Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 385 QSWQHQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMRKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHE 464
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKSTREMKKIPTIILSISYKGVKFIDATTKNLICEHE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907123821 465 IRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFEVAYQLALQAQKS 530
Cdd:cd01274    81 IRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

SAM domain of AIDA1AB-like proteins, repeat 2; SAM (sterile alpha motif) domain repeat 2 of AIDA1AB-like proteins is a protein-protein interaction domain. AIDA1AB-like proteins have two tandem SAM domains. They may form an intramolecular head-to-tail homodimer. One of two basic motifs of the nuclear localization signal (NLS) is located within helix 5 of the SAM2 (motif HKRK). This signal plays a role in decoupling of SAM2 from SAM1, thus facilitating translocation of this type proteins into the nucleus. SAM domains of the AIDA1AB-like subfamily can directly bind ubiquitin and participate in regulating the degradation of ubiquitinated EphA receptors, particularly EPH-A8 receptor. Additionally AIDA1AB-like proteins may participate in the regulation of nucleoplasmic coilin protein interactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907123821 227 DGVSPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLWELELVNVLKVHLLGHRKRIIASLADR 291
Cdd:cd09500     1 DGNSPASVSEWLDSIGLGDYIETFLKHGYTSMERVKRIWEVELTNVLEINKLGHRKRILASLADR 65

Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 385 QSWQHQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMRKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHE 464
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKSTREMKKIPTIILSISYKGVKFIDATTKNLICEHE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907123821 465 IRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFEVAYQLALQAQKS 530
Cdd:cd01274    81 IRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821  397 ESCGYEANYLGSMLIKDLRGTESTQDACAKMRKS-TEHMKKIPTIILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDP 475
Cdd:smart00462   2 SGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAAqGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGP 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1907123821  476 EDLCTFAYITKDLQTSHHYCHVFSTVDVNltYEIILTLGQAFEVAYQLALQAQKS 530
Cdd:smart00462  82 DDLDVFGYIARDPGSSRFACHVFRCEKAA--EDIALAIGQAFQLAYELKLKARSE 134

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 401 YEANYLGSM-------LIKDLRgTESTQDA--CAKM------RKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHEI 465
Cdd:pfam00640   1 FAVRYLGSVevpeeraPDKNTR-MQQAREAirRVKAakinkiRGLSGETGPGTKVDLFISTDGLKLLNPDTQELIHDHPL 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907123821 466 RNIS-CAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDvnLTYEIILTLGQAFEVA 520
Cdd:pfam00640  80 VSISfCADGDPDLMRYFAYIARDKATNKFACHVFESED--GAQDIAQSIGQAFALA 133

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907123821 158 QSVGEWLESIGLQQYEsKLLLNGFDDVRFLGSnvMEEQDLREIGISDPQHRRKLLQAARSL 218
Cdd:pfam00536   6 EDVGEWLESIGLGQYI-DSFRAGYIDGDALLQ--LTEDDLLKLGVTLLGHRKKILYAIQRL 63

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907123821  226 YDGVSPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVkNLWELELVNVLKVHLLGHRKRIIASL 288
Cdd:smart00454   1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLL-LLTSEEDLKELGITKLGHRKKILKAI 62

Ankyrin repeat and sterile alpha motif (SAM) domain-containing (Anks) protein family Phosphotyrosine-binding (PTB) domain; Both AIDA-1b (AbetaPP intracellular domain-associated protein 1b) and Odin (also known as ankyrin repeat and sterile alpha motif domain-containing 1A; ANKS1A) belong to the Anks protein family. Both of these family members interacts with the EphA8 receptor. Ank members consists of ankyrin repeats, a SAM domain and a C-terminal PTB domain which is crucial for interaction with the juxtamembrane (JM) region of EphA8. PTB domains are classified into three groups, namely, phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains of which the Anks PTB is a member. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 385 QSWQHQPEKLIFESCGYEANYLGSMLIKDLRGTESTQDACAKMRKSTEHMKKIPTIILSITYKGVKFIDASNKNVIAEHE 464
Cdd:cd01274     1 TQWRHSPEKLITGSVNYEAHYLGSTEIKELRGTESTKKAIQKLKKSTREMKKIPTIILSISYKGVKFIDATTKNLICEHE 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907123821 465 IRNISCAAQDPEDLCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFEVAYQLALQAQKS 530
Cdd:cd01274    81 IRNISCACQDPEDLNTFAYITKDLKTDHHYCHVFCVLTVDLATEIILTLGQAFEVAYQLALRAQKS 146

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821  397 ESCGYEANYLGSMLIKDLRGTESTQDACAKMRKS-TEHMKKIPTIILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDP 475
Cdd:smart00462   2 SGVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAAqGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGP 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1907123821  476 EDLCTFAYITKDLQTSHHYCHVFSTVDVNltYEIILTLGQAFEVAYQLALQAQKS 530
Cdd:smart00462  82 DDLDVFGYIARDPGSSRFACHVFRCEKAA--EDIALAIGQAFQLAYELKLKARSE 134

Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 399 CGYEANYLGSMLIKDLRGTESTQDACAKMRKSTEHMKKIPT-IILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDPED 477
Cdd:cd00934     1 ASFQVKYLGSVEVGSSRGVDVVEEALKALAAALKSSKRKPGpVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPDN 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1907123821 478 LCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAF 517
Cdd:cd00934    81 PNVFAFIAGEEGGSGFRCHVFQCEDEEEAEEILQAIGQAF 120

SAM domain of Ship2 lipid phosphatase proteins; SAM (sterile alpha motif) domain of Ship2 subfamily is a protein-protein interaction domain. Ship2 proteins are lipid phosphatases (Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2) containing an N-terminal SH2 domain, a central phosphatase domain and a C-terminal SAM domain. Ship2 is involved in a number of PI3K signaling pathways. For example, it plays a role in regulation of the actin cytoskeleton remodeling, in insulin signaling pathways, and in EphA2 receptor endocytosis. SAM domain of Ship2 can interact with SAM domain of other proteins in these pathways, thus participating in signal transduction. In particular, SAM of Ship2 is known to form heterodimers with SAM domain of Eph-A2 receptor tyrosine kinase during receptor endocytosis as well as with SAM domain of PI3K effector protein Arap3 in the actin cytoskeleton signaling network. Since Ship2 plays a role in negatively regulating insulin signaling, it has been suggested that inhibition of its expression or function may contribute in treating type 2 diabetes and obesity-induced insulin resistance.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 153 SRTLEQSVGEWLESIGLQQYESKLLLNGFDDVRFLGSnVMEEqDLREIGISDPQHRRKLL 212
Cdd:cd09491     1 SLSWPKTVSEWLMNLGLQQYEEGLMHNGWDSLEFLSD-ITEE-DLEEAGVTNPAHKRRLL 58

Tyrosine-specific kinase/HM-motif TK (TM/HMTK) Phosphotyrosine-binding (PTB) PH-like fold; TK kinases catalyzes the transfer of the terminal phosphate of ATP to a specific tyrosine residue on its target protein. TK kinases play significant roles in development and cell division. Tyrosine-protein kinases can be divided into two subfamilies: receptor tyrosine kinases, which have an intracellular tyrosine kinase domain, a transmembrane domain and an extracellular ligand-binding domain; and non-receptor (cytoplasmic) tyrosine kinases, which are soluble, cytoplasmic kinases. In HMTK the conserved His-Arg-Asp sequence within the catalytic loop is replaced by a His-Met sequence. TM/HMTK have are 2-3 N-terminal PTB domains. PTB domains in TKs are thought to function analogously to the membrane targeting (PH, myristoylation) and pTyr binding (SH2) domains of Src subgroup kinases. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 401 YEANYLGSMLIKDLRGTESTQDACAKMRksteHMKKIPT-IILSITYKGVKFIDASNKNVIAEHEIRNISCAAQDPEDLC 479
Cdd:cd13161     4 FEAKYLGSVPVKEPKGNDVVMAAVKRLK----DLKLKPKpVVLVVSSEGIRVVERLTGEVLTNVPIKDISFVTVDPKDKK 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1907123821 480 TFAYITKDLQTSHHYCHVFSTVDVNltYEIILTLGQAFEVAYQ 522
Cdd:cd13161    80 LFAFISHDPRLGRITCHVFRCKRGA--QEICDTIAEAFKAAAE 120

Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold; The null mutations in the LDL receptor adaptor protein 1 (LDLRAP1) gene, which serves as an adaptor for LDLR endocytosis in the liver, causes autosomal recessive hypercholesterolemia (ARH). LDLRAP1 contains a single PTB domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd contains mammals, insects, and sponges.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 401 YEANYLGSMLIKDLRGTESTQDACA---KMRKSTEhmKKIPTIILSITYKGVKFIDASNKNVIAEHEIRNIS-CAAqDPE 476
Cdd:cd13159     5 FYLKYLGSTLVEKPKGEGATAEAVKtiiAMAKASG--KKLQKVTLTVSPKGIKVTDSATNETILEVSIYRISyCTA-DAN 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1907123821 477 DLCTFAYITKDLQTSHHYCHVFSTVDVNLTYEIILTLGQAFE 518
Cdd:cd13159    82 HDKVFAFIATNQDNEKLECHAFLCAKRKMAQAVTLTVAQAFN 123

SAM domain (Sterile alpha motif); It has been suggested that SAM is an evolutionarily conserved protein binding domain that is involved in the regulation of numerous developmental processes in diverse eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to homo- and heterooligomerise with other SAM domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907123821 227 DGVSPTSVPSWLDSLGLQDYVHSFlSSGYSSIDTVKNLWELELVNvLKVHLLGHRKRIIASL 288
Cdd:pfam00536   1 DGWSVEDVGEWLESIGLGQYIDSF-RAGYIDGDALLQLTEDDLLK-LGVTLLGHRKKILYAI 60

SAM (Sterile alpha motif ); SAM (Sterile Alpha Motif) domain is a module consisting of approximately 70 amino acids. This domain is found in the Fungi/Metazoa group and in a restricted number of bacteria. Proteins with SAM domains are represented by a wide variety of domain architectures and have different intracellular localization, including nucleus, cytoplasm and membranes. SAM domains have diverse functions. They can interact with proteins, RNAs and membrane lipids, contain site of phosphorylation and/or kinase docking site, and play a role in protein homo and hetero dimerization/oligomerization in processes ranging from signal transduction to regulation of transcription. Mutations in SAM domains have been linked to several diseases.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907123821 159 SVGEWLESIGLQQYESKLLLNGFDDVRFLgsnVMEEQDLREIGISDPQHRRKLLQAAR 216
Cdd:cd09487     1 DVAEWLESLGLEQYADLFRKNEIDGDALL---LLTDEDLKELGITSPGHRKKILRAIQ 55

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907123821  226 YDGVSPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVkNLWELELVNVLKVHLLGHRKRIIASL 288
Cdd:smart00454   1 VSQWSPESVADWLESIGLEQYADNFRKNGIDGALLL-LLTSEEDLKELGITKLGHRKKILKAI 62

SAM (Sterile alpha motif ), SASH1-like; SAM (sterile alpha motif) domain of SASH1-like proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. Proteins of this subfamily are known to be involved in preventing DN thymocytes from premature initiation of programmed cell death and in B cells activation and differentiation. They have been found downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 158 QSVGEWLESIGLQQYESKLLLNGFDDVRFLgsNVMEEQDLREIGISDPQHRRKLLQAARS 217
Cdd:cd09493     3 KTVEELLERINLQEHTSTLLLNGYETLEDF--KDLKESHLNELNITDPEHRAKLLTAAEL 60

Shc-like phosphotyrosine-binding (PTB) domain; Shc is a substrate for receptor tyrosine kinases, which can interact with phosphoproteins at NPXY motifs. Shc contains an PTB domain followed by an SH2 domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Shc-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 439 TIILSITYKGVKFIDASNKNVIAEHEIRNISCAA-QDPEDLCTFAYITKDlQTSHHYCHVFSTVDvNLTYEIILTLGQAF 517
Cdd:cd01209    84 NISLTISTDGLNLVTPDTGQIIANHHMQSISFASgGDPDTYDYVAYVAKD-PVNQRACHVLECGD-GLAQDVIATIGQAF 161

                  ....*....
gi 1907123821 518 EVAYQLALQ 526
Cdd:cd01209   162 ELRFKQYLK 170

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907123821 230 SPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLWELELVNvLKVHLLGHRKRIIASL 288
Cdd:cd09488     1 AFRSVGEWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTR-LGVTLVGHQKKILNSI 58

SAM domain of SAMSN1 subfamily; SAM (sterile alpha motif) domain of SAMSN1 (also known as HACS1 or NASH1) proteins is a predicted protein-protein interaction domain. Members of this group are putative signaling/adaptor proteins. They appear to mediate signal transduction in lymphoid tissues. Murine HACS1 protein likely plays a role in B cell activation and differentiation. Potential binding partners of HACS1 are SLAM, DEC205 and PIR-B receptors and also some unidentified tyrosine-phosphorylated proteins. Proteins of this group were found preferentially expressed in normal hematopietic tissues and in some malignancies including lymphoma, myeloid leukemia and myeloma.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907123821 154 RTLEQSVGEWLESIGLQQYESKLLLNGFDDVRFLGSnvMEEQDLREIGISDPQHRRKLLQAARSL 218
Cdd:cd09561     2 RPKPKTLQELLERIHLQEYTSTLLLNGYETLEDLKD--LKESHLIELNITDPEDRARLLSAAENL 64

SAM domain of SASH1 proteins, repeat 2; SAM (sterile alpha motif) repeat 2 of SASH1 proteins is a protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers if compare to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 159 SVGEWLESIGLQQYESKLLLNGFDDVRFLGSnvMEEQDLREIGISDPQHRRKLLQAARSL 218
Cdd:cd09492     9 SVSDWLVSIGLPMYSPPLLEAGFSTLSRVSS--LSETCLREAGITEERHIRKLLSAARLV 66

SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A5 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A5 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A5 gene is almost exclusively expressed in the nervous system. Murine EPH-A5 receptors participate in axon guidance during embryogenesis and play a role in the adult synaptic plasticity, particularly in neuron-target interactions in multiple neural circuits. Additionally EPH-A5 receptors and its ligand ephrin A5 regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. EphA5 gene expression was found decreased in a few different breast cancer cell lines, thus it might be a potential molecular marker for breast cancer carcinogenesis and progression.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907123821 233 SVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLwELELVNVLKVHLLGHRKRIIASLAD 290
Cdd:cd09546     5 SVGEWLEAIKMGRYTEIFMENGYSSMDAVAQV-TLEDLRRLGVTLVGHQKKIMNSIQE 61

SAM domain of caskin protein repeat 2; SAM (sterile alpha motif) domain repeat 2 of caskin1,2 proteins is a protein-protein interaction domain. Caskin has two tandem SAM domains. Caskin protein is known to interact with membrane-associated guanylate kinase CASK, and may play a role in neural development, synaptic protein targeting, and regulation of gene expression.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 159 SVGEWLESIGLQQYESKLLLNGFDDVRFLGSNVMEeqDLREIGISDPQHRRKLLQAARSL 218
Cdd:cd09498     9 DLLEWLSLLGLPQYHKVLVENGYDSIDFVTDLTWE--DLQDIGITKLGHQKKLMLAIKKL 66

SAM domain of SASH1 proteins, repeat 1; SAM (sterile alpha motif) repeat 1 of SASH1 proteins is a predicted protein-protein interaction domain. Members of this subfamily are putative adaptor proteins. They appear to mediate signal transduction. SASH1 can bind 14-3-3 proteins in response to IGF1/phosphatidylinositol 3-kinase signaling. SASH1 was found upregulated in different tissues including thymus, placenta, lungs and downregulated in some breast tumors, liver metastases and colon cancers, relative to corresponding normal tissues. SASH1 is a potential candidate for a tumor suppressor gene in breast cancers. At the same time, downregulation of SASH1 in colon cancer is associated with metastasis and a poor prognosis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907123821 158 QSVGEWLESIGLQQYESKLLLNGFDDVRFLgsNVMEEQDLREIGISDPQHRRKLLQAARSL 218
Cdd:cd09559     4 KSVEDLLDRINLKEHMPTFLFNGYEDLDTF--KLLEEEDLDELNIRDPEHRAVLLTAVELL 62

JNK-interacting protein-like (JIP) Phosphotyrosine-binding (PTB) domain; JIP is a mitogen-activated protein kinase scaffold protein. JIP consists of a C-terminal SH3 domain, followed by a PTB domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 425 AKMRKSTEHMKKIPTIILSITYKGVKFIDASNKNVIA-------EHEIRNIS-CAAQdPEDLCTFAYITK--DLQTSHhy 494
Cdd:cd01212    32 ATARRLTVHLRPPQSCILEISDRGLKMVDRSKPNKKDgkpcihyFYSLKNISfCGFH-PRNSRYFGFITKhpLLQRFA-- 108

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1907123821 495 CHVF----STVDVNltyEIIltlGQAFEVAYQ 522
Cdd:cd01212   109 CHVFvsqeSTRPVA---ESV---GRAFQRFYQ 134

SAM domain of EPH-A10 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A10 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A10 receptors and appears to mediate cell-cell initiated signal transduction. It was found preferentially expressed in the testis. EphA10 may be involved in the pathogenesis and development of prostate carcinoma and lymphocytic leukemia. It is a potential molecular marker and/or therapy target for these types of cancers.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 159 SVGEWLESIGLQQYESKLLLNGFDDVRFLGSnvMEEQDLREIGISDPQHRRKLLQAARSL 218
Cdd:cd09549     9 SVGEWLEALDLCRYKDNFAAAGYGSLEAVAR--MTAQDVLSLGITSLEHQELLLAGIQAL 66

SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B3 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B3 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B3 receptor protein kinase performs kinase-dependent and kinase-independent functions. It is known to be involved in thymus morphogenesis, in regulation of cell adhesion and migration. Also EphB3 controls cell positioning and ordered migration in the intestinal epithelium and plays a role in the regulation of adult retinal ganglion cell axon plasticity after optic nerve injury. In some experimental models overexpression of EphB3 enhances cell/cell contacts and suppresses colon tumor growth.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907123821 227 DGVSPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLWELELVNVlKVHLLGHRKRIIASLAD 290
Cdd:cd09553     2 DYTTFTTVGDWLDAIKMGRYKENFVSAGFASFDLVAQMTAEDLLRI-GVTLAGHQKKILSSIQD 64

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907123821 159 SVGEWLESIGLQQYESKLLLNGF---DDVRFlgsnvMEEQDLREIGISDPQHRRKLL 212
Cdd:cd09488     4 SVGEWLESIKMGRYKENFTAAGYtslDAVAQ-----MTAEDLTRLGVTLVGHQKKIL 55

SAM domain of SARM1-like, repeat 2; SAM (sterile alpha motif) domain repeat 2 of SARM1-like adaptor proteins is a protein-protein interaction domain. SARM1-like proteins contain two tandem SAM domains. SARM1-like proteins are involved in TLR (Toll-like receptor) signaling. They are responsible for targeted localization of the whole protein to post-synaptic regions of axons. In humans SARM1 expression is detected in kidney and liver.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907123821 162 EWLESIG--LQQYESKLLLNGFDdvRFLGSNVMEEQDLREIGISDPQHRRKLLQAAR 216
Cdd:cd09502    12 NWLQSLGpeYSQYTYQMLNAGID--RNSLPSLTEDQLLEDCGITNGIHRLRILNAIK 66

SAM domain of EPH-A8 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A8 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A8 receptors and appears to mediate cell-cell initiated signal transduction. EPH-A8 receptors are involved in ligand dependent (ephirin A2, A3, A5) regulation of cell adhesion and migration, and in ligand independent regulation of neurite outgrowth in neuronal cells. They perform signaling in kinase dependent and kinase independent manner. EPH-A8 receptors are known to interact with a number of different proteins including PI 3-kinase and AIDA1-like subfamily SAM repeat domain containing proteins. However other domains (not SAM) of EPH-A8 receptors are involved in these interactions.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1907123821 230 SPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLwELELVNVLKVHLLGHRKRIIASL 288
Cdd:cd09550     1 SCLSVDDWLDSIKMGRYKDHFAAGGYSSLGMVMRM-NIEDIRRLGITLMGHQKKILTSI 58

SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B4 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B4 protein kinase performs kinase-dependent and kinase-independent functions. These receptors play a role in the regular vascular system development during embryogenesis. They were found overexpressed in a variety of cancers, including carcinoma of the head and neck, ovarian cancer, bladder cancer, and downregulated in bone myeloma. Thus, EphB4 is a potential biomarker and a target for drug design.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907123821 233 SVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLWELELVNvLKVHLLGHRKRIIASL 288
Cdd:cd09554     5 SVGEWLRAIKMERYEDSFLQAGFTTFQLVSQISTEDLLR-MGVTLAGHQKKILSSI 59

SAM domain of EPH-B2 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B2 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B2 receptors and appears to mediate cell-cell initiated signal transduction. SAM domains of this subfamily form homodimers/oligomers (in head-to-head/tail-to-tail orientation); apparently such clustering is necessary for signaling. EPH-B2 receptor is involved in regulation of synaptic function; it is needed for normal vestibular function, proper formation of anterior commissure, control of cell positioning, and ordered migration in the intestinal epithelium. EPH-B2 plays a tumor suppressor role in colorectal cancer. It was found to be downregulated in gastric cancer and thus may be a negative biomarker for it.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907123821 227 DGVSPTSVPSWLDSLGLQDYVHSFLSSGYSSIDTVKNLWELELVNVlKVHLLGHRKRIIASL 288
Cdd:cd09552     2 DYTSFSTVDEWLDAIKMGQYKESFANAGFTSFDVVSQMTMEDILRV-GVTLAGHQKKILNSI 62

SAM domain of liprin-beta1,2 proteins repeat 1; SAM (sterile alpha motif) domain repeat 1 of liprin-beta1,2 proteins is a protein-protein interaction domain. Liprin-beta protein contain three copies (repeats) of SAM domain. They may form heterodimers with liprins-alpha through their SAM domains. It was suggested based on bioinformatic approaches that the second SAM domain of liprin-beta is potentially able to form polymers. Liprins were originally identified as LAR (leukocyte common antigen-related) transmembrane protein-tyrosine phosphatase-interacting proteins. They participate in mammary gland development, in axon guidance, and in the maintenance of lymphatic vessel integrity.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907123821 158 QSVGEWLESIGLQQYESKLLLNGFDDVRFLGsnvMEEQDL-REIGISDPQHRRKLLQAARS 217
Cdd:cd09563     7 EQVCDWLAELGLGQYVDECRRWVKSGQTLLK---ASPQELeKELGIKHPLHRKKLQLALQA 64

SAM domain of EPH-B1 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B1 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH- B1 receptors. In human vascular endothelial cells it appears to mediate cell-cell initiated signal transduction via the binding of the adaptor protein GRB10 (growth factor) through its SH2 domain to a conserved tyrosine that is phosphorylated. EPH-B1 receptors play a role in neurogenesis, in particular in regulation of proliferation and migration of neural progenitors in the hippocampus and in corneal neovascularization; they are involved in converting the crossed retinal projection to ipsilateral retinal projection. They may be potential targets in angiogenesis-related disorders.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 159 SVGEWLESIGLQQYESKLLLNGFDDVRFLGSnvMEEQDLREIGISDPQHRRKLLQAARSL 218
Cdd:cd09551     8 SVEDWLSAIKMSQYRDNFLSSGFTSLQLVAQ--MTSEDLLRIGVTLAGHQKKILNSIQSM 65

SAM domain of EPH-B4 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B4 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B4 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B4 protein kinase performs kinase-dependent and kinase-independent functions. These receptors play a role in the regular vascular system development during embryogenesis. They were found overexpressed in a variety of cancers, including carcinoma of the head and neck, ovarian cancer, bladder cancer, and downregulated in bone myeloma. Thus, EphB4 is a potential biomarker and a target for drug design.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 159 SVGEWLESIGLQQYESKLLLNGFDDVRFLGSnvMEEQDLREIGISDPQHRRKLLQAARSL 218
Cdd:cd09554     5 SVGEWLRAIKMERYEDSFLQAGFTTFQLVSQ--ISTEDLLRMGVTLAGHQKKILSSIQAM 62

SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A2 subfamily of receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A2 receptors and appears to mediate cell-cell initiated signal transduction. For example, SAM domain of EPH-A2 receptors interacts with SAM domain of Ship2 proteins (SH2 containing phosphoinositide 5-phosphotase-2) forming heterodimers; such recruitment of Ship2 by EPH-A2 attenuates the positive signal for receptor endocytosis. Eph-A2 is found overexpressed in many types of human cancer, including breast, prostate, lung and colon cancer. High level of expression could induce cancer progression by a variety of mechanisms and could be used as a novel tag for cancer immunotherapy. EPH-A2 receptors are attractive targets for drag design.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907123821 158 QSVGEWLESIGLQQYESKLLLNGFDDVRFLgsNVMEEQDLREIGISDPQHRRKL 211
Cdd:cd09543     6 RTVAEWLESIKMQQYTEHFMAAGYNSIDKV--LQMTQEDIKHIGVRLPGHQKRI 57

SAM domain of KIF24-like subfamily; SAM (sterile alpha motif) domain of KIF24 subfamily is a putative protein-protein interaction domain. This subfamily includes proteins related to human kinesin-like protein KIF24. SAM domain is located at the N-terminus followed by kinesin motor domain. Kinesins are proteins involved in a number of different cell processes including microtubule dynamics and axonal transport. Kinesins of this group belong to N-type; they drive microtubule plus end-directed transport. SAM apparently plays the role of adaptor or scaffold domain. In many cases SAM is known as a mediator of dimerization/oligomerization.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907123821 162 EWLESIGLQQYESKLLLNGFDDVRFLGSNVMeeQDLREIGISDPQHRRKLLQAARSL 218
Cdd:cd09541     5 EWLEEAGLQHYYPAFAAGGVTSIEALAQLTM--QDYASLGVQDMEDKQKLFRLIQTL 59

SAM domain of EPH-B3 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-B3 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-B3 receptors and appears to mediate cell-cell initiated signal transduction. EPH-B3 receptor protein kinase performs kinase-dependent and kinase-independent functions. It is known to be involved in thymus morphogenesis, in regulation of cell adhesion and migration. Also EphB3 controls cell positioning and ordered migration in the intestinal epithelium and plays a role in the regulation of adult retinal ganglion cell axon plasticity after optic nerve injury. In some experimental models overexpression of EphB3 enhances cell/cell contacts and suppresses colon tumor growth.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907123821 159 SVGEWLESIGLQQYESKLLLNGFDDVRFLGSnvMEEQDLREIGISDPQHRRKLLQAARSL 218
Cdd:cd09553     8 TVGDWLDAIKMGRYKENFVSAGFASFDLVAQ--MTAEDLLRIGVTLAGHQKKILSSIQDM 65