InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Sh2b1

Summary

InnateDB Protein

IDBP-209518.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Sh2b1

Protein Name

SH2B adaptor protein 1

Synonyms

AI425885; C530001K22Rik; Irip; mKIAA1299; Psm; SH2-B; SH2-Bb; Sh2bpsm1;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000032978

InnateDB Gene

IDBG-209516 (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 (By similarity). Isoforms seem to be differentially involved in IGF-I and PDGF- induced mitogenesis, according the order: isoform 3 > isoform 4 > isoform 1 > isoform 2. {ECO:0000250, ECO:0000269PubMed:11502739, ECO:0000269PubMed:15316008, ECO:0000269PubMed:16098827, ECO:0000269PubMed:9343427}.

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 liver, brain and heart. Isoform 3 is widely expressed. {ECO:0000269PubMed:10594240, ECO:0000269PubMed:9498552}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 29 experimentally validated interaction(s) in this database.
They are also associated with 11 interaction(s) predicted by orthology.

Experimentally validated
Total	29 [view]
Protein-Protein	29 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	11 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004871	signal transducer activity
GO:0005515	protein binding

Biological Process

GO:0006928	cellular component movement
GO:0030032	lamellipodium assembly
GO:0035556	intracellular signal transduction
GO:0045840	positive regulation of mitosis
GO:2000278	regulation of DNA biosynthetic process