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GAB2 (GRB2-associated binding protein 2)

Written2010-01Tilman Brummer
Centre for Biological Systems Analysis (ZBSA), Institute for Biology III, Cluster of Excellence 294 bioss, Albert-Ludwigs-University of Freiburg, Germany

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)KIAA0571
Other alias
HGNC (Hugo) GAB2
LocusID (NCBI) 9846
Atlas_Id 40664
Location 11q14.1  [Link to chromosome band 11q14]
Location_base_pair Starts at 78215290 and ends at 78341880 bp from pter ( according to hg19-Feb_2009)  [Mapping GAB2.png]
Local_order Between the USP35 (ubiquitin specific peptidase 35) and LOC100128085 (hypothetical protein LOC100128085) genes.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ARRB1 (11q13.4) / GAB2 (11q14.1)DIXDC1 (11q23.1) / GAB2 (11q14.1)FUT10 (8p12) / GAB2 (11q14.1)
GAB2 (11q14.1) / FGF7 (15q21.2)GAB2 (11q14.1) / GAB2 (11q14.1)GAB2 (11q14.1) / GAL (11q13.3)
GAB2 (11q14.1) / MYO7A (11q13.5)GAB2 (11q14.1) / NARS2 (11q14.1)GAB2 (11q14.1) / PLXDC1 (17q12)
GAB2 (11q14.1) / PXN (12q24.23)GAB2 (11q14.1) / ST7 (7q31.2)GAB2 (11q14.1) / TENM4 (11q14.1)
GAB2 (11q14.1) / THRSP (11q14.1)INTS4 (11q14.1) / GAB2 (11q14.1)MRPL48 (11q13.4) / GAB2 (11q14.1)
MYO7A (11q13.5) / GAB2 (11q14.1)NSD3 (8p11.23) / GAB2 (11q14.1)SGMS1 (10q11.23) / GAB2 (11q14.1)
SRGAP1 (12q14.2) / GAB2 (11q14.1)

DNA/RNA

Description The GAB2 gene is composed of 10 exons spanning a region of 222666 bp (see Mapping for details).
Pseudogene Not known.

Protein

Note PubMed predicts two distinct subtypes encoded by alternative transcripts. The variant GRB2-associated binding protein 2 isoform b contains an alternate exon 1 compared to transcript variant 1. It maintains the same reading frame, but encodes the shorter isoform (b), which lacks aa 1-38 of isoform a (for details see AA865573, AB011143).
Description Amino acids: 766. Calculated molecular mass: 74,327 kDa. However, presumably due to its richness in proline residues and its high degree of phosphorylation, GAB2 usually runs around 95 kDa in conventional SDS-PAGE gels. GAB2 protein isolated from cells stimulated via growth factors, cytokines or antigen receptors exhibit a prominent electrophoretic mobility shift, which reflects the high degree of feedback phosphorylation events at Ser/thr-residues.
This protein is a member of the GRB2-associated binding protein (GAB)/daughter-of-sevenless (DOS) family and is similar to the well studied GAB1 protein. These docking proteins contain pleckstrin homology (PH) domain, and are recruited to various receptors via small adaptor proteins such as the GRB2 adapter protein.
Expression At low levels, GAB2 is presumably expressed in a wide range of tissues and cell types. Prominent expression is observed in various hematopoietic and neuronal lineages. Aberrant overexpression has been observed in various malignancies such as breast cancer, melanoma, acute myeloid leukemia, ovarian and gastric carcinoma.
Localisation Mainly cytoplasmic in unstimulated cells, however this protein is recruited to the plasmamembrane by various stimuli. This recruitment process requires either the PH domain and/or the small adaptor protein GRB2, either alone or in conjunction with adaptor proteins of the SHC family.
Function Gab/DOS proteins integrate and amplify signals from growth factor, cytokine and antigen receptors as well as from cell adhesion molecules. They also diversify signals by channelling the input information from activated receptors into signalling pathways with distinct biological functions. Gab proteins are subject to a complex regulation by feed-forward and feedback phosphorylation events as well as protein-protein interactions. Gab/DOS docking proteins organise entire signalling subsystems and thereby fulfil an important if not essential role in many physiological processes. GAB2 is implicated in various differentiation processes within the hematopoietic and nervous systems. In particular, GAB2 deficient mice display impaired osteoclast development and consequently display osteopetrosis. GAB2 is also essential for the FceRI-mediated degranulation of murine mast cells.
Aberrant expression and/or signalling by GAB2 has been increasingly linked to human diseases from various forms of neoplasia over inflammation to Alzheimer's disease.
A detailed recent review on GAB2 can be found in Wohrle et al. (2009a).
Homology The closest relative is the putative product of the GAB4 gene, followed by the well studied GAB1 and less studied GAB3 protein. Gab-like proteins have been also identified in Drosophila melanogaster (daughter-of-seveless (DOS)) and Caenorhabditis elegans (Suppressor-of-clear 1 (SOC1)).

Mutations

Germinal No germinal mutations described.
Somatic One somatic missense mutation has been reported in the COSMIC database leading to replacement of P161 by a leucine residue. The functional consequences have not been addressed yet. For details see: http://www.sanger.ac.uk/perl/genetics/CGP/cosmic?action=mut_summary&id=26943.

Implicated in

Note
  
Entity Breast cancer
Note GAB2 is frequently over-expressed in human breast cancer cell lines and primary tumours. Overexpression of GAB2 has been shown to be an early event in breast cancer development. In response to EGF, insulin and bFGF stimulation, GAB2 becomes tyrosine phosphorylated indicating that these RTKs, which are implicated in breast cancer development or progression, use this docking protein to amplify their signals. There might be several, not necessarily mutually exclusive mechanisms by which GAB2 is up-regulated in breast cancer such as the amplification of the GAB2 locus, which resides in a region commonly amplified in breast cancers or the aberrant activity of the E2F transcription factor, which is often dysregulated in tumours and binds directly to the human GAB2 promoter. Furthermore, the expression of both GAB2 mRNA and protein is induced by estradiol in an estrogen receptor-dependent manner. Modelling GAB2 expression levels to those observed in breast cancer in the immortalised, but non-transformed, human mammary epithelial cell MCF-10A implies that overexpression of this docking protein contributes to various aspects of malignant transformation such as increased proliferation and reduced growth factor requirements.
Studies from various laboratories using the MCF-10A model system as well as transgenic mouse models suggest that GAB2 also cooperates with other oncogenes implicated in breast cancer development such as HER2 and SRC. Indeed, a recent study by Bocanegra et al. (2009) has shown that small interfering RNA (siRNA)-mediated knockdown of GAB2 in breast cancer lines with GAB2 amplification revealed a dependency on GAB2 for cell proliferation, cell-cycle progression, survival and invasion, likely mediated through altered phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling. These findings are in agreement with studies in MCF-10A cells in which ectopically expressed GAB2 affects these biological parameters via the same effector pathways. GAB2 knockdown also impaired the proliferation and survival in the BT474 cell line, which contains a ERBB2 amplification, consistent with previous studies implicating GAB2 as an important downstream effector of this receptor tyrosine kinase.
  
  
Entity Melanoma
Note Two recent studies implicate GAB2 in malignant melanoma. Firstly, Horst et al. (2009) have shown that the GAB2 gene is amplified and/or over-expressed in 11% and 50% of human metastatic melanomas, respectively. Moreover, Chernoff et al. (2009) demonstrated that GAB2 amplification is associated with melanoma arising from sun-protected sites and often occurs independently from oncogenic NRAS or BRAF mutations or amplification of the KIT gene. Importantly, knockdown and over-expression experiments revealed that GAB2 enhances the migratory and invasive behaviour of melanoma cells. In contrast to metastatic melanoma, normal human melanocyte lines, melanocytic nevi and primary melanomas displayed low GAB2 expression levels suggesting that GAB2 overexpression might represent a marker of neoplastic progression.
  
  
Entity Myeloid leukemias
Note The first evidence for a critical contribution of GAB2 to leukemogenesis was the observation that myeloid progenitors from GAB2-deficient mice are resistant to transformation by the BCR-ABL oncoprotein, which arises from a chromosomal translocation found in more than 90% of patients with chronic myeloid leukaemia (CML). Phosphorylation of Y177 within the BCR moiety leads to recruitment of the GRB2/GAB2 complex and downstream signalling via SHP2 and PI3K, two crucial events for enhanced proliferation and survival. Similarly, the oncogenic BCR-FGFR1 fusion protein, which consists of a BCR-derived moiety and the tyrosine kinase domain of the fibroblast growth factor receptor 1 (FGFR1), drives the tyrosine phosphorylation of GAB2 in murine bone marrow cells and their malignant transformation through phospho-Y177 mediated GRB2 association.
These findings suggest that GRB2-mediated recruitment of GAB2 to oncogenic fusion protein tyrosine kinases is a critical event for the induction of a CML-like disease.
The contribution of GAB2 to BCR-ABL signaling is further supported by the observation that shRNA-mediated silencing of endogenous GAB2 inhibits proliferation and colony formation of CD34+ cells from CML patients.
GAB2 is also involved in the pathogenesis of several other leukemias. The oncogenic fusion kinases TEL-ABL and TEL-JAK2 engage GAB2 in a similar manner as BCR-ABL.
The gene encoding the GAB2 interaction partner SHP2, represents the most common target of somatic mutations in juvenile myelomonocytic leukemia (JMML), a rare, albeit aggressive myelo-proliferative disorder occurring in children. The most frequently JMML-associated mutation, E76K, confers enhanced catalytic activity to SHP2 and requires GAB2 for transformation of primary murine myeloid progenitors.
  
  
Entity Other neoplasia
Note Amplification and/or over-expression of the human GAB2 gene has been also recently reported for ovarian and gastric carcinoma as well as for acute myeloid leukemia (AML). However, additional functional studies are needed to dissect the role that GAB2 plays in these malignancies.
  

Breakpoints

Note Not known.

Bibliography

Gab2 and Src co-operate in human mammary epithelial cells to promote growth factor independence and disruption of acinar morphogenesis.
Bennett HL, Brummer T, Jeanes A, Yap AS, Daly RJ.
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PMID 17998934
 
A role for the scaffolding adapter GAB2 in breast cancer.
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Genome-wide association studies in Alzheimer's disease.
Bertram L, Tanzi RE.
Hum Mol Genet. 2009 Oct 15;18(R2):R137-45. (REVIEW)
PMID 19808789
 
Focal amplification and oncogene dependency of GAB2 in breast cancer.
Bocanegra M, Bergamaschi A, Kim YH, Miller MA, Rajput AB, Kao J, Langerod A, Han W, Noh DY, Jeffrey SS, Huntsman DG, Borresen-Dale AL, Pollack JR.
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PMID 19881546
 
Amplification of 11q13 in ovarian carcinoma.
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PMID 18314909
 
Phosphorylation-dependent binding of 14-3-3 terminates signalling by the Gab2 docking protein.
Brummer T, Larance M, Herrera Abreu MT, Lyons RJ, Timpson P, Emmerich CH, Fleuren ED, Lehrbach GM, Schramek D, Guilhaus M, James DE, Daly RJ.
EMBO J. 2008 Sep 3;27(17):2305-16.
PMID 19172738
 
Increased proliferation and altered growth factor dependence of human mammary epithelial cells overexpressing the Gab2 docking protein.
Brummer T, Schramek D, Hayes VM, Bennett HL, Caldon CE, Musgrove EA, Daly RJ.
J Biol Chem. 2006 Jan 6;281(1):626-37. Epub 2005 Oct 27.
PMID 16253990
 
THOC5 couples M-CSF receptor signaling to transcription factor expression.
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PMID 19015024
 
Association study of the GAB2 gene with the risk of developing Alzheimer's disease.
Chapuis J, Hannequin D, Pasquier F, Bentham P, Brice A, Leber I, Frebourg T, Deleuze JF, Cousin E, Thaker U, Amouyel P, Mann D, Lendon C, Campion D, Lambert JC.
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Transcriptional regulation of AKT activation by E2F.
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Mol Cell. 2004 Dec 3;16(5):831-7.
PMID 15574337
 
GAB2 amplifications refine molecular classification of melanoma.
Chernoff KA, Bordone L, Horst B, Simon K, Twadell W, Lee K, Cohen JA, Wang S, Silvers DN, Brunner G, Celebi JT.
Clin Cancer Res. 2009 Jul 1;15(13):4288-91. Epub 2009 Jun 9.
PMID 19509136
 
The docking protein Gab2 is overexpressed and estrogen regulated in human breast cancer.
Daly RJ, Gu H, Parmar J, Malaney S, Lyons RJ, Kairouz R, Head DR, Henshall SM, Neel BG, Sutherland RL.
Oncogene. 2002 Aug 1;21(33):5175-81.
PMID 12140767
 
Regulation of the Erk2-Elk1 signaling pathway and megakaryocytic differentiation of Bcr-Abl(+) K562 leukemic cells by Gab2.
Dorsey JF, Cunnick JM, Mane SM, Wu J.
Blood. 2002 Feb 15;99(4):1388-97.
PMID 11830491
 
Overexpression of the oncogenic signal transducer Gab2 occurs early in breast cancer development.
Fleuren ED, O'Toole S, Millar EK, McNeil C, Lopez-Knowles E, Boulghourjian A, Croucher DR, Schramek D, Brummer T, Penninger JM, Sutherland RL, Daly RJ.
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PMID 20087860
 
Gab2 requires membrane targeting and the Met binding motif to promote lamellipodia, cell scatter, and epithelial morphogenesis downstream from the Met receptor.
Frigault MM, Naujokas MA, Park M.
J Cell Physiol. 2008 Mar;214(3):694-705.
PMID 17894413
 
Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic cells, reveals a novel pathway for cytokine-induced gene activation.
Gu H, Pratt KC, Âurekoff SJ, Neel BG.
Mol Cell. 1998 Dec;2(6):729-40.
PMID 9885561
 
Essential role for Gab2 in the allergic response.
Gu H, Saito K, Klaman LD, Shen J, Fleming T, Wang Y, Pratt JC, Lin G, Lim B, Kinet JP, Neel BG.
Nature. 2001 Jul 12;412(6843):186-90.
PMID 11449275
 
Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2.
Harkiolaki M, Tsirka T, Lewitzky M, Simister PC, Joshi D, Bird LE, Jones EY, O'Reilly N, Feller SM.
Structure. 2009 Jun 10;17(6):809-22.
PMID 19523899
 
Gab2-mediated signaling promotes melanoma metastasis.
Horst B, Gruvberger-Saal SK, Hopkins BD, Bordone L, Yang Y, Chernoff KA, Uzoma I, Schwipper V, Liebau J, Nowak NJ, Brunner G, Owens D, Rimm DL, Parsons R, Celebi JT.
Am J Pathol. 2009 Apr;174(4):1524-33.
PMID 19342374
 
The GAB2 gene and the risk of Alzheimer's disease: replication and meta-analysis.
Ikram MA, Liu F, Oostra BA, Hofman A, van Duijn CM, Breteler MM.
Biol Psychiatry. 2009 Jun 1;65(11):995-9. Epub 2008 Dec 31.
PMID 19118819
 
Role of Gab2 in mammary tumorigenesis and metastasis.
Ke Y, Wu D, Princen F, Nguyen T, Pang Y, Lesperance J, Muller WJ, Oshima RG, Feng GS.
Oncogene. 2007 Jul 26;26(34):4951-60. Epub 2007 Feb 19.
PMID 17310989
 
The Src family kinase, Lyn, suppresses osteoclastogenesis in vitro and in vivo.
Kim HJ, Zhang K, Zhang L, Ross FP, Teitelbaum SL, Faccio R.
Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2325-30. Epub 2009 Jan 26.
PMID 19171907
 
Increased expression of Gab2, a scaffolding adaptor of the tyrosine kinase signalling, in gastric carcinomas.
Lee SH, Jeong EG, Nam SW, Lee JY, Yoo NJ, Lee SH.
Pathology. 2007 Jun;39(3):326-9.
PMID 17558859
 
GAB2 is not associated with late-onset Alzheimer's disease in Chinese Han.
Lin K, Tang M, Han H, Guo Y, Lin Y, Ma C.
Neurol Sci. 2009 Nov 19. [Epub ahead of print]
PMID 19924507
 
PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2.
Lynch DK, Daly RJ.
EMBO J. 2002 Jan 15;21(1-2):72-82.
PMID 11782427
 
PLCgamma2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2.
Mao D, Epple H, Uthgenannt B, Novack DV, Faccio R.
J Clin Invest. 2006 Nov;116(11):2869-79. Epub 2006 Oct 19.
PMID 17053833
 
Grb2 associated binder 2 couples B-cell receptor to cell survival.
Maus M, Medgyesi D, Kovesdi D, Csuka D, Koncz G, Sarmay G.
Cell Signal. 2009 Feb;21(2):220-7. Epub 2008 Oct 12.
PMID 18950707
 
A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel-Abl (ETV6-Abl) tyrosine kinase.
Million RP, Harakawa N, Roumiantsev S, Varticovski L, Van Etten RA.
Mol Cell Biol. 2004 Jun;24(11):4685-95.
PMID 15143164
 
The GAB2 signaling scaffold promotes anchorage independence and drives a transcriptional response associated with metastatic progression of breast cancer.
Mira A, Isella C, Renzulli T, Cantarella D, Martelli ML, Medico E.
Oncogene. 2009 Dec 17;28(50):4444-55. Epub 2009 Oct 19.
PMID 19838208
 
GAB2 is not associated with late-onset Alzheimer's disease in Japanese.
Miyashita A, Arai H, Asada T, Imagawa M, Shoji M, Higuchi S, Urakami K, Toyabe S, Akazawa K, Kanazawa I, Ihara Y, Kuwano R.
Eur J Hum Genet. 2009 May;17(5):682-6. Epub 2008 Oct 15.
PMID 18854865
 
Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations.
Mohi MG, Williams IR, Dearolf CR, Chan G, Kutok JL, Cohen S, Morgan K, Boulton C, Shigematsu H, Keilhack H, Akashi K, Gilliland DG, Neel BG.
Cancer Cell. 2005 Feb;7(2):179-91.
PMID 15710330
 
Implication of GAB2 gene polymorphism in Italian patients with Alzheimer's disease.
Nacmias B, Tedde A, Bagnoli S, Cellini E, Guarnieri BM, Piacentini S, Sorbi S.
J Alzheimers Dis. 2009 Mar;16(3):513-5.
PMID 19276544
 
Gab family proteins are essential for postnatal maintenance of cardiac function via neuregulin-1/ErbB signaling.
Nakaoka Y, Nishida K, Narimatsu M, Kamiya A, Minami T, Sawa H, Okawa K, Fujio Y, Koyama T, Maeda M, Sone M, Yamasaki S, Arai Y, Koh GY, Kodama T, Hirota H, Otsu K, Hirano T, Mochizuki N.
J Clin Invest. 2007 Jul;117(7):1771-81.
PMID 17571162
 
Requirement of Gab2 for mast cell development and KitL/c-Kit signaling.
Nishida K, Wang L, Morii E, Park SJ, Narimatsu M, Itoh S, Yamasaki S, Fujishima M, Ishihara K, Hibi M, Kitamura Y, Hirano T.
Blood. 2002 Mar 1;99(5):1866-9.
PMID 11861309
 
The c-Kit/D816V mutation eliminates the differences in signal transduction and biological responses between two isoforms of c-Kit.
Pedersen M, Ronnstrand L, Sun J.
Cell Signal. 2009 Mar;21(3):413-8. Epub 2008 Nov 17.
PMID 19049823
 
GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriers.
Reiman EM, Webster JA, Myers AJ, Hardy J, Dunckley T, Zismann VL, Joshipura KD, Pearson JV, Hu-Lince D, Huentelman MJ, Craig DW, Coon KD, Liang WS, Herbert RH, Beach T, Rohrer KC, Zhao AS, Leung D, Bryden L, Marlowe L, Kaleem M, Mastroeni D, Grover A, Heward CB, Ravid R, Rogers J, Hutton ML, Melquist S, Petersen RC, Alexander GE, Caselli RJ, Kukull W, Papassotiropoulos A, Stephan DA.
Neuron. 2007 Jun 7;54(5):713-20.
PMID 17553421
 
Critical role for Gab2 in transformation by BCR/ABL.
Sattler M, Mohi MG, Pride YB, Quinnan LR, Malouf NA, Podar K, Gesbert F, Iwasaki H, Li S, Van Etten RA, Gu H, Griffin JD, Neel BG.
Cancer Cell. 2002 Jun;1(5):479-92.
PMID 12124177
 
Enhanced sensitivity to inhibition of SHP2, STAT5, and Gab2 expression in chronic myeloid leukemia (CML).
Scherr M, Chaturvedi A, Battmer K, Dallmann I, Schultheis B, Ganser A, Eder M.
Blood. 2006 Apr 15;107(8):3279-87. Epub 2005 Nov 8.
PMID 16278304
 
GAB2 as an Alzheimer disease susceptibility gene: follow-up of genomewide association results.
Schjeide BM, Hooli B, Parkinson M, Hogan MF, DiVito J, Mullin K, Blacker D, Tanzi RE, Bertram L.
Arch Neurol. 2009 Feb;66(2):250-4.
PMID 19204163
 
Common variation in GRB-associated Binding Protein 2 (GAB2) and increased risk for Alzheimer dementia.
Sleegers K, Bettens K, Brouwers N, Engelborghs S, van Miegroet H, De Deyn PP, Van Broeckhoven C.
Hum Mutat. 2009 Feb;30(2):E338-44.
PMID 18853460
 
BCR-ABL oncogenic transformation of NIH 3T3 fibroblasts requires the IL-3 receptor.
Tao WJ, Lin H, Sun T, Samanta AK, Arlinghaus R.
Oncogene. 2008 May 15;27(22):3194-200. Epub 2007 Dec 10.
PMID 18071309
 
The molecular scaffold Gab2 is a crucial component of RANK signaling and osteoclastogenesis.
Wada T, Nakashima T, Oliveira-dos-Santos AJ, Gasser J, Hara H, Schett G, Penninger JM.
Nat Med. 2005 Apr;11(4):394-9. Epub 2005 Mar 6.
PMID 15750601
 
Function, regulation and pathological roles of the Gab/DOS docking proteins.
Wohrle FU, Daly RJ, Brummer T.
Cell Commun Signal. 2009a Sep 8;7:22.
PMID 19737390
 
Lyn regulates BCR-ABL and Gab2 tyrosine phosphorylation and c-Cbl protein stability in imatinib-resistant chronic myelogenous leukemia cells.
Wu J, Meng F, Lu H, Kong L, Bornmann W, Peng Z, Talpaz M, Donato NJ.
Blood. 2008 Apr 1;111(7):3821-9. Epub 2008 Jan 30.
PMID 18235045
 
Genetic screening reveals an essential role of p27kip1 in restriction of breast cancer progression.
Yuan Y, Qin L, Liu D, Wu RC, Mussi P, Zhou S, Songyang Z, Xu J.
Cancer Res. 2007 Sep 1;67(17):8032-42.
PMID 17804714
 
GAB2 is a novel target of 11q amplification in AML/MDS.
Zatkova A, Schoch C, Speleman F, Poppe B, Mannhalter C, Fonatsch C, Wimmer K.
Genes Chromosomes Cancer. 2006 Sep;45(9):798-807.
PMID 16736498
 
Abnormal hematopoiesis in Gab2 mutant mice.
Zhang Y, Diaz-Flores E, Li G, Wang Z, Kang Z, Haviernikova E, Rowe S, Qu CK, Tse W, Shannon KM, Bunting KD.
Blood. 2007 Jul 1;110(1):116-24. Epub 2007 Mar 20.
PMID 17374739
 

Citation

This paper should be referenced as such :
Brummer, T
GAB2 (GRB2-associated binding protein 2)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(10):962-965.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/GAB2ID40664ch11q14.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  MLL amplification in leukemia


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Lung: Translocations in Small Cell Carcinoma


External links

Nomenclature
HGNC (Hugo)GAB2   14458
Cards
AtlasGAB2ID40664ch11q14
Entrez_Gene (NCBI)GAB2  9846  GRB2 associated binding protein 2
Aliases
GeneCards (Weizmann)GAB2
Ensembl hg19 (Hinxton)ENSG00000033327 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000033327 [Gene_View]  chr11:78215290-78341880 [Contig_View]  GAB2 [Vega]
ICGC DataPortalENSG00000033327
TCGA cBioPortalGAB2
AceView (NCBI)GAB2
Genatlas (Paris)GAB2
WikiGenes9846
SOURCE (Princeton)GAB2
Genetics Home Reference (NIH)GAB2
Genomic and cartography
GoldenPath hg38 (UCSC)GAB2  -     chr11:78215290-78341880 -  11q14.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)GAB2  -     11q14.1   [Descripdion]4/!>    (hg19-Feb_2009)
EnsemblGAB2 - 11q14.1 [CytoView hg19]  GAB2 - 11q14.1 [CytoView hg38]
Mapping of homologs : NCBIGAB2 [Mapview hg19]  GAB2 [Mapview hg38]
OMIM606203   
Gene and transcription
Genbank (Entrez)AA865573 AB011143 AB018413 AI858080 BC131711
RefSeq transcript (Entrez)NM_012296 NM_080491
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)GAB2
Cluster EST : UnigeneHs.429434 [ NCBI ]
CGAP (NCI)Hs.429434
Alternative Splicing GalleryENSG00000033327
Gene ExpressionGAB2 [ NCBI-GEO ]   GAB2 [ EBI - ARRAY_EXPRESS ]   GAB2 [ SEEK ]   GAB2 [ MEM ]
Gene Expression Viewer (FireBrowse)GAB2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9846
GTEX Portal (Tissue expression)GAB2
Human Protein AtlasENSG00000033327-GAB2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UQC2   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UQC2  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UQC2
Splice isoforms : SwissVarQ9UQC2
PhosPhoSitePlusQ9UQC2
Domaine pattern : Prosite (Expaxy)PH_DOMAIN (PS50003)   
Domains : Interpro (EBI)PH_dom-like    PH_domain   
Domain families : Pfam (Sanger)PH (PF00169)   
Domain families : Pfam (NCBI)pfam00169   
Domain families : Smart (EMBL)PH (SM00233)  
Conserved Domain (NCBI)GAB2
DMDM Disease mutations9846
Blocks (Seattle)GAB2
PDB (SRS)2VWF    2W0Z    5EWZ    5EXA   
PDB (PDBSum)2VWF    2W0Z    5EWZ    5EXA   
PDB (IMB)2VWF    2W0Z    5EWZ    5EXA   
PDB (RSDB)2VWF    2W0Z    5EWZ    5EXA   
Structural Biology KnowledgeBase2VWF    2W0Z    5EWZ    5EXA   
SCOP (Structural Classification of Proteins)2VWF    2W0Z    5EWZ    5EXA   
CATH (Classification of proteins structures)2VWF    2W0Z    5EWZ    5EXA   
SuperfamilyQ9UQC2
Human Protein Atlas [tissue]ENSG00000033327-GAB2 [tissue]
Peptide AtlasQ9UQC2
HPRD05866
IPIIPI00186990   IPI00749276   IPI00981102   IPI00977608   
Protein Interaction databases
DIP (DOE-UCLA)Q9UQC2
IntAct (EBI)Q9UQC2
FunCoupENSG00000033327
BioGRIDGAB2
STRING (EMBL)GAB2
ZODIACGAB2
Ontologies - Pathways
QuickGOQ9UQC2
Ontology : AmiGOtransmembrane receptor protein tyrosine kinase adaptor activity  protein binding  phosphatidylinositol-3,4,5-trisphosphate binding  cytoplasm  cytosol  plasma membrane  transmembrane receptor protein tyrosine kinase signaling pathway  axon guidance  positive regulation of cell proliferation  osteoclast differentiation  Fc-epsilon receptor signaling pathway  positive regulation of mast cell degranulation  phosphatidylinositol-3,4-bisphosphate binding  phosphatidylinositol-mediated signaling  
Ontology : EGO-EBItransmembrane receptor protein tyrosine kinase adaptor activity  protein binding  phosphatidylinositol-3,4,5-trisphosphate binding  cytoplasm  cytosol  plasma membrane  transmembrane receptor protein tyrosine kinase signaling pathway  axon guidance  positive regulation of cell proliferation  osteoclast differentiation  Fc-epsilon receptor signaling pathway  positive regulation of mast cell degranulation  phosphatidylinositol-3,4-bisphosphate binding  phosphatidylinositol-mediated signaling  
Pathways : KEGGRas signaling pathway    Osteoclast differentiation    Fc epsilon RI signaling pathway    Fc gamma R-mediated phagocytosis    Chronic myeloid leukemia   
REACTOMEQ9UQC2 [protein]
REACTOME PathwaysR-HSA-912526 [pathway]   
NDEx NetworkGAB2
Atlas of Cancer Signalling NetworkGAB2
Wikipedia pathwaysGAB2
Orthology - Evolution
OrthoDB9846
GeneTree (enSembl)ENSG00000033327
Phylogenetic Trees/Animal Genes : TreeFamGAB2
HOVERGENQ9UQC2
HOGENOMQ9UQC2
Homologs : HomoloGeneGAB2
Homology/Alignments : Family Browser (UCSC)GAB2
Gene fusions - Rearrangements
Fusion : MitelmanARRB1/GAB2 [11q13.4/11q14.1]  [t(11;11)(q13;q14)]  
Fusion : MitelmanDIXDC1/GAB2 [11q23.1/11q14.1]  [t(11;11)(q14;q23)]  
Fusion : MitelmanFUT10/GAB2 [8p12/11q14.1]  [t(8;11)(p12;q14)]  
Fusion : MitelmanGAB2/FGF7 [11q14.1/15q21.2]  [t(11;15)(q14;q21)]  
Fusion : MitelmanGAB2/MYO7A [11q14.1/11q13.5]  [t(11;11)(q13;q14)]  
Fusion : MitelmanGAB2/NARS2 [11q14.1/11q14.1]  [t(11;11)(q14;q14)]  
Fusion : MitelmanGAB2/PLXDC1 [11q14.1/17q12]  [t(11;17)(q14;q12)]  
Fusion : MitelmanGAB2/TENM4 [11q14.1/11q14.1]  [t(11;11)(q14;q14)]  
Fusion : MitelmanGAB2/THRSP [11q14.1/11q14.1]  [t(11;11)(q14;q14)]  
Fusion : MitelmanINTS4/GAB2 [11q14.1/11q14.1]  [del(11)(q14)]  [del(11)(q14q14)]  
[t(11;11)(q14;q14)]  
Fusion : MitelmanMYO7A/GAB2 [11q13.5/11q14.1]  [t(11;11)(q13;q14)]  
Fusion : MitelmanSGMS1/GAB2 [10q11.23/11q14.1]  [t(10;11)(q11;q14)]  
Fusion : MitelmanSRGAP1/GAB2 [12q14.2/11q14.1]  [t(11;12)(q14;q14)]  
Fusion : MitelmanWHSC1L1/GAB2 [8p11.23/11q14.1]  [t(8;11)(p12;q14)]  
Fusion : COSMICINTS4 [11q14.1]  -  GAB2 [11q14.1]  [fusion_685]  [fusion_686]  
Fusion: TCGAARRB1 11q13.4 GAB2 11q14.1 BRCA
Fusion: TCGADIXDC1 11q23.1 GAB2 11q14.1 BRCA
Fusion: TCGAFUT10 8p12 GAB2 11q14.1 BRCA
Fusion: TCGAGAB2 11q14.1 FGF7 15q21.2 SKCM
Fusion: TCGAGAB2 11q14.1 MYO7A 11q13.5 BRCA
Fusion: TCGAGAB2 11q14.1 ODZ4 BRCA
Fusion: TCGAGAB2 11q14.1 PLXDC1 17q12 BRCA
Fusion: TCGAGAB2 11q14.1 THRSP 11q14.1 BRCA
Fusion: TCGAINTS4 11q14.1 GAB2 11q14.1 BRCA
Fusion: TCGAMYO7A 11q13.5 GAB2 11q14.1 BRCA
Fusion: TCGASGMS1 10q11.23 GAB2 11q14.1 LUAD
Fusion: TCGASRGAP1 12q14.2 GAB2 11q14.1 BRCA
Fusion: TCGAWHSC1L1 8p11.23 GAB2 11q14.1 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerGAB2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)GAB2
dbVarGAB2
ClinVarGAB2
1000_GenomesGAB2 
Exome Variant ServerGAB2
ExAC (Exome Aggregation Consortium)ENSG00000033327
GNOMAD BrowserENSG00000033327
Genetic variants : HAPMAP9846
Genomic Variants (DGV)GAB2 [DGVbeta]
DECIPHERGAB2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisGAB2 
Mutations
ICGC Data PortalGAB2 
TCGA Data PortalGAB2 
Broad Tumor PortalGAB2
OASIS PortalGAB2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICGAB2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDGAB2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch GAB2
DgiDB (Drug Gene Interaction Database)GAB2
DoCM (Curated mutations)GAB2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)GAB2 (select a term)
intoGenGAB2
NCG5 (London)GAB2
Cancer3DGAB2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM606203   
Orphanet
MedgenGAB2
Genetic Testing Registry GAB2
NextProtQ9UQC2 [Medical]
TSGene9846
GENETestsGAB2
Target ValidationGAB2
Huge Navigator GAB2 [HugePedia]
snp3D : Map Gene to Disease9846
BioCentury BCIQGAB2
ClinGenGAB2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9846
Chemical/Pharm GKB GenePA28478
Clinical trialGAB2
Miscellaneous
canSAR (ICR)GAB2 (select the gene name)
Probes
Litterature
PubMed122 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineGAB2
EVEXGAB2
GoPubMedGAB2
iHOPGAB2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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