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(Top) 1 Function 2 Interactions 3 References 4 Further reading

GRB2-associated-binding protein 1

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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]
Band	4q31.21	End	143,474,568 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 8 (mouse)^[2]

Band	8\|8 C2	Start	81,491,067 bp^[2]
Band	8\|8 C2	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[edit]

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]

Interactions[edit]

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[edit]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000109458 – Ensembl, May 2017

^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031714 – 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 ^c ^d 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.

^ "Entrez Gene: GAB1 GRB2-associated binding protein 1".

^ 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.

^ 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.

^ 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.

^ 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.

^ 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.

^ ^a ^b 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.

^ 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.

^ 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[edit]

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.

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