Sh2b1
entrez
89817
canonical
uniprot
Q62985
canonical
ensembl
ENSRNOG00000049181
resolver
ensp
ENSRNOP00000064854
resolver
ensp
ENSRNOP00000066048
resolver
enst
ENSRNOT00000071241
resolver
enst
ENSRNOT00000074274
resolver
genesymbol
Sh2b1
resolver
genesymbol_syn
Sh2-b
resolver
genesymbol_syn
Sh2bpsm1
resolver
uniprot
A0A8L2QYJ5
resolver
uniprot
M0R617
resolver
uniprot
O55072
resolver
uniprot_entry
A0A8L2QYJ5_RAT
resolver
uniprot_entry
M0R617_RAT
resolver
uniprot_entry
SH2B1_RAT
resolver
uniprot_sec
O55072
resolver
amino_acid_sequence
MNGAPSPEDGVFPSPPALPPPPPPSWQEFCESHARAAALDLARRFRLYLASHPQYAEPGAEAAFSGRFAELFLQHFEAEVARASGSLSPPVLAPLSPGVEIPPSHDLSLESCRVGGPLAVLGPSRSSEDLAGPLPSSVSSSTTSSKPKLKKRFSLRSVGRSVRGSVRGILQWRGAVESPSQAGPLETTSGPPVLGGNSNSNSSGGAGTVGRALANDGTSPGERWTHRFERLRLSRGGGTLRDGAGVIQREELLSFMGAEEAAPDPAGVGRGGGAAGLTSGGGGQPQWQKCRLLLRSEGEGGGGSRLEFFVPPKASRPRLSIPCSTITDVRTATALEMPDRENTFVVKVEGPSEYILETTDALHVKAWVSDIQECLSPGPCPAISPRPMTLPLAPGTSFLTKDNTESLELPCLNHSESLPSQDLLLGPSESNDRLSQGAYGGLSDRPSASFSPSSASIAASHFDSMELLPPELPPRIPIEEGPPAGTVHPLSTPYPPLDTPEAATGSFLFQGEAEGGEGDQPLSGYPWFHGMLSRLKAAQLVLEGGTSSHGVFLVRQSETRRGEYVLTFNFQGKAKHLRLSLNEEGQCRVQHLWFQSIFDMLEHFRVHPIPLESGGSSDVVLVSYVPSQRQQERSTSRDPTQPSEPPPWTDPPHPGAEEASGAPEVAAATAAAAKERQEKEKAGGGGVQEELVPMAELVPMAELEEAIAPGTEAQGGAGSSGDLEVSLMVQLQQLPLGGNGEEGGHPRAINNQYSFV
uniprot
proteins
function
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 1 (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 a 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 IGF1 and PDGF-induced mitogenesis (By similarity). {ECO:0000250, ECO:0000269|PubMed:10377387, ECO:0000269|PubMed:10473609, ECO:0000269|PubMed:10757801, ECO:0000269|PubMed:11238898, ECO:0000269|PubMed:11786545, ECO:0000269|PubMed:16569669, ECO:0000269|PubMed:9343427, ECO:0000269|PubMed:9856458}.
uniprot
proteins
mass_dalton
79637
uniprot
proteins
mutagenesis
MUTAGEN 96; /note="S->A: Reduces in vitro phosphorylation by MAPK1 and/or MAPK3."; /evidence="ECO:0000269|PubMed:10473609"; MUTAGEN 231; /note="L->A: Abolishes nuclear localization; when associated with A-233."; /evidence="ECO:0000269|PubMed:15082760"; MUTAGEN 233; /note="L->A: Abolishes nuclear localization; when associated with A-231."; /evidence="ECO:0000269|PubMed:15082760"; MUTAGEN 439; /note="Y->F: Fails to enhance GH-induced membrane ruffling; when associated with F-494."; /evidence="ECO:0000269|PubMed:12551917"; MUTAGEN 439; /note="Y->F: Reduces phosphorylation by JAK1, JAK2 and PDGFRA."; /evidence="ECO:0000269|PubMed:12551917"; MUTAGEN 494; /note="Y->F: Fails to enhance GH-induced membrane ruffling; when associated with F-439."; /evidence="ECO:0000269|PubMed:12551917"; MUTAGEN 494; /note="Y->F: Reduces phosphorylation by JAK1 and JAK2."; /evidence="ECO:0000269|PubMed:12551917"; MUTAGEN 555; /note="R->E: Reduces interaction with JAK2 and abolishes JAK2 kinase activity; reduces GH-stimulated cell motility; abolishes interaction with PDGFRA."; /evidence="ECO:0000269|PubMed:10377387, ECO:0000269|PubMed:10757801
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on tyrosine residues in response to treatment with growth hormone (GH), IFN-gamma (IFNG), BDNF, PDGF and FGF. Phosphorylated on tyrosine residues by JAK2 and JAK1. Phosphorylated on multiple serine and threonine residues in response to treatment with NGF. Phosphorylated on serine residues. {ECO:0000269|PubMed:10473609, ECO:0000269|PubMed:11751854, ECO:0000269|PubMed:12551917, ECO:0000269|PubMed:9343427, ECO:0000269|PubMed:9856458}.
uniprot
proteins
protein_family
SH2B adapter family
uniprot
proteins
pubmed
10377387
uniprot
proteins
pubmed
10473609
uniprot
proteins
pubmed
10757801
uniprot
proteins
pubmed
11238898
uniprot
proteins
pubmed
11751854
uniprot
proteins
pubmed
11786545
uniprot
proteins
pubmed
11827956
uniprot
proteins
pubmed
12551917
uniprot
proteins
pubmed
15082760
uniprot
proteins
pubmed
16569669
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
9343427
uniprot
proteins
pubmed
9636306
uniprot
proteins
pubmed
9694882
uniprot
proteins
pubmed
9742218
uniprot
proteins
pubmed
9856458
uniprot
proteins
sequence_length
756
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15082760}. Membrane {ECO:0000305|PubMed:15082760}. Nucleus {ECO:0000269|PubMed:15082760}. Note=Shuttles between the nucleus and the cytoplasm.
uniprot
proteins