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Conserved domains on  [gi|1907173526|ref|XP_011239846|]
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SH2 domain-containing protein 6 isoform X1 [Mus musculus]

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 ...
 262-355 1.32e-39

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: 136.29  E-value: 1.32e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173526 262 SVAEDGAYTVRLSSGPHSSQPFTLAVLLRGRVFNIPIRQLDGGHHYALGREGRNhEELFSSVAAMVQHYTKHPLPLVDGH 341
Cdd:cd09929    29 RSNKDGTFLVRDSSGKDSSQPYTLMVLYNDKVYNIQIRFLENTRQYALGTGLRG-EETFSSVAEIIEHHQKTPLLLIDGK 107

                          90
                  ....*....|....
gi 1907173526 342 SGNRGLTYLRFPTK 355
Cdd:cd09929   108 DNTKDSTCLLYAAG 121
 
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 ...
 262-355 1.32e-39

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: 136.29  E-value: 1.32e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173526 262 SVAEDGAYTVRLSSGPHSSQPFTLAVLLRGRVFNIPIRQLDGGHHYALGREGRNhEELFSSVAAMVQHYTKHPLPLVDGH 341
Cdd:cd09929    29 RSNKDGTFLVRDSSGKDSSQPYTLMVLYNDKVYNIQIRFLENTRQYALGTGLRG-EETFSSVAEIIEHHQKTPLLLIDGK 107

                          90
                  ....*....|....
gi 1907173526 342 SGNRGLTYLRFPTK 355
Cdd:cd09929   108 DNTKDSTCLLYAAG 121
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 265-336 8.15e-08

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: 49.15  E-value: 8.15e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907173526  265 EDGAYTVRLSSgpHSSQPFTLAVLLRGRVFNIPIRQLDGGHhYALGREgrnheELFSSVAAMVQHYTKHPLP 336
Cdd:smart00252  21 GDGDFLVRDSE--SSPGDYVLSVRVKGKVKHYRIRRNEDGK-FYLEGG-----RKFPSLVELVEHYQKNSLG 84
SH2 pfam00017
SH2 domain;
265-330 2.33e-07

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 47.60  E-value: 2.33e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907173526 265 EDGAYTVRLSSgphsSQP--FTLAVLLRGRVFNIPIRQLDGGHHYALGREGrnheelFSSVAAMVQHY 330
Cdd:pfam00017  20 PDGTFLVRESE----STPggYTLSVRDDGKVKHYKIQSTDNGGYYISGGVK------FSSLAELVEHY 77
 
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 ...
 262-355 1.32e-39

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: 136.29  E-value: 1.32e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173526 262 SVAEDGAYTVRLSSGPHSSQPFTLAVLLRGRVFNIPIRQLDGGHHYALGREGRNhEELFSSVAAMVQHYTKHPLPLVDGH 341
Cdd:cd09929    29 RSNKDGTFLVRDSSGKDSSQPYTLMVLYNDKVYNIQIRFLENTRQYALGTGLRG-EETFSSVAEIIEHHQKTPLLLIDGK 107

                          90
                  ....*....|....
gi 1907173526 342 SGNRGLTYLRFPTK 355
Cdd:cd09929   108 DNTKDSTCLLYAAG 121
SH2 smart00252
Src homology 2 domains; Src homology 2 domains bind phosphotyrosine-containing polypeptides ...
 265-336 8.15e-08

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: 49.15  E-value: 8.15e-08
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907173526  265 EDGAYTVRLSSgpHSSQPFTLAVLLRGRVFNIPIRQLDGGHhYALGREgrnheELFSSVAAMVQHYTKHPLP 336
Cdd:smart00252  21 GDGDFLVRDSE--SSPGDYVLSVRVKGKVKHYRIRRNEDGK-FYLEGG-----RKFPSLVELVEHYQKNSLG 84
SH2 pfam00017
SH2 domain;
265-330 2.33e-07

SH2 domain;


Pssm-ID: 425423 [Multi-domain]  Cd Length: 77  Bit Score: 47.60  E-value: 2.33e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907173526 265 EDGAYTVRLSSgphsSQP--FTLAVLLRGRVFNIPIRQLDGGHHYALGREGrnheelFSSVAAMVQHY 330
Cdd:pfam00017  20 PDGTFLVRESE----STPggYTLSVRDDGKVKHYKIQSTDNGGYYISGGVK------FSSLAELVEHY 77
SH2_Fps_family cd10361
Src homology 2 (SH2) domain found in feline sarcoma, Fujinami poultry sarcoma, and fes-related ...
 265-337 1.90e-05

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: 42.51  E-value: 1.90e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907173526 265 EDGAYTVRLSSG-PHSSQPFTLAVLLRGRVFNIPIRQLDGGHHYalgregrNHEELFSSVAAMVQHYTKHPLPL 337
Cdd:cd10361    24 NDGDFLVRKTEPkGGGKRKLVLSVRWDGKIRHFVINRDDGGKYY-------IEGKSFKSISELINYYQKTKEPI 90
SH2 cd00173
Src homology 2 (SH2) domain; In general, SH2 domains are involved in signal transduction; they ...
 265-330 9.83e-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: 40.52  E-value: 9.83e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907173526 265 EDGAYTVRLSSGPHSSqpFTLAVLLR-GRVFNIPIRQLDGGHHYALGregrnHEELFSSVAAMVQHY 330
Cdd:cd00173    20 PDGTFLVRESSSEPGD--YVLSVRSGdGKVKHYLIERNEGGYYLLGG-----SGRTFPSLPELVEHY 79
SH2_C-SH2_PLC_gamma_like cd09932
C-terminal Src homology 2 (C-SH2) domain in Phospholipase C gamma; Phospholipase C gamma is a ...
 263-353 1.91e-03

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: 37.24  E-value: 1.91e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907173526 263 VAEDGAYTVRLSSGPHSSqpFTLAVLLRGRVfnipirqldggHHYALGREGR-----NHEelFSSVAAMVQHYTKHPLpl 337
Cdd:cd09932    23 VPRDGAFLVRPSETDPNS--FAISFRAEGKI-----------KHCRIKQEGRlfvigTSQ--FESLVELVSYYEKHPL-- 85

                          90
                  ....*....|....*.
gi 1907173526 338 vdghsgNRGlTYLRFP 353
Cdd:cd09932    86 ------YRK-IKLRYP 94
 
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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