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	OMIM: 608937; MGI: 1201407; HomoloGene: 32122; GeneCards: SH2B1; OMA:SH2B1 - orthologs
Gene location (Human) Chr. Chromosome 16 (human) [1] Band 16p11.2 Start 28,846,600 bp [1] End 28,874,212 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7 F3|7 69.06 cM Start 126,066,166 bp [2] End 126,074,596 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right hemisphere of cerebellum mucosa of transverse colon right lobe of thyroid gland right uterine tube apex of heart left lobe of thyroid gland anterior pituitary right ovary left ovary right frontal lobe Top expressed in neural layer of retina granulocyte muscle of thigh molar lip superior frontal gyrus primary visual cortex thymus ankle quadriceps femoris muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function signaling adaptor activity protein binding transmembrane receptor protein tyrosine kinase adaptor activity Cellular component cytosol nucleus membrane cytoplasm plasma membrane Biological process positive regulation of signal transduction positive regulation of mitotic nuclear division blood coagulation lamellipodium assembly signal transduction regulation of DNA biosynthetic process transmembrane receptor protein tyrosine kinase signaling pathway intracellular signal transduction Sources:Amigo / QuickGO
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_001387404 NM_001387430 NM_001081459 NM_001289538 NM_001289539 NM_001289540 NM_001289541 NM_001289542 NM_011363 RefSeq (protein) NP_001139267 NP_001139268 NP_001139269 NP_001139284 NP_001295222 NP_001295223 NP_056318 NP_001074928 NP_001276467 NP_001276468 NP_001276469 NP_001276470 NP_001276471 NP_035493 Location (UCSC) Chr 16: 28.85 – 28.87 Mb Chr 7: 126.07 – 126.07 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

SH2B adapter protein 1 is a protein that in humans is encoded by the SH2B1 gene. ^{[5] [6] [7]}

Interactions

SH2B1 has been shown to interact with:

• Grb2, ^{[8] [9]}
• Insulin receptor, ^{[6] [9]}
• Janus kinase 2, ^{[10] [11]} and
• TrkA. ^{[8] [12]}

Clinical significance

Variations close to or in the SH2B1 gene have been found to associate with obesity in two very large genome wide association studies of body mass index (BMI). ^{[13] [14]} Furthermore, SH2B1 deletions are associated with severe early-onset obesity. ^[15]

See also

• Genetics of obesity

References

1. GRCh38: Ensembl release 89: ENSG00000178188 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030733 – 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.
5. 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.
6. 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. S2CID   21060861.
7. "Entrez Gene: SH2B1 SH2B adaptor protein 1".
8. 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. S2CID   12354383.
9. 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.
10. 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. doi:10.1128/mcb.17.11.6633. PMC   232517 . PMID   9343427.
11. 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.
12. 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. S2CID   28312468.
13. 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. S2CID   764409.
14. 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.
15. 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. doi:10.1128/mcb.17.11.6633. 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 (Pt 1): 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. S2CID   12354383.
• 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. S2CID   28312468.
• 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.