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Conserved domains on  [gi|1034613211|ref|XP_016859336|]
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SH2 domain-containing protein 6 isoform X9 [Homo sapiens]

Protein Classification

SH2 domain-containing protein( domain architecture ID 61889)

SH2 (Src homology 2) domain-containing protein may act as an intracellular signal-transducing protein

CATH:  3.30.505.10
Gene Ontology:  GO:0007165|GO:0035591|GO:0005515
PubMed:  15680235|7542925|36555586
SCOP:  4001650

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
SH2 super family cl15255
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 227-316 1.27e-46

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.


The actual alignment was detected with superfamily member cd09929:

Pssm-ID: 472789  Cd Length: 121  Bit Score: 153.24  E-value: 1.27e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034613211 227 DGAYTVRPSSGPHGSQPFTLAVLLRGRVFNIPIRRLDGGRHYALGREGRnREELFSSVAAMVQHFMWHPLPLVDRHSGSR 306
Cdd:cd09929    33 DGTFLVRDSSGKDSSQPYTLMVLYNDKVYNIQIRFLENTRQYALGTGLR-GEETFSSVAEIIEHHQKTPLLLIDGKDNTK 111

                          90
                  ....*....|
gi 1034613211 307 ELTCLLFPTK 316
Cdd:cd09929   112 DSTCLLYAAG 121
PHA03247 super family cl33720
large tegument protein UL36; Provisional
 12-249 6.60e-03

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 38.38  E-value: 6.60e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034613211   12 PQPPSLLPwyqgtcqSHCHGCECPRTQRLSHRNSRAPWAELTRMCLQAGATAPTPQMCGLPRLERRCSQPFLPACP---- 87
Cdd:PHA03247  2611 PAPPSPLP-------PDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQASSPpqrp 2683

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034613211   88 RDLETQDHSGPLG-----PSKPSPPLPQPTMLKGAVSLPVAGKQGpifgrREQGASSRVVPGPPKKPDEdlylecepdPV 162
Cdd:PHA03247  2684 RRRAARPTVGSLTsladpPPPPPTPEPAPHALVSATPLPPGPAAA-----RQASPALPAAPAPPAVPAG---------PA 2749

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034613211  163 LALTQTLSFQVLMPSGPlPRTSVVPRPTTAPQETRNGTADAASKEGRKSSLPSVAPTGSASAAEDGAYTVRPSSGPHGSQ 242
Cdd:PHA03247  2750 TPGGPARPARPPTTAGP-PAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPL 2828


                   ....*..
gi 1034613211  243 PFTLAVL 249
Cdd:PHA03247  2829 PPPTSAQ 2835
 
Name Accession Description Interval E-value
SH2_BLNK_SLP-76 cd09929
Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing ...
 227-316 1.27e-46

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: 153.24  E-value: 1.27e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034613211 227 DGAYTVRPSSGPHGSQPFTLAVLLRGRVFNIPIRRLDGGRHYALGREGRnREELFSSVAAMVQHFMWHPLPLVDRHSGSR 306
Cdd:cd09929    33 DGTFLVRDSSGKDSSQPYTLMVLYNDKVYNIQIRFLENTRQYALGTGLR-GEETFSSVAEIIEHHQKTPLLLIDGKDNTK 111

                          90
                  ....*....|
gi 1034613211 307 ELTCLLFPTK 316
Cdd:cd09929   112 DSTCLLYAAG 121
SH2 pfam00017
SH2 domain;
226-291 2.63e-07

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 47.21  E-value: 2.63e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034613211 226 EDGAYTVRPSSGPHGSqpFTLAVLLRGRVFNIPIRRLDGGRHYALGREGrnreelFSSVAAMVQHF 291
Cdd:pfam00017  20 PDGTFLVRESESTPGG--YTLSVRDDGKVKHYKIQSTDNGGYYISGGVK------FSSLAELVEHY 77
PHA03247 PHA03247
large tegument protein UL36; Provisional
 12-249 6.60e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 38.38  E-value: 6.60e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034613211   12 PQPPSLLPwyqgtcqSHCHGCECPRTQRLSHRNSRAPWAELTRMCLQAGATAPTPQMCGLPRLERRCSQPFLPACP---- 87
Cdd:PHA03247  2611 PAPPSPLP-------PDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQASSPpqrp 2683

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034613211   88 RDLETQDHSGPLG-----PSKPSPPLPQPTMLKGAVSLPVAGKQGpifgrREQGASSRVVPGPPKKPDEdlylecepdPV 162
Cdd:PHA03247  2684 RRRAARPTVGSLTsladpPPPPPTPEPAPHALVSATPLPPGPAAA-----RQASPALPAAPAPPAVPAG---------PA 2749

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034613211  163 LALTQTLSFQVLMPSGPlPRTSVVPRPTTAPQETRNGTADAASKEGRKSSLPSVAPTGSASAAEDGAYTVRPSSGPHGSQ 242
Cdd:PHA03247  2750 TPGGPARPARPPTTAGP-PAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPL 2828


                   ....*..
gi 1034613211  243 PFTLAVL 249
Cdd:PHA03247  2829 PPPTSAQ 2835
 
Name Accession Description Interval E-value
SH2_BLNK_SLP-76 cd09929
Src homology 2 (SH2) domain found in B-cell linker (BLNK) protein and SH2 domain-containing ...
 227-316 1.27e-46

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: 153.24  E-value: 1.27e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034613211 227 DGAYTVRPSSGPHGSQPFTLAVLLRGRVFNIPIRRLDGGRHYALGREGRnREELFSSVAAMVQHFMWHPLPLVDRHSGSR 306
Cdd:cd09929    33 DGTFLVRDSSGKDSSQPYTLMVLYNDKVYNIQIRFLENTRQYALGTGLR-GEETFSSVAEIIEHHQKTPLLLIDGKDNTK 111

                          90
                  ....*....|
gi 1034613211 307 ELTCLLFPTK 316
Cdd:cd09929   112 DSTCLLYAAG 121
SH2 pfam00017
SH2 domain;
226-291 2.63e-07

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 47.21  E-value: 2.63e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034613211 226 EDGAYTVRPSSGPHGSqpFTLAVLLRGRVFNIPIRRLDGGRHYALGREGrnreelFSSVAAMVQHF 291
Cdd:pfam00017  20 PDGTFLVRESESTPGG--YTLSVRDDGKVKHYKIQSTDNGGYYISGGVK------FSSLAELVEHY 77
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 226-291 1.75e-05

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: 42.44  E-value: 1.75e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034613211 226 EDGAYTVRPSSGPHGSqpFTLAVLLR-GRVFNIPIRRLDGGRHYALGREGRnreelFSSVAAMVQHF 291
Cdd:cd00173    20 PDGTFLVRESSSEPGD--YVLSVRSGdGKVKHYLIERNEGGYYLLGGSGRT-----FPSLPELVEHY 79
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
 226-298 1.43e-04

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: 40.20  E-value: 1.43e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034613211 226 EDGAYTVRPSSGPHGSQP-FTLAVLLRGRVFNIPIRRLDGGRHYalgregrNREELFSSVAAMVQHFMWHPLPL 298
Cdd:cd10361    24 NDGDFLVRKTEPKGGGKRkLVLSVRWDGKIRHFVINRDDGGKYY-------IEGKSFKSISELINYYQKTKEPI 90
PHA03247 PHA03247
large tegument protein UL36; Provisional
 12-249 6.60e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 38.38  E-value: 6.60e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034613211   12 PQPPSLLPwyqgtcqSHCHGCECPRTQRLSHRNSRAPWAELTRMCLQAGATAPTPQMCGLPRLERRCSQPFLPACP---- 87
Cdd:PHA03247  2611 PAPPSPLP-------PDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQASSPpqrp 2683

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034613211   88 RDLETQDHSGPLG-----PSKPSPPLPQPTMLKGAVSLPVAGKQGpifgrREQGASSRVVPGPPKKPDEdlylecepdPV 162
Cdd:PHA03247  2684 RRRAARPTVGSLTsladpPPPPPTPEPAPHALVSATPLPPGPAAA-----RQASPALPAAPAPPAVPAG---------PA 2749

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034613211  163 LALTQTLSFQVLMPSGPlPRTSVVPRPTTAPQETRNGTADAASKEGRKSSLPSVAPTGSASAAEDGAYTVRPSSGPHGSQ 242
Cdd:PHA03247  2750 TPGGPARPARPPTTAGP-PAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPL 2828


                   ....*..
gi 1034613211  243 PFTLAVL 249
Cdd:PHA03247  2829 PPPTSAQ 2835
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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