SH2B1
entrez
25970
canonical
uniprot
Q9NRF2
canonical
ensembl
ENSG00000178188
resolver
ensp
ENSP00000321221
resolver
ensp
ENSP00000337163
resolver
ensp
ENSP00000352232
resolver
ensp
ENSP00000378903
resolver
ensp
ENSP00000438784
resolver
ensp
ENSP00000481709
resolver
ensp
ENSP00000507475
resolver
ensp
ENSP00000516756
resolver
ensp
ENSP00000563598
resolver
enst
ENST00000538342
resolver
genesymbol
SH2B1
resolver
genesymbol_syn
KIAA1299
resolver
genesymbol_syn
SH2B
resolver
hgnc
HGNC:30417
resolver
uniprot
A8K2R7
resolver
uniprot
B3KNV5
resolver
uniprot
B4DLN5
resolver
uniprot
F6SN47
resolver
uniprot
Q96FK3
resolver
uniprot
Q96SX3
resolver
uniprot
Q9NRF1
resolver
uniprot
Q9NRF3
resolver
uniprot
Q9P2P7
resolver
uniprot
Q9Y3Y3
resolver
uniprot_entry
B3KNV5_HUMAN
resolver
uniprot_entry
B4DLN5_HUMAN
resolver
uniprot_entry
F6SN47_HUMAN
resolver
uniprot_entry
SH2B1_HUMAN
resolver
uniprot_sec
A8K2R7
resolver
uniprot_sec
Q96FK3
resolver
uniprot_sec
Q96SX3
resolver
uniprot_sec
Q9NRF1
resolver
uniprot_sec
Q9NRF3
resolver
uniprot_sec
Q9P2P7
resolver
uniprot_sec
Q9Y3Y3
resolver
amino_acid_sequence
MNGAPSPEDGASPSSPPLPPPPPPSWREFCESHARAAALDFARRFRLYLASHPQYAGPGAEAAFSRRFAELFLQHFEAEVARASGSLSPPILAPLSPGAEISPHDLSLESCRVGGPLAVLGPSRSSEDLAGPLPSSVSSSSTTSSKPKLKKRFSLRSVGRSVRGSVRGILQWRGTVDPPSSAGPLETSSGPPVLGGNSNSNSSGGAGTVGRGLVSDGTSPGERWTHRFERLRLSRGGGALKDGAGMVQREELLSFMGAEEAAPDPAGVGRGGGVAGPPSGGGGQPQWQKCRLLLRSEGEGGGGSRLEFFVPPKASRPRLSIPCSSITDVRTTTALEMPDRENTFVVKVEGPSEYIMETVDAQHVKAWVSDIQECLSPGPCPATSPRPMTLPLAPGTSFLTRENTDSLELSCLNHSESLPSQDLLLGPSESNDRLSQGAYGGLSDRPSASISPSSASIAASHFDSMELLPPELPPRIPIEEGPPTGTVHPLSAPYPPLDTPETATGSFLFQGEPEGGEGDQPLSGYPWFHGMLSRLKAAQLVLTGGTGSHGVFLVRQSETRRGEYVLTFNFQGKAKHLRLSLNEEGQCRVQHLWFQSIFDMLEHFRVHPIPLESGGSSDVVLVSYVPSSQRQQEPTTSHDPPQPPEPPSWTDPPQPGAEEASRAPEVAAAAAAAAKERQEKEKAGGGGVPEELVPVVELVPVVELEEAIAPGSEAQGAGSGGDAGVPPMVQLQQSPLGGDGEEGGHPRAINNQYSFV
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|UniProtKB:Q91ZM2, ECO:0000269|PubMed:11827956, ECO:0000269|PubMed:14565960, ECO:0000269|PubMed:15767667, ECO:0000269|PubMed:16569669, ECO:0000269|PubMed:17471236, ECO:0000269|PubMed:9694882, ECO:0000269|PubMed:9742218}.
uniprot
proteins
mass_dalton
79366
uniprot
proteins
mutagenesis
MUTAGEN 29; /note="F->R: Abolishes self-association and interaction with INSR and IGF1R."; /evidence="ECO:0000269|PubMed:15767667"; MUTAGEN 34; /note="A->D: Abolishes self-association and interaction with INSR and IGF1R."; /evidence="ECO:0000269|PubMed:15767667"; MUTAGEN 38; /note="A->D: Abolishes self-association and interaction with INSR and IGF1R."; /evidence="ECO:0000269|PubMed:15767667"; MUTAGEN 41; /note="F->A: Abolishes self-association and interaction with INSR and IGF1R."; /evidence="ECO:0000269|PubMed:15767667"; MUTAGEN 42; /note="A->D: Abolishes self-association and interaction with INSR and IGF1R."; /evidence="ECO:0000269|PubMed:15767667"; MUTAGEN 48; /note="Y->A: Abolishes self-association and interaction with INSR and IGF1R."; /evidence="ECO:0000269|PubMed:15767667"; MUTAGEN 68; /note="F->A: Abolishes self-association and interaction with INSR and IGF1R."; /evidence="ECO:0000269|PubMed:15767667"; MUTAGEN 72; /note="F->A: Abolishes self-association and interaction with INSR and IGF1R."; /evidence="ECO:0000269|PubMed:15767667"; MUTAGEN 555; /note="R->A: Abolishes self-association and interaction with INSR and IGF1R."; /evidence="ECO:0000269|PubMed:15767667
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on tyrosine residues in response to receptor kinase stimulation. Phosphorylated by RET. {ECO:0000269|PubMed:11751854, ECO:0000269|PubMed:15767667, ECO:0000269|PubMed:9742218}.
uniprot
proteins
protein_family
SH2B adapter family
uniprot
proteins
pubmed
10594240
uniprot
proteins
pubmed
10718198
uniprot
proteins
pubmed
11751854
uniprot
proteins
pubmed
11827956
uniprot
proteins
pubmed
14565960
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15616553
uniprot
proteins
pubmed
15767667
uniprot
proteins
pubmed
16569669
uniprot
proteins
pubmed
17471236
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
9498552
uniprot
proteins
pubmed
9694882
uniprot
proteins
pubmed
9742218
uniprot
proteins
sequence_length
756
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Membrane {ECO:0000305}. Nucleus {ECO:0000250}. Note=Shuttles between the nucleus and the cytoplasm. {ECO:0000250}.
uniprot
proteins