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IID50098
UniprotQ91ZM2
ProteinSH2B adapter protein 1
GeneSh2b1
OrganismMus musculus
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
756
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 519-627 Monomer :
 Evidence X-RAY 2hdv B Reference
       Region 2hdv B 519-519 disorder
       Region 2hdv B 520-612 order
       Region 2hdv B 613-617 disorder
       Region 2hdv B 618-627 order
 Evidence X-RAY 2hdv A Reference
       Region 2hdv A 519-610 order
       Region 2hdv A 611-617 disorder
       Region 2hdv A 618-627 order
Seq 519-627 Hetero dimer : IID50091Complex
 Evidence X-RAY 2hdx F Reference
       Region 2hdx F 519-519 disorder
       Region 2hdx F 520-613 order
       Region 2hdx F 614-617 disorder
       Region 2hdx F 618-627 order
 Evidence X-RAY 2hdx E Reference
       Region 2hdx E 519-519 disorder
       Region 2hdx E 520-627 order
 Evidence X-RAY 2hdx D Reference
       Region 2hdx D 519-519 disorder
       Region 2hdx D 520-613 order
       Region 2hdx D 614-616 disorder
       Region 2hdx D 617-627 order
 Evidence X-RAY 2hdx C Reference
       Region 2hdx C 519-519 disorder
       Region 2hdx C 520-627 order
 Evidence X-RAY 2hdx B Reference
       Region 2hdx B 519-519 disorder
       Region 2hdx B 520-613 order
       Region 2hdx B 614-616 disorder
       Region 2hdx B 617-627 order
 Evidence X-RAY 2hdx A Reference
       Region 2hdx A 519-519 disorder
       Region 2hdx A 520-627 order
Seqphosphorylation
    494-494 Phosphotyrosine; by JAK1
    439-439 Phosphotyrosine; by JAK1
    420-420 Phosphoserine
    417-417 Phosphoserine
    96-96 Phosphoserine
    88-88 Phosphoserine
 
Prediction
NeProc
Disorder 1-21,89-285,375-523,626-756
Order 22-84,286-374,524-625
ProS 1-6,89-102,147-175,186-194,221-230,248-258,270-275,375-392,402-495,505-514,744-756
AlphaFold
Disorder 1-17,85-245,258-285,298-302,376-521,612-617,629-756
Order 18-84,246-257,286-297,303-375,522-611,618-628
Pfam Hmmer
PF00169 247-376 8.9e-13
PF00017 527-604 2.6e-13
SEG 13-25 ,34-50 ,83-99 ,133-151 ,156-168 ,195-205 ,261-285 ,291-307 ,447-460 ,466-483 ,656-682
Function
Function in SwissProt
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.