GRB10

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.^[5][6][7][8]

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; OMA:GRB10 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7p12.1 Start 50,590,063 bp[1] End 50,793,462 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 A1|11 7.15 cM Start 11,880,508 bp[2] End 11,988,683 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in body of pancreas Pars compacta visceral pleura Brodmann area 23 pars reticulata endothelial cell dorsal motor nucleus of vagus nerve middle temporal gyrus pancreatic ductal cell Epithelium of choroid plexus Top expressed in mandibular prominence endocardial cushion atrium maxillary prominence atrioventricular valve Gonadal ridge abdominal wall ureter primitive streak dermis More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding insulin receptor binding identical protein binding Cellular component cytoplasm cytosol plasma membrane protein-containing complex Biological process response to insulin positive regulation of vascular endothelial growth factor receptor 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 axon guidance negative regulation of Wnt signaling pathway positive regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2887 14783 Ensembl ENSG00000106070 ENSMUSG00000020176 UniProt Q13322 Q60760 RefSeq (mRNA) NM_001001549 NM_001001550 NM_001001555 NM_005311 NM_001350814 NM_001350815 NM_001350816 NM_001371008 NM_001371009 NM_001177629 NM_010345 NM_001370603 RefSeq (protein) NP_001001549 NP_001001550 NP_001001555 NP_001337743 NP_001337744 NP_001337745 NP_001357937 NP_001357938 NP_001171100 NP_034475 NP_001357532 Location (UCSC) Chr 7: 50.59 – 50.79 Mb Chr 11: 11.88 – 11.99 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The product of this gene belongs to a small family of adaptor 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.^[5]

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.^[9]

Interactions

GRB10 has been shown to interact with

• Abl gene,^[10][11]
• BCR gene,^[10]
• C-Raf,^[12][13]
• c-Kit,^[14]
• Insulin receptor,^{[11][15][16][17]}>^[18]
• Insulin-like growth factor 1 receptor,^{[18][19][20][21]}
• MAP2K1,^[13] and
• RET proto-oncogene.^[22]

References

1. GRCh38: Ensembl release 89: ENSG00000106070 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020176 – 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. "Entrez Gene: GRB10 growth factor receptor-bound protein 10".
6. 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.
7. 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.
8. 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.
9. 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 in: Bhanoo SN (January 27, 2011). "Altering a Mouse Gene Turns Up Aggression, Study Says". New York Times.
10. Bai RY, Jahn T, Schrem S, Munzert G, Weidner KM, Wang JY, Duyster J (August 1998). "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene. 17 (8): 941–8. doi:10.1038/sj.onc.1202024. PMID 9747873.
11. Frantz JD, Giorgetti-Peraldi S, Ottinger EA, Shoelson SE (January 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.
12. Nantel A, Huber M, Thomas DY (December 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. PMID 10585452.
13. Nantel A, Mohammad-Ali K, Sherk J, Posner BI, Thomas DY (April 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.
14. Jahn T, Seipel P, Urschel S, Peschel C, Duyster J (February 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. PMC 134632. PMID 11809791.
15. Langlais P, Dong LQ, Hu D, Liu F (June 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. PMID 10871840.
16. Hansen H, Svensson U, Zhu J, Laviola L, Giorgino F, Wolf G, Smith RJ, Riedel H (April 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.
17. Liu F, Roth RA (October 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.
18. He W, Rose DW, Olefsky JM, Gustafson TA (March 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.
19. Vecchione A, Marchese A, Henry P, Rotin D, Morrione A (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. PMC 153198. PMID 12697834.
20. Dey BR, Frick K, Lopaczynski W, Nissley SP, Furlanetto RW (June 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. PMID 8776723.
21. Morrione A, Valentinis B, Li S, Ooi JY, Margolis B, Baserga R (July 1996). "Grb10: A new substrate of the insulin-like growth factor I receptor". Cancer Res. 56 (14): 3165–7. PMID 8764099.
22. Pandey A, Duan H, Di Fiore PP, Dixit VM (September 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.

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. S2CID 28801507.
• 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. S2CID 20766311.
• 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. S2CID 6391234.
• Washington University Genome Sequencing Cente (November 1998). "Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. 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. doi:10.1128/MCB.19.9.6217. PMC 84567. PMID 10454568.

External links

• GRB10+Protein at the U.S. 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.