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
Gene location (Human)
Chr.	Chromosome 7 (human)
End	50,793,462 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	11,988,683 bp
RNA expression pattern
	Top expressed in
	body of pancreas; ; visceral pleura; ; Brodmann area 23; ; endothelial cell; ; middle temporal gyrus; ; pancreatic ductal cell; ; kidney tubule; ; metanephric glomerulus; ; parietal pleura; ; superior vestibular nucleus;
	Top expressed in
	endocardial cushion; ; atrium; ; maxillary prominence; ; atrioventricular valve; ; abdominal wall; ; ureter; ; primitive streak; ; dermis; ; medullary collecting duct; ; somite;
	More reference expression data
	; ; ; ;
	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
	2887
	14783
	ENSG00000106070
	ENSMUSG00000020176
	Q13322
	Q60760
NM_001001549; NM_001001550; NM_001001555; NM_005311; NM_001350814;
	NM_001350815; NM_001350816; NM_001371008; NM_001371009
	NM_001177629; NM_010345; NM_001370603
NP_001001549; NP_001001550; NP_001001555; NP_001337743; NP_001337744;
	NP_001337745; NP_001357937; NP_001357938
	NP_001171100; NP_034475; NP_001357532
	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.^[5]^[6]^[7]^[8]

Function edit

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 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.^[9]

Interactions edit

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 edit

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000106070 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020176 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: GRB10 growth factor receptor-bound protein 10".
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b 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.
^ ^a ^b 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.
^ 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.
^ ^a ^b 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b 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.
^ 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.
^ 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.
^ 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.
^ 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.

External links edit

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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000106070 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[entrez-5] "Entrez Gene: GRB10 growth factor receptor-bound protein 10".

[pmid9070953-6] 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.

[pmid9360986-7] 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.

[pmid19487367-8] 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.

[Garfield_2011-9] 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.

[pmid9747873-10] 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.

[pmid9006901-11] 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.

[pmid10585452-12] 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.

[pmid9553107-13] 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.

[pmid11809791-14] 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.

[pmid10871840-15] 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.

[pmid8621530-16] 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.

[pmid7479769-17] 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.

[pmid9506989-18] 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.

[pmid12697834-19] 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.

[pmid8776723-20] 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.

[pmid8764099-21] 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.

[pmid7665556-22] 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.

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