GRB2-associated binding protein 2; GRB2-associated binder-2 (GAB2)

Function

• adapter protein which acts downstream of membrane receptors
• regulates osteoclast differentiation mediating the TNFRSF11A/RANK signaling
• role in regulation of cell proliferation & hematopoiesis
• interacts with grb2, PI-3 kinase, SH2-containing proteins
• phosphorylated on Tyr by
  • thrombopoietin receptor (TPOR)
  • stem cell factor receptor (SCFR)
  • T-cell antigen receptor & B-cell antigen receptor
  • gp130
  • IL-2R
  • IL-3R
  • HCK upon IL6 signaling
• phosphorylated upon stimulation of TNFRSF11A/RANK by TNFSF11/RANK (putative)
• phosphorylated upon EGF stimulation
• dephosphorylated by PTPN11
• in allergic response, GAB2 plays a role in mast cell activation & degranulation through PI-3-kinase regulation
• involved in the regulation of cell proliferation & hematopoiesis
• interacts with SHC1; may mediate interaction with receptors (putative)
• interacts with SYK
• interacts with PI-3 kinase
• interacts with GRB2 (via SH3 2 domain)
• interacts with TNFRSF11A (via cytoplasmic domain)
• interacts (phosphorylated) with 14-3-3 family proteins SFN, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ & YWHAZ
• prevents interaction with GRB2 & attenuates GAB2 signaling
• interacts with HCK

Structure

• the SH3-binding motifs mediate interaction with SHC1 & GRB2 (putative)
• the PH domain mediates phosphatidylinositol 3,4,5-trisphosphate & phosphatidylinositol 3,4-bisphosphate binding
• belongs to the GAB family
• contains 1 PH domain

Compartment

cytoplasm, cell membrane

Alternative splicing

named isoforms=2

More general terms

• GRB2-associated binding protein

Database

• OMIM: https://mirror.omim.org/entry/606203
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9846
• UniProt: http://www.uniprot.org/uniprot/Q9UQC2.html