SH2B1 - SH2B adapter protein 1 - human protein (Function)
 
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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
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GENE REF ISO

Function

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Overview 
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).  
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  • CuratedUniProtKB
GO molecular function 
Protein bindingdefinition[GO:0005515]  
1
  • IPIIntAct
Signal transducer activitydefinition[GO:0004871] silver  
  • IEAInterPro 2 GO
GO biological process 
Cellular component movementdefinition[GO:0006928] silver  
  • IEAOrtholog Compara
Intracellular signal transductiondefinition[GO:0035556] silver  
  • IEAInterPro 2 GO
Lamellipodium assemblydefinition[GO:0030032] silver  
  • IEAOrtholog Compara
Positive regulation of mitosisdefinition[GO:0045840] silver  
  • IEAOrtholog Compara
Regulation of DNA biosynthetic processdefinition[GO:2000278] silver  
  • IEAOrtholog Compara
Pathways 
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  REACT_24970  
Growth hormone receptor signaling  REACT_111133  
Prolactin receptor signaling  REACT_115697  
Signaling by Leptin  REACT_169118  
 

Keywords

Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: SH2B1
GenomeRNAi: 25970
PRO: PR:Q9NRF2