GRB10

GRB10
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3HK0, 1NRV
Identifiers
Aliases	GRB10, GRB-IR, Grb-10, IRBP, MEG1, RSS, growth factor receptor bound protein 10
External IDs	OMIM: 601523 MGI: 103232 HomoloGene: 3882 GeneCards: GRB10
Genetically Related Diseases
systemic scleroderma[1]
Gene ontology Molecular function • protein binding • insulin receptor binding • SH3/SH2 adaptor activity Cellular component • cytoplasm • cytosol • plasma membrane Biological process • response to insulin • positive regulation of vascular endothelial growth factor receptor signaling pathway • negative regulation of Wnt signaling pathway • negative regulation of glucose import • negative regulation of insulin receptor signaling pathway • insulin-like growth factor receptor signaling pathway • negative regulation of phosphorylation • positive regulation of phosphorylation • negative regulation of glycogen biosynthetic process • signal transduction • insulin receptor signaling pathway Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2887	14783
Ensembl	ENSG00000106070	ENSMUSG00000020176
UniProt	Q13322	Q60760
RefSeq (mRNA)	NM_001001549 NM_001001550 NM_001001555 NM_005311	NM_001177629 NM_010345
RefSeq (protein)	NP_001001549.1 NP_001001550.1 NP_001001555.1 NP_005302.3	NP_001171100.1 NP_034475.2
Location (UCSC)	Chr 7: 50.59 – 50.79 Mb	Chr 11: 11.93 – 12.04 Mb
PubMed search	[2]	[3]
Wikidata

View/Edit Human

View/Edit Mouse

Growth factor receptor-bound protein 10 also known as insulin receptor-binding protein Grb-IR is a protein that in humans is encoded by the GRB10 gene.^[4][5][6][7]

Function

The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with insulin receptors and insulin-like growth-factor receptors (e.g., IGF1R and IGF2R). Overexpression of some isoforms of the encoded protein inhibits tyrosine kinase activity and results in growth suppression. This gene is imprinted in a highly isoform- and tissue-specific manner. Alternatively spliced transcript variants encoding different isoforms have been identified.^[4]

Animal studies

Mice whose paternally inherited Grb10 gene is inactivated are more aggressive while those whose maternally inherited allele is inactivated exhibit foetal overgrowth and are significantly bigger than wild-type litter-mates.^[8]

Interactions

GRB10 has been shown to interact with

• Abl gene,^[9][10]
• BCR gene,^[9]
• C-Raf,^[11][12]
• c-Kit,^[13]
• Insulin receptor,^{[10][14][15][16][17]}
• Insulin-like growth factor 1 receptor,^{[17][18][19][20]}
• MAP2K1,^[12] and
• RET proto-oncogene.^[21]

References

1. "Diseases that are genetically associated with GRB10 view/edit references on wikidata".
2. "Human PubMed Reference:".
3. "Mouse PubMed Reference:".
4. "Entrez Gene: GRB10 growth factor receptor-bound protein 10".
5. Jerome CA, Scherer SW, Tsui LC, Gietz RD, Triggs-Raine B (February 1997). "Assignment of growth factor receptor-bound protein 10 (GRB10) to human chromosome 7p11.2-p12". Genomics. 40 (1): 215–6. doi:10.1006/geno.1996.4535. PMID 9070953.
6. Dong LQ, Du H, Porter SG, Kolakowski LF, Lee AV, Mandarino LJ, Fan J, Yee D, Liu F, Mandarino J (November 1997). "Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10gamma". J. Biol. Chem. 272 (46): 29104–12. doi:10.1074/jbc.272.46.29104. PMID 9360986.
7. Monk D, Arnaud P, Frost J, Hills FA, Stanier P, Feil R, Moore GE (August 2009). "Reciprocal imprinting of human GRB10 in placental trophoblast and brain: evolutionary conservation of reversed allelic expression". Hum. Mol. Genet. 18 (16): 3066–74. doi:10.1093/hmg/ddp248. PMID 19487367.
8. Garfield AS, Cowley M, Smith FM, Moorwood K, Stewart-Cox JE, Gilroy K, Baker S, Xia J, Dalley JW, Hurst LD, Wilkinson LS, Isles AR, Ward A (2011). "Distinct physiological and behavioural functions for parental alleles of imprinted Grb10". Nature. 469 (7331): 534–538. Bibcode:2011Natur.469..534G. doi:10.1038/nature09651. PMC 3031026. PMID 21270893. Lay summary – New York Times.
9. Bai, R Y; Jahn T; Schrem S; Munzert G; Weidner K M; Wang J Y; Duyster J (Aug 1998). "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene. 17 (8): 941–8. doi:10.1038/sj.onc.1202024. ISSN 0950-9232. PMID 9747873.
10. Frantz, J D; Giorgetti-Peraldi S; Ottinger E A; Shoelson S E (Jan 1997). "Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains". J. Biol. Chem. 272 (5): 2659–67. doi:10.1074/jbc.272.5.2659. ISSN 0021-9258. PMID 9006901.
11. Nantel, A; Huber M; Thomas D Y (Dec 1999). "Localization of endogenous Grb10 to the mitochondria and its interaction with the mitochondrial-associated Raf-1 pool". J. Biol. Chem. 274 (50): 35719–24. doi:10.1074/jbc.274.50.35719. ISSN 0021-9258. PMID 10585452.
12. Nantel, A; Mohammad-Ali K; Sherk J; Posner B I; Thomas D Y (Apr 1998). "Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases". J. Biol. Chem. 273 (17): 10475–84. doi:10.1074/jbc.273.17.10475. ISSN 0021-9258. PMID 9553107.
13. Jahn, Thomas; Seipel Petra; Urschel Susanne; Peschel Christian; Duyster Justus (Feb 2002). "Role for the adaptor protein Grb10 in the activation of Akt". Mol. Cell. Biol. 22 (4): 979–91. doi:10.1128/MCB.22.4.979-991.2002. ISSN 0270-7306. PMC 134632. PMID 11809791.
14. Langlais, P; Dong L Q; Hu D; Liu F (Jun 2000). "Identification of Grb10 as a direct substrate for members of the Src tyrosine kinase family". Oncogene. 19 (25): 2895–903. doi:10.1038/sj.onc.1203616. ISSN 0950-9232. PMID 10871840.
15. Hansen, H; Svensson U; Zhu J; Laviola L; Giorgino F; Wolf G; Smith R J; Riedel H (Apr 1996). "Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus". J. Biol. Chem. 271 (15): 8882–6. doi:10.1074/jbc.271.15.8882. ISSN 0021-9258. PMID 8621530.
16. Liu, F; Roth R A (Oct 1995). "Grb-IR: a SH2-domain-containing protein that binds to the insulin receptor and inhibits its function". Proc. Natl. Acad. Sci. U.S.A. 92 (22): 10287–91. Bibcode:1995PNAS...9210287L. doi:10.1073/pnas.92.22.10287. ISSN 0027-8424. PMC 40781. PMID 7479769.
17. He, W; Rose D W; Olefsky J M; Gustafson T A (Mar 1998). "Grb10 interacts differentially with the insulin receptor, insulin-like growth factor I receptor, and epidermal growth factor receptor via the Grb10 Src homology 2 (SH2) domain and a second novel domain located between the pleckstrin homology and SH2 domains". J. Biol. Chem. 273 (12): 6860–7. doi:10.1074/jbc.273.12.6860. ISSN 0021-9258. PMID 9506989.
18. Vecchione, Andrea; Marchese Adriano; Henry Pauline; Rotin Daniela; Morrione Andrea (May 2003). "The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor". Mol. Cell. Biol. 23 (9): 3363–72. doi:10.1128/MCB.23.9.3363-3372.2003. ISSN 0270-7306. PMC 153198. PMID 12697834.
19. Dey, B R; Frick K; Lopaczynski W; Nissley S P; Furlanetto R W (Jun 1996). "Evidence for the direct interaction of the insulin-like growth factor I receptor with IRS-1, Shc, and Grb10". Mol. Endocrinol. 10 (6): 631–41. doi:10.1210/mend.10.6.8776723. ISSN 0888-8809. PMID 8776723.
20. Morrione, A; Valentinis B; Li S; Ooi J Y; Margolis B; Baserga R (Jul 1996). "Grb10: A new substrate of the insulin-like growth factor I receptor". Cancer Res. 56 (14): 3165–7. ISSN 0008-5472. PMID 8764099.
21. Pandey, A; Duan H; Di Fiore P P; Dixit V M (Sep 1995). "The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10". J. Biol. Chem. 270 (37): 21461–3. doi:10.1074/jbc.270.37.21461. ISSN 0021-9258. PMID 7665556.

Further reading

• Ramírez-Dueñas ML, Medina C, Ocampo-Campos R, Rivera H (1992). "Severe Silver-Russell syndrome and translocation (17;20) (q25;q13)". Clin. Genet. 41 (1): 51–3. doi:10.1111/j.1399-0004.1992.tb03630.x. PMID 1633648.
• Liu F, Roth RA (1995). "Grb-IR: a SH2-domain-containing protein that binds to the insulin receptor and inhibits its function". Proc. Natl. Acad. Sci. U.S.A. 92 (22): 10287–91. Bibcode:1995PNAS...9210287L. doi:10.1073/pnas.92.22.10287. PMC 40781. PMID 7479769.
• Pandey A, Duan H, Di Fiore PP, Dixit VM (1995). "The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10". J. Biol. Chem. 270 (37): 21461–3. doi:10.1074/jbc.270.37.21461. PMID 7665556.
• Midro AT, Debek K, Sawicka A, et al. (1993). "Second observation of Silver-Russel syndrome in a carrier of a reciprocal translocation with one breakpoint at site 17q25". Clin. Genet. 44 (1): 53–5. doi:10.1111/j.1399-0004.1993.tb03845.x. PMID 8403458.
• Hansen H, Svensson U, Zhu J, et al. (1996). "Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus". J. Biol. Chem. 271 (15): 8882–6. doi:10.1074/jbc.271.15.8882. PMID 8621530.
• Morrione A, Valentinis B, Li S, et al. (1996). "Grb10: A new substrate of the insulin-like growth factor I receptor". Cancer Res. 56 (14): 3165–7. PMID 8764099.
• O'Neill TJ, Rose DW, Pillay TS, et al. (1996). "Interaction of a GRB-IR splice variant (a human GRB10 homolog) with the insulin and insulin-like growth factor I receptors. Evidence for a role in mitogenic signaling". J. Biol. Chem. 271 (37): 22506–13. doi:10.1074/jbc.271.37.22506. PMID 8798417.
• Stein E, Cerretti DP, Daniel TO (1996). "Ligand activation of ELK receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells". J. Biol. Chem. 271 (38): 23588–93. doi:10.1074/jbc.271.38.23588. PMID 8798570.
• Frantz JD, Giorgetti-Peraldi S, Ottinger EA, Shoelson SE (1997). "Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains". J. Biol. Chem. 272 (5): 2659–67. doi:10.1074/jbc.272.5.2659. PMID 9006901.
• Nagase T, Seki N, Ishikawa K, et al. (1997). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". DNA Res. 3 (5): 321–9, 341–54. doi:10.1093/dnares/3.5.321. PMID 9039502.
• He W, Rose DW, Olefsky JM, Gustafson TA (1998). "Grb10 interacts differentially with the insulin receptor, insulin-like growth factor I receptor, and epidermal growth factor receptor via the Grb10 Src homology 2 (SH2) domain and a second novel domain located between the pleckstrin homology and SH2 domains". J. Biol. Chem. 273 (12): 6860–7. doi:10.1074/jbc.273.12.6860. PMID 9506989.
• Nantel A, Mohammad-Ali K, Sherk J, et al. (1998). "Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases". J. Biol. Chem. 273 (17): 10475–84. doi:10.1074/jbc.273.17.10475. PMID 9553107.
• Moutoussamy S, Renaudie F, Lago F, et al. (1998). "Grb10 identified as a potential regulator of growth hormone (GH) signaling by cloning of GH receptor target proteins". J. Biol. Chem. 273 (26): 15906–12. doi:10.1074/jbc.273.26.15906. PMID 9632636.
• Bai RY, Jahn T, Schrem S, et al. (1998). "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene. 17 (8): 941–8. doi:10.1038/sj.onc.1202024. PMID 9747873.
• Mano H, Ohya K, Miyazato A, et al. (1998). "Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase". Genes Cells. 3 (7): 431–41. doi:10.1046/j.1365-2443.1998.00201.x. PMID 9753425.
• "Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. 1999. doi:10.1101/gr.8.11.1097. PMID 9847074.
• Angrist M, Bolk S, Bentley K, et al. (1999). "Genomic structure of the gene for the SH2 and pleckstrin homology domain-containing protein GRB10 and evaluation of its role in Hirschsprung disease". Oncogene. 17 (23): 3065–70. doi:10.1038/sj.onc.1202226. PMID 9881709.
• Wang J, Dai H, Yousaf N, et al. (1999). "Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis". Mol. Cell. Biol. 19 (9): 6217–28. PMC 84567. PMID 10454568.

External links

• GRB10 Protein at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.