SH2B adapter protein 2; adapter protein with pleckstrin homology & Src homology 2 domains; SH2 & PH domain-containing adapter protein APS (SH2B2, APS)

Function

• adapter protein for members of the tyrosine kinase receptor family
• role in coupling immunoreceptors to Ras signaling (putative)
• acts as a negative regulator of cytokine signaling in connection with CBL
• binds to EPOR & suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR
• suppresses PDGF-induced mitogenesis
• may induce cytoskeletal reorganization via interaction with VAV3
• Tyr-phosphorylated by JAK2, KIT & other kinases
• activated by B-cell receptor in response to stimulation with cytokines, IL3, IL5, PDGF, IGF1, IGF2, CSF2/GM-CSF & cross- linking of the B-cell receptor complex
• interacts with several proteins including KIT/c-KIT, SHC, GRB2, EPOR, CBL/c-CBL, PDGFR, VAV1 & VAV3
• interacts with SHC through its N-terminal region, with GRB2 via the phosphorylated C-terminus & with EPOR & KIT via its SH2 domain
• interacts with GRB2 after B-cell antigen receptor stimulation
• interacts with VAV3 via its PH domain

Structure

• belongs to the SH2B adapter family
• contains 1 PH domain
• contains 1 SH2 domain

Compartment

• cytoplasm. cell membrane
• cytoplasmic before PDGF stimulation
• after PDGF stimulation, localized at the cell membrane & peripheral region

Expression

• expressed in spleen, prostate, testis, uterus, small intestine & skeletal muscle
• among haematopoietic cell lines, expressed exclusively in B-cells
• not expressed in most tumor cell lines

More general terms

• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=10603
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:10603
• OMIM: https://mirror.omim.org/entry/605300
• UniProt: http://www.uniprot.org/uniprot/O14492.html