Version 5.4
Homo sapiens Protein: SH2B1
Summary
InnateDB Protein IDBP-239366.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol SH2B1
Protein Name SH2B adaptor protein 1
Synonyms PSM; SH2B;
Species Homo sapiens
Ensembl Protein ENSP00000378903
InnateDB Gene IDBG-23518 (SH2B1)
Protein Structure
UniProt Annotation
Function Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways mediated by Janus kinase (JAK) and receptor tyrosine kinases, including the receptors of insulin (INS), insulin-like growth factor I (IGF1), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), platelet-derived growth factor (PDGF) and fibroblast growth factors (FGFs). In growth hormone (GH) signaling, autophosphorylated ('Tyr-813') JAK2 recruits SH2B1, which in turn is phosphorylated by JAK2 on tyrosine residues. These phosphotyrosines form potential binding sites for other signaling proteins. GH also promotes serine/threonine phosphorylation of SH2B1 and these phosphorylated residues may serve to recruit other proteins to the GHR-JAK2-SH2B1 complexes, such as RAC1. In leptin (LEP) signaling, binds to and potentiates the activation of JAK2 by globally enhancing downstream pathways. In response to leptin, binds simultaneously to both, JAK2 and IRS1 or IRS2, thus mediating formation of a complex of JAK2, SH2B1 and IRS1 or IRS2. Mediates tyrosine phosphorylation of IRS1 and IRS2, resulting in activation of the PI 3-kinase pathway. Acts as positive regulator of NGF-mediated activation of the Akt/Forkhead pathway; prolongs NGF-induced phosphorylation of AKT1 on 'Ser-473' and AKT1 enzymatic activity. Enhances the kinase activity of the cytokine receptor-associated tyrosine kinase JAK2 and of other receptor tyrosine kinases, such as FGFR3 and NTRK1. For JAK2, the mechanism seems to involve dimerization of both, SH2B1 and JAK2. Enhances RET phosphorylation and kinase activity. Isoforms seem to be differentially involved in IGF-I and PDGF-induced mitogenesis (By similarity). {ECO:0000250}.
Subcellular Localization Cytoplasm {ECO:0000250}. Membrane {ECO:0000305}. Nucleus {ECO:0000250}. Note=Shuttles between the nucleus and the cytoplasm. {ECO:0000250}.
Disease Associations
Tissue Specificity Widely expressed with highest levels in skeletal muscle and ovary. {ECO:0000269PubMed:15767667}.
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 23 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.
Experimentally validated
Total 23 [view]
Protein-Protein 23 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 5 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004871 signal transducer activity
GO:0005515 protein binding
Biological Process
GO:0007596 blood coagulation
GO:0035556 intracellular signal transduction
Cellular Component
GO:0005634 nucleus
GO:0005829 cytosol
GO:0016020 membrane
Protein Structure and Domains
PDB ID
InterPro IPR000980 SH2 domain
IPR001849 Pleckstrin homology domain
IPR015012 Phenylalanine zipper
PFAM PF00017
PF14633
PF00169
PF08916
PRINTS PR00401
PIRSF
SMART SM00252
SM00233
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt Q9NRF2
PhosphoSite PhosphoSite-Q9NRF2
TrEMBL H3BVF6
UniProt Splice Variant
Entrez Gene 25970
UniGene Hs.15744
RefSeq XP_005255297
HUGO HGNC:30417
OMIM 608937
CCDS CCDS32424
HPRD 12336
IMGT
EMBL AB037720 AC133550 AF227967 AF227968 AF227969 AK027488 AK290332 AK297080 AL049924 AL713760 BC010704 CH471267
GenPept AAF73912 AAF73913 AAF73914 AAH10704 BAA92537 BAB55148 BAF83021 BAG59597 CAB43208 CAD28530 EAW52000 EAW52004

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

InnateDB is being developed jointly by the Brinkman Laboratory (Simon Fraser University, British Columbia, Canada), the Hancock Laboratory (University of British Columbia, Vancouver, British Columbia) and the Lynn EMBL Australia Group (South Australian Health & Medical Research Institute and Flinders University, Adelaide, Australia).

Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca