SH2B1

SH2B1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2HDV, 2HDX
Identifiers
Aliases	SH2B1, PSM, SH2B, SH2B adaptor protein 1
External IDs	MGI: 1201407 HomoloGene: 32122 GeneCards: SH2B1
Genetically Related Diseases
obesity[1]
Gene ontology Molecular function • signal transducer activity • signaling adaptor activity • protein binding Cellular component • cytosol • nucleus • membrane • cytoplasm Biological process • positive regulation of signal transduction • positive regulation of mitotic nuclear division • blood coagulation • intracellular signal transduction • lamellipodium assembly • signal transduction • regulation of DNA biosynthetic process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	25970	20399
Ensembl	ENSG00000178188	ENSMUSG00000030733
UniProt	Q9NRF2	Q91ZM2
RefSeq (mRNA)	NM_001145795 NM_001145796 NM_001145797 NM_001145812 NM_001308293 NM_001308294 NM_015503	NM_001081459 NM_001289538 NM_001289539 NM_001289540 NM_001289541 NM_001289542 NM_011363
RefSeq (protein)	NP_001139267.1 NP_001139268.1 NP_001139269.1 NP_001139284.1 NP_001295222.1 NP_001295223.1 NP_056318.2	NP_001074928.1 NP_001276467.1 NP_001276468.1 NP_001276469.1 NP_001276470.1 NP_001276471.1 NP_035493.2
Location (UCSC)	Chr 16: 28.85 – 28.87 Mb	Chr 7: 126.47 – 126.48 Mb
PubMed search	[2]	[3]
Wikidata

View/Edit Human

View/Edit Mouse

SH2B adapter protein 1 is a protein that in humans is encoded by the SH2B1 gene.^[4][5][6]

Interactions

SH2B1 has been shown to interact with:

• Grb2,^[7][8]
• Insulin receptor,^[5][8]
• Janus kinase 2,^[9][10] and
• TrkA.^[7][11]

Clinical significance

Variations close to or in the SH2B1 gene have been found to associatate with obesity in two very large genome wide association studies of body mass index (BMI).^[12][13] Furthermore, SH2B1 deletions are associated with severe early-onset obesity.^[14]

See also

• Genetics of obesity

References

1. "Diseases that are genetically associated with SH2B1 view/edit references on wikidata".
2. "Human PubMed Reference:".
3. "Mouse PubMed Reference:".
4. Kong M, Wang CS, Donoghue DJ (Apr 2002). "Interaction of fibroblast growth factor receptor 3 and the adapter protein SH2-B. A role in STAT5 activation". J Biol Chem. 277 (18): 15962–70. doi:10.1074/jbc.M102777200. PMID 11827956.
5. Nelms K, O'Neill TJ, Li S, Hubbard SR, Gustafson TA, Paul WE (Jan 2000). "Alternative splicing, gene localization, and binding of SH2-B to the insulin receptor kinase domain". Mamm Genome. 10 (12): 1160–7. doi:10.1007/s003359901183. PMID 10594240.
6. "Entrez Gene: SH2B1 SH2B adaptor protein 1".
7. Qian X, Riccio A, Zhang Y, Ginty DD (November 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.
8. Kotani K, Wilden P, Pillay TS (October 1998). "SH2-Balpha is an insulin-receptor adapter protein and substrate that interacts with the activation loop of the insulin-receptor kinase". Biochem. J. 335 (1): 103–9. doi:10.1042/bj3350103. PMC 1219757. PMID 9742218.
9. Rui L, Mathews LS, Hotta K, Gustafson TA, Carter-Su C (November 1997). "Identification of SH2-Bbeta as a substrate of the tyrosine kinase JAK2 involved in growth hormone signaling". Mol. Cell. Biol. 17 (11): 6633–44. PMC 232517. PMID 9343427.
10. Xie S, Lin H, Sun T, Arlinghaus RB (October 2002). "Jak2 is involved in c-Myc induction by Bcr-Abl". Oncogene. 21 (47): 7137–46. doi:10.1038/sj.onc.1205942. PMID 12370803.
11. Koch A, Mancini A, Stefan M, Niedenthal R, Niemann H, Tamura T (March 2000). "Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop". FEBS Lett. 469 (1): 72–6. doi:10.1016/s0014-5793(00)01242-4. PMID 10708759.
12. Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, Styrkarsdottir U, Gretarsdottir S, Thorlacius S, Jonsdottir I, Jonsdottir T, Olafsdottir EJ, Olafsdottir GH, Jonsson T, Jonsson F, Borch-Johnsen K, Hansen T, Andersen G, Jorgensen T, Lauritzen T, Aben KK, Verbeek AL, Roeleveld N, Kampman E, Yanek LR, Becker LC, Tryggvadottir L, Rafnar T, Becker DM, Gulcher J, Kiemeney LA, Pedersen O, Kong A, Thorsteinsdottir U, Stefansson K (January 2009). "Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity.". Nat. Genet. 41 (1): 18–24. doi:10.1038/ng.274. PMID 19079260.
13. Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, Berndt SI, Elliott AL, Jackson AU, Lamina C, Lettre G, Lim N, Lyon HN, McCarroll SA, Papadakis K, Qi L, Randall JC, Roccasecca RM, Sanna S, Scheet P, Weedon MN, Wheeler E, Zhao JH, Jacobs LC, Prokopenko I, Soranzo N, Tanaka T, Timpson NJ, Almgren P, Bennett A, Bergman RN, Bingham SA, Bonnycastle LL, Brown M, Burtt NP, Chines P, Coin L, Collins FS, Connell JM, Cooper C, Smith GD, Dennison EM, Deodhar P, Elliott P, Erdos MR, Estrada K, Evans DM, Gianniny L, Gieger C, Gillson CJ, Guiducci C, Hackett R, Hadley D, Hall AS, Havulinna AS, Hebebrand J, Hofman A, Isomaa B, Jacobs KB, Johnson T, Jousilahti P, Jovanovic Z, Khaw KT, Kraft P, Kuokkanen M, Kuusisto J, Laitinen J, Lakatta EG, Luan J, Luben RN, Mangino M, McArdle WL, Meitinger T, Mulas A, Munroe PB, Narisu N, Ness AR, Northstone K, O'Rahilly S, Purmann C, Rees MG, Ridderstråle M, Ring SM, Rivadeneira F, Ruokonen A, Sandhu MS, Saramies J, Scott LJ, Scuteri A, Silander K, Sims MA, Song K, Stephens J, Stevens S, Stringham HM, Tung YC, Valle TT, Van Duijn CM, Vimaleswaran KS, Vollenweider P, Waeber G, Wallace C, Watanabe RM, Waterworth DM, Watkins N, Witteman JC, Zeggini E, Zhai G, Zillikens MC, Altshuler D, Caulfield MJ, Chanock SJ, Farooqi IS, Ferrucci L, Guralnik JM, Hattersley AT, Hu FB, Jarvelin MR, Laakso M, Mooser V, Ong KK, Ouwehand WH, Salomaa V, Samani NJ, Spector TD, Tuomi T, Tuomilehto J, Uda M, Uitterlinden AG, Wareham NJ, Deloukas P, Frayling TM, Groop LC, Hayes RB, Hunter DJ, Mohlke KL, Peltonen L, Schlessinger D, Strachan DP, Wichmann HE, McCarthy MI, Boehnke M, Barroso I, Abecasis GR, Hirschhorn JN (January 2009). "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation.". Nat. Genet. 41 (1): 24–34. doi:10.1038/ng.287. PMC 2695662. PMID 19079261.
14. Bochukova EG, Huang N, Keogh J, Henning E, Purmann C, Blaszczyk K, Saeed S, Hamilton-Shield J, Clayton-Smith J, O'Rahilly S, Hurles ME, Farooqi IS (February 2010). "Large, rare chromosomal deletions associated with severe early-onset obesity". Nature. 463 (7281): 666–70. doi:10.1038/nature08689. PMC 3108883. PMID 19966786.

Further reading

• Rui L, Mathews LS, Hotta K, Gustafson TA, Carter-Su C (1997). "Identification of SH2-Bbeta as a substrate of the tyrosine kinase JAK2 involved in growth hormone signaling.". Mol. Cell. Biol. 17 (11): 6633–44. PMC 232517. PMID 9343427.
• Kotani K, Wilden P, Pillay TS (1998). "SH2-Balpha is an insulin-receptor adapter protein and substrate that interacts with the activation loop of the insulin-receptor kinase.". Biochem. J. 335: 103–9. doi:10.1042/bj3350103. PMC 1219757. PMID 9742218.
• 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.
• Koch A, Mancini A, Stefan M, Niedenthal R, Niemann H, Tamura T (2000). "Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop.". FEBS Lett. 469 (1): 72–6. doi:10.1016/S0014-5793(00)01242-4. PMID 10708759.
• Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro.". DNA Res. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID 10718198.
• Rui L, Gunter DR, Herrington J, Carter-Su C (2000). "Differential binding to and regulation of JAK2 by the SH2 domain and N-terminal region of SH2-bbeta.". Mol. Cell. Biol. 20 (9): 3168–77. doi:10.1128/MCB.20.9.3168-3177.2000. PMC 85611. PMID 10757801.
• 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.
• Ohtsuka S, Takaki S, Iseki M, Miyoshi K, Nakagata N, Kataoka Y, Yoshida N, Takatsu K, Yoshimura A (2002). "SH2-B is required for both male and female reproduction.". Mol. Cell. Biol. 22 (9): 3066–77. doi:10.1128/MCB.22.9.3066-3077.2002. PMC 133757. PMID 11940664.
• Xie S, Lin H, Sun T, Arlinghaus RB (2002). "Jak2 is involved in c-Myc induction by Bcr-Abl.". Oncogene. 21 (47): 7137–46. doi:10.1038/sj.onc.1205942. PMID 12370803.
• Nakayama M, Kikuno R, Ohara O (2003). "Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs.". Genome Res. 12 (11): 1773–84. doi:10.1101/gr.406902. PMC 187542. PMID 12421765.
• O'Brien KB, Argetsinger LS, Diakonova M, Carter-Su C (2003). "YXXL motifs in SH2-Bbeta are phosphorylated by JAK2, JAK1, and platelet-derived growth factor receptor and are required for membrane ruffling.". J. Biol. Chem. 278 (14): 11970–8. doi:10.1074/jbc.M210765200. PMID 12551917.
• Nishi M, Werner ED, Oh BC, Frantz JD, Dhe-Paganon S, Hansen L, Lee J, Shoelson SE (2005). "Kinase activation through dimerization by human SH2-B.". Mol. Cell. Biol. 25 (7): 2607–21. doi:10.1128/MCB.25.7.2607-2621.2005. PMC 1061652. PMID 15767667.
• Donatello S, Fiorino A, Degl'Innocenti D, Alberti L, Miranda C, Gorla L, Bongarzone I, Rizzetti MG, Pierotti MA, Borrello MG (2007). "SH2B1beta adaptor is a key enhancer of RET tyrosine kinase signaling.". Oncogene. 26 (45): 6546–59. doi:10.1038/sj.onc.1210480. PMID 17471236.