Src homology 2 domain found in Signal-transducing adaptor protein 2 (STAP2); STAP2 is a signal-transducing adaptor protein. It is composed of a Pleckstrin homology (PH) and SH2 domains along with several tyrosine phosphorylation sites. The STAP2 protein is the substrate of breast tumor kinase, an Src-type non-receptor tyrosine kinase that mediates the interactions linking proteins involved in signal transduction pathways. STAP2 has alternative splicing variants. STAP2 has been shown to interact with tyrosine-protein kinase 6 (PTK6). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62511215 151 PWCFLQVSRLEAQLLLERYPECGNLLLRPGGDGKDSVSVTTRQILNGSPVVKHYKVKRAGSKYVIDVEDPFSCPSLEAVV 230
Cdd:cd10404   1 PSCFLKVSRLEAQLLLERYPECGNLLLRPGGDGADGVSVTTRQMLNGTPVVRHYKVKREGPKYVIDVEEPFSCTSLDAVV 80

                        90
                ....*....|....*..
gi 62511215 231 NYFVTHTKRALVPFLLD 247
Cdd:cd10404  81 NYFVSHTKKALVPFLLD 97

Src homology 2 domain found in Signal-transducing adaptor protein 2 (STAP2); STAP2 is a signal-transducing adaptor protein. It is composed of a Pleckstrin homology (PH) and SH2 domains along with several tyrosine phosphorylation sites. The STAP2 protein is the substrate of breast tumor kinase, an Src-type non-receptor tyrosine kinase that mediates the interactions linking proteins involved in signal transduction pathways. STAP2 has alternative splicing variants. STAP2 has been shown to interact with tyrosine-protein kinase 6 (PTK6). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62511215 151 PWCFLQVSRLEAQLLLERYPECGNLLLRPGGDGKDSVSVTTRQILNGSPVVKHYKVKRAGSKYVIDVEDPFSCPSLEAVV 230
Cdd:cd10404   1 PSCFLKVSRLEAQLLLERYPECGNLLLRPGGDGADGVSVTTRQMLNGTPVVRHYKVKREGPKYVIDVEEPFSCTSLDAVV 80

                        90
                ....*....|....*..
gi 62511215 231 NYFVTHTKRALVPFLLD 247
Cdd:cd10404  81 NYFVSHTKKALVPFLLD 97

Src homology 2 domain found in Signal-transducing adaptor protein 2 (STAP2); STAP2 is a signal-transducing adaptor protein. It is composed of a Pleckstrin homology (PH) and SH2 domains along with several tyrosine phosphorylation sites. The STAP2 protein is the substrate of breast tumor kinase, an Src-type non-receptor tyrosine kinase that mediates the interactions linking proteins involved in signal transduction pathways. STAP2 has alternative splicing variants. STAP2 has been shown to interact with tyrosine-protein kinase 6 (PTK6). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62511215 151 PWCFLQVSRLEAQLLLERYPECGNLLLRPGGDGKDSVSVTTRQILNGSPVVKHYKVKRAGSKYVIDVEDPFSCPSLEAVV 230
Cdd:cd10404   1 PSCFLKVSRLEAQLLLERYPECGNLLLRPGGDGADGVSVTTRQMLNGTPVVRHYKVKREGPKYVIDVEEPFSCTSLDAVV 80

                        90
                ....*....|....*..
gi 62511215 231 NYFVTHTKRALVPFLLD 247
Cdd:cd10404  81 NYFVSHTKKALVPFLLD 97

Src homology 2 domain found in Signal-transducing adaptor protein (STAP) family; STAP1 and STAP2 are signal-transducing adaptor proteins. They are composed of a Pleckstrin homology (PH) and SH2 domains along with several tyrosine phosphorylation sites. STAP-1 is an ortholog of BRDG1 (BCR downstream signaling 1). STAP1 protein functions as a docking protein acting downstream of Tec tyrosine kinase in B cell antigen receptor signaling. The protein is phosphorylated by Tec and participates in a positive feedback loop, increasing Tec activity. STAP1 has been shown to interact with C19orf2, an unconventional prefoldin RPB5 interactor. The STAP2 protein is the substrate of breast tumor kinase, an Src-type non-receptor tyrosine kinase that mediates the interactions linking proteins involved in signal transduction pathways. STAP2 has alternative splicing variants. STAP2 has been shown to interact with tyrosine-protein kinase 6 (PTK6). In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62511215 151 PWCFLQVSRLEAQLLLERYPECGNLLLRPGGDGkDSVSVTTRQILNGsPVVKHYKVKRAGSKYVIDVEDPFSCPSLEAVV 230
Cdd:cd09939   1 PACFYTVSRKEATELLERNPSCGNMLLRPGSDS-RNYSVTTRQEINI-PVIRHYKVMSVGQNYTIELEKPVTCPNLFSVI 78

                        90
                ....*....|....*.
gi 62511215 231 NYFVTHTKRALVPFLL 246
Cdd:cd09939  79 NYFVKETRGNLRPFIL 94

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62511215 151 PWCFLQVSRLEAQLLLERYPECGNLLLRPGGDGKDSVSVTTRqiLNGSpvVKHYKVKRAGSKYVIDVEDPFscpSLEAVV 230
Cdd:cd09932   5 EWFHANLTREQAEEMLMRVPRDGAFLVRPSETDPNSFAISFR--AEGK--IKHCRIKQEGRLFVIGTSQFE---SLVELV 77

                ....*.
gi 62511215 231 NYFVTH 236
Cdd:cd09932  78 SYYEKH 83

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62511215 151 PWCFLQVSRLEA-QLLLERYPECGNLLLRPGGDGKDSVSVTTRqilnGSPVVKHYKVKRA--GSKYvIDVEDPFscPSLE 227
Cdd:cd10360   1 PWYFSGISRTQAqQLLLSPPNEPGAFLIRPSESSLGGYSLSVR----AQAKVCHYRICMApsGSLY-LQKGRLF--PGLE 73

                ....*.
gi 62511215 228 AVVNYF 233
Cdd:cd10360  74 ELLAYY 79

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62511215 151 PWCFLQVSRLEA--QLLLERYPeCGNLLLRPGGDGKDSVSVTTRQILNGS-PVVKHYKVKR--AGSKYVIDVEdpfSCPS 225
Cdd:cd09933   4 EWFFGKIKRKDAekLLLAPGNP-RGTFLIRESETTPGAYSLSVRDGDDARgDTVKHYRIRKldNGGYYITTRA---TFPT 79

                        90
                ....*....|..
gi 62511215 226 LEAVVNYFVTHT 237
Cdd:cd09933  80 LQELVQHYSKDA 91