GATA2

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GATA binding protein 2
PDB 1gnf EBI.jpg
PDB rendering based on 1gnf.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GATA2 ; DCML; IMD21; MONOMAC; NFE1B
External IDs OMIM137295 MGI95662 HomoloGene32030 GeneCards: GATA2 Gene
Orthologs
Species Human Mouse
Entrez 2624 14461
Ensembl ENSG00000179348 ENSMUSG00000015053
UniProt P23769 O09100
RefSeq (mRNA) NM_001145661 NM_008090
RefSeq (protein) NP_001139133 NP_032116
Location (UCSC) Chr 3:
128.2 – 128.21 Mb
Chr 6:
88.19 – 88.21 Mb
PubMed search [1] [2]

GATA2 is a human gene which makes a protein called GATA binding protein 2 - a transcription factor.[1]

The GATA family of transcription factors, which contain zinc fingers in their DNA binding domain, have emerged as candidate regulators of gene expression in hematopoietic cells.[2] GATA1 is essential for normal primitive and definitive erythropoiesis and is expressed at high levels in erythroid cells, mast cells, and megakaryocytes. GATA2 is expressed in hematopoietic progenitors, including early erythroid cells, mast cells, and megakaryocytes, and also in nonhematopoietic embryonic stem cells. In chicken erythroid progenitors, forced expression of GATA2 promotes proliferation at the expense of differentiation.[3] GATA3 expression is restricted to T-lymphoid cells and some nonhematopoietic cell types, including embryonic stem cells.[4]

Interactions[edit]

GATA2 has been shown to interact with Pituitary-specific positive transcription factor 1,[5] HDAC3,[6] Zinc finger and BTB domain-containing protein 16,[7] LMO2,[8] Promyelocytic leukemia protein[9] and SPI1.[10]

Genetic disorders[edit]

Multiple mutations on GATA2 gene have been recently implicated as the cause of primary immunodeficiency in patients with MonoMAC Syndrome, and cases of dendritic cell, monocyte, B NK lymphoid deficiency and leukemia.[11]

Lung cancer[edit]

GATA2 has recently been implicated in non-small-cell lung cancer - specifically those tumours that are driven by a faulty Ras protein. Targeting processes that occur downstream of GATA2 signalling with clinically approved drugs had a significant effect in mouse models of the disease.[12]

See also[edit]

References[edit]

  1. ^ Lee ME, Temizer DH, Clifford JA, Quertermous T (25 August 1991). "Cloning of the GATA-binding protein that regulates endothelin-1 gene expression in endothelial cells". J. Biol. Chem. 266 (24): 16188–92. PMID 1714909. 
  2. ^ Tsai FY, Keller G, Kuo FC, Weiss M, Chen J, Rosenblatt M, Alt FW, Orkin SH (September 1994). "An early haematopoietic defect in mice lacking the transcription factor GATA-2". Nature 371 (6494): 221–6. doi:10.1038/371221a0. PMID 8078582. 
  3. ^ Briegel K, Lim KC, Plank C, Beug H, Engel JD, Zenke M (June 1993). "Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner". Genes Dev. 7 (6): 1097–109. doi:10.1101/gad.7.6.1097. PMID 8504932. 
  4. ^ "Entrez Gene: GATA2 GATA binding protein 2". 
  5. ^ Dasen, J S; O'Connell S M; Flynn S E; Treier M; Gleiberman A S; Szeto D P; Hooshmand F; Aggarwal A K; Rosenfeld M G (May 1999). "Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types". Cell (UNITED STATES) 97 (5): 587–98. doi:10.1016/S0092-8674(00)80770-9. ISSN 0092-8674. PMID 10367888. 
  6. ^ Ozawa, Y; Towatari M; Tsuzuki S; Hayakawa F; Maeda T; Miyata Y; Tanimoto M; Saito H (October 2001). "Histone deacetylase 3 associates with and represses the transcription factor GATA-2". Blood (United States) 98 (7): 2116–23. doi:10.1182/blood.V98.7.2116. ISSN 0006-4971. PMID 11567998. 
  7. ^ Tsuzuki, Shinobu; Enver Tariq (May 2002). "Interactions of GATA-2 with the promyelocytic leukemia zinc finger (PLZF) protein, its homologue FAZF, and the t(11;17)-generated PLZF-retinoic acid receptor alpha oncoprotein". Blood (United States) 99 (9): 3404–10. doi:10.1182/blood.V99.9.3404. ISSN 0006-4971. PMID 11964310. 
  8. ^ Osada, H; Grutz G; Axelson H; Forster A; Rabbitts T H (October 1995). "Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 92 (21): 9585–9. doi:10.1073/pnas.92.21.9585. ISSN 0027-8424. PMC 40846. PMID 7568177. 
  9. ^ Tsuzuki, S; Towatari M; Saito H; Enver T (September 2000). "Potentiation of GATA-2 Activity through Interactions with the Promyelocytic Leukemia Protein (PML) and the t(15;17)-Generated PML-Retinoic Acid Receptor α Oncoprotein". Mol. Cell. Biol. (UNITED STATES) 20 (17): 6276–86. doi:10.1128/MCB.20.17.6276-6286.2000. ISSN 0270-7306. PMC 86102. PMID 10938104. 
  10. ^ Zhang, P; Behre G; Pan J; Iwama A; Wara-Aswapati N; Radomska H S; Auron P E; Tenen D G; Sun Z (July 1999). "Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 96 (15): 8705–10. doi:10.1073/pnas.96.15.8705. ISSN 0027-8424. PMC 17580. PMID 10411939. 
  11. ^ Dickinson RE, Griffin H, Bigley V, Reynard LN, Hussain R, Haniffa M, Lakey JH, Rahman T, Wang XN, McGovern N, Pagan S, Cookson S, McDonald D, Chua I, Wallis J, Cant A, Wright M, Keavney B, Chinnery PF, Loughlin J, Hambleton S, Santibanez-Koref M, Collin M (September 2011). "Exome sequencing identifies GATA-2 mutation as the cause of dendritic cell, monocyte, B and NK lymphoid deficiency". Blood 118 (10): 2656–8. doi:10.1182/blood-2011-06-360313. PMID 21765025. 
  12. ^ Kumar, M. S.; Hancock, D. C.; Molina-Arcas, M.; Steckel, M.; East, P.; Diefenbacher, M.; Armenteros-Monterroso, E.; Lassailly, F. O.; Matthews, N.; Nye, E.; Stamp, G.; Behrens, A.; Downward, J. (2012). "The GATA2 Transcriptional Network is Requisite for RAS Oncogene-Driven Non-Small Cell Lung Cancer". Cell 149 (3): 642–655. doi:10.1016/j.cell.2012.02.059. PMID 22541434.  edit

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.