UniProtKB - O14796 (SH21B_HUMAN)
Protein
SH2 domain-containing protein 1B
Gene
SH2D1B
Organism
Homo sapiens (Human)
Status
Functioni
Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as CD84, SLAMF1, LY9 and CD244 (PubMed:11689425). In SLAM signaling seems to cooperate with SH2D1A/SAP. Plays a role in regulation of effector functions of natural killer (NK) cells by controlling signal transduction through CD244/2B4 without effecting its tyrosine phosphorylation; downstream signaling involves PLCG1 and ERK activation (PubMed:24687958). Activation of SLAMF7-mediated NK cell function does not effect receptor tyrosine phosphorylation but distal signaling (By similarity). In the context of NK cell-mediated cytotoxicity does not enhance conjugate formation with target cells but stimulates polarization of the microtubule-organizing center and cytotoxic granules toward the NK cell synapse (PubMed:24687958). Negatively regulates CD40-induced cytokine production in dendritic cells downstream of SLAM family receptors probably by inducing activation of the PI3K pathway to inhibit p38 MAPK and JNK activation (By similarity).By similarity1 Publication2 Publications
GO - Molecular functioni
- protein-macromolecule adaptor activity Source: UniProtKB
GO - Biological processi
- adaptive immune response Source: UniProtKB-KW
- innate immune response Source: UniProtKB-KW
- leukocyte activation involved in immune response Source: UniProtKB
- positive regulation of innate immune response Source: UniProtKB
- positive regulation of natural killer cell mediated immunity Source: UniProtKB
- regulation of immune response Source: Reactome
Keywordsi
Biological process | Adaptive immunity, Immunity, Innate immunity |
Enzyme and pathway databases
PathwayCommonsi | O14796 |
Reactomei | R-HSA-198933, Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell |
SignaLinki | O14796 |
Names & Taxonomyi
Protein namesi | Recommended name: SH2 domain-containing protein 1BAlternative name(s): EWS/FLI1-activated transcript 2 Short name: EAT-2 |
Gene namesi | Name:SH2D1B Synonyms:EAT2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:30416, SH2D1B |
MIMi | 608510, gene |
neXtProti | NX_O14796 |
VEuPathDBi | HostDB:ENSG00000198574.5 |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 127 | Y → F: No stimulation of granule polarization during NK-mediated cytotoxicity, abolishes activation of CD244/2B4-mediated cytotoxicity, abolishes augmentation of CD244/2B4-triggered PLCG1 phosphorylation and ERK activation. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 117157 |
OpenTargetsi | ENSG00000198574 |
PharmGKBi | PA142670926 |
Miscellaneous databases
Pharosi | O14796, Tbio |
Genetic variation databases
BioMutai | SH2D1B |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000097724 | 1 – 132 | SH2 domain-containing protein 1BAdd BLAST | 132 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 127 | Phosphotyrosine1 Publication | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
MassIVEi | O14796 |
PaxDbi | O14796 |
PeptideAtlasi | O14796 |
PRIDEi | O14796 |
ProteomicsDBi | 48245 [O14796-1] 48246 [O14796-2] |
PTM databases
iPTMneti | O14796 |
PhosphoSitePlusi | O14796 |
Expressioni
Gene expression databases
Bgeei | ENSG00000198574, Expressed in granulocyte and 114 other tissues |
Genevisiblei | O14796, HS |
Organism-specific databases
HPAi | ENSG00000198574, Tissue enriched (blood) |
Interactioni
Subunit structurei
Binds to the phosphorylated receptors CD84, SLAMF1, LY9 and CD244. Does not bind to non-phosphorylated SLAMF1 (PubMed:11689425).
Interacts with SLAMF7 (via ITSM phosphorylated on 'Tyr-304').
Interacts with Src kinases HCK, LYN, FYN, FGR and LCK (via kinase domains) (By similarity).
Interacts (phosphorylated at Tyr-127) with PLCG1.
By similarity2 PublicationsBinary interactionsi
Hide detailsO14796
Isoform 2 [O14796-2]
With | #Exp. | IntAct |
---|---|---|
WFS1 [O76024] | 3 | EBI-25899828,EBI-720609 |
Protein-protein interaction databases
BioGRIDi | 125563, 28 interactors |
IntActi | O14796, 37 interactors |
MINTi | O14796 |
STRINGi | 9606.ENSP00000356906 |
Miscellaneous databases
RNActi | O14796, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O14796 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 5 – 101 | SH2PROSITE-ProRule annotationAdd BLAST | 97 |
Keywords - Domaini
SH2 domainPhylogenomic databases
eggNOGi | KOG0565, Eukaryota |
GeneTreei | ENSGT00940000163577 |
HOGENOMi | CLU_125532_0_0_1 |
InParanoidi | O14796 |
OMAi | YYHGPLT |
OrthoDBi | 1417830at2759 |
PhylomeDBi | O14796 |
TreeFami | TF343096 |
Family and domain databases
CDDi | cd10342, SH2_SAP1, 1 hit |
Gene3Di | 3.30.505.10, 1 hit |
InterProi | View protein in InterPro IPR035049, EAT2_SH2 IPR000980, SH2 IPR036860, SH2_dom_sf |
Pfami | View protein in Pfam PF00017, SH2, 1 hit |
PRINTSi | PR00401, SH2DOMAIN |
SMARTi | View protein in SMART SM00252, SH2, 1 hit |
SUPFAMi | SSF55550, SSF55550, 1 hit |
PROSITEi | View protein in PROSITE PS50001, SH2, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: O14796-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MDLPYYHGRL TKQDCETLLL KEGVDGNFLL RDSESIPGVL CLCVSFKNIV
60 70 80 90 100
YTYRIFREKH GYYRIQTAEG SPKQVFPSLK ELISKFEKPN QGMVVHLLKP
110 120 130
IKRTSPSLRW RGLKLELETF VNSNSDYVDV LP
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_051347 | 36 | I → T. Corresponds to variant dbSNP:rs35688243Ensembl. | 1 | |
Natural variantiVAR_051348 | 122 | N → K1 PublicationCorresponds to variant dbSNP:rs34001279Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_010341 | 67 – 121 | Missing in isoform 2. 1 PublicationAdd BLAST | 55 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF256653 mRNA Translation: AAL26000.1 AF403479 mRNA Translation: AAL27357.1 AF484964 mRNA Translation: AAM28522.1 AK097162 mRNA Translation: BAC04968.1 AK314743 mRNA Translation: BAG37283.1 AL512785 Genomic DNA No translation available. CH471067 Genomic DNA Translation: EAW90703.1 BC022407 mRNA Translation: AAH22407.1 BC066595 mRNA Translation: AAH66595.1 AF020264 Genomic DNA Translation: AAB70927.1 |
CCDSi | CCDS30928.1 [O14796-1] |
RefSeqi | NP_444512.2, NM_053282.4 [O14796-1] |
Genome annotation databases
Ensembli | ENST00000367929; ENSP00000356906; ENSG00000198574 [O14796-1] |
GeneIDi | 117157 |
KEGGi | hsa:117157 |
UCSCi | uc001gbz.2, human [O14796-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF256653 mRNA Translation: AAL26000.1 AF403479 mRNA Translation: AAL27357.1 AF484964 mRNA Translation: AAM28522.1 AK097162 mRNA Translation: BAC04968.1 AK314743 mRNA Translation: BAG37283.1 AL512785 Genomic DNA No translation available. CH471067 Genomic DNA Translation: EAW90703.1 BC022407 mRNA Translation: AAH22407.1 BC066595 mRNA Translation: AAH66595.1 AF020264 Genomic DNA Translation: AAB70927.1 |
CCDSi | CCDS30928.1 [O14796-1] |
RefSeqi | NP_444512.2, NM_053282.4 [O14796-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5KAZ | X-ray | 1.70 | A | 1-104 | [»] | |
SMRi | O14796 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 125563, 28 interactors |
IntActi | O14796, 37 interactors |
MINTi | O14796 |
STRINGi | 9606.ENSP00000356906 |
PTM databases
iPTMneti | O14796 |
PhosphoSitePlusi | O14796 |
Genetic variation databases
BioMutai | SH2D1B |
Proteomic databases
MassIVEi | O14796 |
PaxDbi | O14796 |
PeptideAtlasi | O14796 |
PRIDEi | O14796 |
ProteomicsDBi | 48245 [O14796-1] 48246 [O14796-2] |
Protocols and materials databases
Antibodypediai | 34320, 237 antibodies |
DNASUi | 117157 |
Genome annotation databases
Ensembli | ENST00000367929; ENSP00000356906; ENSG00000198574 [O14796-1] |
GeneIDi | 117157 |
KEGGi | hsa:117157 |
UCSCi | uc001gbz.2, human [O14796-1] |
Organism-specific databases
CTDi | 117157 |
DisGeNETi | 117157 |
GeneCardsi | SH2D1B |
HGNCi | HGNC:30416, SH2D1B |
HPAi | ENSG00000198574, Tissue enriched (blood) |
MIMi | 608510, gene |
neXtProti | NX_O14796 |
OpenTargetsi | ENSG00000198574 |
PharmGKBi | PA142670926 |
VEuPathDBi | HostDB:ENSG00000198574.5 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0565, Eukaryota |
GeneTreei | ENSGT00940000163577 |
HOGENOMi | CLU_125532_0_0_1 |
InParanoidi | O14796 |
OMAi | YYHGPLT |
OrthoDBi | 1417830at2759 |
PhylomeDBi | O14796 |
TreeFami | TF343096 |
Enzyme and pathway databases
PathwayCommonsi | O14796 |
Reactomei | R-HSA-198933, Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell |
SignaLinki | O14796 |
Miscellaneous databases
BioGRID-ORCSi | 117157, 7 hits in 990 CRISPR screens |
GeneWikii | SH2D1B |
GenomeRNAii | 117157 |
Pharosi | O14796, Tbio |
PROi | PR:O14796 |
RNActi | O14796, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000198574, Expressed in granulocyte and 114 other tissues |
Genevisiblei | O14796, HS |
Family and domain databases
CDDi | cd10342, SH2_SAP1, 1 hit |
Gene3Di | 3.30.505.10, 1 hit |
InterProi | View protein in InterPro IPR035049, EAT2_SH2 IPR000980, SH2 IPR036860, SH2_dom_sf |
Pfami | View protein in Pfam PF00017, SH2, 1 hit |
PRINTSi | PR00401, SH2DOMAIN |
SMARTi | View protein in SMART SM00252, SH2, 1 hit |
SUPFAMi | SSF55550, SSF55550, 1 hit |
PROSITEi | View protein in PROSITE PS50001, SH2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SH21B_HUMAN | |
Accessioni | O14796Primary (citable) accession number: O14796 Secondary accession number(s): B2RBN6 Q969K9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 27, 2001 |
Last sequence update: | September 19, 2002 | |
Last modified: | April 7, 2021 | |
This is version 166 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references