GAB1

GRB2-associated-binding protein 1 is a protein that in humans is encoded by the GAB1 gene.[5]

GAB1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4QSY
Identifiers
Aliases	GAB1, GRB2 associated binding protein 1, DFNB26
External IDs	OMIM: 604439 MGI: 108088 HomoloGene: 1542 GeneCards: GAB1
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q31.21 Start 143,336,762 bp[1] End 143,474,568 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 C2 Start 80,764,438 bp[2] End 80,880,519 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • 1-phosphatidylinositol-3-kinase activity • phosphatidylinositol-4,5-bisphosphate 3-kinase activity Cellular component • cytosol Biological process • insulin receptor signaling pathway • cellular proliferation • phosphatidylinositol phosphorylation • phosphatidylinositol-3-phosphate biosynthetic process • ERBB2 signaling pathway • axon guidance • epidermal growth factor receptor signaling pathway • angiogenesis • actin cytoskeleton reorganization • vascular endothelial growth factor signaling pathway • positive regulation of cell migration by vascular endothelial growth factor signaling pathway • positive regulation of angiogenesis • positive regulation of protein kinase B signaling • endothelial cell chemotaxis to vascular endothelial growth factor • response to hepatocyte growth factor • positive regulation of phosphatidylinositol 3-kinase signaling Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2549	14388
Ensembl	ENSG00000109458	ENSMUSG00000031714
UniProt	Q13480	Q9QYY0
RefSeq (mRNA)	NM_002039 NM_207123	NM_001301298 NM_021356
RefSeq (protein)	NP_002030 NP_997006	NP_001288227 NP_067331
Location (UCSC)	Chr 4: 143.34 – 143.47 Mb	Chr 8: 80.76 – 80.88 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene is a member of the IRS1-like multisubstrate docking protein family. The encoded protein is an important mediator of branching tubulogenesis and plays a central role in cellular growth response, transformation and apoptosis. Two transcript variants encoding different isoforms have been found for this gene.[6] GAB1 functions as an adaptor molecule in BCR signalling pathway.

Interactions

GAB1 has been shown to interact with:

• CRKL,[7]
• Grb2,[5][8][9]
• MAP3K3,[10]
• PIK3R1,[5][11][12]
• PLCG1[5][13] and
• PTPN11.[12][14]

References

1. GRCh38: Ensembl release 89: ENSG00000109458 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031714 - 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. Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ (April 1996). "A Grb2-associated docking protein in EGF- and insulin-receptor signalling". Nature. 379 (6565): 560–4. doi:10.1038/379560a0. PMID 8596638. S2CID 4271970.
6. "Entrez Gene: GAB1 GRB2-associated binding protein 1".
7. Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, Feller SM (April 2000). "Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL". J. Biol. Chem. 275 (15): 10772–8. doi:10.1074/jbc.275.15.10772. PMID 10753869.
8. Oneyama C, Nakano H, Sharma SV (March 2002). "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug". Oncogene. 21 (13): 2037–50. doi:10.1038/sj.onc.1205271. PMID 11960376.
9. Lewitzky M, Kardinal C, Gehring NH, Schmidt EK, Konkol B, Eulitz M, Birchmeier W, Schaeper U, Feller SM (March 2001). "The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif". Oncogene. 20 (9): 1052–62. doi:10.1038/sj.onc.1204202. PMID 11314042.
10. Che W, Lerner-Marmarosh N, Huang Q, Osawa M, Ohta S, Yoshizumi M, Glassman M, Lee JD, Yan C, Berk BC, Abe J (June 2002). "Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-alpha-induced c-Jun and NF-kappaB activation and adhesion molecule expression". Circ. Res. 90 (11): 1222–30. doi:10.1161/01.res.0000021127.83364.7d. PMID 12065326.
11. Bertagnolo V, Marchisio M, Volinia S, Caramelli E, Capitani S (December 1998). "Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells". FEBS Lett. 441 (3): 480–4. doi:10.1016/s0014-5793(98)01593-2. PMID 9891995. S2CID 38371954.
12. Rocchi S, Tartare-Deckert S, Murdaca J, Holgado-Madruga M, Wong AJ, Van Obberghen E (July 1998). "Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules". Mol. Endocrinol. 12 (7): 914–23. doi:10.1210/mend.12.7.0141. PMID 9658397.
13. Ueno E, Haruta T, Uno T, Usui I, Iwata M, Takano A, Kawahara J, Sasaoka T, Ishibashi O, Kobayashi M (July 2001). "Potential role of Gab1 and phospholipase C-gamma in osmotic shock-induced glucose uptake in 3T3-L1 adipocytes". Horm. Metab. Res. 33 (7): 402–6. doi:10.1055/s-2001-16227. PMID 11507676.
14. Saito Y, Hojo Y, Tanimoto T, Abe J, Berk BC (June 2002). "Protein kinase C-alpha and protein kinase C-epsilon are required for Grb2-associated binder-1 tyrosine phosphorylation in response to platelet-derived growth factor". J. Biol. Chem. 277 (26): 23216–22. doi:10.1074/jbc.M200605200. PMID 11940581.

Further reading

• Fixman ED, Holgado-Madruga M, Nguyen L, Kamikura DM, Fournier TM, Wong AJ, Park M (1997). "Efficient cellular transformation by the Met oncoprotein requires a functional Grb2 binding site and correlates with phosphorylation of the Grb2-associated proteins, Cbl and Gab1". J. Biol. Chem. 272 (32): 20167–72. doi:10.1074/jbc.272.32.20167. PMID 9242692.
• Nguyen L, Holgado-Madruga M, Maroun C, Fixman ED, Kamikura D, Fournier T, Charest A, Tremblay ML, Wong AJ, Park M (1997). "Association of the multisubstrate docking protein Gab1 with the hepatocyte growth factor receptor requires a functional Grb2 binding site involving tyrosine 1356". J. Biol. Chem. 272 (33): 20811–9. doi:10.1074/jbc.272.33.20811. PMID 9252406.
• Holgado-Madruga M, Moscatello DK, Emlet DR, Dieterich R, Wong AJ (1997). "Grb2-associated binder-1 mediates phosphatidylinositol 3-kinase activation and the promotion of cell survival by nerve growth factor". Proc. Natl. Acad. Sci. U.S.A. 94 (23): 12419–24. doi:10.1073/pnas.94.23.12419. PMC 24976. PMID 9356464.
• Rocchi S, Tartare-Deckert S, Murdaca J, Holgado-Madruga M, Wong AJ, Van Obberghen E (1998). "Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules". Mol. Endocrinol. 12 (7): 914–23. doi:10.1210/mend.12.7.0141. PMID 9658397.
• Qiu M, Hua S, Agrawal M, Li G, Cai J, Chan E, Zhou H, Luo Y, Liu M (1999). "Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1". Biochem. Biophys. Res. Commun. 253 (2): 443–7. doi:10.1006/bbrc.1998.9795. PMID 9878555.
• Lehr S, Kotzka J, Herkner A, Klein E, Siethoff C, Knebel B, Noelle V, Brüning JC, Klein HW, Meyer HE, Krone W, Müller-Wieland D (1999). "Identification of tyrosine phosphorylation sites in human Gab-1 protein by EGF receptor kinase in vitro". Biochemistry. 38 (1): 151–9. doi:10.1021/bi9818265. PMID 9890893.
• Maroun CR, Holgado-Madruga M, Royal I, Naujokas MA, Fournier TM, Wong AJ, Park M (1999). "The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase". Mol. Cell. Biol. 19 (3): 1784–99. doi:10.1128/MCB.19.3.1784. PMC 83972. PMID 10022866.
• Nishida K, Yoshida Y, Itoh M, Fukada T, Ohtani T, Shirogane T, Atsumi T, Takahashi-Tezuka M, Ishihara K, Hibi M, Hirano T (1999). "Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors". Blood. 93 (6): 1809–16. doi:10.1182/blood.V93.6.1809.406k35_1809_1816. PMID 10068651.
• Gual P, Giordano S, Williams TA, Rocchi S, Van Obberghen E, Comoglio PM (2000). "Sustained recruitment of phospholipase C-gamma to Gab1 is required for HGF-induced branching tubulogenesis". Oncogene. 19 (12): 1509–18. doi:10.1038/sj.onc.1203514. PMID 10734310.
• Braun L, Ghebrehiwet B, Cossart P (2000). "gC1q-R/p32, a C1q-binding protein, is a receptor for the InlB invasion protein of Listeria monocytogenes". EMBO J. 19 (7): 1458–66. doi:10.1093/emboj/19.7.1458. PMC 310215. PMID 10747014.
• Sakkab D, Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, Feller SM (2000). "Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL". J. Biol. Chem. 275 (15): 10772–8. doi:10.1074/jbc.275.15.10772. PMID 10753869.
• Lehr S, Kotzka J, Herkner A, Sikmann A, Meyer HE, Krone W, Müller-Wieland D (2000). "Identification of major tyrosine phosphorylation sites in the human insulin receptor substrate Gab-1 by insulin receptor kinase in vitro". Biochemistry. 39 (35): 10898–907. doi:10.1021/bi000982k. PMID 10978177.
• Sachs M, Brohmann H, Zechner D, Müller T, Hülsken J, Walther I, Schaeper U, Birchmeier C, Birchmeier W (2000). "Essential role of Gab1 for signaling by the c-Met receptor in vivo". J. Cell Biol. 150 (6): 1375–84. doi:10.1083/jcb.150.6.1375. PMC 2150711. PMID 10995442.
• Yart A, Laffargue M, Mayeux P, Chretien S, Peres C, Tonks N, Roche S, Payrastre B, Chap H, Raynal P (2001). "A critical role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by epidermal growth factor". J. Biol. Chem. 276 (12): 8856–64. doi:10.1074/jbc.M006966200. PMID 11134009.
• Ingham RJ, Santos L, Dang-Lawson M, Holgado-Madruga M, Dudek P, Maroun CR, Wong AJ, Matsuuchi L, Gold MR (2001). "The Gab1 docking protein links the b cell antigen receptor to the phosphatidylinositol 3-kinase/Akt signaling pathway and to the SHP2 tyrosine phosphatase". J. Biol. Chem. 276 (15): 12257–65. doi:10.1074/jbc.M010590200. PMID 11278704.
• Lewitzky M, Kardinal C, Gehring NH, Schmidt EK, Konkol B, Eulitz M, Birchmeier W, Schaeper U, Feller SM (2001). "The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif". Oncogene. 20 (9): 1052–62. doi:10.1038/sj.onc.1204202. PMID 11314042.
• Cunnick JM, Mei L, Doupnik CA, Wu J (2001). "Phosphotyrosines 627 and 659 Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2". J. Biol. Chem. 276 (26): 24380–7. doi:10.1074/jbc.M010275200. PMID 11323411.
• Kurokawa K, Iwashita T, Murakami H, Hayashi H, Kawai K, Takahashi M (2001). "Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction". Oncogene. 20 (16): 1929–38. doi:10.1038/sj.onc.1204290. PMID 11360177.
• Kameda H, Risinger JI, Han BB, Baek SJ, Barrett JC, Glasgow WC, Eling TE (2001). "Identification of epidermal growth factor receptor- Grb2-associated binder-1-SHP-2 complex formation and its functional loss during neoplastic cell progression". Cell Growth Differ. 12 (6): 307–18. PMID 11432805.