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Growth factor receptor-bound protein 10
Protein GRB10 PDB 1nrv.png
PDB rendering based on 1nrv.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols GRB10 ; GRB-IR; Grb-10; IRBP; MEG1; RSS
External IDs OMIM601523 MGI103232 HomoloGene3882 GeneCards: GRB10 Gene
RNA expression pattern
PBB GE GRB10 209409 at tn.png
PBB GE GRB10 209410 s at tn.png
PBB GE GRB10 210999 s at tn.png
More reference expression data
Species Human Mouse
Entrez 2887 14783
Ensembl ENSG00000106070 ENSMUSG00000020176
UniProt Q13322 Q60760
RefSeq (mRNA) NM_001001549 NM_001177629
RefSeq (protein) NP_001001549 NP_001171100
Location (UCSC) Chr 7:
50.66 – 50.86 Mb
Chr 11:
11.93 – 12.04 Mb
PubMed search [1] [2]

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.[1][2][3][4]


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.[1]

Animal studies[edit]

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.[5]


GRB10 has been shown to interact with


  1. ^ a b "Entrez Gene: GRB10 growth factor receptor-bound protein 10". 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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 summaryNew York Times. 
  6. ^ a b 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. 
  7. ^ a b 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. 
  8. ^ 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. 
  9. ^ a b 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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. 
  14. ^ a b 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. 
  15. ^ 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. 
  16. ^ 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. 
  17. ^ 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. 
  18. ^ 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[edit]

External links[edit]

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