SH2B2

SH2B2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1Q2H
Identifiers
Aliases	SH2B2, APS, SH2B adaptor protein 2
External IDs	OMIM: 605300 MGI: 1345171 HomoloGene: 10309 GeneCards: SH2B2
Gene location (Human)
Chr.	Chromosome 7 (human)[1]
End	102,321,711 bp[1]
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)[2]
End	136,246,556 bp[2]
Gene ontology
Molecular function	• JAK pathway signal transduction adaptor activity; • GO:0001948 protein binding; • SH3/SH2 adaptor activity; • signaling adaptor activity; • transmembrane receptor protein tyrosine kinase adaptor activity; • identical protein binding;
Cellular component	• cytoplasm; • cytosol; • cell membrane; • membrane; • stress fiber; • ruffle; • actin filament;
Biological process	• insulin receptor signaling pathway; • blood coagulation; • signal transduction; • regulation of JAK-STAT cascade; • positive regulation of signal transduction; • intracellular signal transduction; • B-1 B cell homeostasis; • nervous system development; • cytokine-mediated signaling pathway; • regulation of metabolic process; • actin cytoskeleton organization; • regulation of Ras protein signal transduction; • regulation of immune response; • antigen receptor-mediated signaling pathway; • brown fat cell differentiation;
	Sources:Amigo / QuickGO
Orthologs
	10603
	23921
	ENSG00000160999
	ENSMUSG00000005057
	O14492
	Q9JID9
	NM_020979; NM_001359228; NM_001359229; NM_001359230; NM_001359231
	NM_018825; NM_001302938; NM_001302939
	NP_066189; NP_001346157; NP_001346158; NP_001346159; NP_001346160
	NP_001289867; NP_001289868; NP_061295
	Wikidata
View/Edit Human	View/Edit Mouse

SH2B adapter protein 2 is a protein that in humans is encoded by the SH2B2 gene.[5][6]

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.[6]

Interactions

SH2B2 has been shown to interact with TrkA[7] and Cbl gene.[8][9]

References

GRCh38: Ensembl release 89: ENSG00000160999 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000005057 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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.
"Entrez Gene: SH2B2 SH2B adaptor protein 2".
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.
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.
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.

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. PMC 4710543. PMID 17204555.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000160999 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000005057 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9233773-5] 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.

[entrez-6] "Entrez Gene: SH2B2 SH2B adaptor protein 2".

[pmid9856458-7] 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.

[pmid10374881-8] 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.

[pmid18273061-9] 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.

SH2B2

Function

Interactions

References

Further reading