GRB2-associated-binding protein 1

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; OMA:GAB1 - orthologs
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 81,491,067 bp [2] End 81,607,148 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in secondary oocyte epithelium of colon endothelial cell corpus callosum ventricular zone trigeminal ganglion sural nerve inferior ganglion of vagus nerve spinal ganglia internal globus pallidus Top expressed in vestibular membrane of cochlear duct sciatic nerve vestibular sensory epithelium genital tubercle fossa condyle efferent ductule external carotid artery substantia nigra atrioventricular junction More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding 1-phosphatidylinositol-3-kinase activity phosphatidylinositol-4,5-bisphosphate 3-kinase activity Cellular component cytosol Biological process insulin receptor signaling pathway cell population proliferation phosphatidylinositol phosphate biosynthetic process 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: 81.49 – 81.61 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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 is involved also in the tonic pAKT activity in malignant B cells, and induces PI3K activation irrespectively of BCR stimulation by antigen in chronic lymphocytic leukemia. ^[7]

Interactions

GAB1 has been shown to interact with:

• CRKL, ^[8]
• Grb2, ^{[5] [9] [10]}
• MAP3K3, ^[11]
• PIK3R1, ^{[5] [12] [13]}
• PLCG1 ^{[5] [14]} and
• PTPN11. ^{[13] [15]}

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. Bibcode:1996Natur.379..560H. doi:10.1038/379560a0. PMID   8596638. S2CID   4271970.
6. "Entrez Gene: GAB1 GRB2-associated binding protein 1".
7. Seda V, Vojackova E, Ondrisova L, Kostalova L, Sharma S, Loja T, Pavlasova G, Zicha D, Peskova MK, Krivanek J, Liskova K, Kren L, Benes V, Litzmanova K, Borsky M, Oppelt J, Verner J, Pospisilova S, Brychtova Y, Panovska A, Tan Z, Zhang S, Doubek M, Cerna K, Mayer J, Mraz M (March 2021). "FoxO1-GAB1 Axis Regulates Homing Capacity and Tonic AKT Activity in Chronic Lymphocytic Leukemia". Blood. X (X): 758–772. doi: 10.1182/blood.2020008101 . PMC   8513669 . PMID   33786575.
8. 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.
9. 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. S2CID   23869665.
10. 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.
11. 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.
12. 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. Bibcode:1998FEBSL.441..480B. doi: 10.1016/s0014-5793(98)01593-2 . PMID   9891995. S2CID   38371954.
13. 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.
14. 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. S2CID   9125865.
15. 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. Bibcode:1997PNAS...9412419H. 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. S2CID   22727382.
• 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. S2CID   25346661.
• 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.