SH2B1 - SH2B adapter protein 1 - human protein (Function)
Home Recent activites arrow-down favorite My favorites arrow-down favorite My labels arrow-down Downloads

SH2B1 »  SH2B adapter protein 1
Protein also known as:  Pro-rich, PH and SH2 domain-containing signaling mediator (PSM).
Gene name:  SH2B1
Family name: SH2B adapter
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 78 3


 show evidences
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).  
  • UniProtKB
GO molecular function 
Protein bindingdefinition[GO:0005515]  
  • IntAct
Signal transducer activitydefinition[GO:0004871] silver  
  • InterPro 2 GO
Signaling adaptor activitydefinition[GO:0035591] silver  
  • InterPro 2 GO
GO biological process 
Intracellular signal transductiondefinition[GO:0035556] silver  
  • InterPro 2 GO
Lamellipodium assemblydefinition[GO:0030032] silver  
  • Ortholog Compara
Positive regulation of mitotic nuclear divisiondefinition[GO:0045840] silver  
  • Ortholog Compara
Positive regulation of signal transductiondefinition[GO:0009967]  
  • InterPro 2 GO
Regulation of DNA biosynthetic processdefinition[GO:2000278] silver  
  • Ortholog Compara
According to KEGG, this protein belongs to the following pathway:
Neurotrophin signaling pathway  hsa04722+25970  
According to Reactome, this protein belongs to the following pathways:
Factors involved in megakaryocyte development and platelet production  R-HSA-983231  
Growth hormone receptor signaling  R-HSA-982772  
Prolactin receptor signaling  R-HSA-1170546  
Signaling by Leptin  R-HSA-2586552  


Technical term 
Reference proteome  definition   [KW-1185]

Further external links

GeneWiki: SH2B1
GenomeRNAi: 25970