GRB7

GRB7
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3PQZ, 1MW4, 1WGR, 2L4K, 2QMS, 4WWQ, 4X6S, 5EEL, 5EEQ, 5D0J
Identifiers
Aliases	GRB7, entrez:2886, growth factor receptor bound protein 7
External IDs	OMIM: 601522 MGI: 102683 HomoloGene: 3881 GeneCards: GRB7
Gene location (Human)
Chr.	Chromosome 17 (human)[1]
End	39,747,291 bp[1]
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)[2]
End	98,455,373 bp[2]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• GO:0001948 protein binding; • phosphatidylinositol binding; • identical protein binding; • RNA binding; • protein kinase binding; • lipid binding;
Cellular component	• cytoplasm; • cytosol; • cell projection; • membrane; • focal adhesion; • cell membrane; • cell junction; • Stress granule;
Biological process	• negative regulation of translation; • epidermal growth factor receptor signaling pathway; • positive regulation of cell migration; • leukocyte migration; • signal transduction; • stress granule assembly; • ERBB2 signaling pathway; • positive regulation of signal transduction; • axon guidance; • insulin receptor signaling pathway; • negative regulation of insulin receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	2886
	14786
	ENSG00000141738
	ENSMUSG00000019312
	Q14451
	Q03160
	NM_001030002; NM_001242442; NM_001242443; NM_005310; NM_001330207
	NM_010346
	NP_001025173; NP_001229371; NP_001229372; NP_001317136; NP_005301
	NP_034476
	Wikidata
View/Edit Human	View/Edit Mouse

Growth factor receptor-bound protein 7, also known as GRB7, is a protein that in humans is encoded by the GRB7 gene.[5][6]

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 epidermal growth factor receptor (EGFR) and ephrin receptors. The protein plays a role in the integrin signaling pathway and cell migration by binding with focal adhesion kinase (FAK). Alternative splicing results in multiple transcript variants encoding different isoforms, although the full-length natures of only two of the variants have been determined to date.[5]

Clinical significance

GRB7 is an SH2-domain adaptor protein that binds to receptor tyrosine kinases and provides the intra-cellular direct link to the Ras proto-oncogene. Human GRB7 is located on the long arm of chromosome 17, next to the ERBB2 (alias HER2/neu) proto-oncogene.

These two genes are commonly co-amplified (present in excess copies) in breast cancers. GRB7 thought to be involved in migration , is well known to be over-expressed in testicular germ cell tumors, esophageal cancers, and gastric cancers.

Interactions

GRB7 has been shown to interact with:

Model organisms

Model organisms have been used in the study of GRB7 function. A conditional knockout mouse line called Grb7^{tm1b(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.[12] Male and female animals underwent a standardized phenotypic screen[13] to determine the effects of deletion.[14][15][16][17] Additional screens performed: - In-depth immunological phenotyping[18]

*Grb7* knockout mouse phenotype
Characteristic	Phenotype
All data available at.[13][18]
Peripheral blood leukocytes 6 Weeks	Normal
Haematology 6 Weeks	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Bone Marrow Immunophenotyping	Normal
Epidermal Immune Composition	Normal
Trichuris Challenge	Normal

References

GRCh38: Ensembl release 89: ENSG00000141738 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000019312 - 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.
"Entrez Gene: GRB7 growth factor receptor-bound protein 7".
Tanaka S, Mori M, Akiyoshi T, Tanaka Y, Mafune K, Wands JR, Sugimachi K (Aug 1998). "A novel variant of human Grb7 is associated with invasive esophageal carcinoma". The Journal of Clinical Investigation. 102 (4): 821–7. doi:10.1172/JCI2921. PMC 508945. PMID 9710451.
Han DC, Shen TL, Miao H, Wang B, Guan JL (Nov 2002). "EphB1 associates with Grb7 and regulates cell migration". The Journal of Biological Chemistry. 277 (47): 45655–61. doi:10.1074/jbc.M203165200. PMID 12223469.
Kasus-Jacobi A, Béréziat V, Perdereau D, Girard J, Burnol AF (Apr 2000). "Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2". Oncogene. 19 (16): 2052–9. doi:10.1038/sj.onc.1203469. PMID 10803466.
Han DC, Guan JL (Aug 1999). "Association of focal adhesion kinase with Grb7 and its role in cell migration". The Journal of Biological Chemistry. 274 (34): 24425–30. doi:10.1074/jbc.274.34.24425. PMID 10446223.
Pandey A, Liu X, Dixon JE, Di Fiore PP, Dixit VM (May 1996). "Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7". The Journal of Biological Chemistry. 271 (18): 10607–10. doi:10.1074/jbc.271.18.10607. PMID 8631863.
Vayssière B, Zalcman G, Mahé Y, Mirey G, Ligensa T, Weidner KM, Chardin P, Camonis J (Feb 2000). "Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family". FEBS Letters. 467 (1): 91–6. doi:10.1016/s0014-5793(99)01530-6. PMID 10664463. S2CID 4901644.
Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
"International Mouse Phenotyping Consortium".
Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
"Infection and Immunity Immunophenotyping (3i) Consortium".

External links

GRB7+Adaptor+Protein at the US National Library of Medicine Medical Subject Headings (MeSH)

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000141738 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000019312 - 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: GRB7 growth factor receptor-bound protein 7".

[pmid9710451-6] Tanaka S, Mori M, Akiyoshi T, Tanaka Y, Mafune K, Wands JR, Sugimachi K (Aug 1998). "A novel variant of human Grb7 is associated with invasive esophageal carcinoma". The Journal of Clinical Investigation. 102 (4): 821–7. doi:10.1172/JCI2921. PMC 508945. PMID 9710451.

[pmid12223469-7] Han DC, Shen TL, Miao H, Wang B, Guan JL (Nov 2002). "EphB1 associates with Grb7 and regulates cell migration". The Journal of Biological Chemistry. 277 (47): 45655–61. doi:10.1074/jbc.M203165200. PMID 12223469.

[pmid10803466-8] Kasus-Jacobi A, Béréziat V, Perdereau D, Girard J, Burnol AF (Apr 2000). "Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2". Oncogene. 19 (16): 2052–9. doi:10.1038/sj.onc.1203469. PMID 10803466.

[pmid10446223-9] Han DC, Guan JL (Aug 1999). "Association of focal adhesion kinase with Grb7 and its role in cell migration". The Journal of Biological Chemistry. 274 (34): 24425–30. doi:10.1074/jbc.274.34.24425. PMID 10446223.

[pmid8631863-10] Pandey A, Liu X, Dixon JE, Di Fiore PP, Dixit VM (May 1996). "Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7". The Journal of Biological Chemistry. 271 (18): 10607–10. doi:10.1074/jbc.271.18.10607. PMID 8631863.

[pmid10664463-11] Vayssière B, Zalcman G, Mahé Y, Mirey G, Ligensa T, Weidner KM, Chardin P, Camonis J (Feb 2000). "Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family". FEBS Letters. 467 (1): 91–6. doi:10.1016/s0014-5793(99)01530-6. PMID 10664463. S2CID 4901644.

[mgp_reference-12] Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.

[IMPCsearch_ref-13] "International Mouse Phenotyping Consortium".

[pmid21677750-14] Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.

[mouse_library-15] Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-16] Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.

[pmid23870131-17] White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.

[iii_ref-18] "Infection and Immunity Immunophenotyping (3i) Consortium".