NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|18375644|ref|NP_542168|]
View 

tyrosine-protein phosphatase non-receptor type 11 isoform 2 [Homo sapiens]

Protein Classification

SH2_N-SH2_SHP_like and SH2_C-SH2_SHP_like domain-containing protein( domain architecture ID 12969960)

protein containing domains SH2_N-SH2_SHP_like, SH2_C-SH2_SHP_like, and PTP_DSP_cys

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
PTP_DSP_cys super family cl28904
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
 272-459 1.51e-156

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.


The actual alignment was detected with superfamily member cd14605:

Pssm-ID: 475123 [Multi-domain]  Cd Length: 253  Bit Score: 443.69  E-value: 1.51e-156
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 272 ENKNKNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMPEFETKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSR 351
Cdd:cd14605   1 ENKNKNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMPEFETKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 352 VIVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSD 431
Cdd:cd14605  81 VIVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYILRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSD 160

                       170       180
                ....*....|....*....|....*...
gi 18375644 432 PGGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14605 161 PGGVLDFLEEVHHKQESIMDAGPVVVHC 188
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 5-103 1.64e-65

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: 205.33  E-value: 1.64e-65
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   5 RWFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEKFATLAELVQYYMEH 84
Cdd:cd10340   1 RWFHPVISGIEAENLLKTRGVDGSFLARPSKSNPGDFTLSVRRGDEVTHIKIQNTGDYYDLYGGEKFATLSELVQYYMEQ 80

                        90
                ....*....|....*....
gi 18375644  85 HGQLKEKNGDVIELKYPLN 103
Cdd:cd10340  81 HGQLREKNGDVIELKYPLN 99
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 111-218 1.74e-62

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: 197.50  E-value: 1.74e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 111 RWFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGDDkgesndgksKVTHVMIRCQELKYDVGGGERFDSL 190
Cdd:cd09931   1 RWFHGHLSGKEAEKLLLEKGKPGSFLVRESQSKPGDFVLSVRTDDD---------KVTHIMIRCQGGKYDVGGGEEFDSL 71

                        90       100
                ....*....|....*....|....*...
gi 18375644 191 TDLVEHYKKNPMVETLGTVLQLKQPLNT 218
Cdd:cd09931  72 TDLVEHYKKNPMVETSGTVVHLKQPLNA 99
 
Name Accession Description Interval E-value
PTPc-N11 cd14605
catalytic domain of tyrosine-protein phosphatase non-receptor type 11; Tyrosine-protein ...
 272-459 1.51e-156

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: 443.69  E-value: 1.51e-156
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 272 ENKNKNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMPEFETKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSR 351
Cdd:cd14605   1 ENKNKNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMPEFETKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 352 VIVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSD 431
Cdd:cd14605  81 VIVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYILRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSD 160

                       170       180
                ....*....|....*....|....*...
gi 18375644 432 PGGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14605 161 PGGVLDFLEEVHHKQESIMDAGPVVVHC 188
PTPc smart00194
Protein tyrosine phosphatase, catalytic domain;
246-459 3.52e-84

Protein tyrosine phosphatase, catalytic domain;


Pssm-ID: 214550 [Multi-domain]  Cd Length: 259  Bit Score: 259.51  E-value: 3.52e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644    246 GFWEEFETLQQqECKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDpnEPVSDYINANIIMpefetkcnNSKPKK 325
Cdd:smart00194   1 GLEEEFEKLDR-LKPDDESCTVAAFPENRDKNRYKDVLPYDHTRVKLKPPP--GEGSDYINASYID--------GPNGPK 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644    326 SYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDE-YALKEYGVMRVRNVKESAAHDYTLRELKLS 404
Cdd:smart00194  70 AYIATQGPLPSTVEDFWRMVWEQKVTVIVMLTELVEKGREKCAQYWPDEeGEPLTYGDITVTLKSVEKVDDYTIRTLEVT 149

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 18375644    405 KVGQGNTeRTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESimDAGPVVVHC 459
Cdd:smart00194 150 NTGCSET-RTVTHYHYTNWPDHGVPESPESILDLIRAVRKSQST--STGPIVVHC 201
Y_phosphatase pfam00102
Protein-tyrosine phosphatase;
273-459 3.87e-74

Protein-tyrosine phosphatase;


Pssm-ID: 459674 [Multi-domain]  Cd Length: 234  Bit Score: 232.52  E-value: 3.87e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   273 NKNKNRYKNILPFDHTRVVLhdgDPNEPVSDYINANIIMPEFEtkcnnskpKKSYIATQGCLQNTVNDFWRMVFQENSRV 352
Cdd:pfam00102   1 NLEKNRYKDVLPYDHTRVKL---TGDPGPSDYINASYIDGYKK--------PKKYIATQGPLPNTVEDFWRMVWEEKVTI 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   353 IVMTTKEVERGKSKCVKYWPDEY-ALKEYGVMRVRNVKESAAH-DYTLRELKLSKvGQGNTERTVWQYHFRTWPDHGVPS 430
Cdd:pfam00102  70 IVMLTELEEKGREKCAQYWPEEEgESLEYGDFTVTLKKEKEDEkDYTVRTLEVSN-GGSEETRTVKHFHYTGWPDHGVPE 148

                         170       180
                  ....*....|....*....|....*....
gi 18375644   431 DPGGVLDFLEEVhHKQESIMDAGPVVVHC 459
Cdd:pfam00102 149 SPNSLLDLLRKV-RKSSLDGRSGPIVVHC 176
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 5-103 1.64e-65

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: 205.33  E-value: 1.64e-65
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   5 RWFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEKFATLAELVQYYMEH 84
Cdd:cd10340   1 RWFHPVISGIEAENLLKTRGVDGSFLARPSKSNPGDFTLSVRRGDEVTHIKIQNTGDYYDLYGGEKFATLSELVQYYMEQ 80

                        90
                ....*....|....*....
gi 18375644  85 HGQLKEKNGDVIELKYPLN 103
Cdd:cd10340  81 HGQLREKNGDVIELKYPLN 99
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 111-218 1.74e-62

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: 197.50  E-value: 1.74e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 111 RWFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGDDkgesndgksKVTHVMIRCQELKYDVGGGERFDSL 190
Cdd:cd09931   1 RWFHGHLSGKEAEKLLLEKGKPGSFLVRESQSKPGDFVLSVRTDDD---------KVTHIMIRCQGGKYDVGGGEEFDSL 71

                        90       100
                ....*....|....*....|....*...
gi 18375644 191 TDLVEHYKKNPMVETLGTVLQLKQPLNT 218
Cdd:cd09931  72 TDLVEHYKKNPMVETSGTVVHLKQPLNA 99
PHA02742 PHA02742
protein tyrosine phosphatase; Provisional
 227-459 6.27e-36

protein tyrosine phosphatase; Provisional


Pssm-ID: 165109 [Multi-domain]  Cd Length: 303  Bit Score: 134.74  E-value: 6.27e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  227 ESRVRELSKlaettdkvkqgfwEEFETLQQQecKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVL--HDGdpnepVSDY 304
Cdd:PHA02742  21 ESNLAEILK-------------EEHEHIMQE--IVAFSCNESLELKNMKKCRYPDAPCFDRNRVILkiEDG-----GDDF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  305 INANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYW-PDEYALKEYGVM 383
Cdd:PHA02742  81 INASYV--------DGHNAKGRFICTQAPLEETALDFWQAIFQDQVRVIVMITKIMEDGKEACYPYWmPHERGKATHGEF 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  384 RVRNVKESAAHDYTLRELKLSKVGQGnTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQ---------ESIMDAGP 454
Cdd:PHA02742 153 KIKTKKIKSFRNYAVTNLCLTDTNTG-ASLDIKHFAYEDWPHGGLPRDPNKFLDFVLAVREADlkadvdikgENIVKEPP 231


                 ....*
gi 18375644  455 VVVHC 459
Cdd:PHA02742 232 ILVHC 236
SH2 pfam00017
SH2 domain;
6-81 2.15e-31

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 115.01  E-value: 2.15e-31
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18375644     6 WFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDY-YDLYGGEKFATLAELVQYY 81
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNGgYYISGGVKFSSLAELVEHY 77
COG5599 COG5599
Protein tyrosine phosphatase [Signal transduction mechanisms];
234-460 2.62e-30

Protein tyrosine phosphatase [Signal transduction mechanisms];


Pssm-ID: 444335 [Multi-domain]  Cd Length: 282  Bit Score: 118.66  E-value: 2.62e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 234 SKLAETTDKVKQGFWEEFETLQQQeckLLYSRKEGQRQENKN---KNRYKNILPFDHTRVVLHDGdpnepvsdYINANII 310
Cdd:COG5599   3 PKNPIAIKSEEEKINSRLSTLTNE---LAPSHNDPQYLQNINgspLNRFRDIQPYKETALRANLG--------YLNANYI 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 311 mpefetkcnNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKS--KCVKYWPDEyalKEYGVMRVRNV 388
Cdd:COG5599  72 ---------QVIGNHRYIATQYPLEEQLEDFFQMLFDNNTPVLVVLASDDEISKPkvKMPVYFRQD---GEYGKYEVSSE 139

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18375644 389 KESAAH---DYTLRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSDPgGVLDFLEEVHHKQE-SIMDAGPVVVHCR 460
Cdd:COG5599 140 LTESIQlrdGIEARTYVLTIKGTGQKKIEIPVLHVKNWPDHGAISAE-ALKNLADLIDKKEKiKDPDKLLPVVHCR 214
SH2 pfam00017
SH2 domain;
112-197 2.17e-29

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 109.61  E-value: 2.17e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGDdkgesndgksKVTHVMIRCQE-LKYDVGGGERFDSL 190
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPDGTFLVRESESTPGGYTLSVRDDG----------KVKHYKIQSTDnGGYYISGGVKFSSL 70


                  ....*..
gi 18375644   191 TDLVEHY 197
Cdd:pfam00017  71 AELVEHY 77
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 110-201 3.39e-27

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: 103.85  E-value: 3.39e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644    110 ERWFHGHLSGKEAEKLLTEKGkHGSFLVRESQSHPGDFVLSVRTGDdkgesndgksKVTHVMIRCQEL-KYDVGGGERFD 188
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEG-DGDFLVRDSESSPGDYVLSVRVKG----------KVKHYRIRRNEDgKFYLEGGRKFP 69

                           90
                   ....*....|...
gi 18375644    189 SLTDLVEHYKKNP 201
Cdd:smart00252  70 SLVELVEHYQKNS 82
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 6-84 1.31e-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: 96.91  E-value: 1.31e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644      6 WFHPNITGVEAENLLLTRGvDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGD-YYDLYGGEKFATLAELVQYYMEH 84
Cdd:smart00252   3 WYHGFISREEAEKLLKNEG-DGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDgKFYLEGGRKFPSLVELVEHYQKN 81
 
Name Accession Description Interval E-value
PTPc-N11 cd14605
catalytic domain of tyrosine-protein phosphatase non-receptor type 11; Tyrosine-protein ...
 272-459 1.51e-156

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: 443.69  E-value: 1.51e-156
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 272 ENKNKNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMPEFETKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSR 351
Cdd:cd14605   1 ENKNKNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMPEFETKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 352 VIVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSD 431
Cdd:cd14605  81 VIVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYILRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSD 160

                       170       180
                ....*....|....*....|....*...
gi 18375644 432 PGGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14605 161 PGGVLDFLEEVHHKQESIMDAGPVVVHC 188
PTPc-N11_6 cd14544
catalytic domain of tyrosine-protein phosphatase non-receptor type 11 and type 6; ...
 273-459 1.86e-127

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: 369.48  E-value: 1.86e-127
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 273 NKNKNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMPEFETKCNnSKPKKSYIATQGCLQNTVNDFWRMVFQENSRV 352
Cdd:cd14544   1 NKGKNRYKNILPFDHTRVILKDRDPNVPGSDYINANYIRNENEGPTT-DENAKTYIATQGCLENTVSDFWSMVWQENSRV 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 353 IVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSDP 432
Cdd:cd14544  80 IVMTTKEVERGKNKCVRYWPDEGMQKQYGPYRVQNVSEHDTTDYTLRELQVSKLDQGDPIREIWHYQYLSWPDHGVPSDP 159

                       170       180
                ....*....|....*....|....*..
gi 18375644 433 GGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14544 160 GGVLNFLEDVNQRQESLPHAGPIVVHC 186
PTPc-N6 cd14606
catalytic domain of tyrosine-protein phosphatase non-receptor type 6; Tyrosine-protein ...
 256-459 1.63e-93

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: 283.69  E-value: 1.63e-93
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 256 QQECKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMPEFetkCNNSKPKKSYIATQGCLQ 335
Cdd:cd14606   1 KQEVKNLHQRLEGQRPENKSKNRYKNILPFDHSRVILQGRDSNIPGSDYINANYVKNQL---LGPDENAKTYIASQGCLE 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 336 NTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTERTV 415
Cdd:cd14606  78 ATVNDFWQMAWQENSRVIVMTTREVEKGRNKCVPYWPEVGMQRAYGPYSVTNCGEHDTTEYKLRTLQVSPLDNGELIREI 157

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 18375644 416 WQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14606 158 WHYQYLSWPDHGVPSEPGGVLSFLDQINQRQESLPHAGPIIVHC 201
PTPc smart00194
Protein tyrosine phosphatase, catalytic domain;
246-459 3.52e-84

Protein tyrosine phosphatase, catalytic domain;


Pssm-ID: 214550 [Multi-domain]  Cd Length: 259  Bit Score: 259.51  E-value: 3.52e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644    246 GFWEEFETLQQqECKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDpnEPVSDYINANIIMpefetkcnNSKPKK 325
Cdd:smart00194   1 GLEEEFEKLDR-LKPDDESCTVAAFPENRDKNRYKDVLPYDHTRVKLKPPP--GEGSDYINASYID--------GPNGPK 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644    326 SYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDE-YALKEYGVMRVRNVKESAAHDYTLRELKLS 404
Cdd:smart00194  70 AYIATQGPLPSTVEDFWRMVWEQKVTVIVMLTELVEKGREKCAQYWPDEeGEPLTYGDITVTLKSVEKVDDYTIRTLEVT 149

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 18375644    405 KVGQGNTeRTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESimDAGPVVVHC 459
Cdd:smart00194 150 NTGCSET-RTVTHYHYTNWPDHGVPESPESILDLIRAVRKSQST--STGPIVVHC 201
Y_phosphatase pfam00102
Protein-tyrosine phosphatase;
273-459 3.87e-74

Protein-tyrosine phosphatase;


Pssm-ID: 459674 [Multi-domain]  Cd Length: 234  Bit Score: 232.52  E-value: 3.87e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   273 NKNKNRYKNILPFDHTRVVLhdgDPNEPVSDYINANIIMPEFEtkcnnskpKKSYIATQGCLQNTVNDFWRMVFQENSRV 352
Cdd:pfam00102   1 NLEKNRYKDVLPYDHTRVKL---TGDPGPSDYINASYIDGYKK--------PKKYIATQGPLPNTVEDFWRMVWEEKVTI 69

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   353 IVMTTKEVERGKSKCVKYWPDEY-ALKEYGVMRVRNVKESAAH-DYTLRELKLSKvGQGNTERTVWQYHFRTWPDHGVPS 430
Cdd:pfam00102  70 IVMLTELEEKGREKCAQYWPEEEgESLEYGDFTVTLKKEKEDEkDYTVRTLEVSN-GGSEETRTVKHFHYTGWPDHGVPE 148

                         170       180
                  ....*....|....*....|....*....
gi 18375644   431 DPGGVLDFLEEVhHKQESIMDAGPVVVHC 459
Cdd:pfam00102 149 SPNSLLDLLRKV-RKSSLDGRSGPIVVHC 176
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 5-103 1.64e-65

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: 205.33  E-value: 1.64e-65
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   5 RWFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEKFATLAELVQYYMEH 84
Cdd:cd10340   1 RWFHPVISGIEAENLLKTRGVDGSFLARPSKSNPGDFTLSVRRGDEVTHIKIQNTGDYYDLYGGEKFATLSELVQYYMEQ 80

                        90
                ....*....|....*....
gi 18375644  85 HGQLKEKNGDVIELKYPLN 103
Cdd:cd10340  81 HGQLREKNGDVIELKYPLN 99
SH2_C-SH2_SHP_like cd09931
C-terminal Src homology 2 (C-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 111-218 1.74e-62

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: 197.50  E-value: 1.74e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 111 RWFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGDDkgesndgksKVTHVMIRCQELKYDVGGGERFDSL 190
Cdd:cd09931   1 RWFHGHLSGKEAEKLLLEKGKPGSFLVRESQSKPGDFVLSVRTDDD---------KVTHIMIRCQGGKYDVGGGEEFDSL 71

                        90       100
                ....*....|....*....|....*...
gi 18375644 191 TDLVEHYKKNPMVETLGTVLQLKQPLNT 218
Cdd:cd09931  72 TDLVEHYKKNPMVETSGTVVHLKQPLNA 99
PTPc cd00047
catalytic domain of protein tyrosine phosphatases; Protein tyrosine phosphatases (PTP, EC 3.1. ...
 304-459 2.94e-59

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: 192.89  E-value: 2.94e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIIMPEfetkcnnsKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEY-ALKEYGV 382
Cdd:cd00047   1 YINASYIDGY--------RGPKEYIATQGPLPNTVEDFWRMVWEQKVSVIVMLTNLVEKGREKCERYWPEEGgKPLEYGD 72

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18375644 383 MRVRNVKESAAHDYTLRELKLSKVGQGNTeRTVWQYHFRTWPDHGVPSDPGGVLDFLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd00047  73 ITVTLVSEEELSDYTIRTLELSPKGCSES-REVTHLHYTGWPDHGVPSSPEDLLALVRRV--RKEARKPNGPIVVHC 146
PTPc-N9 cd14543
catalytic domain of tyrosine-protein phosphatase non-receptor type 9; Tyrosine-protein ...
 244-459 1.17e-54

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: 183.33  E-value: 1.17e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 244 KQGFWEEFETLQQQ--ECKLLYSRKEGqrqeNKNKNRYKNILPFDHTRVVLHDGDPNEPvSDYINANIImpefetkcNNS 321
Cdd:cd14543   2 KRGIYEEYEDIRREppAGTFLCSLAPA----NQEKNRYGDVLCLDQSRVKLPKRNGDER-TDYINANFM--------DGY 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 322 KPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWP-DEYALKEYGVMRVRNVKESAAHDYTLRE 400
Cdd:cd14543  69 KQKNAYIATQGPLPKTYSDFWRMVWEQKVLVIVMTTRVVERGRVKCGQYWPlEEGSSLRYGDLTVTNLSVENKEHYKKTT 148

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 401 LKLSKVgQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMDA-----------GPVVVHC 459
Cdd:cd14543 149 LEIHNT-ETDESRQVTHFQFTSWPDFGVPSSAAALLDFLGEVRQQQALAVKAmgdrwkghppgPPIVVHC 217
R3-PTPc cd14548
catalytic domain of R3 subfamily receptor-type tyrosine-protein phosphatases and similar ...
 278-459 3.15e-54

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: 180.63  E-value: 3.15e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 278 RYKNILPFDHTRVVLhDGDPNEPVSDYINANIImpefetKCNNSKpkKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTT 357
Cdd:cd14548   1 RYTNILPYDHSRVKL-IPINEEEGSDYINANYI------PGYNSP--REFIATQGPLPGTKDDFWRMVWEQNSHTIVMLT 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 358 KEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQgntERTVWQYHFRTWPDHGVPSDPGGVLD 437
Cdd:cd14548  72 QCMEKGRVKCDHYWPFDQDPVYYGDITVTMLSESVLPDWTIREFKLERGDE---VRSVRQFHFTAWPDHGVPEAPDSLLR 148

                       170       180
                ....*....|....*....|..
gi 18375644 438 FLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd14548 149 FVRLV--RDYIKQEKGPTIVHC 168
R-PTPc-LAR-1 cd14553
catalytic domain of LAR family receptor-type tyrosine-protein phosphatases, repeat 1; The LAR ...
 273-459 4.19e-54

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: 181.06  E-value: 4.19e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 273 NKNKNRYKNILPFDHTRVVLH--DGDPNepvSDYINANIimpefetkCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENS 350
Cdd:cd14553   3 NKPKNRYANVIAYDHSRVILQpiEGVPG---SDYINANY--------CDGYRKQNAYIATQGPLPETFGDFWRMVWEQRS 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 351 RVIVMTTKEVERGKSKCVKYWPDEyALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTeRTVWQYHFRTWPDHGVPS 430
Cdd:cd14553  72 ATIVMMTKLEERSRVKCDQYWPTR-GTETYGLIQVTLLDTVELATYTVRTFALHKNGSSEK-REVRQFQFTAWPDHGVPE 149

                       170       180
                ....*....|....*....|....*....
gi 18375644 431 DPGGVLDFLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd14553 150 HPTPFLAFLRRV--KACNPPDAGPIVVHC 176
PTPc-N18 cd14603
catalytic domain of tyrosine-protein phosphatase non-receptor type 18; Tyrosine-protein ...
 249-459 1.59e-53

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: 180.41  E-value: 1.59e-53
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 249 EEFETLQQQECKL----LYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDpNEPVSDYINANIIMPEFETKCnnskpk 324
Cdd:cd14603   2 GEFSEIRACSAAFkadyVCSTVAGGRKENVKKNRYKDILPYDQTRVILSLLQ-EEGHSDYINANFIKGVDGSRA------ 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 325 ksYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAH-DYTLRELKL 403
Cdd:cd14603  75 --YIATQGPLSHTVLDFWRMIWQYGVKVILMACREIEMGKKKCERYWAQEQEPLQTGPFTITLVKEKRLNeEVILRTLKV 152

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 18375644 404 SKVgqgNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESimDAGPVVVHC 459
Cdd:cd14603 153 TFQ---KESRSVSHFQYMAWPDHGIPDSPDCMLAMIELARRLQGS--GPEPLCVHC 203
PTPc-N1_2 cd14545
catalytic domain of tyrosine-protein phosphatase non-receptor type 1 and type 2; ...
 274-459 2.10e-52

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: 176.04  E-value: 2.10e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 274 KNKNRYKNILPFDHTRVVLHDGDpnepvSDYINANIImpEFETKcnnskpKKSYIATQGCLQNTVNDFWRMVFQENSRVI 353
Cdd:cd14545   1 LNRYRDRDPYDHDRSRVKLKQGD-----NDYINASLV--EVEEA------KRSYILTQGPLPNTSGHFWQMVWEQNSKAV 67

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 354 VMTTKEVERGKSKCVKYWP----DEYALKEYGvMRVRNVKESAAHDYTLRELKLSKVgQGNTERTVWQYHFRTWPDHGVP 429
Cdd:cd14545  68 IMLNKLMEKGQIKCAQYWPqgegNAMIFEDTG-LKVTLLSEEDKSYYTVRTLELENL-KTQETREVLHFHYTTWPDFGVP 145

                       170       180       190
                ....*....|....*....|....*....|
gi 18375644 430 SDPGGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14545 146 ESPAAFLNFLQKVRESGSLSSDVGPPVVHC 175
PTPc-KIM cd14547
catalytic domain of the kinase interaction motif (KIM) family of protein-tyrosine phosphatases; ...
 277-459 1.57e-51

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: 173.74  E-value: 1.57e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 277 NRYKNILPFDHTRVVLhDGDPNEPVSDYINANIIM-PEFETKCnnskpkksYIATQGCLQNTVNDFWRMVFQENSRVIVM 355
Cdd:cd14547   1 NRYKTILPNEHSRVCL-PSVDDDPLSSYINANYIRgYDGEEKA--------YIATQGPLPNTVADFWRMVWQEKTPIIVM 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 356 TTKEVERgKSKCVKYWPDEYALkEYG--VMRVRNVKESaaHDYTLRELKLSKVGQgntERTVWQYHFRTWPDHGVPSDPG 433
Cdd:cd14547  72 ITNLTEA-KEKCAQYWPEEENE-TYGdfEVTVQSVKET--DGYTVRKLTLKYGGE---KRYLKHYWYTSWPDHKTPEAAQ 144

                       170       180
                ....*....|....*....|....*.
gi 18375644 434 GVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14547 145 PLLSLVQEVEEARQTEPHRGPIVVHC 170
PTP_fungal cd18533
fungal protein tyrosine phosphatases; This subfamily contains Saccharomyces cerevisiae ...
 304-459 2.38e-49

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: 167.43  E-value: 2.38e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIIMPEfetkcnnSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALKEYGVM 383
Cdd:cd18533   1 YINASYITLP-------GTSSKRYIATQGPLPATIGDFWKMIWQNNVGVIVMLTPLVENGREKCDQYWPSGEYEGEYGDL 73

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18375644 384 RVRNVKESAAHD--YTLRELKLSKVGQgnTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd18533  74 TVELVSEEENDDggFIVREFELSKEDG--KVKKVYHIQYKSWPDFGVPDSPEDLLTLIKLKRELNDSASLDPPIIVHC 149
R-PTPc-J cd14615
catalytic domain of receptor-type tyrosine-protein phosphatase J; Receptor-type ...
 277-459 3.19e-49

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: 167.69  E-value: 3.19e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 277 NRYKNILPFDHTRVVLhdGDPNEPVSDYINANIiMPEFETKcnnskpkKSYIATQGCLQNTVNDFWRMVFQENSRVIVMT 356
Cdd:cd14615   1 NRYNNVLPYDISRVKL--SVQSHSTDDYINANY-MPGYNSK-------KEFIAAQGPLPNTVKDFWRMVWEKNVYAIVML 70

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 357 TKEVERGKSKCVKYWPDEYAlKEYGVMRVRNVKESAAHDYTLRELKLSKVgQGNTERTVWQYHFRTWPDHGVPSDPGGVL 436
Cdd:cd14615  71 TKCVEQGRTKCEEYWPSKQK-KDYGDITVTMTSEIVLPEWTIRDFTVKNA-QTNESRTVRHFHFTSWPDHGVPETTDLLI 148

                       170       180
                ....*....|....*....|...
gi 18375644 437 DFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14615 149 NFRHLVREYMKQNPPNSPILVHC 171
R-PTPc-H cd14619
catalytic domain of receptor-type tyrosine-protein phosphatase H; Receptor-type ...
 277-459 3.45e-49

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: 167.76  E-value: 3.45e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 277 NRYKNILPFDHTRVVLHDGDPnEPVSDYINANIiMPEFetkcNNSKpkkSYIATQGCLQNTVNDFWRMVFQENSRVIVMT 356
Cdd:cd14619   1 NRFRNVLPYDWSRVPLKPIHE-EPGSDYINANY-MPGY----WSSQ---EFIATQGPLPQTVGDFWRMIWEQQSSTIVML 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 357 TKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTeRTVWQYHFRTWPDHGVPSDPGGVL 436
Cdd:cd14619  72 TNCMEAGRVKCEHYWPLDYTPCTYGHLRVTVVSEEVMENWTVREFLLKQVEEQKT-LSVRHFHFTAWPDHGVPSSTDTLL 150

                       170       180
                ....*....|....*....|...
gi 18375644 437 DFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14619 151 AFRRLLRQWLDQTMSGGPTVVHC 173
R-PTP-LAR-2 cd14554
PTP-like domain of the LAR family receptor-type tyrosine-protein phosphatases, repeat 2; The ...
 273-459 1.20e-48

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: 166.55  E-value: 1.20e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 273 NKNKNRYKNILPFDHTRVVLH-----DGdpnepvSDYINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQ 347
Cdd:cd14554   6 NKFKNRLVNILPYESTRVCLQpirgvEG------SDYINASFI--------DGYRQRGAYIATQGPLAETTEDFWRMLWE 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 348 ENSRVIVMTTKEVERGKSKCVKYWPDEYALKeYGVMRVRNVKESAAHDYTLRELKLSKVGQGnTERTVWQYHFRTWPDHG 427
Cdd:cd14554  72 HNSTIIVMLTKLREMGREKCHQYWPAERSAR-YQYFVVDPMAEYNMPQYILREFKVTDARDG-QSRTVRQFQFTDWPEQG 149

                       170       180       190
                ....*....|....*....|....*....|..
gi 18375644 428 VPSDPGGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14554 150 VPKSGEGFIDFIGQVHKTKEQFGQEGPITVHC 181
R-PTPc-T-1 cd14630
catalytic domain of receptor-type tyrosine-protein phosphatase T, repeat 1; Receptor-type ...
 272-459 1.49e-48

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: 166.35  E-value: 1.49e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 272 ENKNKNRYKNILPFDHTRVVLH--DGDPNepvSDYINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQEN 349
Cdd:cd14630   2 ENRNKNRYGNIISYDHSRVRLQllDGDPH---SDYINANYI--------DGYHRPRHYIATQGPMQETVKDFWRMIWQEN 70

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 350 SRVIVMTTKEVERGKSKCVKYWPDEYALkeYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTeRTVWQYHFRTWPDHGVP 429
Cdd:cd14630  71 SASVVMVTNLVEVGRVKCVRYWPDDTEV--YGDIKVTLIETEPLAEYVIRTFTVQKKGYHEI-REIRQFHFTSWPDHGVP 147

                       170       180       190
                ....*....|....*....|....*....|
gi 18375644 430 SDPGGVLDFLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd14630 148 CYATGLLGFVRQV--KFLNPPDAGPIVVHC 175
PTPc-N3 cd14600
catalytic domain of tyrosine-protein phosphatase non-receptor type 3; Tyrosine-protein ...
 262-459 5.46e-48

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: 166.18  E-value: 5.46e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 262 LYSRKEG------QRQENKNKNRYKNILPFDHTRVVLHDGDpnepvsDYINANIIMPEFE-TKCNNSkpkksYIATQGCL 334
Cdd:cd14600  23 LYRKKPGlaitcaKLPQNMDKNRYKDVLPYDATRVVLQGNE------DYINASYVNMEIPsANIVNK-----YIATQGPL 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 335 QNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNtERT 414
Cdd:cd14600  92 PHTCAQFWQVVWEQKLSLIVMLTTLTERGRTKCHQYWPDPPDVMEYGGFRVQCHSEDCTIAYVFREMLLTNTQTGE-ERT 170

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 18375644 415 VWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQesiMDAGPVVVHC 459
Cdd:cd14600 171 VTHLQYVAWPDHGVPDDSSDFLEFVNYVRSKR---VENEPVLVHC 212
R-PTPc-G-1 cd17667
catalytic domain of receptor-type tyrosine-protein phosphatase G, repeat 1; Receptor-type ...
 247-459 4.22e-47

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: 163.67  E-value: 4.22e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 247 FWEEFETLQQQECKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLHD-GDPNEPVSDYINANIImpefetkcNNSKPKK 325
Cdd:cd17667   1 FSEDFEEVQRCTADMNITAEHSNHPDNKHKNRYINILAYDHSRVKLRPlPGKDSKHSDYINANYV--------DGYNKAK 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 326 SYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYAlKEYG--VMRVRNVKESAAHD---YTLRE 400
Cdd:cd17667  73 AYIATQGPLKSTFEDFWRMIWEQNTGIIVMITNLVEKGRRKCDQYWPTENS-EEYGniIVTLKSTKIHACYTvrrFSIRN 151

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18375644 401 LKLSKVGQGNT-----ERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESimDAGPVVVHC 459
Cdd:cd17667 152 TKVKKGQKGNPkgrqnERTVIQYHYTQWPDMGVPEYALPVLTFVRRSSAARTP--EMGPVLVHC 213
R5-PTPc-1 cd14549
catalytic domain of R5 subfamily receptor-type tyrosine-protein phosphatases, repeat 1; The R5 ...
 304-459 5.19e-47

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: 160.98  E-value: 5.19e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEyALKEYGVM 383
Cdd:cd14549   1 YINANYV--------DGYNKARAYIATQGPLPSTFDDFWRMVWEQNSAIIVMITNLVERGRRKCDQYWPKE-GTETYGNI 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 384 RVRNVKESAAHDYTLR-----ELKLSKVGQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEV-HHKQEsimDAGPVVV 457
Cdd:cd14549  72 QVTLLSTEVLATYTVRtfslkNLKLKKVKGRSSERVVYQYHYTQWPDHGVPDYTLPVLSFVRKSsAANPP---GAGPIVV 148


                ..
gi 18375644 458 HC 459
Cdd:cd14549 149 HC 150
PTPc-N12 cd14604
catalytic domain of tyrosine-protein phosphatase non-receptor type 12; Tyrosine-protein ...
 262-459 1.07e-46

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: 163.18  E-value: 1.07e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 262 LYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDPNEPvSDYINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDF 341
Cdd:cd14604  46 IYPTATGEKEENVKKNRYKDILPFDHSRVKLTLKTSSQD-SDYINANFI--------KGVYGPKAYIATQGPLANTVIDF 116

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 342 WRMVFQENSRVIVMTTKEVERGKSKCVKYWP--DEYALKeYGVMRVRNVKESAAHDYTLRELKLSKvgqGNTERTVWQYH 419
Cdd:cd14604 117 WRMIWEYNVAIIVMACREFEMGRKKCERYWPlyGEEPMT-FGPFRISCEAEQARTDYFIRTLLLEF---QNETRRLYQFH 192

                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 18375644 420 FRTWPDHGVPSDPGGVLDFLEEVHHKQESimDAGPVVVHC 459
Cdd:cd14604 193 YVNWPDHDVPSSFDSILDMISLMRKYQEH--EDVPICIHC 230
R-PTPc-B cd14617
catalytic domain of receptor-type tyrosine-protein phosphatase B; Receptor-type ...
 277-459 3.21e-46

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: 160.08  E-value: 3.21e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 277 NRYKNILPFDHTRVVLHDGDpNEPVSDYINANIImpefetKCNNSKpkKSYIATQGCLQNTVNDFWRMVFQENSRVIVMT 356
Cdd:cd14617   1 NRYNNILPYDSTRVKLSNVD-DDPCSDYINASYI------PGNNFR--REYIATQGPLPGTKDDFWKMVWEQNVHNIVMV 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 357 TKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSDPGGVL 436
Cdd:cd14617  72 TQCVEKGRVKCDHYWPADQDSLYYGDLIVQMLSESVLPEWTIREFKICSEEQLDAPRLVRHFHYTVWPDHGVPETTQSLI 151

                       170       180
                ....*....|....*....|...
gi 18375644 437 DFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14617 152 QFVRTVRDYINRTPGSGPTVVHC 174
PTPc-N1 cd14608
catalytic domain of tyrosine-protein phosphatase non-receptor type 1; Tyrosine-protein ...
 266-459 6.39e-46

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: 160.58  E-value: 6.39e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 266 KEGQRQENKNKNRYKNILPFDHTRVVLHDGDpnepvSDYINANIIMPEfetkcnnsKPKKSYIATQGCLQNTVNDFWRMV 345
Cdd:cd14608  18 RVAKLPKNKNRNRYRDVSPFDHSRIKLHQED-----NDYINASLIKME--------EAQRSYILTQGPLPNTCGHFWEMV 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 346 FQENSRVIVMTTKEVERGKSKCVKYWP---DEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTeRTVWQYHFRT 422
Cdd:cd14608  85 WEQKSRGVVMLNRVMEKGSLKCAQYWPqkeEKEMIFEDTNLKLTLISEDIKSYYTVRQLELENLTTQET-REILHFHYTT 163

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 18375644 423 WPDHGVPSDPGGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14608 164 WPDFGVPESPASFLNFLFKVRESGSLSPEHGPVVVHC 200
R-PTPc-V cd14618
catalytic domain of receptor-type tyrosine-protein phosphatase V; Receptor-type ...
 277-459 8.88e-46

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: 158.95  E-value: 8.88e-46
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 277 NRYKNILPFDHTRVVLHDGdPNEPVSDYINANIImPEFetkcnnSKPKKsYIATQGCLQNTVNDFWRMVFQENSRVIVMT 356
Cdd:cd14618   1 NRYPHVLPYDHSRVRLSQL-GGEPHSDYINANFI-PGY------TSPQE-FIATQGPLKKTIEDFWRLVWEQQVCNIIML 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 357 TKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQgNTERTVWQYHFRTWPDHGVPSDPGGVL 436
Cdd:cd14618  72 TVGMENGRVLCDHYWPSESTPVSYGHITVHLLAQSSEDEWTRREFKLWHEDL-RKERRVKHLHYTAWPDHGIPESTSSLM 150

                       170       180
                ....*....|....*....|...
gi 18375644 437 DFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14618 151 AFRELVREHVQATKGKGPTLVHC 173
R-PTPc-A-1 cd14621
catalytic domain of receptor-type tyrosine-protein phosphatase A, repeat 1; Receptor-type ...
 247-459 1.16e-45

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: 160.57  E-value: 1.16e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 247 FWEEFETLQQqeCKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLhdgDPNE--PVSDYINANIImpefetkcNNSKPK 324
Cdd:cd14621  28 FREEFNALPA--CPIQATCEAASKEENKEKNRYVNILPYDHSRVHL---TPVEgvPDSDYINASFI--------NGYQEK 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 325 KSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEyALKEYGVMRVRNVKESAAHDYTLRELKLS 404
Cdd:cd14621  95 NKFIAAQGPKEETVNDFWRMIWEQNTATIVMVTNLKERKECKCAQYWPDQ-GCWTYGNIRVSVEDVTVLVDYTVRKFCIQ 173

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18375644 405 KVGQ---GNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESImdAGPVVVHC 459
Cdd:cd14621 174 QVGDvtnKKPQRLITQFHFTSWPDFGVPFTPIGMLKFLKKVKNCNPQY--AGAIVVHC 229
PTPc-N2 cd14607
catalytic domain of tyrosine-protein phosphatase non-receptor type 2; Tyrosine-protein ...
 263-459 1.50e-45

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: 158.98  E-value: 1.50e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 263 YSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDpnepvSDYINANIIMPEfetkcnnsKPKKSYIATQGCLQNTVNDFW 342
Cdd:cd14607  14 YPHRVAKYPENRNRNRYRDVSPYDHSRVKLQNTE-----NDYINASLVVIE--------EAQRSYILTQGPLPNTCCHFW 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 343 RMVFQENSRVIVMTTKEVERGKSKCVKYWP----DEYALKEYGvMRVRNVKESAAHDYTLRELKLSKVGQGNTeRTVWQY 418
Cdd:cd14607  81 LMVWQQKTKAVVMLNRIVEKDSVKCAQYWPtdeeEVLSFKETG-FSVKLLSEDVKSYYTVHLLQLENINSGET-RTISHF 158

                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 18375644 419 HFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14607 159 HYTTWPDFGVPESPASFLNFLFKVRESGSLSPEHGPAVVHC 199
PTPc-N3_4 cd14541
catalytic domain of tyrosine-protein phosphatase non-receptor type 21 and type 14; ...
 303-459 1.80e-45

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: 157.49  E-value: 1.80e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 303 DYINANIImpefetkcNNSKPKKS----YIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALK 378
Cdd:cd14541   1 DYINANYV--------NMEIPGSGivnrYIAAQGPLPNTCADFWQMVWEQKSTLIVMLTTLVERGRVKCHQYWPDLGETM 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 379 EYGVMRVRNVKESAAHDYTLRELKLSKVgQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMDagPVVVH 458
Cdd:cd14541  73 QFGNLQITCVSEEVTPSFAFREFILTNT-NTGEERHITQMQYLAWPDHGVPDDSSDFLDFVKRVRQNRVGMVE--PTVVH 149


                .
gi 18375644 459 C 459
Cdd:cd14541 150 C 150
R-PTPc-F-1 cd14626
catalytic domain of receptor-type tyrosine-protein phosphatase F, repeat 1; Receptor-type ...
 234-459 3.03e-45

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: 159.05  E-value: 3.03e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 234 SKLAETTDKVKQG----FWEEFETLQ--QQeckllYSRKEGQRQENKNKNRYKNILPFDHTRVVLHDGDpNEPVSDYINA 307
Cdd:cd14626   1 SDLADNIERLKANdglkFSQEYESIDpgQQ-----FTWENSNLEVNKPKNRYANVIAYDHSRVILTSVD-GVPGSDYINA 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 308 NIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEyALKEYGVMRVRN 387
Cdd:cd14626  75 NYI--------DGYRKQNAYIATQGPLPETLSDFWRMVWEQRTATIVMMTRLEEKSRVKCDQYWPIR-GTETYGMIQVTL 145

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18375644 388 VKESAAHDYTLRELKLSKVGQgNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd14626 146 LDTVELATYSVRTFALYKNGS-SEKREVRQFQFMAWPDHGVPEYPTPILAFLRRV--KACNPPDAGPMVVHC 214
PTPc-N13 cd14597
catalytic domain of tyrosine-protein phosphatase non-receptor type 13; Tyrosine-protein ...
 271-459 1.48e-43

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: 153.06  E-value: 1.48e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 271 QENKNKNRYKNILPFDHTRVVLhdGDPNepvsDYINANII-MPEfetkcnnSKPKKSYIATQGCLQNTVNDFWRMVFQEN 349
Cdd:cd14597   1 KENRKKNRYKNILPYDTTRVPL--GDEG----GYINASFIkMPV-------GDEEFVYIACQGPLPTTVADFWQMVWEQK 67

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 350 SRVIVMTTKEVERGKSKCVKYWPDEYALKEY--GVMRVRNVKESAAHDYTLRELKLSKVgQGNTERTVWQYHFRTWPDHG 427
Cdd:cd14597  68 STVIAMMTQEVEGGKIKCQRYWPEILGKTTMvdNRLQLTLVRMQQLKNFVIRVLELEDI-QTREVRHITHLNFTAWPDHD 146

                       170       180       190
                ....*....|....*....|....*....|..
gi 18375644 428 VPSDPGGVLDFLEEVHHkqesIMDAGPVVVHC 459
Cdd:cd14597 147 TPSQPEQLLTFISYMRH----IHKSGPIITHC 174
R-PTPc-E-1 cd14620
catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 1; Receptor-type ...
 279-459 2.01e-43

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: 152.40  E-value: 2.01e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 279 YKNILPFDHTRVVLHDGDPNePVSDYINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTK 358
Cdd:cd14620   1 YPNILPYDHSRVILSQLDGI-PCSDYINASYI--------DGYKEKNKFIAAQGPKQETVNDFWRMVWEQKSATIVMLTN 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 359 EVERGKSKCVKYWPDEyALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTE--RTVWQYHFRTWPDHGVPSDPGGVL 436
Cdd:cd14620  72 LKERKEEKCYQYWPDQ-GCWTYGNIRVAVEDCVVLVDYTIRKFCIQPQLPDGCKapRLVTQLHFTSWPDFGVPFTPIGML 150

                       170       180
                ....*....|....*....|...
gi 18375644 437 DFLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd14620 151 KFLKKV--KSVNPVHAGPIVVHC 171
PTPc-N7 cd14612
catalytic domain of tyrosine-protein phosphatase non-receptor type 7; Tyrosine-protein ...
 276-459 4.06e-43

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: 152.30  E-value: 4.06e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 276 KNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMPEfetkcnNSKPKkSYIATQGCLQNTVNDFWRMVFQENSRVIVM 355
Cdd:cd14612  18 KDRYKTILPNPQSRVCLRRAGSQEEEGSYINANYIRGY------DGKEK-AYIATQGPMLNTVSDFWEMVWQEECPIIVM 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 356 TTKEVERgKSKCVKYWPDEYAlkEYG--VMRVRNVKESAahDYTLRELKLSKVGQgntERTVWQYHFRTWPDHGVPSDPG 433
Cdd:cd14612  91 ITKLKEK-KEKCVHYWPEKEG--TYGrfEIRVQDMKECD--GYTIRDLTIQLEEE---SRSVKHYWFSSWPDHQTPESAG 162

                       170       180
                ....*....|....*....|....*.
gi 18375644 434 GVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14612 163 PLLRLVAEVEESRQTAASPGPIVVHC 188
PTPc-N22 cd14602
catalytic domain of tyrosine-protein phosphatase non-receptor type 22; Tyrosine-protein ...
 276-459 5.01e-43

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: 151.53  E-value: 5.01e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 276 KNRYKNILPFDHTRVVLH----DGDpnepvSDYINANIIMPEFEtkcnnskpKKSYIATQGCLQNTVNDFWRMVFQENSR 351
Cdd:cd14602   1 KNRYKDILPYDHSRVELSlitsDED-----SDYINANFIKGVYG--------PRAYIATQGPLSTTLLDFWRMIWEYSVL 67

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 352 VIVMTTKEVERGKSKCVKYW--PDEYALkEYGVMRVRNVKESAAHDYTLRELklsKVGQGNTERTVWQYHFRTWPDHGVP 429
Cdd:cd14602  68 IIVMACMEFEMGKKKCERYWaePGEMQL-EFGPFSVTCEAEKRKSDYIIRTL---KVKFNSETRTIYQFHYKNWPDHDVP 143

                       170       180       190
                ....*....|....*....|....*....|
gi 18375644 430 SDPGGVLDFLEEVHHKQESimDAGPVVVHC 459
Cdd:cd14602 144 SSIDPILELIWDVRCYQED--DSVPICIHC 171
R-PTPc-R cd14611
catalytic domain of receptor-type tyrosine-protein phosphatase R; Receptor-type ...
 276-459 5.18e-43

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: 151.22  E-value: 5.18e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 276 KNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVM 355
Cdd:cd14611   2 KNRYKTILPNPHSRVCLKPKNSNDSLSTYINANYIR-------GYGGKEKAFIATQGPMINTVNDFWQMVWQEDSPVIVM 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 356 TTKEVERGKsKCVKYWPDEYALKEYGVMRVRNVKEsaAHDYTLRELKLSkvgQGNTERTVWQYHFRTWPDHGVPSDPGGV 435
Cdd:cd14611  75 ITKLKEKNE-KCVLYWPEKRGIYGKVEVLVNSVKE--CDNYTIRNLTLK---QGSQSRSVKHYWYTSWPDHKTPDSAQPL 148

                       170       180
                ....*....|....*....|....
gi 18375644 436 LDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14611 149 LQLMLDVEEDRLASPGRGPVVVHC 172
R-PTPc-M-1 cd14633
catalytic domain of receptor-type tyrosine-protein phosphatase M, repeat 1; Receptor-type ...
 246-459 2.35e-42

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: 150.96  E-value: 2.35e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 246 GFWEEFETLQQQECKLLYSRKegqRQENKNKNRYKNILPFDHTRVVLH--DGDPNepvSDYINANIImpefetkcNNSKP 323
Cdd:cd14633  16 GFKEEYESFFEGQSAPWDSAK---KDENRMKNRYGNIIAYDHSRVRLQpiEGETS---SDYINGNYI--------DGYHR 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 324 KKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALkeYGVMRVRNVKESAAHDYTLRELKL 403
Cdd:cd14633  82 PNHYIATQGPMQETIYDFWRMVWHENTASIIMVTNLVEVGRVKCCKYWPDDTEI--YKDIKVTLIETELLAEYVIRTFAV 159

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 18375644 404 SKVGQGNTeRTVWQYHFRTWPDHGVPSDPGGVLDFLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd14633 160 EKRGVHEI-REIRQFHFTGWPDHGVPYHATGLLGFVRQV--KSKSPPNAGPLVVHC 212
PTPc-N22_18_12 cd14542
catalytic domain of tyrosine-protein phosphatase non-receptor type 22, type 18 and type 12; ...
 304-459 5.65e-42

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: 147.95  E-value: 5.65e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIIMpefetkcNNSKPKkSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYA-LKEYGV 382
Cdd:cd14542   1 YINANFIK-------GVSGSK-AYIATQGPLPNTVLDFWRMIWEYNVQVIVMACREFEMGKKKCERYWPEEGEeQLQFGP 72

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18375644 383 MRVRNVKESA-AHDYTLRELKLSKvgqGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESimDAGPVVVHC 459
Cdd:cd14542  73 FKISLEKEKRvGPDFLIRTLKVTF---QKESRTVYQFHYTAWPDHGVPSSVDPILDLVRLVRDYQGS--EDVPICVHC 145
PTPc-N5 cd14613
catalytic domain of tyrosine-protein phosphatase non-receptor type 5; Tyrosine-protein ...
 276-459 2.29e-41

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: 148.09  E-value: 2.29e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 276 KNRYKNILPFDHTRVVLHDGDPNEPVSDYINANIIMpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVM 355
Cdd:cd14613  28 KNRYKTILPNPHSRVCLTSPDQDDPLSSYINANYIR-------GYGGEEKVYIATQGPTVNTVGDFWRMVWQERSPIIVM 100

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 356 TTKeVERGKSKCVKYWPDEYALkeYGVMRVRNVKESAAHDYTLRELKLSKvgqGNTERTVWQYHFRTWPDHGVPSDPGGV 435
Cdd:cd14613 101 ITN-IEEMNEKCTEYWPEEQVT--YEGIEITVKQVIHADDYRLRLITLKS---GGEERGLKHYWYTSWPDQKTPDNAPPL 174

                       170       180
                ....*....|....*....|....*
gi 18375644 436 LDFLEEVHH-KQESIMDAGPVVVHC 459
Cdd:cd14613 175 LQLVQEVEEaRQQAEPNCGPVIVHC 199
R-PTP-S-2 cd14627
PTP-like domain of receptor-type tyrosine-protein phosphatase S, repeat 2; Receptor-type ...
 273-459 1.57e-40

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: 146.80  E-value: 1.57e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 273 NKNKNRYKNILPFDHTRVVLhdgdpnEPV-----SDYINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQ 347
Cdd:cd14627  53 NKFKNRLVNIMPYETTRVCL------QPIrgvegSDYINASFI--------DGYRQQKAYIATQGPLAETTEDFWRMLWE 118

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 348 ENSRVIVMTTKEVERGKSKCVKYWPDEYALKeYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTeRTVWQYHFRTWPDHG 427
Cdd:cd14627 119 NNSTIVVMLTKLREMGREKCHQYWPAERSAR-YQYFVVDPMAEYNMPQYILREFKVTDARDGQS-RTVRQFQFTDWPEQG 196

                       170       180       190
                ....*....|....*....|....*....|..
gi 18375644 428 VPSDPGGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14627 197 VPKSGEGFIDFIGQVHKTKEQFGQDGPISVHC 228
R-PTP-D-2 cd14628
PTP-like domain of receptor-type tyrosine-protein phosphatase D, repeat 2; Receptor-type ...
 273-459 2.63e-40

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: 146.42  E-value: 2.63e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 273 NKNKNRYKNILPFDHTRVVLhdgdpnEPV-----SDYINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQ 347
Cdd:cd14628  52 NKFKNRLVNIMPYESTRVCL------QPIrgvegSDYINASFI--------DGYRQQKAYIATQGPLAETTEDFWRMLWE 117

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 348 ENSRVIVMTTKEVERGKSKCVKYWPDEYALKeYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTeRTVWQYHFRTWPDHG 427
Cdd:cd14628 118 HNSTIVVMLTKLREMGREKCHQYWPAERSAR-YQYFVVDPMAEYNMPQYILREFKVTDARDGQS-RTVRQFQFTDWPEQG 195

                       170       180       190
                ....*....|....*....|....*....|..
gi 18375644 428 VPSDPGGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14628 196 VPKSGEGFIDFIGQVHKTKEQFGQDGPISVHC 227
R-PTP-N2 cd14610
PTP-like domain of receptor-type tyrosine-protein phosphatase N2; Receptor-type ...
 268-459 8.95e-40

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: 144.43  E-value: 8.95e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 268 GQRQENKNKNRYKNILPFDHTRVVLHdGDPNEPVSDYINANIIMpefetkcnNSKPKK-SYIATQGCLQNTVNDFWRMVF 346
Cdd:cd14610  39 AQREENVQKNRSLAVLPYDHSRIILK-AENSHSHSDYINASPIM--------DHDPRNpAYIATQGPLPATVADFWQMVW 109

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 347 QENSRVIVMTTKEVERGKSKCVKYWPDEYAlKEYGVMRVRNVKESA-AHDYTLRELKLSKVgQGNTERTVWQYHFRTWPD 425
Cdd:cd14610 110 ESGCVVIVMLTPLAENGVKQCYHYWPDEGS-NLYHIYEVNLVSEHIwCEDFLVRSFYLKNL-QTNETRTVTQFHFLSWND 187

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 18375644 426 HGVPSDPGGVLDFLEEVH--HKQESImdagPVVVHC 459
Cdd:cd14610 188 QGVPASTRSLLDFRRKVNkcYRGRSC----PIIVHC 219
R-PTPc-O cd14614
catalytic domain of receptor-type tyrosine-protein phosphatase O; Receptor-type ...
 273-459 1.06e-39

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: 143.11  E-value: 1.06e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 273 NKNKNRYKNILPFDHTRVVLHDGDPNEPvSDYINANIImPEFetkcnnSKPKKsYIATQGCLQNTVNDFWRMVFQENSRV 352
Cdd:cd14614  12 NRCKNRYTNILPYDFSRVKLVSMHEEEG-SDYINANYI-PGY------NSPQE-YIATQGPLPETRNDFWKMVLQQKSQI 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 353 IVMTTKEVERGKSKCVKYWPDEYALKEYGVMRVRNVKESAAHDYTLRELKLSkvgQGNTERTVWQYHFRTWPDHGVPSDP 432
Cdd:cd14614  83 IVMLTQCNEKRRVKCDHYWPFTEEPVAYGDITVEMLSEEEQPDWAIREFRVS---YADEVQDVMHFNYTAWPDHGVPTAN 159

                       170       180
                ....*....|....*....|....*....
gi 18375644 433 GG--VLDFLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd14614 160 AAesILQFVQMV--RQQAVKSKGPMIIHC 186
PTPc-N20_13 cd14538
catalytic domain of tyrosine-protein phosphatase non-receptor type 20 and type 13; ...
 304-459 1.17e-39

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: 141.74  E-value: 1.17e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPD--EYALKEYG 381
Cdd:cd14538   1 YINASHI------RIPVGGDTYHYIACQGPLPNTTGDFWQMVWEQKSEVIAMVTQDVEGGKVKCHRYWPDslNKPLICGG 74

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18375644 382 VMRVRNVKESAAHDYTLRELKLSKVGQGnTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHkqesIMDAGPVVVHC 459
Cdd:cd14538  75 RLEVSLEKYQSLQDFVIRRISLRDKETG-EVHHITHLNFTTWPDHGTPQSADPLLRFIRYMRR----IHNSGPIVVHC 147
R-PTPc-S-1 cd14625
catalytic domain of receptor-type tyrosine-protein phosphatase S, repeat 1; Receptor-type ...
 233-459 1.44e-39

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: 144.08  E-value: 1.44e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 233 LSKLAETTDKVKQG----FWEEFETLQ--QQeckllYSRKEGQRQENKNKNRYKNILPFDHTRVVLHdgdPNEPV--SDY 304
Cdd:cd14625   6 ISELAEHTERLKANdnlkLSQEYESIDpgQQ-----FTWEHSNLEVNKPKNRYANVIAYDHSRVILQ---PIEGImgSDY 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 305 INANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEyALKEYGVMR 384
Cdd:cd14625  78 INANYI--------DGYRKQNAYIATQGPLPETFGDFWRMVWEQRSATVVMMTKLEEKSRIKCDQYWPSR-GTETYGMIQ 148

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18375644 385 VRNVKESAAHDYTLRELKLSKVGQgNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd14625 149 VTLLDTIELATFCVRTFSLHKNGS-SEKREVRQFQFTAWPDHGVPEYPTPFLAFLRRV--KTCNPPDAGPIVVHC 220
R-PTP-F-2 cd14629
PTP-like domain of receptor-type tyrosine-protein phosphatase F, repeat 2; Receptor-type ...
 250-459 1.59e-39

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: 144.10  E-value: 1.59e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 250 EFETLQQQECKLLYSRKEGQRQE-------NKNKNRYKNILPFDHTRVVLhdgdpnEPV-----SDYINANIImpefetk 317
Cdd:cd14629  23 ESVTAMELEFKLLANSKAHTSRFisanlpcNKFKNRLVNIMPYELTRVCL------QPIrgvegSDYINASFI------- 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 318 cNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALKeYGVMRVRNVKESAAHDYT 397
Cdd:cd14629  90 -DGYRQQKAYIATQGPLAETTEDFWRMLWEHNSTIVVMLTKLREMGREKCHQYWPAERSAR-YQYFVVDPMAEYNMPQYI 167

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18375644 398 LRELKLSKVGQGNTeRTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMDAGPVVVHC 459
Cdd:cd14629 168 LREFKVTDARDGQS-RTIRQFQFTDWPEQGVPKTGEGFIDFIGQVHKTKEQFGQDGPITVHC 228
R-PTPc-D-1 cd14624
catalytic domain of receptor-type tyrosine-protein phosphatase D, repeat 1; Receptor-type ...
 235-459 4.06e-39

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: 142.95  E-value: 4.06e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 235 KLAETTDKVKQG----FWEEFETLQ--QQeckllYSRKEGQRQENKNKNRYKNILPFDHTRVVLhDGDPNEPVSDYINAN 308
Cdd:cd14624   8 ELADHIERLKANdnlkFSQEYESIDpgQQ-----FTWEHSNLEVNKPKNRYANVIAYDHSRVLL-SAIEGIPGSDYINAN 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 309 IImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEyALKEYGVMRVRNV 388
Cdd:cd14624  82 YI--------DGYRKQNAYIATQGALPETFGDFWRMIWEQRSATVVMMTKLEERSRVKCDQYWPSR-GTETYGLIQVTLL 152

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18375644 389 KESAAHDYTLRELKLSKVGQgNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd14624 153 DTVELATYCVRTFALYKNGS-SEKREVRQFQFTAWPDHGVPEHPTPFLAFLRRV--KTCNPPDAGPMVVHC 220
PTPc-N21_14 cd14540
catalytic domain of tyrosine-protein phosphatase non-receptor type 21 and type 14; ...
 304-459 5.97e-39

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: 140.28  E-value: 5.97e-39
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIIMPEFETKcnnskpKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPD---EYALKEY 380
Cdd:cd14540   1 YINASHITATVGGK------QRFYIAAQGPLQNTVGDFWQMVWEQGVYLVVMVTAEEEGGREKCFRYWPTlggEHDALTF 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 381 GVMRVRNVKESAAHDYTLRELKLSKVgQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMDAG------- 453
Cdd:cd14540  75 GEYKVSTKFSVSSGCYTTTGLRVKHT-LSGQSRTVWHLQYTDWPDHGCPEDVSGFLDFLEEINSVRRHTNQDVaghnrnp 153


                ....*.
gi 18375644 454 PVVVHC 459
Cdd:cd14540 154 PTLVHC 159
R-PTPc-U-1 cd14632
catalytic domain of receptor-type tyrosine-protein phosphatase U, repeat 1; Receptor-type ...
 304-459 5.51e-38

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: 137.49  E-value: 5.51e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALkeYGVM 383
Cdd:cd14632   1 YINANYI--------DGYHRSNHFIATQGPKQEMVYDFWRMVWQEHCSSIVMITKLVEVGRVKCSKYWPDDSDT--YGDI 70

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18375644 384 RVRNVKESAAHDYTLRELKLSKVGQgNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd14632  71 KITLLKTETLAEYSVRTFALERRGY-SARHEVKQFHFTSWPEHGVPYHATGLLAFIRRV--KASTPPDAGPVVVHC 143
R-PTPc-typeIIb-1 cd14555
catalytic domain of type IIb (or R2B) subfamily receptor-type tyrosine-protein phosphatases, ...
 304-459 8.10e-38

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: 136.97  E-value: 8.10e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALkeYGVM 383
Cdd:cd14555   1 YINANYI--------DGYHRPNHYIATQGPMQETVYDFWRMVWQENSASIVMVTNLVEVGRVKCSRYWPDDTEV--YGDI 70

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18375644 384 RVRNVKESAAHDYTLRELKLSKVGQgNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd14555  71 KVTLVETEPLAEYVVRTFALERRGY-HEIREVRQFHFTGWPDHGVPYHATGLLGFIRRV--KASNPPSAGPIVVHC 143
R-PTPc-A-E-2 cd14552
catalytic domain of receptor-type tyrosine-protein phosphatase A and E, repeat 2; ...
 304-459 1.43e-37

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: 136.24  E-value: 1.43e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALkEYGVM 383
Cdd:cd14552   1 YINASFI--------DGYRQKDAYIATQGPLDHTVEDFWRMIWEWKSCSIVMLTEIKERSQNKCAQYWPEDGSV-SSGDI 71

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18375644 384 RVRNVKESAAHDYTLRELKLSKvGQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVhHKQESIMDAGPVVVHC 459
Cdd:cd14552  72 TVELKDQTDYEDYTLRDFLVTK-GKGGSTRTVRQFHFHGWPEVGIPDNGKGMIDLIAAV-QKQQQQSGNHPITVHC 145
R-PTPc-K-1 cd14631
catalytic domain of receptor-type tyrosine-protein phosphatase K, repeat 1; Receptor-type ...
 289-459 2.09e-37

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: 136.30  E-value: 2.09e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 289 RVVLHDGDpNEPVSDYINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCV 368
Cdd:cd14631   1 RVILQPVE-DDPSSDYINANYI--------DGYQRPSHYIATQGPVHETVYDFWRMIWQEQSACIVMVTNLVEVGRVKCY 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 369 KYWPDEYALkeYGVMRVRNVKESAAHDYTLRELKLSKVGQgNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVhhKQES 448
Cdd:cd14631  72 KYWPDDTEV--YGDFKVTCVEMEPLAEYVVRTFTLERRGY-NEIREVKQFHFTGWPDHGVPYHATGLLSFIRRV--KLSN 146

                       170
                ....*....|.
gi 18375644 449 IMDAGPVVVHC 459
Cdd:cd14631 147 PPSAGPIVVHC 157
R-PTP-N cd14609
PTP-like domain of receptor-type tyrosine-protein phosphatase N; Receptor-type ...
 268-459 4.60e-37

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: 137.09  E-value: 4.60e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 268 GQRQENKNKNRYKNILPFDHTRVVLHdGDPNEPVSDYINANIIMpefetkcnNSKPK-KSYIATQGCLQNTVNDFWRMVF 346
Cdd:cd14609  37 AQGEANVKKNRNPDFVPYDHARIKLK-AESNPSRSDYINASPII--------EHDPRmPAYIATQGPLSHTIADFWQMVW 107

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 347 QENSRVIVMTTKEVERGKSKCVKYWPDEYAlKEYGVMRVRNVKESA-AHDYTLRELKLSKVgQGNTERTVWQYHFRTWPD 425
Cdd:cd14609 108 ENGCTVIVMLTPLVEDGVKQCDRYWPDEGS-SLYHIYEVNLVSEHIwCEDFLVRSFYLKNV-QTQETRTLTQFHFLSWPA 185

                       170       180       190
                ....*....|....*....|....*....|....
gi 18375644 426 HGVPSDPGGVLDFLEEVHHKQESimDAGPVVVHC 459
Cdd:cd14609 186 EGIPSSTRPLLDFRRKVNKCYRG--RSCPIIVHC 217
R-PTPc-A-E-1 cd14551
catalytic domain of receptor-type tyrosine-protein phosphatase A and E, repeat 1; ...
 304-459 2.05e-36

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: 133.11  E-value: 2.05e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEyALKEYGVM 383
Cdd:cd14551   1 YINASYI--------DGYQEKNKFIAAQGPKDETVNDFWRMIWEQGSATIVMVTNLKERKEKKCSQYWPDQ-GCWTYGNL 71

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644 384 RVRNVKESAAHDYTLRELKLSKVGQGNTE---RTVWQYHFRTWPDHGVPSDPGGVLDFLEEVhhKQESIMDAGPVVVHC 459
Cdd:cd14551  72 RVRVEDTVVLVDYTTRKFCIQKVNRGIGEkrvRLVTQFHFTSWPDFGVPFTPIGMLKFLKKV--KSANPPRAGPIVVHC 148
PHA02742 PHA02742
protein tyrosine phosphatase; Provisional
 227-459 6.27e-36

protein tyrosine phosphatase; Provisional


Pssm-ID: 165109 [Multi-domain]  Cd Length: 303  Bit Score: 134.74  E-value: 6.27e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  227 ESRVRELSKlaettdkvkqgfwEEFETLQQQecKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVL--HDGdpnepVSDY 304
Cdd:PHA02742  21 ESNLAEILK-------------EEHEHIMQE--IVAFSCNESLELKNMKKCRYPDAPCFDRNRVILkiEDG-----GDDF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  305 INANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYW-PDEYALKEYGVM 383
Cdd:PHA02742  81 INASYV--------DGHNAKGRFICTQAPLEETALDFWQAIFQDQVRVIVMITKIMEDGKEACYPYWmPHERGKATHGEF 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  384 RVRNVKESAAHDYTLRELKLSKVGQGnTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQ---------ESIMDAGP 454
Cdd:PHA02742 153 KIKTKKIKSFRNYAVTNLCLTDTNTG-ASLDIKHFAYEDWPHGGLPRDPNKFLDFVLAVREADlkadvdikgENIVKEPP 231


                 ....*
gi 18375644  455 VVVHC 459
Cdd:PHA02742 232 ILVHC 236
R-PTPc-Q cd14616
catalytic domain of receptor-type tyrosine-protein phosphatase Q; Receptor-type ...
 277-459 9.79e-36

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: 131.95  E-value: 9.79e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 277 NRYKNILPFDHTRVVLHdGDPNEPVSDYINANIIMPEFetkCNNSkpkksYIATQGCLQNTVNDFWRMVFQENSRVIVMT 356
Cdd:cd14616   1 NRFPNIKPYNNNRVKLI-ADAGVPGSDYINASYISGYL---CPNE-----FIATQGPLPGTVGDFWRMVWETRAKTIVML 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 357 TKEVERGKSKCVKYWP-DEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNTERtvwQYHFRTWPDHGVPSDPGGV 435
Cdd:cd14616  72 TQCFEKGRIRCHQYWPeDNKPVTVFGDIVITKLMEDVQIDWTIRDLKIERHGDYMMVR---QCNFTSWPEHGVPESSAPL 148

                       170       180
                ....*....|....*....|....
gi 18375644 436 LDFLEEVHHKQESimDAGPVVVHC 459
Cdd:cd14616 149 IHFVKLVRASRAH--DNTPMIVHC 170
PTPc-N4 cd14601
catalytic domain of tyrosine-protein phosphatase non-receptor type 4; Tyrosine-protein ...
 303-459 2.77e-35

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: 130.45  E-value: 2.77e-35
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 303 DYINANIImpefetkcNNSKPKKS----YIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALK 378
Cdd:cd14601   1 DYINANYI--------NMEIPSSSiinrYIACQGPLPNTCSDFWQMTWEQGSSMVVMLTTQVERGRVKCHQYWPEPSGSS 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 379 EYGVMRVRNVKESAAHDYTLRELKLSKVgQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQesimdAG---PV 455
Cdd:cd14601  73 SYGGFQVTCHSEEGNPAYVFREMTLTNL-EKNESRPLTQIQYIAWPDHGVPDDSSDFLDFVCLVRNKR-----AGkdePV 146


                ....
gi 18375644 456 VVHC 459
Cdd:cd14601 147 VVHC 150
R-PTPc-A-2 cd14623
catalytic domain of receptor-type tyrosine-protein phosphatase A, repeat 2; Receptor-type ...
 278-459 8.36e-34

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: 126.70  E-value: 8.36e-34
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 278 RYKNILPFDHTRVVL--HDGDPNepvSDYINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVM 355
Cdd:cd14623   1 RVLQIIPYEFNRVIIpvKRGEEN---TDYVNASFI--------DGYRQKDSYIASQGPLQHTIEDFWRMIWEWKSCSIVM 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 356 TTKEVERGKSKCVKYWPDEyALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQgNTERTVWQYHFRTWPDHGVPSDPGGV 435
Cdd:cd14623  70 LTELEERGQEKCAQYWPSD-GSVSYGDITIELKKEEECESYTVRDLLVTNTRE-NKSRQIRQFHFHGWPEVGIPSDGKGM 147

                       170       180
                ....*....|....*....|....
gi 18375644 436 LDFLEEVhHKQESIMDAGPVVVHC 459
Cdd:cd14623 148 INIIAAV-QKQQQQSGNHPITVHC 170
R-PTPc-Z-1 cd17668
catalytic domain of receptor-type tyrosine-protein phosphatase Z, repeat 1; Receptor-type ...
 304-459 8.43e-33

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: 123.55  E-value: 8.43e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYAlKEYGVM 383
Cdd:cd17668   1 YINANYV--------DGYNKPKAYIAAQGPLKSTAEDFWRMIWEHNVEVIVMITNLVEKGRRKCDQYWPADGS-EEYGNF 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 384 RV--RNVKESAAH---DYTLRELKLSKVGQG--NTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMdaGPVV 456
Cdd:cd17668  72 LVtqKSVQVLAYYtvrNFTLRNTKIKKGSQKgrPSGRVVTQYHYTQWPDMGVPEYTLPVLTFVRKASYAKRHAV--GPVV 149


                ...
gi 18375644 457 VHC 459
Cdd:cd17668 150 VHC 152
PTPc-N14 cd14599
catalytic domain of tyrosine-protein phosphatase non-receptor type 14; Tyrosine-protein ...
 272-459 5.07e-32

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: 123.57  E-value: 5.07e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 272 ENKNKNRYKNILPFDHTRVVLHDGDPNEpvSDYINANIImpefetKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSR 351
Cdd:cd14599  37 ENAERNRIREVVPYEENRVELVPTKENN--TGYINASHI------KVTVGGEEWHYIATQGPLPHTCHDFWQMVWEQGVN 108

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 352 VIVMTTKEVERGKSKCVKYWP---DEYALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQGNtERTVWQYHFRTWPDHGV 428
Cdd:cd14599 109 VIAMVTAEEEGGRSKSHRYWPklgSKHSSATYGKFKVTTKFRTDSGCYATTGLKVKHLLSGQ-ERTVWHLQYTDWPDHGC 187

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 18375644 429 PSDPGGVLDFLEE---VHHKQESIMDAG-----PVVVHC 459
Cdd:cd14599 188 PEEVQGFLSYLEEiqsVRRHTNSMLDSTkncnpPIVVHC 226
R-PTP-C-2 cd14558
PTP-like domain of receptor-type tyrosine-protein phosphatase C, repeat 2; Receptor-type ...
 304-460 5.66e-32

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: 120.96  E-value: 5.66e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYalKEYGVM 383
Cdd:cd14558   1 YINASFI--------DGYWGPKSLIATQGPLPDTIADFWQMIFQKKVKVIVMLTELKEGDQEQCAQYWGDEK--KTYGDI 70

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 384 RVRNVKESAAHDYTLRELKLsKVGQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMDAG----PVVVHC 459
Cdd:cd14558  71 EVELKDTEKSPTYTVRVFEI-THLKRKDSRTVYQYQYHKWKGEELPEKPKDLVDMIKSIKQKLPYKNSKHgrsvPIVVHC 149


                .
gi 18375644 460 R 460
Cdd:cd14558 150 S 150
SH2 pfam00017
SH2 domain;
6-81 2.15e-31

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 115.01  E-value: 2.15e-31
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18375644     6 WFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDY-YDLYGGEKFATLAELVQYY 81
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPDGTFLVRESESTPGGYTLSVRDDGKVKHYKIQSTDNGgYYISGGVKFSSLAELVEHY 77
PHA02738 PHA02738
hypothetical protein; Provisional
 229-459 1.32e-30

hypothetical protein; Provisional


Pssm-ID: 222923 [Multi-domain]  Cd Length: 320  Bit Score: 120.41  E-value: 1.32e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  229 RVRELsKLAETTDKVKQGFWEEFETLQQQecKLLYSRKEG---QRQENKNKNRYKNILPFDHTRVVLhdgdPNEP-VSDY 304
Cdd:PHA02738   5 KFREL-KYAEFLALMEKSDCEEVITREHQ--KVISEKVDGtfnAEKKNRKLNRYLDAVCFDHSRVIL----PAERnRGDY 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  305 INANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPD-EYALKEYGVM 383
Cdd:PHA02738  78 INANYV--------DGFEYKKKFICGQAPTRQTCYDFYRMLWMEHVQIIVMLCKKKENGREKCFPYWSDvEQGSIRFGKF 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  384 RVRNVKESAAHDYTLRELKLSKvGQGNTErTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESI-----------MDA 452
Cdd:PHA02738 150 KITTTQVETHPHYVKSTLLLTD-GTSATQ-TVTHFNFTAWPDHDVPKNTSEFLNFVLEVRQCQKELaqeslqighnrLQP 227


                 ....*..
gi 18375644  453 GPVVVHC 459
Cdd:PHA02738 228 PPIVVHC 234
R-PTPc-C-1 cd14557
catalytic domain of receptor-type tyrosine-protein phosphatase C, repeat 1; Receptor-type ...
 304-459 1.32e-30

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: 117.24  E-value: 1.32e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPD-EYALKEYGV 382
Cdd:cd14557   1 YINASYI--------DGFKEPRKYIAAQGPKDETVDDFWRMIWEQKSTVIVMVTRCEEGNRNKCAQYWPSmEEGSRAFGD 72

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18375644 383 MRVRNVKESAAHDYTLRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESImdAGPVVVHC 459
Cdd:cd14557  73 VVVKINEEKICPDYIIRKLNINNKKEKGSGREVTHIQFTSWPDHGVPEDPHLLLKLRRRVNAFNNFF--SGPIVVHC 147
PTPc-N20 cd14596
catalytic domain of tyrosine-protein phosphatase non-receptor type 20; Tyrosine-protein ...
 304-459 1.95e-30

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: 117.16  E-value: 1.95e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINAN-IIMPEFETKcnnskpkKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDE-YALKEYG 381
Cdd:cd14596   1 YINASyITMPVGEEE-------LFYIATQGPLPSTIDDFWQMVWENRSDVIAMMTREVERGKVKCHRYWPETlQEPMELE 73

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18375644 382 VMRVRNVKESAAHDYTLRELKLSKVGQGNTeRTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHkqesIMDAGPVVVHC 459
Cdd:cd14596  74 NYQLRLENYQALQYFIIRIIKLVEKETGEN-RLIKHLQFTTWPDHGTPQSSDQLVKFICYMRK----VHNTGPIVVHC 146
COG5599 COG5599
Protein tyrosine phosphatase [Signal transduction mechanisms];
234-460 2.62e-30

Protein tyrosine phosphatase [Signal transduction mechanisms];


Pssm-ID: 444335 [Multi-domain]  Cd Length: 282  Bit Score: 118.66  E-value: 2.62e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 234 SKLAETTDKVKQGFWEEFETLQQQeckLLYSRKEGQRQENKN---KNRYKNILPFDHTRVVLHDGdpnepvsdYINANII 310
Cdd:COG5599   3 PKNPIAIKSEEEKINSRLSTLTNE---LAPSHNDPQYLQNINgspLNRFRDIQPYKETALRANLG--------YLNANYI 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 311 mpefetkcnNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKS--KCVKYWPDEyalKEYGVMRVRNV 388
Cdd:COG5599  72 ---------QVIGNHRYIATQYPLEEQLEDFFQMLFDNNTPVLVVLASDDEISKPkvKMPVYFRQD---GEYGKYEVSSE 139

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18375644 389 KESAAH---DYTLRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSDPgGVLDFLEEVHHKQE-SIMDAGPVVVHCR 460
Cdd:COG5599 140 LTESIQlrdGIEARTYVLTIKGTGQKKIEIPVLHVKNWPDHGAISAE-ALKNLADLIDKKEKiKDPDKLLPVVHCR 214
R-PTP-N-N2 cd14546
PTP-like domain of receptor-type tyrosine-protein phosphatase-like N and N2; Receptor-type ...
 304-459 6.74e-30

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: 115.62  E-value: 6.74e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIIMpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYAlKEYGVM 383
Cdd:cd14546   1 YINASTIY-------DHDPRNPAYIATQGPLPHTIADFWQMIWEQGCVVIVMLTRLQENGVKQCARYWPEEGS-EVYHIY 72

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18375644 384 RVRNVKE-SAAHDYTLRELKLSKVgQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMdaGPVVVHC 459
Cdd:cd14546  73 EVHLVSEhIWCDDYLVRSFYLKNL-QTSETRTVTQFHFLSWPDEGIPASAKPLLEFRRKVNKSYRGRS--CPIVVHC 146
SH2 pfam00017
SH2 domain;
112-197 2.17e-29

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 109.61  E-value: 2.17e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGDdkgesndgksKVTHVMIRCQE-LKYDVGGGERFDSL 190
Cdd:pfam00017   1 WYHGKISRQEAERLLLNGKPDGTFLVRESESTPGGYTLSVRDDG----------KVKHYKIQSTDnGGYYISGGVKFSSL 70


                  ....*..
gi 18375644   191 TDLVEHY 197
Cdd:pfam00017  71 AELVEHY 77
SH2_N-SH2_SHP_like cd10340
N-terminal Src homology 2 (N-SH2) domain found in SH2 domain Phosphatases (SHP) proteins; The ...
 111-217 2.23e-29

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: 110.57  E-value: 2.23e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 111 RWFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGDdkgesndgksKVTHVMIRCQELKYDVGGGERFDSL 190
Cdd:cd10340   1 RWFHPVISGIEAENLLKTRGVDGSFLARPSKSNPGDFTLSVRRGD----------EVTHIKIQNTGDYYDLYGGEKFATL 70

                        90       100
                ....*....|....*....|....*....
gi 18375644 191 TDLVEHYKKNP--MVETLGTVLQLKQPLN 217
Cdd:cd10340  71 SELVQYYMEQHgqLREKNGDVIELKYPLN 99
PTP-N23 cd14539
PTP-like domain of tyrosine-protein phosphatase non-receptor type 23; Tyrosine-protein ...
 304-459 5.14e-29

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: 112.86  E-value: 5.14e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIIMpEFETKCnnskpkKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALK-EYGV 382
Cdd:cd14539   1 YINASLIE-DLTPYC------PRFIATQAPLPGTAADFWLMVYEQQVSVIVMLVSEQENEKQKVHRYWPTERGQAlVYGA 73

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644 383 MRVRNVKESAAHDYTLRELKLSKVGQgNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEV--HHKQESIMDAgPVVVHC 459
Cdd:cd14539  74 ITVSLQSVRTTPTHVERIISIQHKDT-RLSRSVVHLQFTTWPELGLPDSPNPLLRFIEEVhsHYLQQRSLQT-PIVVHC 150
R-PTPc-E-2 cd14622
catalytic domain of receptor-type tyrosine-protein phosphatase E, repeat 2; Receptor-type ...
 303-459 6.20e-29

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: 112.79  E-value: 6.20e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 303 DYINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWPDEYALKeYGV 382
Cdd:cd14622   1 DYINASFI--------DGYRQKDYFIATQGPLAHTVEDFWRMVWEWKCHTIVMLTELQEREQEKCVQYWPSEGSVT-HGE 71

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18375644 383 MRVRNVKESAAHDYTLRELKLSkVGQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVhHKQESIMDAGPVVVHC 459
Cdd:cd14622  72 ITIEIKNDTLLETISIRDFLVT-YNQEKQTRLVRQFHFHGWPEIGIPAEGKGMIDLIAAV-QKQQQQTGNHPIVVHC 146
R-PTPc-typeIIb-2 cd14556
PTP domain of type IIb (or R2B) subfamily receptor-type tyrosine-protein phosphatases, repeat ...
 304-459 1.20e-28

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: 111.73  E-value: 1.20e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTkEVERGKSKCVKYWPDEyALKEYGVM 383
Cdd:cd14556   1 YINAALL--------DSYKQPAAFIVTQHPLPNTVTDFWRLVYDYGCTSIVMLN-QLDPKDQSCPQYWPDE-GSGTYGPI 70

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18375644 384 RVRNVKESAAHDYTLRELKLSKVGQGNTE-RTVWQYHFRTWPDHG-VPSDPGGVLDFLEEVHHKQESiMDAGPVVVHC 459
Cdd:cd14556  71 QVEFVSTTIDEDVISRIFRLQNTTRPQEGyRMVQQFQFLGWPRDRdTPPSKRALLKLLSEVEKWQEQ-SGEGPIVVHC 147
PTPc-N21 cd14598
catalytic domain of tyrosine-protein phosphatase non-receptor type 21; Tyrosine-protein ...
 304-459 3.22e-28

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: 111.22  E-value: 3.22e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetKCNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVKYWP---DEYALKEY 380
Cdd:cd14598   1 YINASHI------KVTVGGKEWDYIATQGPLQNTCQDFWQMVWEQGVAIIAMVTAEEEGGREKSFRYWPrlgSRHNTVTY 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 381 GVMRVRNVKESAAHDYTLRELKLSKVGQGNtERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVH----HKQESIMDAG--- 453
Cdd:cd14598  75 GRFKITTRFRTDSGCYATTGLKIKHLLTGQ-ERTVWHLQYTDWPEHGCPEDLKGFLSYLEEIQsvrrHTNSTIDPKSpnp 153


                ....*.
gi 18375644 454 PVVVHC 459
Cdd:cd14598 154 PVLVHC 159
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 110-201 3.39e-27

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: 103.85  E-value: 3.39e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644    110 ERWFHGHLSGKEAEKLLTEKGkHGSFLVRESQSHPGDFVLSVRTGDdkgesndgksKVTHVMIRCQEL-KYDVGGGERFD 188
Cdd:smart00252   1 QPWYHGFISREEAEKLLKNEG-DGDFLVRDSESSPGDYVLSVRVKG----------KVKHYRIRRNEDgKFYLEGGRKFP 69

                           90
                   ....*....|...
gi 18375644    189 SLTDLVEHYKKNP 201
Cdd:smart00252  70 SLVELVEHYQKNS 82
PHA02747 PHA02747
protein tyrosine phosphatase; Provisional
 269-459 3.82e-27

protein tyrosine phosphatase; Provisional


Pssm-ID: 165114 [Multi-domain]  Cd Length: 312  Bit Score: 110.86  E-value: 3.82e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  269 QRQENKNKNRYKNILPFDHTRVVLHDGdpNEPVSDYINANIImPEFEtkcnnsKPKKsYIATQGCLQNTVNDFWRMVFQE 348
Cdd:PHA02747  47 EKPENQPKNRYWDIPCWDHNRVILDSG--GGSTSDYIHANWI-DGFE------DDKK-FIATQGPFAETCADFWKAVWQE 116

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  349 NSRVIVM-TTKEVERGKSKCVKYW-PDEYALKEYGVMRVRNVKESAAHDYTLRELKLSKvGQGNTERTVWQYHFRTWPDH 426
Cdd:PHA02747 117 HCSIIVMlTPTKGTNGEEKCYQYWcLNEDGNIDMEDFRIETLKTSVRAKYILTLIEITD-KILKDSRKISHFQCSEWFED 195

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|.
gi 18375644  427 GVPSDPGGVLDFLEEVHHKQESIMD--------AGPVVVHC 459
Cdd:PHA02747 196 ETPSDHPDFIKFIKIIDINRKKSGKlfnpkdalLCPIVVHC 236
PTPc_plant_PTP1 cd17658
protein tyrosine phosphatase 1 from Arabidopsis thaliana and similar plant PTPs; Arabidopsis ...
 304-459 5.42e-27

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: 107.55  E-value: 5.42e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefETKCNNSKPKksYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGK-SKCVKYWPDEYAL-KEYG 381
Cdd:cd17658   1 YINASLV----ETPASESLPK--FIATQGPLPHTFEDFWEMVIQQRCPVIIMLTRLVDNYStAKCADYFPAEENEsREFG 74

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644 382 VMRVRNVKES-AAHDYTLRELKLSKVGQGNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESimdAGPVVVHC 459
Cdd:cd17658  75 RISVTNKKLKhSQHSITLRVLEVQYIESEEPPLSVLHIQYPEWPDHGVPKDTRSVRELLKRLYGIPPS---AGPIVVHC 150
PHA02746 PHA02746
protein tyrosine phosphatase; Provisional
 234-459 6.69e-26

protein tyrosine phosphatase; Provisional


Pssm-ID: 165113 [Multi-domain]  Cd Length: 323  Bit Score: 107.42  E-value: 6.69e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  234 SKLAETTDKVKqgFWE--EFETLQQQECKLLYSRKEGQRQENKNKNRYKNILPFDHTRVVLH-----------DGDPNEP 300
Cdd:PHA02746  12 FDFFDKTNHAK--FCEfvLLEHAEVMDIPIRGTTNHFLKKENLKKNRFHDIPCWDHSRVVINaheslkmfdvgDSDGKKI 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  301 V-------SDYINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTkEVERGKSKCVKYW-- 371
Cdd:PHA02746  90 EvtsednaENYIHANFV--------DGFKEANKFICAQGPKEDTSEDFFKLISEHESQVIVSLT-DIDDDDEKCFELWtk 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  372 PDEYALKeYG--VMRVRNVKESAAhdYTLRELKLSKVGQgNTERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESI 449
Cdd:PHA02746 161 EEDSELA-FGrfVAKILDIIEELS--FTKTRLMITDKIS-DTSREIHHFWFPDWPDNGIPTGMAEFLELINKVNEEQAEL 236

                        250
                 ....*....|....*...
gi 18375644  450 M--------DAGPVVVHC 459
Cdd:PHA02746 237 IkqadndpqTLGPIVVHC 254
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 6-84 1.31e-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: 96.91  E-value: 1.31e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644      6 WFHPNITGVEAENLLLTRGvDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGD-YYDLYGGEKFATLAELVQYYMEH 84
Cdd:smart00252   3 WYHGFISREEAEKLLKNEG-DGDFLVRDSESSPGDYVLSVRVKGKVKHYRIRRNEDgKFYLEGGRKFPSLVELVEHYQKN 81
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 111-197 1.88e-23

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: 93.67  E-value: 1.88e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 111 RWFHGHLSGKEAEKLLTEKgKHGSFLVRESQSHPGDFVLSVRTGDDkgesndgksKVTHVMIRCQELKYDVGGGE--RFD 188
Cdd:cd00173   1 PWFHGSISREEAERLLRGK-PDGTFLVRESSSEPGDYVLSVRSGDG---------KVKHYLIERNEGGYYLLGGSgrTFP 70


                ....*....
gi 18375644 189 SLTDLVEHY 197
Cdd:cd00173  71 SLPELVEHY 79
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 5-81 4.15e-21

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: 87.13  E-value: 4.15e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   5 RWFHPNITGVEAENLLLTRgVDGSFLARPSKSNPGDFTLSVR-RNGAVTHIKIQNTGDYYDLYGGEK--FATLAELVQYY 81
Cdd:cd00173   1 PWFHGSISREEAERLLRGK-PDGTFLVRESSSEPGDYVLSVRsGDGKVKHYLIERNEGGYYLLGGSGrtFPSLPELVEHY 79
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
 109-200 1.62e-20

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: 86.10  E-value: 1.62e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEK-LLTEKGKHGSFLVRESQSHPGDFVLSVRTGDDKGESNdgkskVTHVMIRcqelKYDVGGG--- 184
Cdd:cd09933   2 AEEWFFGKIKRKDAEKlLLAPGNPRGTFLIRESETTPGAYSLSVRDGDDARGDT-----VKHYRIR----KLDNGGYyit 72

                        90
                ....*....|....*...
gi 18375644 185 --ERFDSLTDLVEHYKKN 200
Cdd:cd09933  73 trATFPTLQELVQHYSKD 90
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
 111-200 5.94e-20

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: 84.26  E-value: 5.94e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 111 RWFHGHLSGKEAEKLLTEKgKHGSFLVRESQSHPGDFVLSVRTGDdkgesndgksKVTHVMIRCQELKYDVGGGERFDSL 190
Cdd:cd09937   4 PWFHGKISREEAERLLQPP-EDGLFLVRESTNYPGDYTLCVSFEG----------KVEHYRVIYRNGKLTIDEEEYFENL 72

                        90
                ....*....|
gi 18375644 191 TDLVEHYKKN 200
Cdd:cd09937  73 IQLVEHYTKD 82
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 6-81 4.36e-19

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: 81.32  E-value: 4.36e-19
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18375644   6 WFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEKFATLAELVQYY 81
Cdd:cd10354   2 WFHGKISREEAYNMLVKVGGPGSFLVRESDNTPGDYSLSFRVNEGIKHFKIIPTGNNQFMMGGRYFSSLDDVIDRY 77
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 3-103 8.28e-18

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: 78.46  E-value: 8.28e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLyGGEKFATLAELVQYYM 82
Cdd:cd09932   3 SKEWFHANLTREQAEEMLMRVPRDGAFLVRPSETDPNSFAISFRAEGKIKHCRIKQEGRLFVI-GTSQFESLVELVSYYE 81

                        90       100
                ....*....|....*....|.
gi 18375644  83 EHhgQLKEKngdvIELKYPLN 103
Cdd:cd09932  82 KH--PLYRK----IKLRYPVN 96
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
 112-201 1.59e-17

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: 77.31  E-value: 1.59e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGDDkgesndgkskVTHVMI-RCQELKYDVgGGERFDSL 190
Cdd:cd09941   5 WFHGKISRAEAEEILMNQRPDGAFLIRESESSPGDFSLSVKFGND----------VQHFKVlRDGAGKYFL-WVVKFNSL 73

                        90
                ....*....|.
gi 18375644 191 TDLVEHYKKNP 201
Cdd:cd09941  74 NELVDYHRTTS 84
SH2_Cterm_RasGAP cd10354
C-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 112-197 4.31e-17

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: 75.54  E-value: 4.31e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGddkgesndgkSKVTHVMIRCQELKYDVGGGERFDSLT 191
Cdd:cd10354   2 WFHGKISREEAYNMLVKVGGPGSFLVRESDNTPGDYSLSFRVN----------EGIKHFKIIPTGNNQFMMGGRYFSSLD 71


                ....*.
gi 18375644 192 DLVEHY 197
Cdd:cd10354  72 DVIDRY 77
SH2_Grb2_like cd09941
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar ...
 6-85 6.42e-17

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: 75.77  E-value: 6.42e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKI--QNTGDYYdLYgGEKFATLAELVQYYME 83
Cdd:cd09941   5 WFHGKISRAEAEEILMNQRPDGAFLIRESESSPGDFSLSVKFGNDVQHFKVlrDGAGKYF-LW-VVKFNSLNELVDYHRT 82


                ..
gi 18375644  84 HH 85
Cdd:cd09941  83 TS 84
R5-PTP-2 cd14550
PTP-like domain of R5 subfamily receptor-type tyrosine-protein phosphatases, repeat 2; The R5 ...
 304-460 1.55e-16

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: 77.75  E-value: 1.55e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIIMPEFETKcnnskpkkSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCvkYWPDEYALKEYGVM 383
Cdd:cd14550   1 YINASYLQGYRRSN--------EFIITQHPLEHTIKDFWQMIWDHNSQTIVMLTDNELNEDEPI--YWPTKEKPLECETF 70

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 384 RVRNVKE-----SAAHDYTLRELKLSKVgQGNTERTVWQYHFRTWPDHGVPsdPGGVLDFLEEVH-HKQESimdAGPVVV 457
Cdd:cd14550  71 KVTLSGEdhsclSNEIRLIVRDFILEST-QDDYVLEVRQFQCPSWPNPCSP--IHTVFELINTVQeWAQQR---DGPIVV 144


                ...
gi 18375644 458 HCR 460
Cdd:cd14550 145 HDR 147
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 109-202 2.15e-16

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: 74.31  E-value: 2.15e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSG--KEAEKLLTE--KGKHGSFLVRESQSHPGDFVLS-VRTGddkgesndgksKVTHVMIRCQ----ELKY 179
Cdd:cd10341   3 TEPWFHGKLGDgrDEAEKLLLEycEGGDGTFLVRESETFVGDYTLSfWRNG-----------KVQHCRIRSRqengEKKY 71

                        90       100
                ....*....|....*....|...
gi 18375644 180 DVGGGERFDSLTDLVEHYKKNPM 202
Cdd:cd10341  72 YLTDNLVFDSLYELIDYYRQNPL 94
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
 6-82 2.66e-16

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: 74.09  E-value: 2.66e-16
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18375644   6 WFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLyGGEKFATLAELVQYYM 82
Cdd:cd09943   3 WYYGRITRHQAETLLNEHGHEGDFLIRDSESNPGDYSVSLKAPGRNKHFKVQVVDNVYCI-GQRKFHTMDELVEHYK 78
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
 6-101 6.78e-16

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: 72.81  E-value: 6.78e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAEnLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQ--NTGDYYdLYGGEKFATLAELVQYYME 83
Cdd:cd09935   5 WYHGPISRNAAE-YLLSSGINGSFLVRESESSPGQYSISLRYDGRVYHYRISedSDGKVY-VTQEHRFNTLAELVHHHSK 82

                        90
                ....*....|....*...
gi 18375644  84 HHgqlkekNGDVIELKYP 101
Cdd:cd09935  83 NA------DGLITTLRYP 94
SH2_Src_family cd09933
Src homology 2 (SH2) domain found in the Src family of non-receptor tyrosine kinases; The Src ...
 6-84 3.20e-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: 71.07  E-value: 3.20e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRG-VDGSFLARPSKSNPGDFTLSVR-----RNGAVTHIKIQN--TGDYYdLYGGEKFATLAEL 77
Cdd:cd09933   5 WFFGKIKRKDAEKLLLAPGnPRGTFLIRESETTPGAYSLSVRdgddaRGDTVKHYRIRKldNGGYY-ITTRATFPTLQEL 83


                ....*..
gi 18375644  78 VQYYMEH 84
Cdd:cd09933  84 VQHYSKD 90
SH2_ABL cd09935
Src homology 2 (SH2) domain found in Abelson murine lymphosarcoma virus (ABL) proteins; ...
 112-210 1.69e-14

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: 68.95  E-value: 1.69e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTeKGKHGSFLVRESQSHPGDFVLSVRtgddkgesNDGksKVTHVMI-RCQELKYDVGGGERFDSL 190
Cdd:cd09935   5 WYHGPISRNAAEYLLS-SGINGSFLVRESESSPGQYSISLR--------YDG--RVYHYRIsEDSDGKVYVTQEHRFNTL 73

                        90       100
                ....*....|....*....|
gi 18375644 191 TDLVEHYKKNPmvETLGTVL 210
Cdd:cd09935  74 AELVHHHSKNA--DGLITTL 91
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
 112-216 1.83e-14

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: 68.90  E-value: 1.83e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTgddkgesnDGKSKvtHVMIRCQELKYDVgGGERFDSLT 191
Cdd:cd10408   3 WYYGKVTRHQAEMALNERGNEGDFLIRDSESSPNDFSVSLKA--------QGKNK--HFKVQLKECVYCI-GQRKFSSME 71

                        90       100
                ....*....|....*....|....*.
gi 18375644 192 DLVEHYKKNPMVET-LGTVLQLKQPL 216
Cdd:cd10408  72 ELVEHYKKAPIFTSeQGEKLYLIKAL 97
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 109-217 2.26e-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: 68.83  E-value: 2.26e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTgddkgesnDGKSKvtHVMIRcQELKYDVGGGERFD 188
Cdd:cd09932   3 SKEWFHANLTREQAEEMLMRVPRDGAFLVRPSETDPNSFAISFRA--------EGKIK--HCRIK-QEGRLFVIGTSQFE 71

                        90       100
                ....*....|....*....|....*....
gi 18375644 189 SLTDLVEHYKKNPMVETlgtvLQLKQPLN 217
Cdd:cd09932  72 SLVELVSYYEKHPLYRK----IKLRYPVN 96
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 110-197 2.38e-14

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: 68.17  E-value: 2.38e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 110 ERWFHGHLSGKEAEKLLTEKGK-HGSFLVRESQSHPGDFVLSVRTgddkgesndgKSKVTHVMIRCQ--ELKYDVGGGER 186
Cdd:cd10347   1 LRWYHGKISREVAEALLLREGGrDGLFLVRESTSAPGDYVLSLLA----------QGEVLHYQIRRHgeDAFFSDDGPLI 70

                        90
                ....*....|.
gi 18375644 187 FDSLTDLVEHY 197
Cdd:cd10347  71 FHGLDTLIEHY 81
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
414-460 2.44e-14

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 68.92  E-value: 2.44e-14
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 18375644    414 TVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMDAGPVVVHCR 460
Cdd:smart00404   1 TVKHYHYTGWPDHGVPESPDSILELLRAVKKNLNQSESSGPVVVHCS 47
PTPc_DSPc smart00012
Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine ...
 414-460 2.44e-14

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: 68.92  E-value: 2.44e-14
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 18375644    414 TVWQYHFRTWPDHGVPSDPGGVLDFLEEVHHKQESIMDAGPVVVHCR 460
Cdd:smart00012   1 TVKHYHYTGWPDHGVPESPDSILELLRAVKKNLNQSESSGPVVVHCS 47
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
 112-216 2.77e-14

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: 68.52  E-value: 2.77e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTgddkgesnDGKSKvtHVMIRCQELKYDVgGGERFDSLT 191
Cdd:cd10409   3 WYYGNVTRHQAECALNERGVEGDFLIRDSESSPSDFSVSLKA--------VGKNK--HFKVQLVDNVYCI-GQRRFNSMD 71

                        90       100
                ....*....|....*....|....*.
gi 18375644 192 DLVEHYKKNPMVET-LGTVLQLKQPL 216
Cdd:cd10409  72 ELVEHYKKAPIFTSeHGEKLYLVKAL 97
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 5-103 3.21e-14

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: 68.57  E-value: 3.21e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   5 RWFHPNITGVEAENLLLTRGV-DGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQ-NTGDYYDLYGGEKFATLAELVQYYM 82
Cdd:cd09938   2 PFFYGSITREEAEEYLKLAGMsDGLFLLRQSLRSLGGYVLSVCHGRKFHHYTIErQLNGTYAIAGGKAHCGPAELCEYHS 81

                        90       100
                ....*....|....*....|.
gi 18375644  83 ehhgqlKEKNGDVIELKYPLN 103
Cdd:cd09938  82 ------TDLDGLVCLLRKPCN 96
SH2_Nck_family cd09943
Src homology 2 (SH2) domain found in the Nck family; Nck proteins are adaptors that modulate ...
 112-202 7.77e-14

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: 67.15  E-value: 7.77e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTGddkgesndGKSKvtHVMIRCQELKYDVgGGERFDSLT 191
Cdd:cd09943   3 WYYGRITRHQAETLLNEHGHEGDFLIRDSESNPGDYSVSLKAP--------GRNK--HFKVQVVDNVYCI-GQRKFHTMD 71

                        90
                ....*....|.
gi 18375644 192 DLVEHYKKNPM 202
Cdd:cd09943  72 ELVEHYKKAPI 82
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
 108-200 7.94e-14

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: 66.78  E-value: 7.94e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 108 TSERWFHGHLSGKEAEKLLTekgKHGSFLVRESQSHPGD---FVLSVRTgddkgesndgKSKVTHVMIRCQELKYDVGGG 184
Cdd:cd10361   4 ENEPYYHGLLPREDAEELLK---NDGDFLVRKTEPKGGGkrkLVLSVRW----------DGKIRHFVINRDDGGKYYIEG 70

                        90
                ....*....|....*.
gi 18375644 185 ERFDSLTDLVEHYKKN 200
Cdd:cd10361  71 KSFKSISELINYYQKT 86
SH2_Src_Src42 cd10370
Src homology 2 (SH2) domain found in the Src oncogene at 42A (Src42); Src42 is a member of the ...
 109-201 8.06e-14

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: 67.14  E-value: 8.06e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEK-LLTEKGKHGSFLVRESQSHPGDFVLSVRTGDdkgesndgksKVTHVMIRcqelKYDVGG---G 184
Cdd:cd10370   2 AEPWYFGKIKRIEAEKkLLLPENEHGAFLIRDSESRHNDYSLSVRDGD----------TVKHYRIR----QLDEGGffiA 67

                        90
                ....*....|....*....
gi 18375644 185 ER--FDSLTDLVEHYKKNP 201
Cdd:cd10370  68 RRttFRTLQELVEHYSKDS 86
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
 1-81 1.04e-13

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: 66.73  E-value: 1.04e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   1 MTSRRWFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDlYGGEKFATLAELVQY 80
Cdd:cd10355   3 LQSLGWYHGNLTRHAAEALLLSNGVDGSYLLRNSNEGTGLFSLSVRAKDSVKHFHVEYTGYSFK-FGFNEFSSLQDFVKH 81


                .
gi 18375644  81 Y 81
Cdd:cd10355  82 F 82
SH2_Nterm_RasGAP cd10353
N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 90-197 2.27e-13

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: 66.01  E-value: 2.27e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  90 EKNGDVIELKYPlncadPTSErWFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRtgddkgesndGKSKVTH 169
Cdd:cd10353   5 EEEEVAIPLTAP-----PTNQ-WYHGRLDRTIAEERLRQAGKLGSYLIRESDRRPGSFVLSFL----------SRTGVNH 68

                        90       100
                ....*....|....*....|....*...
gi 18375644 170 VMIRCQELKYDVgGGERFDSLTDLVEHY 197
Cdd:cd10353  69 FRIIAMCGDYYI-GGRRFSSLSDLIGYY 95
SH2_Nck2 cd10409
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
 6-81 2.64e-13

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: 65.83  E-value: 2.64e-13
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18375644   6 WFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLyGGEKFATLAELVQYY 81
Cdd:cd10409   3 WYYGNVTRHQAECALNERGVEGDFLIRDSESSPSDFSVSLKAVGKNKHFKVQLVDNVYCI-GQRRFNSMDELVEHY 77
SH2_N-SH2_PLC_gamma_like cd10341
N-terminal Src homology 2 (N-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 6-85 5.09e-13

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: 64.68  E-value: 5.09e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITG--VEAENLLL--TRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGD-----YYdLYGGEKFATLAE 76
Cdd:cd10341   6 WFHGKLGDgrDEAEKLLLeyCEGGDGTFLVRESETFVGDYTLSFWRNGKVQHCRIRSRQEngekkYY-LTDNLVFDSLYE 84


                ....*....
gi 18375644  77 LVQYYMEHH 85
Cdd:cd10341  85 LIDYYRQNP 93
SH2_Nterm_shark_like cd10347
N-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 5-81 7.13e-13

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: 63.94  E-value: 7.13e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   5 RWFHPNITGVEAENLLLTRGV-DGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGD--YYDLYGGEKFATLAELVQYY 81
Cdd:cd10347   2 RWYHGKISREVAEALLLREGGrDGLFLVRESTSAPGDYVLSLLAQGEVLHYQIRRHGEdaFFSDDGPLIFHGLDTLIEHY 81
R-PTPc-U-2 cd14637
PTP domain of receptor-type tyrosine-protein phosphatase U, repeat 2; Receptor-type ...
 304-459 9.62e-13

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: 67.24  E-value: 9.62e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINAnIIMPEFETKCNnskpkksYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKS-KCVKYWPDEyALKEYGV 382
Cdd:cd14637   1 YINA-ALTDSYTRSAA-------FIVTLHPLQNTTTDFWRLVYDYGCTSVVMLNQLNQSNSAwPCLQYWPEP-GLQQYGP 71

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644 383 MRVRNVKESAAHDYTLRELKLSKVGQGNTER-TVWQYHFRTW-PDHGVPSDPGGVLDFLEEVHHKQESIMDaGPVVVHC 459
Cdd:cd14637  72 MEVEFVSGSADEDIVTRLFRVQNITRLQEGHlMVRHFQFLRWsAYRDTPDSKKAFLHLLASVEKWQRESGE-GRTVVHC 149
SH2_csk_like cd09937
Src homology 2 (SH2) domain found in Carboxyl-Terminal Src Kinase (Csk); Both the C-terminal ...
 5-81 1.99e-12

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: 63.08  E-value: 1.99e-12
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18375644   5 RWFHPNITGVEAENLLLTRGvDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEKFATLAELVQYY 81
Cdd:cd09937   4 PWFHGKISREEAERLLQPPE-DGLFLVRESTNYPGDYTLCVSFEGKVEHYRVIYRNGKLTIDEEEYFENLIQLVEHY 79
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
 110-199 2.11e-12

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: 63.12  E-value: 2.11e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 110 ERWFHGHLSGKEAEK-LLTEKGKHGSFLVRESQSHPGDFVLSVRTGDDKGESndgkskVTHVMIRC-QELKYDVGGGERF 187
Cdd:cd10371   3 EKWFFRTISRKDAERqLLAPMNKAGSFLIRESESNKGAFSLSVKDVTTQGEV------VKHYKIRSlDNGGYYISPRITF 76

                        90
                ....*....|..
gi 18375644 188 DSLTDLVEHYKK 199
Cdd:cd10371  77 PTLQALVQHYSK 88
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
 109-197 2.98e-12

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: 62.58  E-value: 2.98e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEK-LLTEKGKHGSFLVRESQSHPGDFVLSVRTGDdkgeSNDGKSkVTHVMIRcqelKYDVGG---G 184
Cdd:cd10362   2 PEPWFFKNLSRNDAERqLLAPGNTHGSFLIRESETTAGSFSLSVRDFD----QNQGEV-VKHYKIR----NLDNGGfyiS 72

                        90
                ....*....|....*
gi 18375644 185 ER--FDSLTDLVEHY 197
Cdd:cd10362  73 PRitFPGLHELVRHY 87
SH2_Nck1 cd10408
Src homology 2 (SH2) domain found in Nck; Nck proteins are adaptors that modulate actin ...
 6-81 3.35e-12

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: 62.36  E-value: 3.35e-12
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18375644   6 WFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLyGGEKFATLAELVQYY 81
Cdd:cd10408   3 WYYGKVTRHQAEMALNERGNEGDFLIRDSESSPNDFSVSLKAQGKNKHFKVQLKECVYCI-GQRKFSSMEELVEHY 77
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 3-88 4.72e-12

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: 62.44  E-value: 4.72e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLTRG-VDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGD----YYDLYGGE-KFATLAE 76
Cdd:cd09944   4 SQPWFHGGISRDEAARLIRQQGlVDGVFLVRESQSNPGAFVLSLKHGQKIKHYQIIPIEDegqwYFTLDDGVtKFYDLLQ 83

                        90
                ....*....|..
gi 18375644  77 LVQYYMEHHGQL 88
Cdd:cd09944  84 LVEFYQLNAGSL 95
SH2_Grb7_family cd09944
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 109-200 9.99e-12

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: 61.28  E-value: 9.99e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEKLLTEKG-KHGSFLVRESQSHPGDFVLSVRTGDdkgesndgksKVTHVMIRCQElkyDVG----- 182
Cdd:cd09944   4 SQPWFHGGISRDEAARLIRQQGlVDGVFLVRESQSNPGAFVLSLKHGQ----------KIKHYQIIPIE---DEGqwyft 70

                        90       100
                ....*....|....*....|.
gi 18375644 183 ---GGERFDSLTDLVEHYKKN 200
Cdd:cd09944  71 lddGVTKFYDLLQLVEFYQLN 91
SH2_DAPP1_BAM32_like cd10355
Src homology 2 domain found in dual adaptor for phosphotyrosine and 3-phosphoinositides ( ...
 112-203 1.01e-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: 1.01e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRtgddkgesndGKSKVTHVMIRCQELKYDVGGGErFDSLT 191
Cdd:cd10355   8 WYHGNLTRHAAEALLLSNGVDGSYLLRNSNEGTGLFSLSVR----------AKDSVKHFHVEYTGYSFKFGFNE-FSSLQ 76

                        90
                ....*....|..
gi 18375644 192 DLVEHYKKNPMV 203
Cdd:cd10355  77 DFVKHFANQPLI 88
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
 109-199 1.40e-11

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: 61.13  E-value: 1.40e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEK-LLTEKGKHGSFLVRESQSHPGDFVLSVRTGDdkGESNDgksKVTHVMIRcqelKYDVGG---- 183
Cdd:cd10363   2 TEEWFFKGISRKDAERqLLAPGNMLGSFMIRDSETTKGSYSLSVRDYD--PQHGD---TVKHYKIR----TLDNGGfyis 72

                        90
                ....*....|....*..
gi 18375644 184 -GERFDSLTDLVEHYKK 199
Cdd:cd10363  73 pRSTFSTLQELVDHYKK 89
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
 6-102 1.75e-11

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: 60.53  E-value: 1.75e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSV-RRNGAVTHIKIQNTGDYYDLYGGE-----KFATLAELVQ 79
Cdd:cd10343   5 WYHGNITRSKAEELLSKAGKDGSFLVRDSESVSGAYALCVlYQNCVHTYRILPNAEDKLSVQASEgvpvrFFTTLPELIE 84

                        90       100
                ....*....|....*....|...
gi 18375644  80 YYmehhgqLKEKNGDVIELKYPL 102
Cdd:cd10343  85 FY------QKENMGLVTHLLYPV 101
R-PTPc-T-2 cd14634
PTP domain of receptor-type tyrosine-protein phosphatase T, repeat 2; Receptor-type ...
 304-459 2.08e-11

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: 63.12  E-value: 2.08e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTkEVERGKSkCVKYWPDEYALKeYGVM 383
Cdd:cd14634   1 YINAALM--------DSHKQPAAFIVTQHPLPNTVADFWRLVFDYNCSSVVMLN-EMDAAQL-CMQYWPEKTSCC-YGPI 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 384 RVRNVKESAAHDYTLRELKLSKVGQ-GNTERTVWQYHFRTWPDH-GVPSDPGGVLDFLEEVHHKQESiMDA--GPVVVHC 459
Cdd:cd14634  70 QVEFVSADIDEDIISRIFRICNMARpQDGYRIVQHLQYIGWPAYrDTPPSKRSILKVVRRLEKWQEQ-YDGreGRTVVHC 148
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 ...
 109-197 2.50e-11

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: 60.02  E-value: 2.50e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEK-LLTEKGKHGSFLVRESQSHPGDFVLSVRTGDD-KGEsndgksKVTHVMIRcqelKYDVGG--- 183
Cdd:cd10418   2 AEEWYFGKLGRKDAERqLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDmKGD------HVKHYKIR----KLDNGGyyi 71

                        90
                ....*....|....*.
gi 18375644 184 --GERFDSLTDLVEHY 197
Cdd:cd10418  72 ttRAQFETLQQLVQHY 87
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 3.08e-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: 59.83  E-value: 3.08e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAEN-LLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQ--NTGDYYdLYGGEKFATLAELVQ 79
Cdd:cd10370   2 AEPWYFGKIKRIEAEKkLLLPENEHGAFLIRDSESRHNDYSLSVRDGDTVKHYRIRqlDEGGFF-IARRTTFRTLQELVE 80

                        90       100
                ....*....|....*....|..
gi 18375644  80 YYMehhgqlKEKNGDVIELKYP 101
Cdd:cd10370  81 HYS------KDSDGLCVNLRKP 96
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
 5-90 3.39e-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: 59.61  E-value: 3.39e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   5 RWFHPNITGVEAENLLLTRgVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKI-QNTGDYYDLYGGEKFATLAELVQYYME 83
Cdd:cd09940   6 LWFVGEMERDTAENRLENR-PDGTYLVRVRPQGETQYALSIKYNGDVKHMKIeQRSDGLYYLSESRHFKSLVELVNYYER 84


                ....*..
gi 18375644  84 HhgQLKE 90
Cdd:cd09940  85 N--SLGE 89
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
 6-101 5.70e-11

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: 59.31  E-value: 5.70e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRgVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEKFATLAELVQYYMEHh 85
Cdd:cd10406   7 WFAGNMERQQTDNLLKSH-ASGTYLIRERPAEAERFAISIKFNDEVKHIKVVEKDNWIHITEAKKFESLLELVEYYQCH- 84

                        90
                ....*....|....*...
gi 18375644  86 gQLKE--KNGDVIeLKYP 101
Cdd:cd10406  85 -SLKEsfKQLDTT-LKYP 100
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
 112-198 6.48e-11

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: 59.02  E-value: 6.48e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLtEKGKHGSFLVRESQSHPGDFVLSVRtgddkgESndgkSKVTHVMI------RCQELKYDVGGGE 185
Cdd:cd09926   9 WYFGPMSRQEAQELL-QGQRHGVFLVRDSSTIPGDYVLSVS------EN----SRVSHYIInslgqpAPNQSRYRIGDQE 77

                        90
                ....*....|...
gi 18375644 186 rFDSLTDLVEHYK 198
Cdd:cd09926  78 -FDDLPALLEFYK 89
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, ...
 112-202 6.84e-11

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: 58.59  E-value: 6.84e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKgKHGSFLVRESQSHPGDFVLSVRtgddkgeSNDGkskVTHVMI-RCQELKYDVGGGER-FDS 189
Cdd:cd09945   3 WYHGAITRIEAESLLRPC-KEGSYLVRNSESTKQDYSLSLK-------SAKG---FMHMRIqRNETGQYILGQFSRpFET 71

                        90
                ....*....|...
gi 18375644 190 LTDLVEHYKKNPM 202
Cdd:cd09945  72 IPEMIRHYCLNKL 84
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
 109-197 7.23e-11

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: 58.76  E-value: 7.23e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEK-LLTEKGKHGSFLVRESQSHPGDFVLSVRTGDD-KGEsndgksKVTHVMIRcqelKYDVGG--- 183
Cdd:cd10367   2 AEEWYFGKIGRKDAERqLLSPGNPRGAFLIRESETTKGAYSLSIRDWDQnRGD------HVKHYKIR----KLDTGGyyi 71

                        90
                ....*....|....*.
gi 18375644 184 --GERFDSLTDLVEHY 197
Cdd:cd10367  72 ttRAQFDTVQELVQHY 87
SH2_Grb14 cd10414
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ...
 3-88 7.69e-11

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: 58.79  E-value: 7.69e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLTRG-VDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLY-----GGEKFATLAE 76
Cdd:cd10414   4 SQPWFHHKISRDEAQRLIIQQGlVDGVFLVRDSQSNPRTFVLSMSHGQKIKHFQIIPVEDDGELFhtlddGHTRFTDLIQ 83

                        90
                ....*....|..
gi 18375644  77 LVQYYMEHHGQL 88
Cdd:cd10414  84 LVEFYQLNKGVL 95
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
 110-215 9.19e-11

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: 58.51  E-value: 9.19e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 110 ERWFHGHLSGKEAEKLLTEKgkhGSFLVRESQSHPGDFVLsvrTGDDKGESN-----DGKSKV-THVMIrcqelkydvgg 183
Cdd:cd09925   7 EPWYHGKMSRRDAESLLQTD---GDFLVRESTTTPGQYVL---TGMQNGQPKhlllvDPEGVVrTKDRV----------- 69

                        90       100       110
                ....*....|....*....|....*....|...
gi 18375644 184 gerFDSLTDLVEHYKKNPM-VETLGTVLQLKQP 215
Cdd:cd09925  70 ---FESISHLINYHVTNGLpIISEGSELHLRRP 99
SH2_BLNK_SLP-76 cd09929
Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing ...
 112-203 1.25e-10

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: 58.86  E-value: 1.25e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESQ----SHPgdFVLSVRTgddkgesndgKSKVTHVMIRCQELK--YDVG--- 182
Cdd:cd09929  13 WYAGNIDRKEAEEALRRSNKDGTFLVRDSSgkdsSQP--YTLMVLY----------NDKVYNIQIRFLENTrqYALGtgl 80

                        90       100
                ....*....|....*....|..
gi 18375644 183 -GGERFDSLTDLVEHYKKNPMV 203
Cdd:cd09929  81 rGEETFSSVAEIIEHHQKTPLL 102
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
 112-215 1.54e-10

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: 57.80  E-value: 1.54e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESqSHPGDFVLSVRTGddkgesNDGKSKVTHVMIRCQ-ELKYDVGGGERFDSL 190
Cdd:cd09934   8 WYVGDMSRQRAESLLKQEDKEGCFVVRNS-STKGLYTVSLFTK------VPGSPHVKHYHIKQNaRSEFYLAEKHCFETI 80

                        90       100
                ....*....|....*....|....*
gi 18375644 191 TDLVEHYKKNPMvetlGTVLQLKQP 215
Cdd:cd09934  81 PELINYHQHNSG----GLATRLKYP 101
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
 6-81 1.73e-10

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: 56.89  E-value: 1.73e-10
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644   6 WFHPNITGVEAENLLLT-RGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKI--QNTGDYYdLYGGEKFATLAELVQYY 81
Cdd:cd10360   2 WYFSGISRTQAQQLLLSpPNEPGAFLIRPSESSLGGYSLSVRAQAKVCHYRIcmAPSGSLY-LQKGRLFPGLEELLAYY 79
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
 109-197 1.79e-10

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: 57.73  E-value: 1.79e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEK-LLTEKGKHGSFLVRESQSHPGDFVLSVRTGDD-KGEsndgksKVTHVMIRcqelKYDVGG--- 183
Cdd:cd10368   2 AEEWYFGKLGRKDAERqLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDmKGD------HVKHYKIR----KLDNGGyyi 71

                        90
                ....*....|....*.
gi 18375644 184 --GERFDSLTDLVEHY 197
Cdd:cd10368  72 ttRAQFETLQQLVQHY 87
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
 6-96 1.83e-10

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: 58.50  E-value: 1.83e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTrgvDGSFLARPSKSNPGDFTLSVRRNGAVTHIKI----QNTGDYYD----LYGGEKFATLAEL 77
Cdd:cd10337   8 WYHGRIPRQVAESLVQR---EGDFLVRDSLSSPGDYVLTCRWKGQPLHFKInrvvLRPSEAYTrvqyQFEDEQFDSIPAL 84

                        90
                ....*....|....*....
gi 18375644  78 VQYYMEHHGQLKEKNGDVI 96
Cdd:cd10337  85 VHFYVGNRRPISQASGAII 103
SH2_SH2B_family cd10346
Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein ...
 112-202 1.84e-10

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: 57.43  E-value: 1.84e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKG--KHGSFLVRESQSHPGDFVLSVRTgddkgesnDGKSKvtHVMI--------RCQELkydv 181
Cdd:cd10346  10 WFHGTLSRSDAAQLVLHSGadGHGVFLVRQSETRRGEFVLTFNF--------QGRAK--HLRLtlnekgqcRVQHL---- 75

                        90       100
                ....*....|....*....|.
gi 18375644 182 gggeRFDSLTDLVEHYKKNPM 202
Cdd:cd10346  76 ----WFPSIFDMLEHFRQNPI 92
SH2_BCAR3 cd10337
Src homology 2 (SH2) domain in the Breast Cancer Anti-estrogen Resistance protein 3; BCAR3 is ...
 109-219 1.98e-10

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: 58.50  E-value: 1.98e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEKLLtekGKHGSFLVRESQSHPGDFVLSVRTgddkgesndgKSKVTHVMIRCQELKYDVG------ 182
Cdd:cd10337   5 SHAWYHGRIPRQVAESLV---QREGDFLVRDSLSSPGDYVLTCRW----------KGQPLHFKINRVVLRPSEAytrvqy 71

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 18375644 183 --GGERFDSLTDLVEHYKKN--PMVETLGTVLQlkQPLNTT 219
Cdd:cd10337  72 qfEDEQFDSIPALVHFYVGNrrPISQASGAIIS--RPVNRT 110
R-PTPc-K-2 cd14636
PTP domain of receptor-type tyrosine-protein phosphatase K, repeat 2; Receptor-type ...
 304-459 2.21e-10

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: 60.04  E-value: 2.21e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTkEVERGKSkCVKYWPDEYALKeYGVM 383
Cdd:cd14636   1 YINAALM--------DSYRQPAAFIVTQHPLPNTVKDFWRLVYDYGCTSIVMLN-EVDLAQG-CPQYWPEEGMLR-YGPI 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 384 RVRNVKESAAHDYTLRELK---LSKVGQGNTerTVWQYHFRTWPDH-GVPSDPGGVLDFLEEVHHKQESIMDA-GPVVVH 458
Cdd:cd14636  70 QVECMSCSMDCDVISRIFRicnLTRPQEGYL--MVQQFQYLGWASHrEVPGSKRSFLKLILQVEKWQEECDEGeGRTIIH 147


                .
gi 18375644 459 C 459
Cdd:cd14636 148 C 148
SH2_Tec_family cd09934
Src homology 2 (SH2) domain found in Tec-like proteins; The Tec protein tyrosine kinase is the ...
 6-101 3.77e-10

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: 57.02  E-value: 3.77e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRGVDGSFLARPSkSNPGDFTLSV----RRNGAVTH--IKIQNTGDYYDlygGEK--FATLAEL 77
Cdd:cd09934   8 WYVGDMSRQRAESLLKQEDKEGCFVVRNS-STKGLYTVSLftkvPGSPHVKHyhIKQNARSEFYL---AEKhcFETIPEL 83

                        90       100
                ....*....|....*....|....
gi 18375644  78 VQYYMEHHGQLkekngdVIELKYP 101
Cdd:cd09934  84 INYHQHNSGGL------ATRLKYP 101
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 6-82 4.49e-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: 55.89  E-value: 4.49e-10
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644   6 WFHPNITGVEAENLLLTRG-VDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGD-YYDLYGGEKFATLAELVQYYM 82
Cdd:cd10348   2 WLHGALDRNEAVEILKQKAdADGSFLVRYSRRRPGGYVLTLVYENHVYHFEIQNRDDkWFYIDDGPYFESLEHLIEHYT 80
SH2_Grb14 cd10414
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 14 (Grb14) ...
 109-200 6.04e-10

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: 56.48  E-value: 6.04e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEKLLTEKGK-HGSFLVRESQSHPGDFVLSVRTGddkgesndgkSKVTHVMI----RCQELKYDVGG 183
Cdd:cd10414   4 SQPWFHHKISRDEAQRLIIQQGLvDGVFLVRDSQSNPRTFVLSMSHG----------QKIKHFQIipveDDGELFHTLDD 73

                        90
                ....*....|....*...
gi 18375644 184 GE-RFDSLTDLVEHYKKN 200
Cdd:cd10414  74 GHtRFTDLIQLVEFYQLN 91
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 4-103 7.68e-10

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: 55.88  E-value: 7.68e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   4 RRWFHPNITGVEAENLLLTRGvDGSFLARPSkSNPGDFTLSVRRNGAVTHIKIQNT------GDYYDLYGgekfaTLAEL 77
Cdd:cd09930   6 RTWLVGDINRTQAEELLRGKP-DGTFLIRES-STQGCYACSVVCNGEVKHCVIYKTetgygfAEPYNLYE-----SLKEL 78

                        90       100
                ....*....|....*....|....*..
gi 18375644  78 VQYYmeHHGQLKEKNGDV-IELKYPLN 103
Cdd:cd09930  79 VLHY--AHNSLEQHNDSLtVTLAYPVL 103
SH2_Cterm_shark_like cd10348
C-terminal Src homology 2 (SH2) domain found in SH2 domains, ANK, and kinase domain (shark) ...
 112-197 8.80e-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: 55.12  E-value: 8.80e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGK-HGSFLVRESQSHPGDFVLSVRTGDdkgesndgksKVTHVMIRCQELK-YDVGGGERFDS 189
Cdd:cd10348   2 WLHGALDRNEAVEILKQKADaDGSFLVRYSRRRPGGYVLTLVYEN----------HVYHFEIQNRDDKwFYIDDGPYFES 71


                ....*...
gi 18375644 190 LTDLVEHY 197
Cdd:cd10348  72 LEHLIEHY 79
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
 109-200 1.35e-09

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: 55.06  E-value: 1.35e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEKLLTE-KGKHGSFLVRESQSHPGDFVLSVRTGDDKGESNdgkskVTHVMIRcqelKYDVGG---- 183
Cdd:cd10365   2 AEEWYFGKITRRESERLLLNaENPRGTFLVRESETTKGAYCLSVSDFDNAKGLN-----VKHYKIR----KLDSGGfyit 72

                        90
                ....*....|....*...
gi 18375644 184 -GERFDSLTDLVEHYKKN 200
Cdd:cd10365  73 sRTQFNSLQQLVAYYSKH 90
PHA02740 PHA02740
protein tyrosine phosphatase; Provisional
 324-459 1.56e-09

protein tyrosine phosphatase; Provisional


Pssm-ID: 165107 [Multi-domain]  Cd Length: 298  Bit Score: 58.82  E-value: 1.56e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644  324 KKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVErgKSKCVKYWP-DEYALKEYGVMRVRNVKESAAHDYTLRELK 402
Cdd:PHA02740  90 EQKFICIINLCEDACDKFLQALSDNKVQIIVLISRHAD--KKCFNQFWSlKEGCVITSDKFQIETLEIIIKPHFNLTLLS 167

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18375644  403 LS-KVGQgntERTVWQYHFRTWPDHGVPSDPGGVLDFLEEVH------HKQESIMDAGPVVVHC 459
Cdd:PHA02740 168 LTdKFGQ---AQKISHFQYTAWPADGFSHDPDAFIDFFCNIDdlcadlEKHKADGKIAPIIIDC 228
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
 109-199 1.57e-09

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: 54.99  E-value: 1.57e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEK-LLTEKGKHGSFLVRESQSHPGDFVLSVRTGDDKgesndGKSKVTHVMIRcqelKYDVGG---G 184
Cdd:cd10364   2 TEEWFFKDITRKDAERqLLAPGNSAGAFLIRESETLKGSYSLSVRDYDPQ-----HGDVIKHYKIR----SLDNGGyyiS 72

                        90
                ....*....|....*..
gi 18375644 185 ER--FDSLTDLVEHYKK 199
Cdd:cd10364  73 PRitFPCISDMIKHYQK 89
R-PTPc-M-2 cd14635
PTP domain of receptor-type tyrosine-protein phosphatase M, repeat 2; Receptor-type ...
 304-459 1.84e-09

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: 57.39  E-value: 1.84e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIImpefetkcNNSKPKKSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTkEVERGKsKCVKYWPdEYALKEYGVM 383
Cdd:cd14635   1 YINAALM--------DSYKQPSAFIVTQHPLPNTVKDFWRLVLDYHCTSIVMLN-DVDPAQ-LCPQYWP-ENGVHRHGPI 69

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644 384 RVRNVKESAAHDYTLRELKLSKVGQ-GNTERTVWQYHFRTWPDH-GVPSDPGGVLDFLEEVHHKQESIMDA-GPVVVHC 459
Cdd:cd14635  70 QVEFVSADLEEDIISRIFRIYNAARpQDGYRMVQQFQFLGWPMYrDTPVSKRSFLKLIRQVDKWQEEYNGGeGRTVVHC 148
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
 111-208 1.88e-09

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: 54.90  E-value: 1.88e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 111 RWFHGHLSGKEAEKLLTEKGKhGSFLVRESQSHPGdFVLSVRtgddkgesndGKSKVTHVMI-RCQELKYDVGG-GERFD 188
Cdd:cd10417   8 PWFHGFITRKQTEQLLRDKAL-GSFLIRLSDRATG-YILSYR----------GSDRCRHFVInQLRNRRYLISGdTSSHS 75

                        90       100
                ....*....|....*....|...
gi 18375644 189 SLTDLVEHYKK---NPMVETLGT 208
Cdd:cd10417  76 TLAELVRHYQEvqlEPFGETLTA 98
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
 109-200 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: 54.50  E-value: 1.97e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEK-LLTEKGKHGSFLVRESQSHPGDFVLSVRtgddkgesnDGKSkVTHVMI-RCQELKYDVGGGER 186
Cdd:cd10369   2 AEPWFFGAIKRADAEKqLLYSENQTGAFLIRESESQKGEFSLSVL---------DGGV-VKHYRIrRLDEGGFFLTRRKT 71

                        90
                ....*....|....
gi 18375644 187 FDSLTDLVEHYKKN 200
Cdd:cd10369  72 FSTLNEFVNYYTTT 85
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
 7-83 2.34e-09

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: 54.29  E-value: 2.34e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   7 FHPNITGVEAENLLLTRGvDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEK-FATLAELV-----QY 80
Cdd:cd10352   9 YHGLISREEAEQLLSGAS-DGSYLIRESSRDDGYYTLSLRFNGKVKNYKLYYDGKNHYHYVGEKrFDTIHDLVadgliTL 87


                ...
gi 18375644  81 YME 83
Cdd:cd10352  88 YME 90
SH2_Src_Lck cd10362
Src homology 2 (SH2) domain in lymphocyte cell kinase (Lck); Lck is a member of the Src ...
 6-81 2.35e-09

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: 54.49  E-value: 2.35e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRG-VDGSFLARPSKSNPGDFTLSVR-----RNGAVTHIKIQN--TGDYYdLYGGEKFATLAEL 77
Cdd:cd10362   5 WFFKNLSRNDAERQLLAPGnTHGSFLIRESETTAGSFSLSVRdfdqnQGEVVKHYKIRNldNGGFY-ISPRITFPGLHEL 83


                ....
gi 18375644  78 VQYY 81
Cdd:cd10362  84 VRHY 87
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
 110-218 4.58e-09

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: 53.80  E-value: 4.58e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 110 ERWFHGHLSGKEAEKLLTEKGKHGSFLVRESqSHPGDFVLSVRTGDDkgesNDGKSKVTHVMIRCQ-ELKYDVGGGERFD 188
Cdd:cd10399   6 YDWFAGNISRSQSEQLLRQKGKEGAFMVRNS-SQVGMYTVSLFSKAV----NDKKGTVKHYHVHTNaENKLYLAENYCFD 80

                        90       100       110
                ....*....|....*....|....*....|
gi 18375644 189 SLTDLVEHYKKNpmveTLGTVLQLKQPLNT 218
Cdd:cd10399  81 SIPKLIHYHQHN----SAGMITRLRHPVST 106
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, ...
 6-81 4.83e-09

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: 53.59  E-value: 4.83e-09
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18375644   6 WFHPNITGVEAENLLlTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNT--GDYYDLYGGEKFATLAELVQYY 81
Cdd:cd09945   3 WYHGAITRIEAESLL-RPCKEGSYLVRNSESTKQDYSLSLKSAKGFMHMRIQRNetGQYILGQFSRPFETIPEMIRHY 79
SH2_SHIP cd10343
Src homology 2 (SH2) domain found in SH2-containing inositol-5'-phosphatase (SHIP) and ...
 112-216 4.86e-09

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: 53.60  E-value: 4.86e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSVRTgddkgesndGKSKVTHVMIRCQELKYDVGGGE-----R 186
Cdd:cd10343   5 WYHGNITRSKAEELLSKAGKDGSFLVRDSESVSGAYALCVLY---------QNCVHTYRILPNAEDKLSVQASEgvpvrF 75

                        90       100       110
                ....*....|....*....|....*....|
gi 18375644 187 FDSLTDLVEHYKKnpmvETLGTVLQLKQPL 216
Cdd:cd10343  76 FTTLPELIEFYQK----ENMGLVTHLLYPV 101
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
 101-197 4.95e-09

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: 53.65  E-value: 4.95e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 101 PLNCADPTSERWFHGHLSGKEAEKLLTEKG-KHGSFLVRESQSHPGDFVLSVRTgddkgESNDGKSKVTHVMI-RCQELK 178
Cdd:cd10344   1 PSNYVAKVYHGWLFEGLSREKAEELLMLPGnQVGSFLIRESETRRGCYSLSVRH-----RGSQSRDSVKHYRIfRLDNGW 75

                        90
                ....*....|....*....
gi 18375644 179 YDVGGGERFDSLTDLVEHY 197
Cdd:cd10344  76 FYISPRLTFQCLEDMVNHY 94
SH2_SH2D2A_SH2D7 cd10349
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ...
 111-197 6.41e-09

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: 52.53  E-value: 6.41e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 111 RWFHGHLSGKEAEKLLTEKGKhGSFLVRESQSHPGdFVLSVRtgddkgesndGKSKVTHVMI-RCQELKYDVGGGE-RFD 188
Cdd:cd10349   1 AWFHGFITRREAERLLEPKPQ-GCYLVRFSESAVT-FVLSYR----------SRTCCRHFLLaQLRDGRHVVLGEDsAHA 68


                ....*....
gi 18375644 189 SLTDLVEHY 197
Cdd:cd10349  69 RLQDLLLHY 77
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
 2-90 6.49e-09

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: 53.47  E-value: 6.49e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   2 TSRRWFHPNITGVEAENLLLTRgVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEKFATLAELVQYY 81
Cdd:cd10407   3 SCQPWYAGAMERLQAETELINR-VNSTYLVRHRTKESGEYAISIKYNNEVKHIKILTRDGFFHIAENRKFKSLMELVEYY 81


                ....*....
gi 18375644  82 mEHHgQLKE 90
Cdd:cd10407  82 -KHH-SLKE 88
SH2_Nterm_RasGAP cd10353
N-terminal Src homology 2 (SH2) domain found in Ras GTPase-activating protein 1 (GAP); RasGAP ...
 5-81 6.90e-09

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: 53.30  E-value: 6.90e-09
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18375644   5 RWFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNT-GDYYdlYGGEKFATLAELVQYY 81
Cdd:cd10353  20 QWYHGRLDRTIAEERLRQAGKLGSYLIRESDRRPGSFVLSFLSRTGVNHFRIIAMcGDYY--IGGRRFSSLSDLIGYY 95
SH2_Vav1 cd10405
Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the ...
 6-84 7.62e-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: 53.09  E-value: 7.62e-09
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644   6 WFHPNITGVEAENLLLTRGvDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEKFATLAELVQYYMEH 84
Cdd:cd10405   7 WYAGPMERAGAESILANRS-DGTYLVRQRVKDAAEFAISIKYNVEVKHIKIMTAEGLYRITEKKAFRGLTELVEFYQQN 84
SH2_SOCS3 cd10384
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 115-197 7.66e-09

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: 53.20  E-value: 7.66e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 115 GHLSGKEAEKLLTEKgKHGSFLVRESQSHPGDFVLSVRTgddkgesndgKSKVTHVMIRCQE----LKYDVGGGE---RF 187
Cdd:cd10384  15 STVSGKEANLLLSAE-PAGTFLIRDSSDQRHFFTLSVKT----------ESGTKNLRIQCEGgsfsLQTDPRSTQpvpRF 83

                        90
                ....*....|
gi 18375644 188 DSLTDLVEHY 197
Cdd:cd10384  84 DCVLKLVHHY 93
SH2_ShkA_ShkC cd10356
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC) ...
 3-78 8.52e-09

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: 53.38  E-value: 8.52e-09
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18375644   3 SRRWFHPNITGVEAENLLLTRGVdGSFLARPSKSNPGDFTLS-VRRNGAVTHIKIQNTGDYYDlYGGEKFATLAELV 78
Cdd:cd10356   9 ECAWFHGDISTSESENRLNGKPE-GTFLVRFSTSEPGAYTISkVSKNGGISHQRIHRPGGKFQ-VNNSKYLSVKELI 83
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 109-200 1.14e-08

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: 52.60  E-value: 1.14e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEKLLTEKGK-HGSFLVRESQSHPGDFVLSVRTgddkgesndgKSKVTHVMI-RCQE---LKYDVGG 183
Cdd:cd10413   4 TQPWFHGRISREESQRLIGQQGLvDGVFLVRESQRNPQGFVLSLCH----------LQKVKHYLIlPSEEegrLYFSMDD 73

                        90
                ....*....|....*...
gi 18375644 184 GE-RFDSLTDLVEHYKKN 200
Cdd:cd10413  74 GQtRFTDLLQLVEFHQLN 91
SH2_SH2D4B cd10351
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ...
 6-83 1.19e-08

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: 52.58  E-value: 1.19e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRgVDGSFLARPSKSNPGdFTLSVRRNGAVTHIKIQNTGDYYDLYGGE--KFATLAELVQYYME 83
Cdd:cd10351   9 WFHGIISREEAEALLMNA-TEGSFLVRVSEKIWG-YTLSYRLQSGFKHFLVDASGDFYSFLGVDpnRHATLTDLIDFHKE 86
R-PTP-Z-2 cd17669
catalytic domain of receptor-type tyrosine-protein phosphatase Z, repeat 2; Receptor-type ...
 304-458 1.30e-08

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: 55.00  E-value: 1.30e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIIMPEFETKcnnskpkkSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVkYWPDEYALKEYGVM 383
Cdd:cd17669   1 YINASYIMGYYQSN--------EFIITQHPLLHTIKDFWRMIWDHNAQLIVMLPDGQNMAEDEFV-YWPNKDEPINCETF 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 384 RVRNVKE-----SAAHDYTLRELKLSKVgQGNTERTVWQYHFRTWPDhgvPSDP-GGVLDFLEEVhhKQESIMDAGPVVV 457
Cdd:cd17669  72 KVTLIAEehkclSNEEKLIIQDFILEAT-QDDYVLEVRHFQCPKWPN---PDSPiSKTFELISII--KEEAANRDGPMIV 145


                .
gi 18375644 458 H 458
Cdd:cd17669 146 H 146
SH2_SHF cd10392
Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought ...
 6-102 1.36e-08

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: 52.38  E-value: 1.36e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLL-LTRgvDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEK--FATLAELVQYYM 82
Cdd:cd10392   3 WYHGAISRTDAENLLrLCK--EASYLVRNSETSKNDFSLSLKSSQGFMHMKLSRTKEHKYVLGQNSppFSSVPEIIHHYA 80

                        90       100
                ....*....|....*....|
gi 18375644  83 EHhgQLKEKNGDVIELKYPL 102
Cdd:cd10392  81 SR--KLPIKGAEHMSLLYPV 98
SH2_N-SH2_Zap70_Syk_like cd09938
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 111-217 1.50e-08

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: 52.40  E-value: 1.50e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 111 RWFHGHLSGKEAEKLLTEKG-KHGSFLVRESQSHPGDFVLSVRTGddkgesndgkSKVTHVMIRCQ-ELKYDVGGGERFD 188
Cdd:cd09938   2 PFFYGSITREEAEEYLKLAGmSDGLFLLRQSLRSLGGYVLSVCHG----------RKFHHYTIERQlNGTYAIAGGKAHC 71

                        90       100
                ....*....|....*....|....*....
gi 18375644 189 SLTDLVEHYKKNPMvetlGTVLQLKQPLN 217
Cdd:cd09938  72 GPAELCEYHSTDLD----GLVCLLRKPCN 96
SH2_SHD cd10390
Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression ...
 112-202 1.79e-08

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: 52.01  E-value: 1.79e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTeKGKHGSFLVRESQSHPGDFVLSVRtgddkgeSNDGKSKVTHVMIRCQELKYDVGGGErFDSLT 191
Cdd:cd10390   3 WFHGPLSRADAENLLS-LCKEGSYLVRLSETRPQDCSLSLR-------SSQGFLHLKFARTRENQVVLGQHSGP-FPSVP 73

                        90
                ....*....|.
gi 18375644 192 DLVEHYKKNPM 202
Cdd:cd10390  74 ELVLHYSSRPL 84
SH2_BLNK_SLP-76 cd09929
Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing ...
 1-84 2.57e-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: 51.93  E-value: 2.57e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   1 MTSRRWFHPNITGVEAENLLLTRGVDGSFLARPS----KSNPgdFTLSVRRNGAVTHIKI---QNTGDYY---DLYGGEK 70
Cdd:cd09929   8 LLPKEWYAGNIDRKEAEEALRRSNKDGTFLVRDSsgkdSSQP--YTLMVLYNDKVYNIQIrflENTRQYAlgtGLRGEET 85

                        90
                ....*....|....
gi 18375644  71 FATLAELVQYYMEH 84
Cdd:cd09929  86 FSSVAEIIEHHQKT 99
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 6-102 3.84e-08

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: 51.17  E-value: 3.84e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAeNLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEKFATLAELVQYYMEHh 85
Cdd:cd09942   9 WYWGDISREEV-NEKMRDTPDGTFLVRDASTMKGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFNSVVELINYYRNN- 86

                        90
                ....*....|....*...
gi 18375644  86 gQLKEKNGDV-IELKYPL 102
Cdd:cd09942  87 -SLAEYNRKLdVKLLYPV 103
SH2_SHD cd10390
Src homology 2 domain found in SH2 domain-containing adapter proteins D (SHD); The expression ...
 6-102 4.22e-08

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: 50.85  E-value: 4.22e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLlTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEK--FATLAELVQYYME 83
Cdd:cd10390   3 WFHGPLSRADAENLL-SLCKEGSYLVRLSETRPQDCSLSLRSSQGFLHLKFARTRENQVVLGQHSgpFPSVPELVLHYSS 81

                        90
                ....*....|....*....
gi 18375644  84 HhgQLKEKNGDVIELKYPL 102
Cdd:cd10390  82 R--PLPVQGAEHLALLYPV 98
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 6-80 4.29e-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: 51.08  E-value: 4.29e-08
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18375644   6 WFHPNITGVEAENLLLTRG-VDGSFLARPSKSNpGDFTLSVRRNGAVTHIKI-QNTGDYYDLYGGEKFATLAELVQY 80
Cdd:cd10402  12 WYHGSIARDEAERRLYSGAqPDGKFLLRERKES-GTYALSLVYGKTVYHYRIdQDKSGKYSIPEGTKFDTLWQLVEY 87
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
 6-104 4.44e-08

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: 50.99  E-value: 4.44e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRGVDGSFLARPSkSNPGDFTLSV------RRNGAVTHIKIQNT-GDYYDLYGGEKFATLAELV 78
Cdd:cd10397   8 WYSKNMTRSQAEQLLKQEGKEGGFIVRDS-SKAGKYTVSVfaksagDPQGVIRHYVVCSTpQSQYYLAEKHLFSTIPELI 86

                        90       100
                ....*....|....*....|....*.
gi 18375644  79 QYYmEHHGQlkeknGDVIELKYPLNC 104
Cdd:cd10397  87 NYH-QHNAA-----GLISRLKYPVSS 106
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 ...
 110-199 4.56e-08

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: 50.83  E-value: 4.56e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 110 ERWFHGHLSGKEAEK-LLTEKGKHGSFLVRESQSHPGDFVLSVRTGDD-KGEsndgksKVTHVMIRcqelKYDVGG---- 183
Cdd:cd10419   3 EEWYFGKLGRKDAERqLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDmKGD------HVKHYKIR----KLDNGGyyit 72

                        90
                ....*....|....*..
gi 18375644 184 -GERFDSLTDLVEHYKK 199
Cdd:cd10419  73 tRAQFETLQQLVQHYSE 89
R-PTP-G-2 cd17670
PTP-like domain of receptor-type tyrosine-protein phosphatase G, repeat 2; Receptor-type ...
 304-458 5.13e-08

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: 53.14  E-value: 5.13e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 304 YINANIIMPEFETKcnnskpkkSYIATQGCLQNTVNDFWRMVFQENSRVIVMTTKEVERGKSKCVkYWPDE--------- 374
Cdd:cd17670   1 YINASYIMGYYRSN--------EFIITQHPLPHTTKDFWRMIWDHNAQIIVMLPDNQGLAEDEFV-YWPSReesmnceaf 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 375 -YALKEYGVMRVRNVKESAAHDYTLRELKLSKVGQgntertVWQYHFRTWPDhgvPSDP-GGVLDFLEEVhhKQESIMDA 452
Cdd:cd17670  72 tVTLISKDRLCLSNEEQIIIHDFILEATQDDYVLE------VRHFQCPKWPN---PDAPiSSTFELINVI--KEEALTRD 140


                ....*.
gi 18375644 453 GPVVVH 458
Cdd:cd17670 141 GPTIVH 146
SH2_Vav1 cd10405
Src homology 2 (SH2) domain found in the Vav1 proteins; Proto-oncogene vav is a member of the ...
 112-212 6.36e-08

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: 50.40  E-value: 6.36e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKhGSFLVRESQSHPGDFVLSVRTgddkgesndgKSKVTHVMIRCQELKYDVGGGERFDSLT 191
Cdd:cd10405   7 WYAGPMERAGAESILANRSD-GTYLVRQRVKDAAEFAISIKY----------NVEVKHIKIMTAEGLYRITEKKAFRGLT 75

                        90       100
                ....*....|....*....|....
gi 18375644 192 DLVEHYKKNPM---VETLGTVLQL 212
Cdd:cd10405  76 ELVEFYQQNSLkdcFKSLDTTLQF 99
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
 109-200 6.53e-08

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: 50.40  E-value: 6.53e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEKLLTEKG-KHGSFLVRESQSHPGDFVLSVRTGDDKGESNdgkskVTHVMIRcqelKYDVGG---- 183
Cdd:cd10366   2 AEEWYFGKMGRKDAERLLLNPGnQRGIFLVRESETTKGAYSLSIRDWDEVRGDN-----VKHYKIR----KLDNGGyyit 72

                        90
                ....*....|....*...
gi 18375644 184 -GERFDSLTDLVEHYKKN 200
Cdd:cd10366  73 tRAQFDTLQKLVKHYTEH 90
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
 112-198 7.12e-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: 49.51  E-value: 7.12e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLteKGKH-GSFLVRESqSHPGD-FVLSVRTGddkgesndgkSKVTHVMIRCQE----LKYDVGGGE 185
Cdd:cd09923   2 WYWGGITRYEAEELL--AGKPeGTFLVRDS-SDSRYlFSVSFRTY----------GRTLHARIEYSNgrfsFDSSDPSVP 68

                        90
                ....*....|...
gi 18375644 186 RFDSLTDLVEHYK 198
Cdd:cd09923  69 RFPCVVELIEHYV 81
SH2_Src_HCK cd10363
Src homology 2 (SH2) domain found in HCK; HCK is a member of the Src non-receptor type ...
 3-101 1.01e-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: 49.96  E-value: 1.01e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLTRG-VDGSFLARPSKSNPGDFTLSVR-----RNGAVTHIKIQ--NTGDYYdLYGGEKFATL 74
Cdd:cd10363   2 TEEWFFKGISRKDAERQLLAPGnMLGSFMIRDSETTKGSYSLSVRdydpqHGDTVKHYKIRtlDNGGFY-ISPRSTFSTL 80

                        90       100
                ....*....|....*....|....*..
gi 18375644  75 AELVQYYMehhgqlKEKNGDVIELKYP 101
Cdd:cd10363  81 QELVDHYK------KGNDGLCQKLSVP 101
SH2_Src_Fgr cd10367
Src homology 2 (SH2) domain found in Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene ...
 3-83 1.04e-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: 49.90  E-value: 1.04e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLTRG-VDGSFLARPSKSNPGDFTLSVR-----RNGAVTHIKIQ--NTGDYYdLYGGEKFATL 74
Cdd:cd10367   2 AEEWYFGKIGRKDAERQLLSPGnPRGAFLIRESETTKGAYSLSIRdwdqnRGDHVKHYKIRklDTGGYY-ITTRAQFDTV 80


                ....*....
gi 18375644  75 AELVQYYME 83
Cdd:cd10367  81 QELVQHYME 89
SH2_cSH2_p85_like cd09930
C-terminal Src homology 2 (cSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 112-210 1.35e-07

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: 49.72  E-value: 1.35e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLteKGK-HGSFLVRESQShPGDFVLSVRTgddkgesndgKSKVTHVMIRCQELKYdvGGGERFD-- 188
Cdd:cd09930   8 WLVGDINRTQAEELL--RGKpDGTFLIRESST-QGCYACSVVC----------NGEVKHCVIYKTETGY--GFAEPYNly 72

                        90       100
                ....*....|....*....|....*.
gi 18375644 189 -SLTDLVEHYKKNPMVE---TLGTVL 210
Cdd:cd09930  73 eSLKELVLHYAHNSLEQhndSLTVTL 98
SH2_Tec_Itk cd10396
Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member ...
 6-104 1.75e-07

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: 49.40  E-value: 1.75e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRGVDGSFLARPSkSNPGDFTLSV------RRNGAVTHIKIQNTGD---YYDLYGGEKFATLAE 76
Cdd:cd10396   8 WYNKNINRSKAEKLLRDEGKEGGFMVRDS-SQPGLYTVSLytkaggEGNPCIRHYHIKETNDspkKYYLAEKHVFNSIPE 86

                        90       100
                ....*....|....*....|....*...
gi 18375644  77 LVQYYmEHHGQlkeknGDVIELKYPLNC 104
Cdd:cd10396  87 LIEYH-KHNAA-----GLVTRLRYPVSS 108
SH2_SHF cd10392
Src homology 2 domain found in SH2 domain-containing adapter protein F (SHF); SHF is thought ...
 112-202 1.97e-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: 48.91  E-value: 1.97e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLtEKGKHGSFLVRESQSHPGDFVLSVRtgddkgeSNDGkskVTHVMI-RCQELKYDVG-GGERFDS 189
Cdd:cd10392   3 WYHGAISRTDAENLL-RLCKEASYLVRNSETSKNDFSLSLK-------SSQG---FMHMKLsRTKEHKYVLGqNSPPFSS 71

                        90
                ....*....|....*
gi 18375644 190 LTDLVEHY--KKNPM 202
Cdd:cd10392  72 VPEIIHHYasRKLPI 86
SH2_Src_Blk cd10371
Src homology 2 (SH2) domain found in B lymphoid kinase (Blk); Blk is a member of the Src ...
 5-81 2.59e-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: 2.59e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   5 RWFHPNITGVEAENLLLTR-GVDGSFLARPSKSNPGDFTLSVR----RNGAVTHIKIQ--NTGDYYdLYGGEKFATLAEL 77
Cdd:cd10371   4 KWFFRTISRKDAERQLLAPmNKAGSFLIRESESNKGAFSLSVKdvttQGEVVKHYKIRslDNGGYY-ISPRITFPTLQAL 82


                ....
gi 18375644  78 VQYY 81
Cdd:cd10371  83 VQHY 86
SH2_SH2D4A cd10350
Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains ...
 108-212 2.68e-07

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: 48.77  E-value: 2.68e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 108 TSERWFHGHLSGKEAEKLLTEKGkHGSFLVRESQSHPGdFVLSVRtgddkgeSNDGkskVTHVMIRCQELKYDVGGGERF 187
Cdd:cd10350   5 TIAPWFHGILTLKKANELLLSTM-PGSFLIRVSEKIKG-YALSYL-------SEEG---CKHFLIDASADSYSFLGVDQL 72

                        90       100
                ....*....|....*....|....*..
gi 18375644 188 D--SLTDLVEHYKKNPmVETLGTVLQL 212
Cdd:cd10350  73 QhaTLADLVEYHKEEP-ITSLGKELLL 98
SH2_Grb10 cd10415
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) ...
 3-88 2.75e-07

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: 48.86  E-value: 2.75e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLTRG-VDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLY-----GGEKFATLAE 76
Cdd:cd10415   4 TQHWFHGRISREESHRIIKQQGlVDGLFLLRDSQSNPKAFVLTLCHHQKIKNFQILPCEDDGQTFfslddGNTKFSDLIQ 83

                        90
                ....*....|..
gi 18375644  77 LVQYYMEHHGQL 88
Cdd:cd10415  84 LVDFYQLNKGVL 95
SH2_a2chimerin_b2chimerin cd10352
Src homology 2 (SH2) domain found in alpha2-chimerin and beta2-chimerin proteins; Chimerins ...
 113-194 2.79e-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: 48.13  E-value: 2.79e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 113 FHGHLSGKEAEKLLTEKGKhGSFLVRESQSHPGDFVLSVRTGDdkgesndgkskvthvMIRCQELKYDVG------GGER 186
Cdd:cd10352   9 YHGLISREEAEQLLSGASD-GSYLIRESSRDDGYYTLSLRFNG---------------KVKNYKLYYDGKnhyhyvGEKR 72


                ....*...
gi 18375644 187 FDSLTDLV 194
Cdd:cd10352  73 FDTIHDLV 80
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
 112-216 2.93e-07

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: 48.79  E-value: 2.93e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESqSHPGDFVLSVRTGDDKgesnDGKSKVTHVMIRCQELK-YDVGGGERFDSL 190
Cdd:cd10398   8 WYHKNITRNQAERLLRQESKEGAFIVRDS-RHLGSYTISVFTRARR----STEASIKHYQIKKNDSGqWYVAERHLFQSI 82

                        90       100
                ....*....|....*....|....*.
gi 18375644 191 TDLVEHYKKNpmveTLGTVLQLKQPL 216
Cdd:cd10398  83 PELIQYHQHN----AAGLMSRLRYPV 104
SH2_Src_Frk cd10369
Src homology 2 (SH2) domain found in the Fyn-related kinase (Frk); Frk is a member of the Src ...
 6-81 3.16e-07

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: 48.34  E-value: 3.16e-07
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644   6 WFHPNITGVEAE-NLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQ--NTGDYYdLYGGEKFATLAELVQYY 81
Cdd:cd10369   5 WFFGAIKRADAEkQLLYSENQTGAFLIRESESQKGEFSLSVLDGGVVKHYRIRrlDEGGFF-LTRRKTFSTLNEFVNYY 82
SH2_SOCS7 cd10388
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 6-84 3.57e-07

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: 48.12  E-value: 3.57e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRgVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEKFA----TLAELVQYY 81
Cdd:cd10388  12 WYWGPMSWEDAEKVLSNK-PDGSFLVRDSSDDRYIFSLSFRSQGSVHHTRIEQYQGTFSLGSRNKFVdrsqSLVEFIERA 90


                ...
gi 18375644  82 MEH 84
Cdd:cd10388  91 VEH 93
SH2_Vav_family cd09940
Src homology 2 (SH2) domain found in the Vav family; Vav proteins are involved in several ...
 111-211 4.16e-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: 48.06  E-value: 4.16e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 111 RWFHGHLSGKEAEKLLtEKGKHGSFLVRESQSHPGDFVLSVRTGDDkgesndgkskVTHVMIrCQEL--KYDVGGGERFD 188
Cdd:cd09940   6 LWFVGEMERDTAENRL-ENRPDGTYLVRVRPQGETQYALSIKYNGD----------VKHMKI-EQRSdgLYYLSESRHFK 73

                        90       100
                ....*....|....*....|....*.
gi 18375644 189 SLTDLVEHYKKNPMVE---TLGTVLQ 211
Cdd:cd09940  74 SLVELVNYYERNSLGEnfaGLDTTLK 99
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 ...
 3-83 5.36e-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: 5.36e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLTRG-VDGSFLARPSKSNPGDFTLSVR-----RNGAVTHIKIQ--NTGDYYdLYGGEKFATL 74
Cdd:cd10418   2 AEEWYFGKLGRKDAERQLLSFGnPRGTFLIRESETTKGAYSLSIRdwddmKGDHVKHYKIRklDNGGYY-ITTRAQFETL 80


                ....*....
gi 18375644  75 AELVQYYME 83
Cdd:cd10418  81 QQLVQHYSE 89
SH2_SH2B3 cd10412
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), ...
 112-202 5.58e-07

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: 47.58  E-value: 5.58e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKG--KHGSFLVRESQSHPGDFVLsvrTGDDKGESNDGKSKVTHV-MIRCQELkydvgggeRFD 188
Cdd:cd10412  10 WFHGPISRVKAAQLVQLQGpdAHGVFLVRQSETRRGEYVL---TFNFQGRAKHLRLSLTERgQCRVQHL--------HFP 78

                        90
                ....*....|....
gi 18375644 189 SLTDLVEHYKKNPM 202
Cdd:cd10412  79 SVVDMLHHFQRSPI 92
SH2_SLAP cd10344
Src homology 2 domain found in Src-like adaptor proteins; SLAP belongs to the subfamily of ...
 5-83 5.67e-07

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: 47.87  E-value: 5.67e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   5 RWFHPNITGVEAENLLLTRGVD-GSFLARPSKSNPGDFTLSVRRNG-----AVTHIKI---QNTGDYYDlyGGEKFATLA 75
Cdd:cd10344  11 GWLFEGLSREKAEELLMLPGNQvGSFLIRESETRRGCYSLSVRHRGsqsrdSVKHYRIfrlDNGWFYIS--PRLTFQCLE 88


                ....*...
gi 18375644  76 ELVQYYME 83
Cdd:cd10344  89 DMVNHYSE 96
SH2_Grb7 cd10413
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 7 (Grb7) ...
 3-88 7.71e-07

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: 47.59  E-value: 7.71e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLTRG-VDGSFLARPSKSNPGDFTLSVRRNGAVTH---IKIQNTGD-YYDLYGGE-KFATLAE 76
Cdd:cd10413   4 TQPWFHGRISREESQRLIGQQGlVDGVFLVRESQRNPQGFVLSLCHLQKVKHyliLPSEEEGRlYFSMDDGQtRFTDLLQ 83

                        90
                ....*....|..
gi 18375644  77 LVQYYMEHHGQL 88
Cdd:cd10413  84 LVEFHQLNRGIL 95
SH2_SH2D2A_SH2D7 cd10349
Src homology 2 domain found in the SH2 domain containing protein 2A and 7 (SH2D2A and SH2D7); ...
 5-81 7.97e-07

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: 46.75  E-value: 7.97e-07
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644   5 RWFHPNITGVEAENLLLTRGVdGSFLARPSKSNPGdFTLSVRRNGAVTHIKIQNTGDYYDLYGGEK--FATLAELVQYY 81
Cdd:cd10349   1 AWFHGFITRREAERLLEPKPQ-GCYLVRFSESAVT-FVLSYRSRTCCRHFLLAQLRDGRHVVLGEDsaHARLQDLLLHY 77
SH2_SH2D4A cd10350
Src homology 2 domain found in the SH2 domain containing protein 4A (SH2D4A); SH2D4A contains ...
 6-83 9.33e-07

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: 47.23  E-value: 9.33e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTrGVDGSFLARPSKSNPGdFTLSVRRNGAVTHIKIQNTGDYYDLYGGEKF--ATLAELVQYYME 83
Cdd:cd10350   9 WFHGILTLKKANELLLS-TMPGSFLIRVSEKIKG-YALSYLSEEGCKHFLIDASADSYSFLGVDQLqhATLADLVEYHKE 86
SH2_ShkD_ShkE cd10357
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases D and E (ShkD and ShkE) ...
 1-57 9.35e-07

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: 46.73  E-value: 9.35e-07
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644   1 MTSRRWFHPNITGVEAENLLLTRgVDGSFLARPSKSNPGD--FTLSVRRNGAVTHIKIQ 57
Cdd:cd10357   7 LLAKSWFHGDISRDEAEKRLRGR-PEGTFLIRLSSTDPKKtpFTISKKKKSKPVHKRIS 64
SH2_SHB cd10389
Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in ...
 6-102 1.02e-06

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: 47.01  E-value: 1.02e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLL-LTRgvDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDL-YGGEKFATLAELVQYYME 83
Cdd:cd10389   3 WYHGAISRGDAENLLrLCK--ECSYLVRNSQTSKHDYSLSLKSNQGFMHMKLAKTKEKYVLgQNSPPFDSVPEVIHYYTT 80

                        90
                ....*....|....*....
gi 18375644  84 HhgQLKEKNGDVIELKYPL 102
Cdd:cd10389  81 R--KLPIKGAEHLSLLYPV 97
SH2_SH2B1 cd10410
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, ...
 107-202 1.17e-06

Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B1 (SH2-B, PSM), 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: 198273  Cd Length: 97  Bit Score: 46.55  E-value: 1.17e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 107 PTSE-RWFHGHLSGKEAEKLLTEKG--KHGSFLVRESQSHPGDFVLSVR-TGDDK----GESNDGKSKVTHVMircqelk 178
Cdd:cd10410   4 PLSGyPWFHGMLSRLKAAQLVLEGGtgSHGVFLVRQSETRRGEYVLTFNfQGKAKhlrlSLNEEGQCRVQHLW------- 76

                        90       100
                ....*....|....*....|....
gi 18375644 179 ydvgggerFDSLTDLVEHYKKNPM 202
Cdd:cd10410  77 --------FQSIFDMLEHFRVHPI 92
SH2_Src_Src cd10365
Src homology 2 (SH2) domain found in tyrosine kinase sarcoma (Src); Src is a member of the Src ...
 3-95 1.18e-06

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: 46.97  E-value: 1.18e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLT-RGVDGSFLARPSKSNPGDFTLSV-----RRNGAVTHIKIQ--NTGDYYdLYGGEKFATL 74
Cdd:cd10365   2 AEEWYFGKITRRESERLLLNaENPRGTFLVRESETTKGAYCLSVsdfdnAKGLNVKHYKIRklDSGGFY-ITSRTQFNSL 80

                        90       100
                ....*....|....*....|.
gi 18375644  75 AELVQYYMEHHGQLKEKNGDV 95
Cdd:cd10365  81 QQLVAYYSKHADGLCHRLTTV 101
SH2_SHC cd09925
Src homology 2 (SH2) domain found in SH2 adaptor protein C (SHC); SHC is involved in a wide ...
 6-86 1.26e-06

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: 46.96  E-value: 1.26e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLltrGVDGSFLARPSKSNPGDFTLSVRRNGAVTHI------KIQNTGDYydlyggeKFATLAELVQ 79
Cdd:cd09925   9 WYHGKMSRRDAESLL---QTDGDFLVRESTTTPGQYVLTGMQNGQPKHLllvdpeGVVRTKDR-------VFESISHLIN 78


                ....*..
gi 18375644  80 YYMEHHG 86
Cdd:cd09925  79 YHVTNGL 85
SH2_C-SH2_Zap70 cd10402
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 112-215 1.63e-06

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: 46.45  E-value: 1.63e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAE-KLLTEKGKHGSFLVRESQSHpGDFVLSVRTGddkgesndgkSKVTHVMI-RCQELKYDVGGGERFDS 189
Cdd:cd10402  12 WYHGSIARDEAErRLYSGAQPDGKFLLRERKES-GTYALSLVYG----------KTVYHYRIdQDKSGKYSIPEGTKFDT 80

                        90       100
                ....*....|....*....|....*.
gi 18375644 190 LTDLVEHYKKNPMvetlGTVLQLKQP 215
Cdd:cd10402  81 LWQLVEYLKLKPD----GLIFVLRES 102
SH2_SH2D7 cd10417
Src homology 2 domain found in the SH2 domain containing protein 7 (SH2D7); SH2D7 contains a ...
 5-83 2.16e-06

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: 46.04  E-value: 2.16e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   5 RWFHPNITGVEAENLLLTRGVdGSFLARPSKSNPGdFTLSVRRNGAVTHIKIQNTGDYYDLYGGEK--FATLAELVQYYM 82
Cdd:cd10417   8 PWFHGFITRKQTEQLLRDKAL-GSFLIRLSDRATG-YILSYRGSDRCRHFVINQLRNRRYLISGDTssHSTLAELVRHYQ 85


                .
gi 18375644  83 E 83
Cdd:cd10417  86 E 86
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
 6-85 2.24e-06

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: 45.60  E-value: 2.24e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTrgvDGSFLAR---PSKSNPGDFTLSVRRNGAVTHIKIQ-NTGDYYDLYGgEKFATLAELVQYY 81
Cdd:cd10361   8 YYHGLLPREDAEELLKN---DGDFLVRktePKGGGKRKLVLSVRWDGKIRHFVINrDDGGKYYIEG-KSFKSISELINYY 83


                ....
gi 18375644  82 MEHH 85
Cdd:cd10361  84 QKTK 87
SH2_nSH2_p85_like cd09942
N-terminal Src homology 2 (nSH2) domain found in p85; Phosphoinositide 3-kinases (PI3Ks) are ...
 112-211 2.41e-06

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: 46.16  E-value: 2.41e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKgKHGSFLVRESQSHPGDFVLSVRtgddKGESN--------DGKSKVTHVMircqelkydvgg 183
Cdd:cd09942   9 WYWGDISREEVNEKMRDT-PDGTFLVRDASTMKGDYTLTLR----KGGNNklikifhrDGKYGFSDPL------------ 71

                        90       100       110
                ....*....|....*....|....*....|.
gi 18375644 184 geRFDSLTDLVEHYKKNPMVE---TLGTVLQ 211
Cdd:cd09942  72 --TFNSVVELINYYRNNSLAEynrKLDVKLL 100
SH2_Src_Fyn cd10368
Src homology 2 (SH2) domain found in Fyn; Fyn is a member of the Src non-receptor type ...
 3-83 2.48e-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: 45.79  E-value: 2.48e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLTRG-VDGSFLARPSKSNPGDFTLSVR-----RNGAVTHIKIQ--NTGDYYdLYGGEKFATL 74
Cdd:cd10368   2 AEEWYFGKLGRKDAERQLLSFGnPRGTFLIRESETTKGAYSLSIRdwddmKGDHVKHYKIRklDNGGYY-ITTRAQFETL 80


                ....*....
gi 18375644  75 AELVQYYME 83
Cdd:cd10368  81 QQLVQHYSE 89
SH2_SAP1a cd10400
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked ...
 7-102 2.65e-06

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: 45.99  E-value: 2.65e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   7 FHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGdyydlyGGEKFATLAELVQ--YYMEH 84
Cdd:cd10400   6 YHGKISRETGEKLLLAAGLDGSYLLRDSESVPGVYCLCVLYKGYVYTYRVSQTE------TGSWSAETAPGVHkrLFRKV 79

                        90       100
                ....*....|....*....|..
gi 18375644  85 HGQL----KEKNGDVIELKYPL 102
Cdd:cd10400  80 KNLIsafqKPDQGIVTPLQYPV 101
SH2_Src_Lyn cd10364
Src homology 2 (SH2) domain found in Lyn; Lyn is a member of the Src non-receptor type ...
 3-91 2.74e-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: 45.75  E-value: 2.74e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLTRGVD-GSFLARPSKSNPGDFTLSVR-----RNGAVTHIKIQ--NTGDYYdLYGGEKFATL 74
Cdd:cd10364   2 TEEWFFKDITRKDAERQLLAPGNSaGAFLIRESETLKGSYSLSVRdydpqHGDVIKHYKIRslDNGGYY-ISPRITFPCI 80

                        90
                ....*....|....*..
gi 18375644  75 AELVQYYMEHHGQLKEK 91
Cdd:cd10364  81 SDMIKHYQKQSDGLCRR 97
SH2_Tec_Txk cd10398
Src homology 2 (SH2) domain found in Tec protein, Txk; A member of the Tec protein tyrosine ...
 6-102 3.43e-06

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: 45.71  E-value: 3.43e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRGVDGSFLARPSkSNPGDFTLSV----RRN--GAVTH--IKIQNTGDYydlYGGEK--FATLA 75
Cdd:cd10398   8 WYHKNITRNQAERLLRQESKEGAFIVRDS-RHLGSYTISVftraRRSteASIKHyqIKKNDSGQW---YVAERhlFQSIP 83

                        90       100
                ....*....|....*....|....*..
gi 18375644  76 ELVQYYmEHHGQlkeknGDVIELKYPL 102
Cdd:cd10398  84 ELIQYH-QHNAA-----GLMSRLRYPV 104
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
 112-201 3.73e-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: 45.27  E-value: 3.73e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGK-HGSFLVRESQSHpGDFVLSVRtgddkgesNDGKskVTHVMI-RCQELKYDVGGGERFDS 189
Cdd:cd10401   5 WFHGKISREESEQILLIGSKtNGKFLIRERDNN-GSYALCLL--------HDGK--VLHYRIdKDKTGKLSIPDGKKFDT 73

                        90
                ....*....|..
gi 18375644 190 LTDLVEHYKKNP 201
Cdd:cd10401  74 LWQLVEHYSYKP 85
SH2_SH2B2 cd10411
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), ...
 112-202 4.25e-06

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: 44.99  E-value: 4.25e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKG--KHGSFLVRESQSHPGDFVLSVR-TGDDK----GESNDGKSKVTHVMircqelkydvggg 184
Cdd:cd10411  10 WFHGTLSRVKAAQLVLAGGprSHGLFVIRQSETRPGEYVLTFNfQGKAKhlrlSLNGHGQCHVQHLW------------- 76

                        90
                ....*....|....*...
gi 18375644 185 erFDSLTDLVEHYKKNPM 202
Cdd:cd10411  77 --FQSVFDMLRHFHTHPI 92
SH2_PTK6_Brk cd10358
Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast ...
 109-215 4.29e-06

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: 45.12  E-value: 4.29e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEA-EKLLTEKGKHGSFLVRESQSHPGDFVLSVRtgddkgesnDGKSKVTHVMIRCQELKYDVGGGERF 187
Cdd:cd10358   1 SEPWFFGCISRSEAvRRLQAEGNATGAFLIRVSEKPSADYVLSVR---------DTQAVRHYKIWRRAGGRLHLNEAVSF 71

                        90       100
                ....*....|....*....|....*...
gi 18375644 188 DSLTDLVEHYKknpmVETLGTVLQLKQP 215
Cdd:cd10358  72 LSLPELVNYHR----AQSLSHGLRLAAP 95
SH2_Tec_Btk cd10397
Src homology 2 (SH2) domain found in Tec protein, Bruton's tyrosine kinase (Btk); A member of ...
 112-218 4.29e-06

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: 45.21  E-value: 4.29e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESqSHPGDFVLSVRTgddKGeSNDGKSKVTHVMIRC-QELKYDVGGGERFDSL 190
Cdd:cd10397   8 WYSKNMTRSQAEQLLKQEGKEGGFIVRDS-SKAGKYTVSVFA---KS-AGDPQGVIRHYVVCStPQSQYYLAEKHLFSTI 82

                        90       100
                ....*....|....*....|....*...
gi 18375644 191 TDLVEHYKKNpmveTLGTVLQLKQPLNT 218
Cdd:cd10397  83 PELINYHQHN----AAGLISRLKYPVSS 106
SH2_SOCS6 cd10387
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 6-82 5.36e-06

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: 44.83  E-value: 5.36e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRgVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYG---GEKFATLAELVQYYM 82
Cdd:cd10387  12 WYWGPITRWEAEGKLANV-PDGSFLVRDSSDDRYLLSLSFRSHGKTLHTRIEHSNGRFSFYEqpdVEGHTSIVDLIEHSI 90
SH2_SAP1a cd10400
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP) 1a; The X-linked ...
 113-151 5.44e-06

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: 44.83  E-value: 5.44e-06
                        10        20        30
                ....*....|....*....|....*....|....*....
gi 18375644 113 FHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSV 151
Cdd:cd10400   6 YHGKISRETGEKLLLAAGLDGSYLLRDSESVPGVYCLCV 44
SH2_SOCS3 cd10384
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 11-82 1.22e-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: 1.22e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644  11 ITGVEAeNLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEK-------FATLAELVQYYM 82
Cdd:cd10384  17 VSGKEA-NLLLSAEPAGTFLIRDSSDQRHFFTLSVKTESGTKNLRIQCEGGSFSLQTDPRstqpvprFDCVLKLVHHYM 94
SH2_Vav2 cd10406
Src homology 2 (SH2) domain found in the Vav2 proteins; Proto-oncogene vav is a member of the ...
 106-206 1.25e-05

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: 43.90  E-value: 1.25e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 106 DPTSERWFHGHLSGKEAEKLLTEKGKhGSFLVRESQSHPGDFVLSVRTGDDkgesndgkskVTHVMIRCQELKYDVGGGE 185
Cdd:cd10406   1 DYTAYPWFAGNMERQQTDNLLKSHAS-GTYLIRERPAEAERFAISIKFNDE----------VKHIKVVEKDNWIHITEAK 69

                        90       100
                ....*....|....*....|.
gi 18375644 186 RFDSLTDLVEHYKKNPMVETL 206
Cdd:cd10406  70 KFESLLELVEYYQCHSLKESF 90
SH2_C-SH2_Syk_like cd10401
C-terminal Src homology 2 (SH2) domain found in Spleen tyrosine kinase (Syk) proteins; ZAP-70 ...
 6-81 1.40e-05

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: 43.73  E-value: 1.40e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18375644   6 WFHPNITGVEAENLLL-TRGVDGSFLARPSKSNpGDFTLSVRRNGAVTHIKIQ--NTGDYyDLYGGEKFATLAELVQYY 81
Cdd:cd10401   5 WFHGKISREESEQILLiGSKTNGKFLIRERDNN-GSYALCLLHDGKVLHYRIDkdKTGKL-SIPDGKKFDTLWQLVEHY 81
SH2_Grb10 cd10415
Src homology 2 (SH2) domain found in the growth factor receptor bound, subclass 10 (Grb10) ...
 109-200 1.42e-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: 43.86  E-value: 1.42e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 109 SERWFHGHLSGKEAEKLLTEKGK-HGSFLVRESQSHPGDFVLSVRTgddkgesndgKSKVTHVMIRCQELKYDV-----G 182
Cdd:cd10415   4 TQHWFHGRISREESHRIIKQQGLvDGLFLLRDSQSNPKAFVLTLCH----------HQKIKNFQILPCEDDGQTffsldD 73

                        90
                ....*....|....*...
gi 18375644 183 GGERFDSLTDLVEHYKKN 200
Cdd:cd10415  74 GNTKFSDLIQLVDFYQLN 91
SH2_SH2D4B cd10351
Src homology 2 domain found in the SH2 domain containing protein 4B (SH2D4B); SH2D4B contains ...
 112-211 1.44e-05

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: 43.72  E-value: 1.44e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKhGSFLVRESQSHPGdFVLSVRTgddkgesndgKSKVTHVMIRCQELKYDVGGGE--RFDS 189
Cdd:cd10351   9 WFHGIISREEAEALLMNATE-GSFLVRVSEKIWG-YTLSYRL----------QSGFKHFLVDASGDFYSFLGVDpnRHAT 76

                        90       100
                ....*....|....*....|..
gi 18375644 190 LTDLVEHYKKNPMVETLGTVLQ 211
Cdd:cd10351  77 LTDLIDFHKEEIITTSGGELLQ 98
SH2_Srm cd10360
Src homology 2 (SH2) domain found in Src-related kinase lacking C-terminal regulatory tyrosine ...
 112-197 1.46e-05

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: 43.02  E-value: 1.46e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLL-TEKGKHGSFLVRESQSHPGDFVLSVRtgddkgesndGKSKVTHVMI-RCQELKYDVGGGERFDS 189
Cdd:cd10360   2 WYFSGISRTQAQQLLlSPPNEPGAFLIRPSESSLGGYSLSVR----------AQAKVCHYRIcMAPSGSLYLQKGRLFPG 71


                ....*...
gi 18375644 190 LTDLVEHY 197
Cdd:cd10360  72 LEELLAYY 79
SH2_CRK_like cd09926
Src homology 2 domain found in cancer-related signaling adaptor protein CRK; SH2 domain in the ...
 6-85 1.69e-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: 43.62  E-value: 1.69e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRGvDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLY-----GGEKFATLAELVQY 80
Cdd:cd09926   9 WYFGPMSRQEAQELLQGQR-HGVFLVRDSSTIPGDYVLSVSENSRVSHYIINSLGQPAPNQsryriGDQEFDDLPALLEF 87


                ....*
gi 18375644  81 YMEHH 85
Cdd:cd09926  88 YKLHY 92
SH2_Tec_Itk cd10396
Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk); A member ...
 112-200 2.25e-05

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: 43.24  E-value: 2.25e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESqSHPGDFVLSVRTgddkGESNDGKSKVTHVMIR---CQELKYDVGGGERFD 188
Cdd:cd10396   8 WYNKNINRSKAEKLLRDEGKEGGFMVRDS-SQPGLYTVSLYT----KAGGEGNPCIRHYHIKetnDSPKKYYLAEKHVFN 82

                        90
                ....*....|..
gi 18375644 189 SLTDLVEHYKKN 200
Cdd:cd10396  83 SIPELIEYHKHN 94
SH2_C-SH2_Zap70_Syk_like cd10345
C-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 ...
 6-80 2.29e-05

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: 43.14  E-value: 2.29e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18375644   6 WFHPNITGVEAENLLLTRG-VDGSFLARPSKSNpGDFTLSVRRNGAVTHIKI-QNTGDYYDLYGGEKFATLAELVQY 80
Cdd:cd10345   2 WFHGKISREESEQIVLIGSkTNGKFLIRARDNN-GSYALCLLHEGKVLHYRIdKDKTGKLSIPEGKKFDTLWQLVEH 77
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 ...
 4-83 2.35e-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: 2.35e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   4 RRWFHPNITGVEAENLLLTRG-VDGSFLARPSKSNPGDFTLSVR-----RNGAVTHIKIQ--NTGDYYdLYGGEKFATLA 75
Cdd:cd10419   3 EEWYFGKLGRKDAERQLLSFGnPRGTFLIRESETTKGAYSLSIRdwddmKGDHVKHYKIRklDNGGYY-ITTRAQFETLQ 81


                ....*...
gi 18375644  76 ELVQYYME 83
Cdd:cd10419  82 QLVQHYSE 89
SH2_SOCS_family cd09923
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) family; SH2 ...
 6-82 2.38e-05

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: 42.57  E-value: 2.38e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLltRGV-DGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYG----GEKFATLAELVQY 80
Cdd:cd09923   2 WYWGGITRYEAEELL--AGKpEGTFLVRDSSDSRYLFSVSFRTYGRTLHARIEYSNGRFSFDSsdpsVPRFPCVVELIEH 79


                ..
gi 18375644  81 YM 82
Cdd:cd09923  80 YV 81
SH2_Vav3 cd10407
Src homology 2 (SH2) domain found in the Vav3 proteins; Proto-oncogene vav is a member of the ...
 106-212 3.09e-05

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: 42.69  E-value: 3.09e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 106 DPTSERWFHGHLSGKEAEKLLTEKgKHGSFLVRESQSHPGDFVLSVRTGDDkgesndgkskVTHVMIRCQELKYDVGGGE 185
Cdd:cd10407   1 DYSCQPWYAGAMERLQAETELINR-VNSTYLVRHRTKESGEYAISIKYNNE----------VKHIKILTRDGFFHIAENR 69

                        90       100       110
                ....*....|....*....|....*....|
gi 18375644 186 RFDSLTDLVEHYKKNPMVE---TLGTVLQL 212
Cdd:cd10407  70 KFKSLMELVEYYKHHSLKEgfrSLDTTLQF 99
SH2_HSH2_like cd09946
Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function ...
 112-202 3.21e-05

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: 42.96  E-value: 3.21e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLtEKGKHGSFLVRESQSHPGdFVLSVRtgddkgesndGKSKVTHVMIRCQELKYDVGGGER--FDS 189
Cdd:cd09946   9 WFHGAISREAAENML-ESQPLGSFLIRVSHSHVG-YTLSYK----------AQSSCRHFMVKLLDDGTFMIPGEKvaHTS 76

                        90
                ....*....|...
gi 18375644 190 LTDLVEHYKKNPM 202
Cdd:cd09946  77 LHALVTFHQQKPI 89
SH2_SOCS7 cd10388
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 112-195 3.25e-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: 198251  Cd Length: 101  Bit Score: 42.73  E-value: 3.25e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKgKHGSFLVRESQSHPGDFVLSVRTgddkgesndgKSKVTHVMIRCQELKYDVGGGERFD--- 188
Cdd:cd10388  12 WYWGPMSWEDAEKVLSNK-PDGSFLVRDSSDDRYIFSLSFRS----------QGSVHHTRIEQYQGTFSLGSRNKFVdrs 80


                ....*...
gi 18375644 189 -SLTDLVE 195
Cdd:cd10388  81 qSLVEFIE 88
SH2_ShkA_ShkC cd10356
Src homology 2 (SH2) domain found in SH2 domain-bearing protein kinases A and C (ShkA and ShkC) ...
 109-150 3.88e-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: 42.98  E-value: 3.88e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 18375644 109 SERWFHGHLSGKEAEKLLTEKgKHGSFLVRESQSHPGDFVLS 150
Cdd:cd10356   9 ECAWFHGDISTSESENRLNGK-PEGTFLVRFSTSEPGAYTIS 49
SH2_SH2B_family cd10346
Src homology 2 (SH2) domain found in SH2B adapter protein family; The SH2B adapter protein ...
 6-56 5.83e-05

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: 42.02  E-value: 5.83e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 18375644   6 WFHPNITGVEAENLLLTRGVD--GSFLARPSKSNPGDFTLSVRRNGAVTHIKI 56
Cdd:cd10346  10 WFHGTLSRSDAAQLVLHSGADghGVFLVRQSETRRGEFVLTFNFQGRAKHLRL 62
SH2_SOCS2 cd10383
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 106-197 6.16e-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: 198246  Cd Length: 103  Bit Score: 42.18  E-value: 6.16e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 106 DPTSERWFHGHLSGKEAEKLLTEkGKHGSFLVRESqSHpGDFVLSVRTGDDKGESN------DGKSKVTHVMIRCQELKy 179
Cdd:cd10383   3 ELSQTGWYWGSMTVNEAKEKLQD-APEGTFLVRDS-SH-SDYLLTISVKTSAGPTNlrieyqDGKFRLDSIICVKSKLK- 78

                        90
                ....*....|....*...
gi 18375644 180 dvgggeRFDSLTDLVEHY 197
Cdd:cd10383  79 ------QFDSVVHLIEYY 90
SH2_Src_Yes cd10366
Src homology 2 (SH2) domain found in Yes; Yes is a member of the Src non-receptor type ...
 3-84 7.32e-05

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: 41.93  E-value: 7.32e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLTRGVD-GSFLARPSKSNPGDFTLSVR-----RNGAVTHIKIQ--NTGDYYdLYGGEKFATL 74
Cdd:cd10366   2 AEEWYFGKMGRKDAERLLLNPGNQrGIFLVRESETTKGAYSLSIRdwdevRGDNVKHYKIRklDNGGYY-ITTRAQFDTL 80

                        90
                ....*....|
gi 18375644  75 AELVQYYMEH 84
Cdd:cd10366  81 QKLVKHYTEH 90
SH2_Tensin_like cd09927
Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. ...
 2-46 7.89e-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: 42.03  E-value: 7.89e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 18375644   2 TSRRWFHPNITGVEAENLLLTRgVDGSFLARPSKSNPGDFTLSVR 46
Cdd:cd09927   1 TSKYWYKPNISRDQAIALLKDK-PPGTFLVRDSTTYKGAYGLAVK 44
SH2_SH2D2A cd10416
Src homology 2 domain found in the SH2 domain containing protein 2A (SH2D2A); SH2D2A contains ...
 108-202 7.98e-05

Src homology 2 domain found in the SH2 domain containing protein 2A (SH2D2A); SH2D2A 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: 198279  Cd Length: 102  Bit Score: 41.56  E-value: 7.98e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 108 TSERWFHGHLSGKEAEKLLTEKgKHGSFLVRESQShPGDFVLSVRTGDD-----KGESNDGKskvtHVMIrcqelkydvG 182
Cdd:cd10416   5 AAPAWFHGFITRREAERLLEPK-PQGCYLVRFSES-AVTFVLTYRSRTCcrhflLAQLRDGR----HVVL---------G 69

                        90       100
                ....*....|....*....|
gi 18375644 183 GGERFDSLTDLVEHYKKNPM 202
Cdd:cd10416  70 EDSAHARLQDLLLHYTAHPL 89
SH2_Tensin_like cd09927
Src homology 2 domain found in Tensin-like proteins; SH2 domain found in Tensin-like proteins. ...
 108-196 8.61e-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: 42.03  E-value: 8.61e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 108 TSERWFHGHLSGKEAEKLLTEKgKHGSFLVRESQSHPGDFVLSVR------TGDDKGESNDGKSK-VTHVMIRCQELKYD 180
Cdd:cd09927   1 TSKYWYKPNISRDQAIALLKDK-PPGTFLVRDSTTYKGAYGLAVKvatpppGVNPFEAKGDPESElVRHFLIEPSPKGVK 79

                        90       100
                ....*....|....*....|
gi 18375644 181 VGGGER---FDSLTDLV-EH 196
Cdd:cd09927  80 LKGCPNepvFGSLSALVyQH 99
SH2_SH2B3 cd10412
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B3 (Lnk), ...
 1-59 1.86e-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: 40.65  E-value: 1.86e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18375644   1 MTSRRWFHPNITGVEAENLLLTRGVD--GSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNT 59
Cdd:cd10412   5 LSCYPWFHGPISRVKAAQLVQLQGPDahGVFLVRQSETRRGEYVLTFNFQGRAKHLRLSLT 65
SH2_HSH2_like cd09946
Src homology 2 domain found in hematopoietic SH2 (HSH2) protein; HSH2 is thought to function ...
 6-81 2.46e-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: 2.46e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18375644   6 WFHPNITGVEAENLLLTRGVdGSFLARPSKSNPGdFTLSVRRNGAVTHIKIQNTGDYYDLYGGEK--FATLAELVQYY 81
Cdd:cd09946   9 WFHGAISREAAENMLESQPL-GSFLIRVSHSHVG-YTLSYKAQSSCRHFMVKLLDDGTFMIPGEKvaHTSLHALVTFH 84
SH2_SAP1 cd10342
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP)1; The X-linked ...
 112-151 2.83e-04

Src homology 2 (SH2) domain found in SLAM-associated protein (SAP)1; 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: 198205  Cd Length: 103  Bit Score: 40.01  E-value: 2.83e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLTEKGKHGSFLVRESQSHPGDFVLSV 151
Cdd:cd10342   5 VYHGKISRETGEKLLLATGLDGSYLLRDSESVPGVYCLCV 44
SH2_SAP1 cd10342
Src homology 2 (SH2) domain found in SLAM-associated protein (SAP)1; The X-linked ...
 6-102 3.00e-04

Src homology 2 (SH2) domain found in SLAM-associated protein (SAP)1; 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: 198205  Cd Length: 103  Bit Score: 40.01  E-value: 3.00e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKI-QNTGDYYDLYGGEK-----FATLAELVQ 79
Cdd:cd10342   5 VYHGKISRETGEKLLLATGLDGSYLLRDSESVPGVYCLCVLYHGYIYTYRVsQTETGSWSAETAPGvhkryFRKIKNLIS 84

                        90       100
                ....*....|....*....|...
gi 18375644  80 YYMehhgqlKEKNGDVIELKYPL 102
Cdd:cd10342  85 AFQ------KPDQGIVIPLQYPV 101
SH2_SH2B2 cd10411
Src homology 2 (SH2) domain found in SH2B adapter proteins (SH2B1, SH2B2, SH2B3); SH2B2 (APS), ...
 6-84 1.08e-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: 38.45  E-value: 1.08e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRGV--DGSFLARPSKSNPGDFTLSVRRNGAVTHIK--IQNTGDYY--DLYggekFATLAELVQ 79
Cdd:cd10411  10 WFHGTLSRVKAAQLVLAGGPrsHGLFVIRQSETRPGEYVLTFNFQGKAKHLRlsLNGHGQCHvqHLW----FQSVFDMLR 85


                ....*
gi 18375644  80 YYMEH 84
Cdd:cd10411  86 HFHTH 90
SH2_SHB cd10389
Src homology 2 domain found in SH2 domain-containing adapter protein B (SHB); SHB functions in ...
 112-197 1.15e-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: 38.15  E-value: 1.15e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLtEKGKHGSFLVRESQSHPGDFVLSVRtgddkgeSNDGkskVTHVMIRCQELKYDVG-GGERFDSL 190
Cdd:cd10389   3 WYHGAISRGDAENLL-RLCKECSYLVRNSQTSKHDYSLSLK-------SNQG---FMHMKLAKTKEKYVLGqNSPPFDSV 71


                ....*..
gi 18375644 191 TDLVEHY 197
Cdd:cd10389  72 PEVIHYY 78
SH2_SHE cd10391
Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed ...
 6-102 1.75e-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: 37.63  E-value: 1.75e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLlTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDyyDLYGGEK----FATLAELVQYY 81
Cdd:cd10391   3 WYHGSISRAEAESRL-QPCKEASYLVRNSESGNSKYSIALKTSQGCVHIIVAQTKD--NKYTLNQtsavFDSIPEVVHYY 79

                        90       100
                ....*....|....*....|.
gi 18375644  82 MEHhgQLKEKNGDVIELKYPL 102
Cdd:cd10391  80 SNE--KLPFKGAEHMTLLHPV 98
SH2_PTK6_Brk cd10358
Src homology 2 domain found in protein-tyrosine kinase-6 (PTK6) which is also known as breast ...
 3-81 1.89e-03

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: 37.80  E-value: 1.89e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   3 SRRWFHPNITGVEAENLLLTR-GVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKI-QNTGDYYDLYGGEKFATLAELVQY 80
Cdd:cd10358   1 SEPWFFGCISRSEAVRRLQAEgNATGAFLIRVSEKPSADYVLSVRDTQAVRHYKIwRRAGGRLHLNEAVSFLSLPELVNY 80


                .
gi 18375644  81 Y 81
Cdd:cd10358  81 H 81
SH2_SOCS1 cd10382
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 115-203 2.14e-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: 198245  Cd Length: 98  Bit Score: 37.34  E-value: 2.14e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 115 GHLSGKEAEKLLtEKGKHGSFLVRESQSHPGDFVLSVRTgddkgesndgKSKVTHVMIRCQELKYDV-GGGERFDSLTDL 193
Cdd:cd10382  15 GPLSVEEAHAKL-KREPVGTFLIRDSRQKNCFFALSVKM----------ASGPVSIRILFKAGKFSLdGSKESFDCLFKL 83

                        90
                ....*....|....
gi 18375644 194 VEHY----KKNPMV 203
Cdd:cd10382  84 LEHYvaspKKMLGR 97
SH2_SH2D2A cd10416
Src homology 2 domain found in the SH2 domain containing protein 2A (SH2D2A); SH2D2A contains ...
 2-84 2.18e-03

Src homology 2 domain found in the SH2 domain containing protein 2A (SH2D2A); SH2D2A 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: 198279  Cd Length: 102  Bit Score: 37.71  E-value: 2.18e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   2 TSRRWFHPNITGVEAENLLLTRGVdGSFLARPSKSNPgDFTLSVRRNGAVTHIKIQNTGDYYDLYGGEK--FATLAELVQ 79
Cdd:cd10416   5 AAPAWFHGFITRREAERLLEPKPQ-GCYLVRFSESAV-TFVLTYRSRTCCRHFLLAQLRDGRHVVLGEDsaHARLQDLLL 82


                ....*
gi 18375644  80 YYMEH 84
Cdd:cd10416  83 HYTAH 87
SH2_CIS cd10718
Src homology 2 (SH2) domain found in cytokine-inducible SH2-containing protein (CIS); CIS ...
 6-82 2.34e-03

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: 37.05  E-value: 2.34e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRGvDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYGG-------EKFATLAELV 78
Cdd:cd10718   6 WYWGSITASEAHQALQKAP-EGTFLVRDSSHPSYMLTLSVKTTRGPTNVRIEYSDGSFRLDSSslarprlLSFPDVVSLV 84


                ....
gi 18375644  79 QYYM 82
Cdd:cd10718  85 QHYV 88
SH2_STAT_family cd09919
Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) ...
 110-170 2.50e-03

Src homology 2 (SH2) domain found in signal transducer and activator of transcription (STAT) family; STAT proteins mediate the signaling of cytokines and a number of growth factors from the receptors of these extracellular signaling molecules to the cell nucleus. STATs are specifically phosphorylated by receptor-associated Janus kinases, receptor tyrosine kinases, or cytoplasmic tyrosine kinases. The phosphorylated STAT molecules dimerize by reciprocal binding of their SH2 domains to the phosphotyrosine residues. These dimeric STATs translocate into the nucleus, bind to specific DNA sequences, and regulate the transcription of their target genes. However there are a number of unphosphorylated STATs that travel between the cytoplasm and nucleus and some STATs that exist as dimers in unstimulated cells that can exert biological functions independent of being activated by a receptor. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6. There are 6 conserved domains in STAT: N-terminal domain (NTD), coiled-coil domain (CCD), DNA-binding domain (DBD), alpha-helical linker domain (LD), SH2 domain, and transactivation domain (TAD). NTD is involved in dimerization of unphosphorylated STATs monomers and for the tetramerization between STAT1, STAT3, STAT4 and STAT5 on promoters with two or more tandem STAT binding sites. It also plays a role in promoting interactions with transcriptional co-activators such as CREB binding protein (CBP)/p300, as well as being important for nuclear import and deactivation of STATs involving tyrosine de-phosphorylation. The CCD interacts with other proteins, such as IFN regulatory protein 9 (IRF-9/p48) with STAT1 and c-JUN with STAT3 and is also thought to participate in the negative regulation of these proteins. Distinct genes are bound to STATs via their DBD domain. This domain is also involved in nuclear translocation of activated STAT1 and STAT3 phosphorylated dimers upon cytokine stimulation. LD links the DNA-binding and SH2 domains and is important for the transcriptional activation of STAT1 in response to IFN-gamma. It also plays a role in protein-protein interactions and has also been implicated in the constitutive nucleocytoplasmic shuttling of unphosphorylated STATs in resting cells. The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. Residues within this domain may be particularly important for some cellular functions mediated by the STATs as well as residues adjacent to this domain. The TAD interacts with several proteins, namely minichromosome maintenance complex component 5 (MCM5), breast cancer 1 (BRCA1) and CBP/p300. TAD also contains a modulatory phosphorylation site that regulates STAT activity and is necessary for maximal transcription of a number of target genes. The conserved tyrosine residue present in the C-terminus is crucial for dimerization via interaction with the SH2 domain upon the interaction of the ligand with the receptor. STAT activation by tyrosine phosphorylation also determines nuclear import and retention, DNA binding to specific DNA elements in the promoters of responsive genes, and transcriptional activation of STAT dimers. In addition to the SH2 domain there is a coiled-coil domain, a DNA binding domain, and a transactivation domain in the STAT 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: 198175  Cd Length: 115  Bit Score: 37.56  E-value: 2.50e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18375644 110 ERWFHGHLSGKEAEKLLtEKGKHGSFLVRESQSHPGDFVLSVrtgddKGESNDGKSKVTHV 170
Cdd:cd09919  19 DGLIMGFISKEEAEDLL-KKKPPGTFLLRFSDSELGGITIAW-----VNEDPDGQSQVIHL 73
SH2_Tec_Bmx cd10399
Src homology 2 (SH2) domain found in Tec protein, Bmx; A member of the Tec protein tyrosine ...
 6-103 3.55e-03

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: 37.24  E-value: 3.55e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644   6 WFHPNITGVEAENLLLTRGVDGSFLARPSkSNPGDFTLSV------RRNGAVTHIKIQ-NTGDYYDLYGGEKFATLAELV 78
Cdd:cd10399   8 WFAGNISRSQSEQLLRQKGKEGAFMVRNS-SQVGMYTVSLfskavnDKKGTVKHYHVHtNAENKLYLAENYCFDSIPKLI 86

                        90       100
                ....*....|....*....|....*
gi 18375644  79 qYYMEHHGQlkeknGDVIELKYPLN 103
Cdd:cd10399  87 -HYHQHNSA-----GMITRLRHPVS 105
SH2_SOCS1 cd10382
Src homology 2 (SH2) domain found in suppressor of cytokine signaling (SOCS) proteins; SH2 ...
 13-83 7.29e-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: 198245  Cd Length: 98  Bit Score: 35.80  E-value: 7.29e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18375644  13 GVEAENLLLTRGVDGSFLARPSKSNPGDFTLSVRRNGAVTHIKIQNTGDYYDLYG-GEKFATLAELVQYYME 83
Cdd:cd10382  18 SVEEAHAKLKREPVGTFLIRDSRQKNCFFALSVKMASGPVSIRILFKAGKFSLDGsKESFDCLFKLLEHYVA 89
SH2_SHE cd10391
Src homology 2 domain found in SH2 domain-containing adapter protein E (SHE); SHE is expressed ...
 112-197 7.41e-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: 36.09  E-value: 7.41e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18375644 112 WFHGHLSGKEAEKLLtEKGKHGSFLVRESQSHPGDFVLSVRTgddkgesndgKSKVTHVMI-RCQELKYDVGGGER-FDS 189
Cdd:cd10391   3 WYHGSISRAEAESRL-QPCKEASYLVRNSESGNSKYSIALKT----------SQGCVHIIVaQTKDNKYTLNQTSAvFDS 71


                ....*...
gi 18375644 190 LTDLVEHY 197
Cdd:cd10391  72 IPEVVHYY 79
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH