SH2B2

SH2B adaptor protein 2
PDB rendering based on 1q2h.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1Q2H​
Identifiers
Symbols	SH2B2 ; APS
External IDs	OMIM: 605300 MGI: 1345171 HomoloGene: 10309 GeneCards: SH2B2 Gene
Gene ontology Molecular function • signal transducer activity • SH3/SH2 adaptor activity • protein binding • JAK pathway signal transduction adaptor activity Cellular component • cytoplasm • cytosol • plasma membrane Biological process • signal transduction • blood coagulation • insulin receptor signaling pathway • positive regulation of signal transduction • intracellular signal transduction • regulation of JAK-STAT cascade Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10603	23921
Ensembl	ENSG00000160999	ENSMUSG00000005057
UniProt	O14492	Q9JID9
RefSeq (mRNA)	NM_020979	NM_001302938
RefSeq (protein)	NP_066189	NP_001289867
Location (UCSC)	Chr 7: 102.29 – 102.32 Mb	Chr 5: 136.22 – 136.25 Mb
PubMed search

SH2B adapter protein 2 is a protein that in humans is encoded by the SH2B2 gene.^[1][2]

Function

The protein encoded by this gene is expressed in B lymphocytes and contains pleckstrin homology and src homology 2 (SH2) domains. In Burkitt lymphoma cell lines, it is tyrosine phosphorylated in response to B cell receptor stimulation. Because it binds Shc independent of stimulation and Grb2 after stimulation, it appears to play a role in signal transduction from the receptor to Shc/Grb2.^[2]

Interactions

SH2B2 has been shown to interact with TrkA^[3] and Cbl gene.^[4][5]

References

1. Yokouchi M, Suzuki R, Masuhara M, Komiya S, Inoue A, Yoshimura A (Aug 1997). "Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation". Oncogene 15 (1): 7–15. doi:10.1038/sj.onc.1201163. PMID 9233773.
2. "Entrez Gene: SH2B2 SH2B adaptor protein 2".
3. Qian X, Riccio A, Zhang Y, Ginty DD (Nov 1998). "Identification and characterization of novel substrates of Trk receptors in developing neurons". Neuron 21 (5): 1017–29. doi:10.1016/S0896-6273(00)80620-0. PMID 9856458.
4. Wakioka T, Sasaki A, Mitsui K, Yokouchi M, Inoue A, Komiya S, Yoshimura A (May 1999). "APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl". Leukemia 13 (5): 760–7. doi:10.1038/sj/leu/2401397. PMID 10374881.
5. Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J (Mar 2008). "Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates". EMBO J. 27 (5): 804–16. doi:10.1038/emboj.2008.18. PMC 2265755. PMID 18273061.

Further reading

• Glöckner G, Scherer S, Schattevoy R, Boright A, Weber J, Tsui LC, Rosenthal A (1998). "Large-Scale Sequencing of Two Regions in Human Chromosome 7q22: Analysis of 650 kb of Genomic Sequence around the EPO and CUTL1 Loci Reveals 17 Genes". Genome Res. 8 (10): 1060–73. doi:10.1101/gr.8.10.1060. PMC 310788. PMID 9799793.
• Qian X, Riccio A, Zhang Y, Ginty DD (1999). "Identification and characterization of novel substrates of Trk receptors in developing neurons". Neuron 21 (5): 1017–29. doi:10.1016/S0896-6273(00)80620-0. PMID 9856458.
• Yokouchi M, Wakioka T, Sakamoto H, Yasukawa H, Ohtsuka S, Sasaki A, Ohtsubo M, Valius M, Inoue A, Komiya S, Yoshimura A (1999). "APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis". Oncogene 18 (3): 759–67. doi:10.1038/sj.onc.1202326. PMID 9989826.
• Moodie SA, Alleman-Sposeto J, Gustafson TA (1999). "Identification of the APS protein as a novel insulin receptor substrate". J. Biol. Chem. 274 (16): 11186–93. doi:10.1074/jbc.274.16.11186. PMID 10196204.
• Wakioka T, Sasaki A, Mitsui K, Yokouchi M, Inoue A, Komiya S, Yoshimura A (1999). "APS, an adaptor protein containing Pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl". Leukemia 13 (5): 760–7. doi:10.1038/sj/leu/2401397. PMID 10374881.
• Iseki M, Takaki S, Takatsu K (2000). "Molecular cloning of the mouse APS as a member of the Lnk family adaptor proteins". Biochem. Biophys. Res. Commun. 272 (1): 45–54. doi:10.1006/bbrc.2000.2736. PMID 10872802.
• O'Brien KB, O'Shea JJ, Carter-Su C (2002). "SH2-B family members differentially regulate JAK family tyrosine kinases". J. Biol. Chem. 277 (10): 8673–81. doi:10.1074/jbc.M109165200. PMID 11751854.
• Liu J, Kimura A, Baumann CA, Saltiel AR (2002). "APS Facilitates c-Cbl Tyrosine Phosphorylation and GLUT4 Translocation in Response to Insulin in 3T3-L1 Adipocytes". Mol. Cell. Biol. 22 (11): 3599–609. doi:10.1128/MCB.22.11.3599-3609.2002. PMC 133825. PMID 11997497.
• Yabana N, Shibuya M (2002). "Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity". Oncogene 21 (50): 7720–9. doi:10.1038/sj.onc.1205927. PMID 12400014.
• Ahn MY, Katsanakis KD, Bheda F, Pillay TS (2004). "Primary and essential role of the adaptor protein APS for recruitment of both c-Cbl and its associated protein CAP in insulin signaling". J. Biol. Chem. 279 (20): 21526–32. doi:10.1074/jbc.M307740200. PMID 15031295.
• Wilcox A, Katsanakis KD, Bheda F, Pillay TS (2004). "Asb6, an adipocyte-specific ankyrin and SOCS box protein, interacts with APS to enable recruitment of elongins B and C to the insulin receptor signaling complex". J. Biol. Chem. 279 (37): 38881–8. doi:10.1074/jbc.M406101200. PMID 15231829.
• Hu J, Hubbard SR (2005). "Structural characterization of a novel Cbl phosphotyrosine recognition motif in the APS family of adapter proteins". J. Biol. Chem. 280 (19): 18943–9. doi:10.1074/jbc.M414157200. PMID 15737992.
• Iseki M, Kubo-Akashi C, Kwon SM, Yamaguchi A, Takatsu K, Takaki S (2005). "APS, an adaptor molecule containing PH and SH2 domains, has a negative regulatory role in B cell proliferation". Biochem. Biophys. Res. Commun. 330 (3): 1005–13. doi:10.1016/j.bbrc.2005.03.073. PMID 15809095.
• Katsanakis KD, Pillay TS (2006). "Cross-talk between the two divergent insulin signaling pathways is revealed by the protein kinase B (Akt)-mediated phosphorylation of adapter protein APS on serine 588". J. Biol. Chem. 280 (45): 37827–32. doi:10.1074/jbc.M505959200. PMID 16141217.
• Li M, Li Z, Morris DL, Rui L (2007). "Identification of SH2B2beta as an inhibitor for SH2B1- and SH2B2alpha-promoted Janus kinase-2 activation and insulin signaling". Endocrinology 148 (4): 1615–21. doi:10.1210/en.2006-1010. PMID 17204555.