHRPGGKFQ-VNNSKYLSVKELIA 84


                  ....*...
gi 1938958509  80 YYTQQQGI 87
Cdd:cd10356    85 GEAQALGI 92
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
 113-193 7.13e-06

Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins are a family of phorbol ester- and diacylglycerol-responsive GTPase-activating proteins. Alpha1-chimerin (formerly known as n-chimerin) and alpha2-chimerin are alternatively spliced products of a single gene, as are beta1- and beta2-chimerin. alpha1- and beta1-chimerin have a relatively short N-terminal region that does not encode any recognizable domains, whereas alpha2- and beta2-chimerin both include a functional SH2 domain that can bind to phosphotyrosine motifs within receptors. All of the isoforms contain a GAP domain with specificity in vitro for Rac1 and a diacylglycerol (DAG)-binding C1 domain which allows them to translocate to membranes in response to DAG signaling and anchors them in close proximity to activated Rac. Other C1 domain-containing diacylglycerol receptors including: PKC, Munc-13 proteins, phorbol ester binding scaffolding proteins involved in Ca2+-stimulated exocytosis, and RasGRPs, diacylglycerol-activated guanine-nucleotide exchange factors (GEFs) for Ras and Rap1. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198215  Cd Length: 91  Bit Score: 44.66  E-value: 7.13e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 113 YHGHMSGGQAESLLQAKGEPwTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMCEGG-RYTVGGSETFDSLTD 191
Cdd:cd10352     9 YHGLISREEAEQLLSGASDG-SYLIRESSRDDGYYTLSLRFNG---------KVKNYKLYYDGKnHYHYVGEKRFDTIHD 78


                  ..
gi 1938958509 192 LV 193
Cdd:cd10352    79 LV 80
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 3-88 8.57e-06

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb7 is part of the Grb7 family of proteins which also includes Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198276  Cd Length: 108  Bit Score: 44.90  E-value: 8.57e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   3 SRGWFHRDLSGPDAETLLKGRG-VPGSFLARPSRKNQGDFSLSVRVDDQVTHIRI----QNSGDFYDLYGGE-KFATLTE 76
Cdd:cd10413     4 TQPWFHGRISREESQRLIGQQGlVDGVFLVRESQRNPQGFVLSLCHLQKVKHYLIlpseEEGRLYFSMDDGQtRFTDLLQ 83

                          90
                  ....*....|..
gi 1938958509  77 LVEYYTQQQGIL 88
Cdd:cd10413    84 LVEFHQLNRGIL 95
SH2_SHF cd10392
Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought ...
 112-196 1.00e-05

Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought to play a role in PDGF-receptor signaling and regulation of apoptosis. SHF is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. SHF contains four putative tyrosine phosphorylation sites and an SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198255  Cd Length: 98  Bit Score: 44.29  E-value: 1.00e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPwTFLVRESLSQPGDFVLSVLNDQPkagpgsplrVTHIKV-MCEGGRYTVG-GSETFDSL 189
Cdd:cd10392     3 WYHGAISRTDAENLLRLCKEA-SYLVRNSETSKNDFSLSLKSSQG---------FMHMKLsRTKEHKYVLGqNSPPFSSV 72


                  ....*..
gi 1938958509 190 TDLVEHF 196
Cdd:cd10392    73 PEIIHHY 79
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
 110-214 1.08e-05

Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine kinase Bmx is expressed in the endothelium of large arteries, fetal endocardium, adult endocardium of the left ventricle, bone marrow, lung, testis, granulocytes, myeloid cell lines, and prostate cell lines. Bmx is involved in the regulation of Rho and serum response factor (SRF). Bmx has been shown to interact with PAK1, PTK2, PTPN21, and RUFY1. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains. It is not present in Txk and the type 1 splice form of the Drosophila homolog. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198262  Cd Length: 106  Bit Score: 44.56  E-value: 1.08e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 110 ERWYHGHMSGGQAESLLQAKGEPWTFLVRESlSQPGDFVLSVLNDQPKAGPGSpLRVTHIKVMCEgGRYTVGGSETFDSL 189
Cdd:cd10399     6 YDWFAGNISRSQSEQLLRQKGKEGAFMVRNS-SQVGMYTVSLFSKAVNDKKGT-VKHYHVHTNAE-NKLYLAENYCFDSI 82

                          90       100
                  ....*....|....*....|....*
gi 1938958509 190 TDLVEHFKktgiEEASGAFVYLRQP 214
Cdd:cd10399    83 PKLIHYHQ----HNSAGMITRLRHP 103
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 112-203 1.24e-05

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198195  Cd Length: 110  Bit Score: 44.62  E-value: 1.24e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLL--QAKGepwTFLVRESLSQPGDFVLSVLndqpKAGpgsplRVTHIKVMCEGGRYTVGGSETFDSL 189
Cdd:cd09942     9 WYWGDISREEVNEKMrdTPDG---TFLVRDASTMKGDYTLTLR----KGG-----NNKLIKIFHRDGKYGFSDPLTFNSV 76

                          90
                  ....*....|....
gi 1938958509 190 TDLVEHFKKTGIEE 203
Cdd:cd09942    77 VELINYYRNNSLAE 90
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
 112-195 1.25e-05

Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of the Tec protein tyrosine kinase Btk is expressed in bone marrow, spleen, all hematopoietic cells except T lymphocytes and plasma cells where it plays a crucial role in B cell maturation and mast cell activation. Btk has been shown to interact with GNAQ, PLCG2, protein kinase D1, B-cell linker, SH3BP5, caveolin 1, ARID3A, and GTF2I. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. Two tyrosine phosphorylation (pY) sites have been identified in Btk: one located in the activation loop of the catalytic domain which regulates the transition between open (active) and closed (inactive) states and the other in its SH3 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198260 [Multi-domain]  Cd Length: 106  Bit Score: 44.44  E-value: 1.25e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESlSQPGDFVLSVLNdqpKAGPGSPLRVTHIKVMC-EGGRYTVGGSETFDSLT 190
Cdd:cd10397     8 WYSKNMTRSQAEQLLKQEGKEGGFIVRDS-SKAGKYTVSVFA---KSAGDPQGVIRHYVVCStPQSQYYLAEKHLFSTIP 83


                  ....*
gi 1938958509 191 DLVEH 195
Cdd:cd10397    84 ELINY 88
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
 6-85 1.32e-05

Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199832  Cd Length: 102  Bit Score: 44.11  E-value: 1.32e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVpGSFLARPSRKNQGdFSLSVRVDDQVTHIRIQNSGDFYDLYGGEK--FATLTELVEYYTQ 83
Cdd:cd10417     9 WFHGFITRKQTEQLLRDKAL-GSFLIRLSDRATG-YILSYRGSDRCRHFVINQLRNRRYLISGDTssHSTLAELVRHYQE 86


                  ..
gi 1938958509  84 QQ 85
Cdd:cd10417    87 VQ 88
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
 112-153 1.62e-05

Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and SLAM-associated protein (SAP); The SH2-containing inositol-5'-phosphatase, SHIP (also called SHIP1/SHIP1a), is a hematopoietic-restricted phosphatidylinositide phosphatase that translocates to the plasma membrane after extracellular stimulation and hydrolyzes the phosphatidylinositol-3-kinase (PI3K)-generated second messenger PI-3,4,5-P3 (PIP3) to PI-3,4-P2. As a result, SHIP dampens down PIP3 mediated signaling and represses the proliferation, differentiation, survival, activation, and migration of hematopoietic cells. PIP3 recruits lipid-binding pleckstrin homology(PH) domain-containing proteins to the inner wall of the plasma membrane and activates them. PH domain-containing downstream effectors include the survival/proliferation enhancing serine/threonine kinase, Akt (protein kinase B), the tyrosine kinase, Btk, the regulator of protein translation, S6K, and the Rac and cdc42 guanine nucleotide exchange factor, Vav. SHIP is believed to act as a tumor suppressor during leukemogenesis and lymphomagenesis, and may play a role in activating the immune system to combat cancer. SHIP contains an N-terminal SH2 domain, a centrally located phosphatase domain that specifically hydrolyzes the 5'-phosphate from PIP3, PI-4,5-P2 and inositol-1,3,4,5- tetrakisphosphate (IP4), a C2 domain, that is an allosteric activating site when bound by SHIP's enzymatic product, PI-3,4-P2; 2 NPXY motifs that bind proteins with a phosphotyrosine binding (Shc, Dok 1, Dok 2) or an SH2 (p85a, SHIP2) domain; and a proline-rich domain consisting of four PxxP motifs that bind a subset of SH3-containing proteins including Grb2, Src, Lyn, Hck, Abl, PLCg1, and PIAS1. The SH2 domain of SHIP binds to the tyrosine phosphorylated forms of Shc, SHP-2, Doks, Gabs, CD150, platelet-endothelial cell adhesion molecule, Cas, c-Cbl, immunoreceptor tyrosine-based inhibitory motifs (ITIMs), and immunoreceptor tyrosine-based activation motifs (ITAMs). The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX(V/I), which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198206  Cd Length: 103  Bit Score: 43.97  E-value: 1.62e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLN 153
Cdd:cd10343     5 WYHGNITRSKAEELLSKAGKDGSFLVRDSESVSGAYALCVLY 46
SH2_SOCS3 cd10384
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 112-196 1.71e-05

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198247  Cd Length: 101  Bit Score: 43.96  E-value: 1.71e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKgEPWTFLVRESLSQPGDFVLSVlndqpKAGPGsplrVTHIKVMCEGGRY---TVGGSE---- 184
Cdd:cd10384    12 FYWSTVSGKEANLLLSAE-PAGTFLIRDSSDQRHFFTLSV-----KTESG----TKNLRIQCEGGSFslqTDPRSTqpvp 81

                          90
                  ....*....|..
gi 1938958509 185 TFDSLTDLVEHF 196
Cdd:cd10384    82 RFDCVLKLVHHY 93
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 112-217 1.85e-05

C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, a inter SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and 2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: 1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, 2) p85 iSH2 domain with C2 domain of p110alpha, and 3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198184  Cd Length: 104  Bit Score: 43.94  E-value: 1.85e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLqaKGEP-WTFLVRESlSQPGDFVLSVL-NDQpkagpgsplrVTHIKVMCEGGRYtvGGSETFD-- 187
Cdd:cd09930     8 WLVGDINRTQAEELL--RGKPdGTFLIRES-STQGCYACSVVcNGE----------VKHCVIYKTETGY--GFAEPYNly 72

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1938958509 188 -SLTDLVEHFKKTGIEEASGAF-VYLRQPYYA 217
Cdd:cd09930    73 eSLKELVLHYAHNSLEQHNDSLtVTLAYPVLA 104
SH2_Tensin_like cd09927
Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. ...
 108-159 1.98e-05

Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. The Tensins are a family of intracellular proteins that interact with receptor tyrosine kinases (RTKs), integrins, and actin. They are thought act as signaling bridges between the extracellular space and the cytoskeleton. There are four homologues: Tensin1, Tensin2 (TENC1, C1-TEN), Tensin3 and Tensin4 (cten), all of which contain a C-terminal tandem SH2-PTB domain pairing, as well as actin-binding regions that may localize them to focal adhesions. The isoforms of Tensin2 and Tensin3 contain N-terminal C1 domains, which are atypical and not expected to bind to phorbol esters. Tensins 1-3 contain a phosphatase (PTPase) and C2 domain pairing which resembles PTEN (phosphatase and tensin homologue deleted on chromosome 10) protein. PTEN is a lipid phosphatase that dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to yield phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). As PtdIns(3,4,5)P3 is the product of phosphatidylinositol 3-kinase (PI3K) activity, PTEN is therefore a key negative regulator of the PI3K pathway. Because of their PTEN-like domains, the Tensins may also possess phosphoinositide-binding or phosphatase capabilities. However, only Tensin2 and Tensin3 have the potential to be phosphatases since only their PTPase domains contain a cysteine residue that is essential for catalytic activity. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198181 [Multi-domain]  Cd Length: 116  Bit Score: 43.96  E-value: 1.98e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1938958509 108 TSERWYHGHMSGGQAESLLQAKgEPWTFLVRESLSQPGDFVLSVLNDQPKAG 159
Cdd:cd09927     1 TSKYWYKPNISRDQAIALLKDK-PPGTFLVRDSTTYKGAYGLAVKVATPPPG 51
SH2_ShkA_ShkC cd10356
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC) ...
 109-193 2.39e-05

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkA and shkC. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198219  Cd Length: 113  Bit Score: 43.75  E-value: 2.39e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKGEPwTFLVRESLSQPGDFVLSVLNDQpkaGPgsplrVTHIKVMCEGGRYTVGGSEtFDS 188
Cdd:cd10356     9 ECAWFHGDISTSESENRLNGKPEG-TFLVRFSTSEPGAYTISKVSKN---GG-----ISHQRIHRPGGKFQVNNSK-YLS 78


                  ....*
gi 1938958509 189 LTDLV 193
Cdd:cd10356    79 VKELI 83
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 109-150 2.67e-05

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. There are 3 members of the Grb7 family of proteins: Grb7, Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb14 binds to Fibroblast Growth Factor Receptor (FGFR). Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198197 [Multi-domain]  Cd Length: 108  Bit Score: 43.56  E-value: 2.67e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKGE-PWTFLVRESLSQPGDFVLS 150
Cdd:cd09944     4 SQPWFHGGISRDEAARLIRQQGLvDGVFLVRESQSNPGAFVLS 46
SH2_Grb10 cd10415
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) ...
 6-88 2.83e-05

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb10 is part of the Grb7 family of proteins which also includes Grb7, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb10 has been shown to interact with many different proteins, including the insulin and IGF1 receptors, platelet-derived growth factor (PDGF) receptor-beta, Ret, Kit, Raf1 and MEK1, and Nedd4. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198278  Cd Length: 108  Bit Score: 43.47  E-value: 2.83e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRG-VPGSFLARPSRKNQGDFSLSVRVDDQVTHIRI---QNSGD-FYDLY-GGEKFATLTELVE 79
Cdd:cd10415     7 WFHGRISREESHRIIKQQGlVDGLFLLRDSQSNPKAFVLTLCHHQKIKNFQIlpcEDDGQtFFSLDdGNTKFSDLIQLVD 86


                  ....*....
gi 1938958509  80 YYTQQQGIL 88
Cdd:cd10415    87 FYQLNKGVL 95
SH2_Src_Fyn_isoform_b_like cd10419
Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src ...
 6-84 3.45e-05

Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform b type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198282  Cd Length: 101  Bit Score: 43.12  E-value: 3.45e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVP-GSFLARPSRKNQGDFSLSVR-----VDDQVTHIRIQ--NSGDFYdLYGGEKFATLTEL 77
Cdd:cd10419     5 WYFGKLGRKDAERQLLSFGNPrGTFLIRESETTKGAYSLSIRdwddmKGDHVKHYKIRklDNGGYY-ITTRAQFETLQQL 83


                  ....*..
gi 1938958509  78 VEYYTQQ 84
Cdd:cd10419    84 VQHYSEK 90
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
 6-84 5.17e-05

Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src non-receptor type tyrosine kinase family of proteins. Src is thought to play a role in the regulation of embryonic development and cell growth. Members here include v-Src and c-Src. v-Src lacks the C-terminal inhibitory phosphorylation site and is therefore constitutively active as opposed to normal cellular src (c-Src) which is only activated under certain circumstances where it is required (e.g. growth factor signaling). v-Src is an oncogene whereas c-Src is a proto-oncogene. c-Src consists of three domains, an N-terminal SH3 domain, a central SH2 domain and a tyrosine kinase domain. The SH2 and SH3 domains work together in the auto-inhibition of the kinase domain. The phosphorylation of an inhibitory tyrosine near the c-terminus of the protein produces a binding site for the SH2 domain which then facilitates binding of the SH3 domain to a polyproline site within the linker between the SH2 domain and the kinase domain. Binding of the SH3 domain inactivates the enzyme. This allows for multiple mechanisms for c-Src activation: dephosphorylation of the C-terminal tyrosine by a protein tyrosine phosphatase, binding of the SH2 domain by a competitive phospho-tyrosine residue, or competitive binding of a polyproline binding site to the SH3 domain. Unlike most other Src members Src lacks cysteine residues in the SH4 domain that undergo palmitylation. Serine and threonine phosphorylation sites have also been identified in the unique domains of Src and are believed to modulate protein-protein interactions or regulate catalytic activity. Alternatively spliced forms of Src, which contain 6- or 11-amino acid insertions in the SH3 domain, are expressed in CNS neurons. c-Src has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198228  Cd Length: 101  Bit Score: 42.34  E-value: 5.17e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVP-GSFLARPSRKNQGDFSLSVRVDD-----QVTHIRIQ--NSGDFYdLYGGEKFATLTEL 77
Cdd:cd10365     5 WYFGKITRRESERLLLNAENPrGTFLVRESETTKGAYCLSVSDFDnakglNVKHYKIRklDSGGFY-ITSRTQFNSLQQL 83


                  ....*..
gi 1938958509  78 VEYYTQQ 84
Cdd:cd10365    84 VAYYSKH 90
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
 6-82 5.40e-05

Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the CRK proteins. CRKI (SH2-SH3) and CRKII (SH2-SH3-SH3) are splicing isoforms of the oncoprotein CRK. CRKs regulate transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 domain of CRK associates with tyrosine-phosphorylated receptors or components of focal adhesions, such as p130Cas and paxillin. CRK transmits signals to small G proteins through effectors that bind its SH3 domain, such as C3G, the guanine-nucleotide exchange factor (GEF) for Rap1 and R-Ras, and DOCK180, the GEF for Rac6. The binding of p130Cas to the CRK-C3G complex activates Rap1, leading to regulation of cell adhesion, and activates R-Ras, leading to JNK-mediated activation of cell proliferation, whereas the binding of CRK DOCK180 induces Rac1-mediated activation of cellular migration. The activity of the different splicing isoforms varies greatly with CRKI displaying substantial transforming activity, CRKII less so, and phosphorylated CRKII with no biological activity whatsoever. CRKII has a linker region with a phosphorylated Tyr and an additional C-terminal SH3 domain. The phosphorylated Tyr creates a binding site for its SH2 domain which disrupts the association between CRK and its SH2 target proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198180 [Multi-domain]  Cd Length: 106  Bit Score: 42.46  E-value: 5.40e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKG--RGVpgsFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGD------FYDLyGGEKFATLTEL 77
Cdd:cd09926     9 WYFGPMSRQEAQELLQGqrHGV---FLVRDSSTIPGDYVLSVSENSRVSHYIINSLGQpapnqsRYRI-GDQEFDDLPAL 84


                  ....*
gi 1938958509  78 VEYYT 82
Cdd:cd09926    85 LEFYK 89
SH2_Tensin_like cd09927
Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. ...
 3-48 5.81e-05

Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. The Tensins are a family of intracellular proteins that interact with receptor tyrosine kinases (RTKs), integrins, and actin. They are thought act as signaling bridges between the extracellular space and the cytoskeleton. There are four homologues: Tensin1, Tensin2 (TENC1, C1-TEN), Tensin3 and Tensin4 (cten), all of which contain a C-terminal tandem SH2-PTB domain pairing, as well as actin-binding regions that may localize them to focal adhesions. The isoforms of Tensin2 and Tensin3 contain N-terminal C1 domains, which are atypical and not expected to bind to phorbol esters. Tensins 1-3 contain a phosphatase (PTPase) and C2 domain pairing which resembles PTEN (phosphatase and tensin homologue deleted on chromosome 10) protein. PTEN is a lipid phosphatase that dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) to yield phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). As PtdIns(3,4,5)P3 is the product of phosphatidylinositol 3-kinase (PI3K) activity, PTEN is therefore a key negative regulator of the PI3K pathway. Because of their PTEN-like domains, the Tensins may also possess phosphoinositide-binding or phosphatase capabilities. However, only Tensin2 and Tensin3 have the potential to be phosphatases since only their PTPase domains contain a cysteine residue that is essential for catalytic activity. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198181 [Multi-domain]  Cd Length: 116  Bit Score: 42.80  E-value: 5.81e-05
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1938958509   3 SRGWFHRDLSGPDAETLLKGRgVPGSFLARPSRKNQGDFSLSVRVD 48
Cdd:cd09927     2 SKYWYKPNISRDQAIALLKDK-PPGTFLVRDSTTYKGAYGLAVKVA 46
SH2_SHB cd10389
Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in ...
 6-102 6.44e-05

Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198252  Cd Length: 97  Bit Score: 42.00  E-value: 6.44e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKgRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDL-YGGEKFATLTELVEYYTQQ 84
Cdd:cd10389     3 WYHGAISRGDAENLLR-LCKECSYLVRNSQTSKHDYSLSLKSNQGFMHMKLAKTKEKYVLgQNSPPFDSVPEVIHYYTTR 81

                          90
                  ....*....|....*...
gi 1938958509  85 QgiLQDRDGTIIHLKYPL 102
Cdd:cd10389    82 K--LPIKGAEHLSLLYPV 97
SH2_ShkD_ShkE cd10357
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases D and E (ShkD and ShkE) ...
 1-57 6.61e-05

Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases D and E (ShkD and ShkE); SH2-bearing genes cloned from Dictyostelium include two transcription factors, STATa and STATc, and a signaling factor, SHK1 (shkA). A database search of the Dictyostelium discoideum genome revealed two additional putative STAT sequences, dd-STATb and dd-STATd, and four additional putative SHK genes, dd-SHK2 (shkB), dd-SHK3 (shkC), dd-SHK4 (shkD), and dd-SHK5 (shkE). This model contains members of shkD and shkE. All of the SHK members are most closely related to the protein kinases found in plants. However these kinases in plants are not conjugated to any SH2 or SH2-like sequences. Alignment data indicates that the SHK SH2 domains carry some features of the STAT SH2 domains in Dictyostelium. When STATc's linker domain was used for a BLAST search, the sequence between the protein kinase domain and the SH2 domain (the linker) of SHK was recovered, suggesting a close relationship among these molecules within this region. SHK's linker domain is predicted to contain an alpha-helix which is indeed homologous to that of STAT. Based on the phylogenetic alignment, SH2 domains can be grouped into two categories, STAT-type and Src-type. SHK family members are in between, but are closer to the STAT-type which indicates a close relationship between SHK and STAT families in their SH2 domains and further supports the notion that SHKs linker-SH2 domain evolved from STAT or STATL (STAT-like Linker-SH2) domain found in plants. In SHK, STAT, and SPT6, the linker-SH2 domains all reside exclusively in the C-terminal regions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198220  Cd Length: 87  Bit Score: 41.73  E-value: 6.61e-05
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509   1 MLSRGWFHRDLSGPDAETLLKGRgVPGSFLARPSRKN--QGDFSLSVRVDDQVTHIRIQ 57
Cdd:cd10357     7 LLAKSWFHGDISRDEAEKRLRGR-PEGTFLIRLSSTDpkKTPFTISKKKKSKPVHKRIS 64
SH2_Src_Fyn_isoform_b_like cd10419
Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src ...
 110-198 9.58e-05

Src homology 2 (SH2) domain found in Fyn isoform b like proteins; Fyn is a member of the Src non-receptor type tyrosine kinase family of proteins. This cd contains the SH2 domain found in Fyn isoform b type proteins. Fyn is involved in the control of cell growth and is required in the following pathways: T and B cell receptor signaling, integrin-mediated signaling, growth factor and cytokine receptor signaling, platelet activation, ion channel function, cell adhesion, axon guidance, fertilization, entry into mitosis, and differentiation of natural killer cells, oligodendrocytes and keratinocytes. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the Fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. Fyn is primarily localized to the cytoplasmic leaflet of the plasma membrane. Tyrosine phosphorylation of target proteins by Fyn serves to either regulate target protein activity, and/or to generate a binding site on the target protein that recruits other signaling molecules. FYN has been shown to interact with a number of proteins including: BCAR1, Cbl, Janus kinase, nephrin, Sky, tyrosine kinase, Wiskott-Aldrich syndrome protein, and Zap-70. Fyn has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198282  Cd Length: 101  Bit Score: 41.58  E-value: 9.58e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 110 ERWYHGHMSGGQAESLLQAKGEP-WTFLVRESLSQPGDFVLSVLNDQPKAGPgsplRVTHIKV-MCEGGRYTVGGSETFD 187
Cdd:cd10419     3 EEWYFGKLGRKDAERQLLSFGNPrGTFLIRESETTKGAYSLSIRDWDDMKGD----HVKHYKIrKLDNGGYYITTRAQFE 78

                          90
                  ....*....|.
gi 1938958509 188 SLTDLVEHFKK 198
Cdd:cd10419    79 TLQQLVQHYSE 89
SH2_SOCS3 cd10384
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 5-81 9.94e-05

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198247  Cd Length: 101  Bit Score: 41.65  E-value: 9.94e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   5 GWFHRDLSGPDAETLLKGRgVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQ-NSGDFY---DLYGGE---KFATLTEL 77
Cdd:cd10384    11 GFYWSTVSGKEANLLLSAE-PAGTFLIRDSSDQRHFFTLSVKTESGTKNLRIQcEGGSFSlqtDPRSTQpvpRFDCVLKL 89


                  ....
gi 1938958509  78 VEYY 81
Cdd:cd10384    90 VHHY 93
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 112-214 1.04e-04

C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70); ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the C-terminus SH2 domains of Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198265  Cd Length: 105  Bit Score: 41.83  E-value: 1.04e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEP-WTFLVRESLSQpGDFVLSVLNDQPkagpgsplrVTHIKVMCE-GGRYTVGGSETFDSL 189
Cdd:cd10402    12 WYHGSIARDEAERRLYSGAQPdGKFLLRERKES-GTYALSLVYGKT---------VYHYRIDQDkSGKYSIPEGTKFDTL 81

                          90       100
                  ....*....|....*....|....*
gi 1938958509 190 TDLVEHFKKtgieEASGAFVYLRQP 214
Cdd:cd10402    82 WQLVEYLKL----KPDGLIFVLRES 102
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
 3-107 1.09e-04

Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is part of a growing family of guanine nucleotide exchange factors is responsible for activation of Ras-family GTPases, including Sos1 and 2, GRF1 and 2, CalDAG-GEF/GRP1-4, C3G, cAMP-GEF/Epac 1 and 2, PDZ-GEFs, MR-GEF, RalGDS family members, RalGPS, RasGEF, Smg GDS, and phospholipase C(epsilon). 12102558 21262352 BCAR3 binds to the carboxy-terminus of BCAR1/p130Cas, a focal adhesion adapter protein. Over expression of BCAR1 (p130Cas) and BCAR3 induces estrogen independent growth in normally estrogen-dependent cell lines. They have been linked to resistance to anti-estrogens in breast cancer, Rac activation, and cell motility, though the BCAR3/p130Cas complex is not required for this activity in BCAR3. Many BCAR3-mediated signaling events in epithelial and mesenchymal cells are independent of p130Cas association. Structurally these proteins contain a single SH2 domain upstream of their RasGEF domain, which is responsible for the ability of BCAR3 to enhance p130Cas over-expression-induced migration. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198200 [Multi-domain]  Cd Length: 136  Bit Score: 42.32  E-value: 1.09e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   3 SRGWFHRDLSGPDAETLLKGrgvPGSFLARPSRKNQGDFSLSVRVDDQVTHIRI----QNSGDFYD----LYGGEKFATL 74
Cdd:cd10337     5 SHAWYHGRIPRQVAESLVQR---EGDFLVRDSLSSPGDYVLTCRWKGQPLHFKInrvvLRPSEAYTrvqyQFEDEQFDSI 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1938958509  75 TELVEYY-------TQQQG--ILQDRDGTiihlkYPLNCSDP 107
Cdd:cd10337    82 PALVHFYvgnrrpiSQASGaiISRPVNRT-----VPLRCLEE 118
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
 6-102 1.14e-04

Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine kinase Txk is expressed in thymus, spleen, lymph node, T lymphocytes, NK cells, mast cell lines, and myeloid cell line. Txk plays a role in TCR signal transduction, T cell development, and selection which is analogous to the function of Itk. Txk has been shown to interact with IFN-gamma. Unlike most of the Tec family members Txk lacks a PH domain. Instead Txk has a unique region containing a palmitoylated cysteine string which has a similar membrane tethering function as the PH domain. Txk also has a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP and crucial to the function of the PH domain. It is not present in Txk which is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198261  Cd Length: 106  Bit Score: 41.86  E-value: 1.14e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRkNQGDFSLSVRVDDQ------VTHIRIQNSgDFYDLYGGEK--FATLTEL 77
Cdd:cd10398     8 WYHKNITRNQAERLLRQESKEGAFIVRDSR-HLGSYTISVFTRARrsteasIKHYQIKKN-DSGQWYVAERhlFQSIPEL 85

                          90       100
                  ....*....|....*....|....*
gi 1938958509  78 VEYYTQQQGilqdrdGTIIHLKYPL 102
Cdd:cd10398    86 IQYHQHNAA------GLMSRLRYPV 104
SH2_Nterm_SPT6_like cd09918
N-terminal Src homology 2 (SH2) domain found in Spt6; N-terminal SH2 domain in Spt6. Spt6 is ...
 7-81 1.49e-04

N-terminal Src homology 2 (SH2) domain found in Spt6; N-terminal SH2 domain in Spt6. Spt6 is an essential transcription elongation factor and histone chaperone that binds the C-terminal repeat domain (CTD) of RNA polymerase II. Spt6 contains a tandem SH2 domain with a novel structure and CTD-binding mode. The tandem SH2 domain binds to a serine 2-phosphorylated CTD peptide in vitro, whereas its N-terminal SH2 subdomain does not. CTD binding requires a positively charged crevice in the C-terminal SH2 subdomain, which lacks the canonical phospho-binding pocket of SH2 domains. The tandem SH2 domain is apparently required for transcription elongation in vivo as its deletion in cells is lethal in the presence of 6-azauracil. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198174  Cd Length: 85  Bit Score: 40.68  E-value: 1.49e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   7 FHrDLSGPDAETLLKGRGVpGSFLARPSRKNQGDFSLSVRVDDQVT-HIRIQ-------NSGDFYDLYGGEKFATLTELV 78
Cdd:cd09918     5 FK-NVNYKQAEAYLKSKDV-GEVVIRPSSKGVDHLTVTWKVADGVYqHIDIEelnkenpFSLGKELIIGGEEYEDLDEII 82


                  ...
gi 1938958509  79 EYY 81
Cdd:cd09918    83 ARF 85
SH2_SHD cd10390
Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression ...
 6-84 1.88e-04

Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression of SHD is restricted to the brain. SHD may be a physiological substrate of c-Abl and may function as an adapter protein in the central nervous system. It is also thought to be involved in apoptotic regulation. SHD contains five YXXP motifs, a substrate sequence preferred by Abl tyrosine kinases, in addition to a poly-proline rich region and a C-terminal SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198253  Cd Length: 98  Bit Score: 40.84  E-value: 1.88e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKgRGVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEK--FATLTELVEYYTQ 83
Cdd:cd10390     3 WFHGPLSRADAENLLS-LCKEGSYLVRLSETRPQDCSLSLRSSQGFLHLKFARTRENQVVLGQHSgpFPSVPELVLHYSS 81


                  .
gi 1938958509  84 Q 84
Cdd:cd10390    82 R 82
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
 112-214 1.95e-04

Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine kinase Txk is expressed in thymus, spleen, lymph node, T lymphocytes, NK cells, mast cell lines, and myeloid cell line. Txk plays a role in TCR signal transduction, T cell development, and selection which is analogous to the function of Itk. Txk has been shown to interact with IFN-gamma. Unlike most of the Tec family members Txk lacks a PH domain. Instead Txk has a unique region containing a palmitoylated cysteine string which has a similar membrane tethering function as the PH domain. Txk also has a zinc-binding motif, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP and crucial to the function of the PH domain. It is not present in Txk which is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198261  Cd Length: 106  Bit Score: 41.08  E-value: 1.95e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESlSQPGDFVLSVLNdQPKAGPGSPLRVTHIKvMCEGGRYTVGGSETFDSLTD 191
Cdd:cd10398     8 WYHKNITRNQAERLLRQESKEGAFIVRDS-RHLGSYTISVFT-RARRSTEASIKHYQIK-KNDSGQWYVAERHLFQSIPE 84

                          90       100
                  ....*....|....*....|...
gi 1938958509 192 LVEHFKktgiEEASGAFVYLRQP 214
Cdd:cd10398    85 LIQYHQ----HNAAGLMSRLRYP 103
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
 109-198 2.17e-04

Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198229  Cd Length: 101  Bit Score: 40.77  E-value: 2.17e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKG-EPWTFLVRESLSQPGDFVLSVLNDQPKAGPGsplrVTHIKV-MCEGGRYTVGGSETF 186
Cdd:cd10366     2 AEEWYFGKMGRKDAERLLLNPGnQRGIFLVRESETTKGAYSLSIRDWDEVRGDN----VKHYKIrKLDNGGYYITTRAQF 77

                          90
                  ....*....|..
gi 1938958509 187 DSLTDLVEHFKK 198
Cdd:cd10366    78 DTLQKLVKHYTE 89
CDC14_C cd14499
C-terminal dual-specificity phosphatase domain of CDC14 family proteins; The cell division ...
 413-466 2.33e-04

C-terminal dual-specificity phosphatase domain of CDC14 family proteins; The cell division control protein 14 (CDC14) family is highly conserved in all eukaryotes, although the roles of its members seem to have diverged during evolution. Yeast Cdc14, the best characterized member of this family, is a dual-specificity phosphatase that plays key roles in cell cycle control. It preferentially dephosphorylates cyclin-dependent kinase (CDK) targets, which makes it the main antagonist of CDK in the cell. Cdc14 functions at the end of mitosis and it triggers the events that completely eliminates the activity of CDK and other mitotic kinases. It is also involved in coordinating the nuclear division cycle with cytokinesis through the cytokinesis checkpoint, and in chromosome segregation. Cdc14 phosphatases also function in DNA replication, DNA damage checkpoint, and DNA repair. Vertebrates may contain more than one Cdc14 homolog; humans have three (CDC14A, CDC14B, and CDC14C). CDC14 family proteins contain a highly conserved N-terminal pseudophosphatase domain that contributes to substrate specificity and a C-terminal catalytic dual-specificity phosphatase domain with the PTP signature motif.


Pssm-ID: 350349 [Multi-domain]  Cd Length: 174  Bit Score: 42.05  E-value: 2.33e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1938958509 413 HYQyLSWPDHGVPSEpGGVLSFLDQINQrqeslpHAGPIIVHCSAGIGRTGTII 466
Cdd:cd14499    82 HYD-LYFPDGSTPSD-DIVKKFLDICEN------EKGAIAVHCKAGLGRTGTLI 127
SH2_SOCS6 cd10387
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 5-79 2.70e-04

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198250  Cd Length: 100  Bit Score: 40.59  E-value: 2.70e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1938958509   5 GWFHRDLSGPDAETLLKGrgVP-GSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYG---GEKFATLTELVE 79
Cdd:cd10387    11 GWYWGPITRWEAEGKLAN--VPdGSFLVRDSSDDRYLLSLSFRSHGKTLHTRIEHSNGRFSFYEqpdVEGHTSIVDLIE 87
SH2_SH2B3 cd10412
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), ...
 112-206 2.76e-04

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B3 negatively regulates lymphopoiesis and early hematopoiesis. The lnk-deficiency results in enhanced production of B cells, and expansion as well as enhanced function of hematopoietic stem cells (HSCs), demonstrating negative regulatory functions of Sh2b3/Lnk in cytokine signaling. Sh2b3/Lnk also functions in responses controlled by cell adhesion and in crosstalk between integrin- and cytokine-mediated signaling. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198275  Cd Length: 97  Bit Score: 40.26  E-value: 2.76e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPW--TFLVRESLSQPGDFVLSvLNDQPKAgpgSPLRVThikvMCEGGRYTVGGSEtFDSL 189
Cdd:cd10412    10 WFHGPISRVKAAQLVQLQGPDAhgVFLVRQSETRRGEYVLT-FNFQGRA---KHLRLS----LTERGQCRVQHLH-FPSV 80

                          90
                  ....*....|....*..
gi 1938958509 190 TDLVEHFKKTGIEEASG 206
Cdd:cd10412    81 VDMLHHFQRSPIPLECG 97
SH2_SOCS1 cd10382
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 13-81 2.77e-04

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198245  Cd Length: 98  Bit Score: 40.42  E-value: 2.77e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1938958509  13 GP----DAETLLKGRGVpGSFLARPSRknQGD--FSLSVRVDDQVTHIRIQNSGDFYDLYG-GEKFATLTELVEYY 81
Cdd:cd10382    15 GPlsveEAHAKLKREPV-GTFLIRDSR--QKNcfFALSVKMASGPVSIRILFKAGKFSLDGsKESFDCLFKLLEHY 87
SH2_HSH2_like cd09946
Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function ...
 6-83 2.80e-04

Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function as an adapter protein involved in tyrosine kinase signaling. It may also be involved in regulating cytokine signaling and cytoskeletal reorganization in hematopoietic cells. HSH2 contains several putative protein-binding motifs, SH3-binding proline-rich regions, and phosphotyrosine sites, but lacks enzymatic motifs. HSH2 was found to interact with cytokine-regulated tyrosine kinase c-FES and an activated Cdc42-associated tyrosine kinase ACK1. HSH2 binds c-FES through both its C-terminal region and its N-terminal region including the SH2 domain and binds ACK1 via its N-terminal proline-rich region. Both kinases bound and tyrosine-phosphorylated HSH2 in mammalian cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198199  Cd Length: 102  Bit Score: 40.26  E-value: 2.80e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVpGSFLARPSRKNQGdFSLSVRVDDQVTHIRIQNSGDFYDLYGGEK--FATLTELVEYYTQ 83
Cdd:cd09946     9 WFHGAISREAAENMLESQPL-GSFLIRVSHSHVG-YTLSYKAQSSCRHFMVKLLDDGTFMIPGEKvaHTSLHALVTFHQQ 86
SH2_PTK6_Brk cd10358
Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast ...
 3-84 4.62e-04

Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast tumor kinase (Brk); Human protein-tyrosine kinase-6 (PTK6, also known as breast tumor kinase (Brk)) is a member of the non-receptor protein-tyrosine kinase family and is expressed in two-thirds of all breast tumors. PTK6 (9). PTK6 contains a SH3 domain, a SH2 domain, and catalytic domains. For the case of the non-receptor protein-tyrosine kinases, the SH2 domain is typically involved in negative regulation of kinase activity by binding to a phosphorylated tyrosine residue near to the C terminus. The C-terminal sequence of PTK6 (PTSpYENPT where pY is phosphotyrosine) is thought to be a self-ligand for the SH2 domain. The structure of the SH2 domain resembles other SH2 domains except for a centrally located four-stranded antiparallel beta-sheet (strands betaA, betaB, betaC, and betaD). There are also differences in the loop length which might be responsible for PTK6 ligand specificity. There are two possible means of regulation of PTK6: autoinhibitory with the phosphorylation of Tyr playing a role in its negative regulation and autophosphorylation at this site, though it has been shown that PTK6 might phosphorylate signal transduction-associated proteins Sam68 and signal transducing adaptor family member 2 (STAP/BKS) in vivo. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198221  Cd Length: 100  Bit Score: 39.73  E-value: 4.62e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   3 SRGWFHRDLSGPDAETLLKGR-GVPGSFLARPSRKNQGDFSLSVRVDDQVTHIRI--QNSGDFYdLYGGEKFATLTELVE 79
Cdd:cd10358     1 SEPWFFGCISRSEAVRRLQAEgNATGAFLIRVSEKPSADYVLSVRDTQAVRHYKIwrRAGGRLH-LNEAVSFLSLPELVN 79


                  ....*
gi 1938958509  80 YYTQQ 84
Cdd:cd10358    80 YHRAQ 84
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 109-194 4.69e-04

Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) proteins; The Grb family binds to the epidermal growth factor receptor (EGFR, erbB1) via their SH2 domains. Grb7 is part of the Grb7 family of proteins which also includes Grb10, and Grb14. They are composed of an N-terminal Proline-rich domain, a Ras Associating-like (RA) domain, a Pleckstrin Homology (PH) domain, a phosphotyrosine interaction region (PIR, BPS) and a C-terminal SH2 domain. The SH2 domains of Grb7, Grb10 and Grb14 preferentially bind to a different RTK. Grb7 binds strongly to the erbB2 receptor, unlike Grb10 and Grb14 which bind weakly to it. Grb7 family proteins are phosphorylated on serine/threonine as well as tyrosine residues. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198276  Cd Length: 108  Bit Score: 39.89  E-value: 4.69e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 109 SERWYHGHMSGGQAESLLQAKG-EPWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKVMC--EGGR--YTVGGS 183
Cdd:cd10413     4 TQPWFHGRISREESQRLIGQQGlVDGVFLVRESQRNPQGFVLSLCHLQ---------KVKHYLILPseEEGRlyFSMDDG 74

                          90
                  ....*....|..
gi 1938958509 184 ET-FDSLTDLVE 194
Cdd:cd10413    75 QTrFTDLLQLVE 86
DSPc pfam00782
Dual specificity phosphatase, catalytic domain; Ser/Thr and Tyr protein phosphatases. The ...
 431-501 5.73e-04

Dual specificity phosphatase, catalytic domain; Ser/Thr and Tyr protein phosphatases. The enzyme's tertiary fold is highly similar to that of tyrosine-specific phosphatases, except for a "recognition" region.


Pssm-ID: 395632 [Multi-domain]  Cd Length: 127  Bit Score: 40.32  E-value: 5.73e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1938958509 431 VLSFLDQINQRQeslphaGPIIVHCSAGIGRTGTIIvIDMLMesvSTKGLDCDidiqKTIQMVRAQRSGMV 501
Cdd:pfam00782  58 AVEFIDDARQKG------GKVLVHCQAGISRSATLI-IAYLM---KTRNLSLN----EAYSFVKERRPGIS 114
SH2_Tec_Itk cd10396
Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member ...
 112-214 6.41e-04

Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member of the Tec protein tyrosine kinase Itk is expressed thymus, spleen, lymph node, T lymphocytes, NK and mast cells. It plays a role in T-cell proliferation and differentiation, analogous to Tec family kinases Txk. Itk has been shown to interact with Fyn, Wiskott-Aldrich syndrome protein, KHDRBS1, PLCG1, Lymphocyte cytosolic protein 2, Linker of activated T cells, Karyopherin alpha 2, Grb2, and Peptidylprolyl isomerase A. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198259  Cd Length: 108  Bit Score: 39.39  E-value: 6.41e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPWTFLVRESlSQPGDFVLSVLNdqpKA-GPGSP-LRVTHIKVMCEG-GRYTVGGSETFDS 188
Cdd:cd10396     8 WYNKNINRSKAEKLLRDEGKEGGFMVRDS-SQPGLYTVSLYT---KAgGEGNPcIRHYHIKETNDSpKKYYLAEKHVFNS 83

                          90       100
                  ....*....|....*....|....*.
gi 1938958509 189 LTDLVEHFKktgiEEASGAFVYLRQP 214
Cdd:cd10396    84 IPELIEYHK----HNAAGLVTRLRYP 105
SH2_CIS cd10718
Src homology 2 (SH2) domain found in cytokine-inducible SH2-containing protein (CIS); CIS ...
 112-196 6.75e-04

Src homology 2 (SH2) domain found in cytokine-inducible SH2-containing protein (CIS); CIS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The expression of the CIS gene can be induced by IL2, IL3, GM-CSF and EPO in hematopoietic cells. Proteasome-mediated degradation of this protein has been shown to be involved in the inactivation of the erythropoietin receptor. Suppressor of cytokine signalling (SOCS) was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198285  Cd Length: 88  Bit Score: 38.97  E-value: 6.75e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPwTFLVRESlSQPGD-FVLSVlndQPKAGPgsplrvTHIKVMCEGGRYTVGGS------- 183
Cdd:cd10718     6 WYWGSITASEAHQALQKAPEG-TFLVRDS-SHPSYmLTLSV---KTTRGP------TNVRIEYSDGSFRLDSSslarprl 74

                          90
                  ....*....|...
gi 1938958509 184 ETFDSLTDLVEHF 196
Cdd:cd10718    75 LSFPDVVSLVQHY 87
SH2_SOCS1 cd10382
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 113-196 7.62e-04

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198245  Cd Length: 98  Bit Score: 38.88  E-value: 7.62e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 113 YHGHMSGGQAESLLQAkgEPW-TFLVRESLSQPGDFVLSVlndQPKAGPGSplrvthIKVMCEGGRYTVGGS-ETFDSLT 190
Cdd:cd10382    13 YWGPLSVEEAHAKLKR--EPVgTFLIRDSRQKNCFFALSV---KMASGPVS------IRILFKAGKFSLDGSkESFDCLF 81


                  ....*.
gi 1938958509 191 DLVEHF 196
Cdd:cd10382    82 KLLEHY 87
PTP-IVa cd14500
protein tyrosine phosphatase type IVA family; Protein tyrosine phosphatases type IVA (PTP-IVa), ...
 417-499 8.22e-04

protein tyrosine phosphatase type IVA family; Protein tyrosine phosphatases type IVA (PTP-IVa), also known as protein-tyrosine phosphatases of regenerating liver (PRLs) constitute a family of small, prenylated phosphatases that are the most oncogenic of all PTPs. They stimulate progression from G1 into S phase during mitosis and enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. They associate with magnesium transporters of the cyclin M (CNNM) family, which results in increased intracellular magnesium levels that promote oncogenic transformation. Vertebrates contain three members: PRL-1, PRL-2, and PRL-3.


Pssm-ID: 350350 [Multi-domain]  Cd Length: 156  Bit Score: 40.28  E-value: 8.22e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 417 LSWPDHGVPsePGGVLS-FLDQINQR-QESLPHAGPIIVHCSAGIGRTGTIIVIdMLMESvstkGLDCDidiqKTIQMVR 494
Cdd:cd14500    64 WPFDDGSPP--PDDVVDdWLDLLKTRfKEEGKPGACIAVHCVAGLGRAPVLVAI-ALIEL----GMKPE----DAVEFIR 132


                  ....*
gi 1938958509 495 AQRSG 499
Cdd:cd14500   133 KKRRG 137
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
 112-196 8.91e-04

Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (srm); Srm is a nonreceptor protein kinase that has two SH2 domains, a SH3 domain, and a kinase domain with a tyrosine residue for autophosphorylation. However it lacks an N-terminal glycine for myristoylation and a C-terminal tyrosine which suppresses kinase activity when phosphorylated. Srm is most similar to members of the Tec family who other members include: Tec, Btk/Emb, and Itk/Tsk/Emt. However Srm differs in its N-terminal unique domain it being much smaller than in the Tec family and is closer to Src. Srm is thought to be a new family of nonreceptor tyrosine kinases that may be redundant in function. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198223  Cd Length: 79  Bit Score: 38.40  E-value: 8.91e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLL-QAKGEPWTFLVRESLSQPGDFVLSVLNDQpkagpgsplRVTHIKV-MCEGGRYTVGGSETFDSL 189
Cdd:cd10360     2 WYFSGISRTQAQQLLlSPPNEPGAFLIRPSESSLGGYSLSVRAQA---------KVCHYRIcMAPSGSLYLQKGRLFPGL 72


                  ....*..
gi 1938958509 190 TDLVEHF 196
Cdd:cd10360    73 EELLAYY 79
PTPlike_phytase pfam14566
Inositol hexakisphosphate; Inositol hexakisphosphate, often called phytate, is found in ...
 407-472 1.04e-03

Inositol hexakisphosphate; Inositol hexakisphosphate, often called phytate, is found in abundance in seeds and acting as an inorganic phosphate reservoir. Phytases are phosphatases that hydrolyze phytate to less-phosphorylated myo-inositol derivatives and inorganic phosphate. The active-site sequence (HCXXGXGR) of the phytase identified from the gut micro-organizm Selenomonas ruminantium forms a loop (P loop) at the base of a substrate binding pocket that is characteriztic of protein tyrosine phosphatases (PTPs). The depth of this pocket is an important determinant of the substrate specificity of PTPs. In humans this enzyme is thought to aid bone mineralization and salvage the inositol moiety prior to apoptosis.


Pssm-ID: 464208 [Multi-domain]  Cd Length: 157  Bit Score: 39.99  E-value: 1.04e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1938958509 407 LVREIWHYQY--LSWPDHGVPSEpggvlSFLDQINQRQESLPHAGPIIVHCSAGIGRTGTIIVIDMLM 472
Cdd:pfam14566  94 LKAEGPGVDYrrIPITDEKAPLE-----EDFDALISIVKDAPEDTALVFNCQMGRGRTTTAMVIADLV 156
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
 6-104 1.05e-03

Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of the Tec protein tyrosine kinase Btk is expressed in bone marrow, spleen, all hematopoietic cells except T lymphocytes and plasma cells where it plays a crucial role in B cell maturation and mast cell activation. Btk has been shown to interact with GNAQ, PLCG2, protein kinase D1, B-cell linker, SH3BP5, caveolin 1, ARID3A, and GTF2I. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. Btk is implicated in the primary immunodeficiency disease X-linked agammaglobulinemia (Bruton's agammaglobulinemia). The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. Two tyrosine phosphorylation (pY) sites have been identified in Btk: one located in the activation loop of the catalytic domain which regulates the transition between open (active) and closed (inactive) states and the other in its SH3 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198260 [Multi-domain]  Cd Length: 106  Bit Score: 39.05  E-value: 1.05e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRKnQGDFSLSV---RVDDQVTHIRIQN-----SGDFYdLYGGEKFATLTEL 77
Cdd:cd10397     8 WYSKNMTRSQAEQLLKQEGKEGGFIVRDSSK-AGKYTVSVfakSAGDPQGVIRHYVvcstpQSQYY-LAEKHLFSTIPEL 85

                          90       100
                  ....*....|....*....|....*..
gi 1938958509  78 VEYYTQQQGilqdrdGTIIHLKYPLNC 104
Cdd:cd10397    86 INYHQHNAA------GLISRLKYPVSS 106
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
 6-84 1.43e-03

Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type tyrosine kinase family of proteins. Yes is the cellular homolog of the Yamaguchi sarcoma virus oncogene. In humans it is encoded by the YES1 gene which maps to chromosome 18 and is in close proximity to thymidylate synthase. A corresponding Yes pseudogene has been found on chromosome 22. YES1 has been shown to interact with Janus kinase 2, CTNND1,RPL10, and Occludin. Yes1 has a unique N-terminal domain, an SH3 domain, an SH2 domain, a kinase domain and a regulatory tail, as do the other members of the family. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198229  Cd Length: 101  Bit Score: 38.46  E-value: 1.43e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVP-GSFLARPSRKNQGDFSLSVR-----VDDQVTHIRIQ--NSGDFYdLYGGEKFATLTEL 77
Cdd:cd10366     5 WYFGKMGRKDAERLLLNPGNQrGIFLVRESETTKGAYSLSIRdwdevRGDNVKHYKIRklDNGGYY-ITTRAQFDTLQKL 83


                  ....*..
gi 1938958509  78 VEYYTQQ 84
Cdd:cd10366    84 VKHYTEH 90
SH2_SH2D2A_SH2D7 cd10349
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ...
 111-196 1.61e-03

Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); SH2D2A and SH7 both contain a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199830  Cd Length: 77  Bit Score: 37.50  E-value: 1.61e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 111 RWYHGHMSGGQAESLLQAKGEPwTFLVRESLSQPGdFVLSVLndqpkagpgSPLRVTHIKV-MCEGGRYTVGG-SETFDS 188
Cdd:cd10349     1 AWFHGFITRREAERLLEPKPQG-CYLVRFSESAVT-FVLSYR---------SRTCCRHFLLaQLRDGRHVVLGeDSAHAR 69


                  ....*...
gi 1938958509 189 LTDLVEHF 196
Cdd:cd10349    70 LQDLLLHY 77
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 23-81 1.69e-03

N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are essential for cell growth, migration, and survival. p110, the catalytic subunit, is composed of an adaptor-binding domain, a Ras-binding domain, a C2 domain, a helical domain, and a kinase domain. The regulatory unit is called p85 and is composed of an SH3 domain, a RhoGap domain, a N-terminal SH2 (nSH2) domain, an internal SH2 (iSH2) domain, and C-terminal (cSH2) domain. There are 2 inhibitory interactions between p110alpha and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110alpha and (2) p85 iSH2 domain with C2 domain of p110alpha. There are 3 inhibitory interactions between p110beta and p85 of P13K: (1) p85 nSH2 domain with the C2, helical, and kinase domains of p110beta, (2) p85 iSH2 domain with C2 domain of p110alpha, and (3) p85 cSH2 domain with the kinase domain of p110alpha. It is interesting to note that p110beta is oncogenic as a wild type protein while p110alpha lacks this ability. One explanation is the idea that the regulation of p110beta by p85 is unique because of the addition of inhibitory contacts from the cSH2 domain and the loss of contacts in the iSH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198195  Cd Length: 110  Bit Score: 38.46  E-value: 1.69e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509  23 RGVP-GSFLARPSRKNQGDFSLSVRVDDQVTHIRIQNSGDFYDLYGGEKFATLTELVEYY 81
Cdd:cd09942    24 RDTPdGTFLVRDASTMKGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFNSVVELINYY 83
DSP cd14498
dual-specificity phosphatase domain; The dual-specificity phosphatase domain is found in ...
 413-498 1.88e-03

dual-specificity phosphatase domain; The dual-specificity phosphatase domain is found in typical and atypical dual-specificity phosphatases (DUSPs), which function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Typical DUSPs, also called mitogen-activated protein kinase (MAPK) phosphatases (MKPs), deactivate MAPKs by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. All MKPs contain an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain. Atypical DUSPs contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. Also included in this family are dual specificity phosphatase-like domains of catalytically inactive members such as serine/threonine/tyrosine-interacting protein (STYX) and serine/threonine/tyrosine interacting like 1 (STYXL1), as well as active phosphatases with substrates that are not phosphoproteins such as PTP localized to the mitochondrion 1 (PTPMT1), which is a lipid phosphatase, and laforin, which is a glycogen phosphatase.


Pssm-ID: 350348 [Multi-domain]  Cd Length: 135  Bit Score: 38.68  E-value: 1.88e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 413 HYQYLSWPDHgvPSEPggVLSFLDQINQR-QESLPHAGPIIVHCSAGIGRTGTiIVIDMLMESvstkgldCDIDIQKTIQ 491
Cdd:cd14498    47 KYLRIPIEDS--PDED--ILSHFEEAIEFiEEALKKGGKVLVHCQAGVSRSAT-IVIAYLMKK-------YGWSLEEALE 114


                  ....*..
gi 1938958509 492 MVRAQRS 498
Cdd:cd14498   115 LVKSRRP 121
SH2_SH2B2 cd10411
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), ...
 112-206 2.98e-03

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), like other members of the SH2B adapter protein family, contains a pleckstrin homology domain, at least one dimerization domain, and a C-terminal SH2 domain which binds to phosphorylated tyrosines in a variety of tyrosine kinases. SH2B1 and SH2B2 function in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. SH2B2beta, a new isoform of SH2B2, is an endogenous inhibitor of SH2B1 and/or SH2B2 (SH2B2alpha), negatively regulating insulin signaling and/or JAK2-mediated cellular responses. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198274  Cd Length: 97  Bit Score: 37.29  E-value: 2.98e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKG--EPWTFLVRESLSQPGDFVLSvLNDQPKAgpgsplrvTHIKV-MCEGGRYTVgGSETFDS 188
Cdd:cd10411    10 WFHGTLSRVKAAQLVLAGGprSHGLFVIRQSETRPGEYVLT-FNFQGKA--------KHLRLsLNGHGQCHV-QHLWFQS 79

                          90
                  ....*....|....*...
gi 1938958509 189 LTDLVEHFKKTGIEEASG 206
Cdd:cd10411    80 VFDMLRHFHTHPIPLESG 97
SH2_Tec_Itk cd10396
Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member ...
 6-104 3.21e-03

Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member of the Tec protein tyrosine kinase Itk is expressed thymus, spleen, lymph node, T lymphocytes, NK and mast cells. It plays a role in T-cell proliferation and differentiation, analogous to Tec family kinases Txk. Itk has been shown to interact with Fyn, Wiskott-Aldrich syndrome protein, KHDRBS1, PLCG1, Lymphocyte cytosolic protein 2, Linker of activated T cells, Karyopherin alpha 2, Grb2, and Peptidylprolyl isomerase A. Most of the Tec family members have a PH domain (Txk and the short (type 1) splice variant of Drosophila Btk29A are exceptions), a Tec homology (TH) domain, a SH3 domain, a SH2 domain, and a protein kinase catalytic domain. The TH domain consists of a Zn2+-binding Btk motif and a proline-rich region. The Btk motif is found in Tec kinases, Ras GAP, and IGBP. It is crucial for the function of Tec PH domains and it's lack of presence in Txk is not surprising since it lacks a PH domain. The type 1 splice form of the Drosophila homolog also lacks both the PH domain and the Btk motif. The proline-rich regions are highly conserved for the most part with the exception of Bmx whose residues surrounding the PXXP motif are not conserved (TH-like) and Btk29A which is entirely unique with large numbers of glycine residues (TH-extended). Tec family members all lack a C-terminal tyrosine having an autoinhibitory function in its phosphorylated state. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198259  Cd Length: 108  Bit Score: 37.46  E-value: 3.21e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509   6 WFHRDLSGPDAETLLKGRGVPGSFLARPSRkNQGDFSLSVRV------DDQVTHIRIQNSGD---FYDLYGGEKFATLTE 76
Cdd:cd10396     8 WYNKNINRSKAEKLLRDEGKEGGFMVRDSS-QPGLYTVSLYTkaggegNPCIRHYHIKETNDspkKYYLAEKHVFNSIPE 86

                          90       100
                  ....*....|....*....|....*...
gi 1938958509  77 LVEYYTQQQGilqdrdGTIIHLKYPLNC 104
Cdd:cd10396    87 LIEYHKHNAA------GLVTRLRYPVSS 108
SH2_SHB cd10389
Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in ...
 112-196 3.58e-03

Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in generating signaling compounds in response to tyrosine kinase activation. SHB contains proline-rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites, and a SH2 domain. SHB mediates certain aspects of platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK) and SHB regulate apoptosis, proliferation and differentiation. SHB promotes apoptosis and is also required for proper mitogenicity, spreading and tubular morphogenesis in endothelial cells. SHB also plays a role in preventing early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon. SHB is a multifunctional protein that has difference responses in different cells under various conditions. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198252  Cd Length: 97  Bit Score: 37.38  E-value: 3.58e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEpWTFLVRESLSQPGDFVLSVLNDQPkagpgsplrVTHIKVMCEGGRYTVG-GSETFDSLT 190
Cdd:cd10389     3 WYHGAISRGDAENLLRLCKE-CSYLVRNSQTSKHDYSLSLKSNQG---------FMHMKLAKTKEKYVLGqNSPPFDSVP 72


                  ....*.
gi 1938958509 191 DLVEHF 196
Cdd:cd10389    73 EVIHYY 78
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
 6-44 3.62e-03

Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide variety of pathways including regulating proliferation, angiogenesis, invasion and metastasis, and bone metabolism. An adapter protein, SHC has been implicated in Ras activation following the stimulation of a number of different receptors, including growth factors [insulin, epidermal growth factor (EGF), nerve growth factor, and platelet derived growth factor (PDGF)], cytokines [interleukins 2, 3, and 5], erythropoietin, and granulocyte/macrophage colony-stimulating factor, and antigens [T-cell and B-cell receptors]. SHC has been shown to bind to tyrosine-phosphorylated receptors, and receptor stimulation leads to tyrosine phosphorylation of SHC. Upon phosphorylation, SHC interacts with another adapter protein, Grb2, which binds to the Ras GTP/GDP exchange factor mSOS which leads to Ras activation. SHC is composed of an N-terminal domain that interacts with proteins containing phosphorylated tyrosines, a (glycine/proline)-rich collagen-homology domain that contains the phosphorylated binding site, and a C-terminal SH2 domain. SH2 has been shown to interact with the tyrosine-phosphorylated receptors of EGF and PDGF and with the tyrosine-phosphorylated C chain of the T-cell receptor, providing one of the mechanisms of T-cell-mediated Ras activation. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198179  Cd Length: 104  Bit Score: 37.33  E-value: 3.62e-03
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1938958509   6 WFHRDLSGPDAETLLKgrgVPGSFLARPSRKNQGDFSLS 44
Cdd:cd09925     9 WYHGKMSRRDAESLLQ---TDGDFLVRESTTTPGQYVLT 44
DSPc smart00195
Dual specificity phosphatase, catalytic domain;
413-501 3.79e-03

Dual specificity phosphatase, catalytic domain;


Pssm-ID: 214551 [Multi-domain]  Cd Length: 138  Bit Score: 38.03  E-value: 3.79e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509  413 HYQYLSWP---DHGVPSEP--GGVLSFLDQINQRQeslphaGPIIVHCSAGIGRTGTIIvIDMLMesvSTKGLdcdiDIQ 487
Cdd:smart00195  44 DFTYLGVPiddNTETKISPyfPEAVEFIEDAESKG------GKVLVHCQAGVSRSATLI-IAYLM---KTRNM----SLN 109

                           90
                   ....*....|....
gi 1938958509  488 KTIQMVRAQRSGMV 501
Cdd:smart00195 110 DAYDFVKDRRPIIS 123
SH2_SOCS7 cd10388
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 112-210 5.00e-03

Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 domain found in SOCS proteins. SOCS was first recognized as a group of cytokine-inducible SH2 (CIS) domain proteins comprising eight family members in human (CIS and SOCS1-SOCS7). In addition to the SH2 domain, SOCS proteins have a variable N-terminal domain and a conserved SOCS box in the C-terminal domain. SOCS proteins bind to a substrate via their SH2 domain. The prototypical members, CIS and SOCS1-SOCS3, have been shown to regulate growth hormone signaling in vitro and in a classic negative feedback response compete for binding at phosphotyrosine sites in JAK kinase and receptor pathways to displace effector proteins and target bound receptors for proteasomal degradation. Loss of SOCS activity results in excessive cytokine signaling associated with a variety of hematopoietic, autoimmune, and inflammatory diseases and certain cancers. Members (SOCS4-SOCS7) were identified by their conserved SOCS box, an adapter motif of 3 helices that associates substrate binding domains, such as the SOCS SH2 domain, ankryin, and WD40 with ubiquitin ligase components. These show limited cytokine induction. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198251  Cd Length: 101  Bit Score: 36.95  E-value: 5.00e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKgEPWTFLVRESLSQPGDFVLSVlndqpkagpGSPLRVTHIKVMCEGGRYTVGGSETF-DSLT 190
Cdd:cd10388    12 WYWGPMSWEDAEKVLSNK-PDGSFLVRDSSDDRYIFSLSF---------RSQGSVHHTRIEQYQGTFSLGSRNKFvDRSQ 81

                          90       100
                  ....*....|....*....|.
gi 1938958509 191 DLVEhFKKTGIEEA-SGAFVY 210
Cdd:cd10388    82 SLVE-FIERAVEHSrSGRFLY 101
SH2_SAP1a cd10400
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked ...
 113-154 5.31e-03

Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked lymphoproliferative syndrome (XLP) gene encodes SAP (also called SH2D1A/DSHP) a protein that consists of a 5 residue N-terminus, a single SH2 domain, and a short 25 residue C-terminal tail. XLP is characterized by an extreme sensitivity to Epstein-Barr virus. Both T and natural killer (NK) cell dysfunctions have been seen in XLP patients. SAP binds the cytoplasmic tail of Signaling lymphocytic activation molecule (SLAM), 2B4, Ly-9, and CD84. SAP is believed to function as a signaling inhibitor, by blocking or regulating binding of other signaling proteins. SAP and the SAP-like protein EAT-2 recognize the sequence motif TIpYXX[VI], which is found in the cytoplasmic domains of a restricted number of T, B, and NK cell surface receptors and are proposed to be natural inhibitors or regulators of the physiological role of a small family of receptors on the surface of these cells. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198263  Cd Length: 103  Bit Score: 36.75  E-value: 5.31e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1938958509 113 YHGHMSGGQAESLLQAKGEPWTFLVRESLSQPGDFVLSVLND 154
Cdd:cd10400     6 YHGKISRETGEKLLLAAGLDGSYLLRDSESVPGVYCLCVLYK 47
SH2_SHE cd10391
Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed ...
 112-196 6.11e-03

Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed in heart, lung, brain, and skeletal muscle. SHE contains two pTry protein binding domains, protein interaction domain (PID) and a SH2 domain, followed by a glycine-proline rich region, all of which are N-terminal to the phosphotyrosine binding (PTB) domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 198254  Cd Length: 98  Bit Score: 36.47  E-value: 6.11e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 112 WYHGHMSGGQAESLLQAKGEPwTFLVRESLSQPGDFVLSVLNDQPkagpgsplrVTHIKV-MCEGGRYTVG-GSETFDSL 189
Cdd:cd10391     3 WYHGSISRAEAESRLQPCKEA-SYLVRNSESGNSKYSIALKTSQG---------CVHIIVaQTKDNKYTLNqTSAVFDSI 72


                  ....*..
gi 1938958509 190 TDLVEHF 196
Cdd:cd10391    73 PEVVHYY 79
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
 111-202 7.86e-03

Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a single SH2 domain. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.


Pssm-ID: 199832  Cd Length: 102  Bit Score: 36.41  E-value: 7.86e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1938958509 111 RWYHGHMSGGQAESLLQAKGEPwTFLVRESLSQPGdFVLSVLNDQpkagpgsplRVTHIKV-MCEGGRYTVGG-SETFDS 188
Cdd:cd10417     8 PWFHGFITRKQTEQLLRDKALG-SFLIRLSDRATG-YILSYRGSD---------RCRHFVInQLRNRRYLISGdTSSHST 76

                          90
                  ....*....|....
gi 1938958509 189 LTDLVEHFKKTGIE 202
Cdd:cd10417    77 LAELVRHYQEVQLE 90
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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