SH2B1
Description
The SH2B1 (SH2B adaptor protein 1) is a protein-coding gene located on chromosome 16.
SH2B adapter protein 1 is a protein that in humans is encoded by the SH2B1 gene.
== Interactions == SH2B1 has been shown to interact with:
Grb2, Insulin receptor, Janus kinase 2, and TrkA.
== Clinical significance == Variations close to or in the SH2B1 gene have been found to associate with obesity in two very large genome wide association studies of body mass index (BMI). Furthermore, SH2B1 deletions are associated with severe early-onset obesity.
SH2B1 is an adapter protein that interacts with various tyrosine kinase receptors, playing a crucial role in signaling pathways mediated by JAK and receptor tyrosine kinases. This protein is involved in signaling for insulin, IGF1, NGF, BDNF, GDNF, PDGF, and FGFs. SH2B1 enhances the activation of JAK2 in response to growth hormone (GH) and leptin, leading to the recruitment of other signaling proteins. In leptin signaling, SH2B1 forms a complex with JAK2 and IRS1/IRS2, activating the PI3-kinase pathway. SH2B1 positively regulates the Akt/Forkhead pathway in response to NGF, promoting AKT1 phosphorylation and enzymatic activity. Furthermore, SH2B1 enhances the kinase activity of JAK2, FGFR3, and NTRK1, potentially through dimerization with JAK2. SH2B1 also enhances RET phosphorylation and kinase activity. Different isoforms of SH2B1 seem to be involved in IGF-I and PDGF-induced mitogenesis.
SH2B1 is also known as PSM, SH2B.
Associated Diseases
- Severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency
- Proximal 16p11.2 microdeletion syndrome
- Distal 16p11.2 microdeletion syndrome
