GATA2

GATA binding protein 2
PDB rendering based on 1gnf.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1gnf​, 1y0j​
Identifiers
Symbols	GATA2 ; DCML; IMD21; MONOMAC; NFE1B
External IDs	OMIM: 137295 MGI: 95662 HomoloGene: 32030 GeneCards: GATA2 Gene
Gene ontology Molecular function • RNA polymerase II distal enhancer sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • enhancer sequence-specific DNA binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • protein binding • transcription factor binding • zinc ion binding • C2H2 zinc finger domain binding Cellular component • nucleoplasm • cytosol • mast cell granule • protein complex Biological process • negative regulation of transcription from RNA polymerase II promoter • urogenital system development • cell fate determination • neuron migration • embryonic placenta development • transcription, DNA-templated • transcription from RNA polymerase II promoter • phagocytosis • positive regulation of cytosolic calcium ion concentration • blood coagulation • ventral spinal cord interneuron differentiation • cell differentiation in hindbrain • commitment of neuronal cell to specific neuron type in forebrain • central nervous system neuron development • pituitary gland development • response to lipid • somatic stem cell maintenance • regulation of histone acetylation • eosinophil fate commitment • inner ear morphogenesis • mast cell degranulation • negative regulation of fat cell differentiation • positive regulation of erythrocyte differentiation • negative regulation of macrophage differentiation • positive regulation of megakaryocyte differentiation • positive regulation of neuron differentiation • negative regulation of Notch signaling pathway • positive regulation of angiogenesis • positive regulation of transcription from RNA polymerase II promoter • cell maturation • homeostasis of number of cells within a tissue • positive regulation of phagocytosis • positive regulation of phagocytosis, engulfment • definitive hemopoiesis • semicircular canal development • negative regulation of fat cell proliferation • GABAergic neuron differentiation • negative regulation of neural precursor cell proliferation • regulation of forebrain neuron differentiation Sources: Amigo / QuickGO
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: 128.48 – 128.49 Mb	Chr 6: 88.19 – 88.21 Mb
PubMed search

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

Function

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-lymphocyte cells and some nonhematopoietic cell types, including embryonic stem cells.^[4]

Interactions

GATA2 has been shown to interact with:

• HDAC3,^[5]
• LMO2,^[6]
• POU1F1,^[7]
• PML^[8]
• SPI1,^[9] and
• ZBTB16.^[10]

Genetic disorders

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] Mutations in this gene have also been associated with familiar myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) and lymphedema, deafness and myelodysplasia (Emberger syndrome).^[12]

Lung cancer

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.^[13]

See also

• GATA transcription factor
• MonoMAC

References

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. 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 98 (7): 2116–23. doi:10.1182/blood.v98.7.2116. PMID 11567998.
6. Osada H, Grutz G, Axelson H, Forster A, Rabbitts TH (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. 92 (21): 9585–9. doi:10.1073/pnas.92.21.9585. PMC 40846. PMID 7568177.
7. Dasen JS, O'Connell SM, Flynn SE, Treier M, Gleiberman AS, Szeto DP, Hooshmand F, Aggarwal AK, Rosenfeld MG (May 1999). "Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types". Cell 97 (5): 587–98. doi:10.1016/s0092-8674(00)80770-9. PMID 10367888.
8. 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 alpha oncoprotein". Mol. Cell. Biol. 20 (17): 6276–86. doi:10.1128/mcb.20.17.6276-6286.2000. PMC 86102. PMID 10938104.
9. Zhang P, Behre G, Pan J, Iwama A, Wara-Aswapati N, Radomska HS, Auron PE, Tenen DG, Sun Z (July 1999). "Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1". Proc. Natl. Acad. Sci. U.S.A. 96 (15): 8705–10. doi:10.1073/pnas.96.15.8705. PMC 17580. PMID 10411939.
10. Tsuzuki S, Enver T (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 99 (9): 3404–10. doi:10.1182/blood.v99.9.3404. PMID 11964310.
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. Lübking A, Vosberg S, Konstandin NP, Dufour A, Graf A, Krebs S, Blum H, Weber A, Lenhoff S, Ehinger M, Spiekermann K, Greif PA, Cammenga J (2015) Young woman with mild bone marrow dysplasia, GATA2 and ASXL1 mutation treated with allogeneic hematopoietic stem cell transplantation. Leuk Res Rep 4(2):72-5. doi: 10.1016/j.lrr.2015.10.001
13. Kumar MS, Hancock DC, Molina-Arcas M, Steckel M, East P, Diefenbacher M, Armenteros-Monterroso E, Lassailly F, 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.

Further reading

• Minegishi N (2002). "[Transcription factors regulating hematopoiesis: researches spanning from molecule to whole body]". Seikagaku 74 (5): 398–402. PMID 12073612.
• Ohneda K, Yamamoto M (2003). "Roles of hematopoietic transcription factors GATA-1 and GATA-2 in the development of red blood cell lineage". Acta Haematol. 108 (4): 237–45. doi:10.1159/000065660. PMID 12432220.
• Dorfman DM, Wilson DB, Bruns GA, Orkin SH (1992). "Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1 gene expression in endothelial cells". J. Biol. Chem. 267 (2): 1279–85. PMID 1370462.
• Page RL, Wharton JM, Wilkinson WE, Friedman IM, Claypool WD, Karim A, Kowalski KG, McDonald SJ, Gardiner P, Pritchett EL (1992). "Bidisomide (SC-40230), a new antiarrhythmic agent: initial study of tolerability and pharmacokinetics". Clin. Pharmacol. Ther. 51 (4): 371–8. doi:10.1038/clpt.1992.36. PMID 1563207.
• Lee ME, Temizer DH, Clifford JA, Quertermous T (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.
• Zhang R, Min W, Sessa WC (1995). "Functional analysis of the human endothelial nitric oxide synthase promoter. Sp1 and GATA factors are necessary for basal transcription in endothelial cells". J. Biol. Chem. 270 (25): 15320–6. doi:10.1074/jbc.270.25.15320. PMID 7541039.
• Osada H, Grutz G, Axelson H, Forster A, Rabbitts TH (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. 92 (21): 9585–9. doi:10.1073/pnas.92.21.9585. PMC 40846. PMID 7568177.
• Towatari M, May GE, Marais R, Perkins GR, Marshall CJ, Cowley S, Enver T (1995). "Regulation of GATA-2 phosphorylation by mitogen-activated protein kinase and interleukin-3". J. Biol. Chem. 270 (8): 4101–7. doi:10.1074/jbc.270.8.4101. PMID 7876160.
• Tsai FY, Keller G, Kuo FC, Weiss M, Chen J, Rosenblatt M, Alt FW, Orkin SH (1994). "An early haematopoietic defect in mice lacking the transcription factor GATA-2". Nature 371 (6494): 221–6. doi:10.1038/371221a0. PMID 8078582.
• Briegel K, Lim KC, Plank C, Beug H, Engel JD, Zenke M (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.
• Towatari M, Kanei Y, Saito H, Hamaguchi M (1998). "Hematopoietic transcription factor GATA-2 activates transcription from HIV-1 long terminal repeat". AIDS 12 (3): 253–9. doi:10.1097/00002030-199803000-00002. PMID 9517987.
• Dasen JS, O'Connell SM, Flynn SE, Treier M, Gleiberman AS, Szeto DP, Hooshmand F, Aggarwal AK, Rosenfeld MG (1999). "Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types". Cell 97 (5): 587–98. doi:10.1016/S0092-8674(00)80770-9. PMID 10367888.
• Zhang P, Behre G, Pan J, Iwama A, Wara-Aswapati N, Radomska HS, Auron PE, Tenen DG, Sun Z (1999). "Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1". Proc. Natl. Acad. Sci. U.S.A. 96 (15): 8705–10. doi:10.1073/pnas.96.15.8705. PMC 17580. PMID 10411939.
• Wieser R, Volz A, Vinatzer U, Gardiner K, Jäger U, Mitterbauer M, Ziegler A, Fonatsch C (2000). "Transcription factor GATA-2 gene is located near 3q21 breakpoints in myeloid leukemia". Biochem. Biophys. Res. Commun. 273 (1): 239–45. doi:10.1006/bbrc.2000.2947. PMID 10873593.
• Tsuzuki S, Towatari M, Saito H, Enver T (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. 20 (17): 6276–86. doi:10.1128/MCB.20.17.6276-6286.2000. PMC 86102. PMID 10938104.
• Yamashita K, Discher DJ, Hu J, Bishopric NH, Webster KA (2001). "Molecular regulation of the endothelin-1 gene by hypoxia. Contributions of hypoxia-inducible factor-1, activator protein-1, GATA-2, AND p300/CBP". J. Biol. Chem. 276 (16): 12645–53. doi:10.1074/jbc.M011344200. PMID 11278891.
• Ozawa Y, Towatari M, Tsuzuki S, Hayakawa F, Maeda T, Miyata Y, Tanimoto M, Saito H (2001). "Histone deacetylase 3 associates with and represses the transcription factor GATA-2". Blood 98 (7): 2116–23. doi:10.1182/blood.V98.7.2116. PMID 11567998.
• Zhang SB, He QY, Zhao H, Gui CY, Jiang C, Qian RL (2002). "Function of GATA transcription factors in hydroxyurea-induced HEL cells". Cell Res. 11 (4): 301–10. doi:10.1038/sj.cr.7290100. PMID 11787775.
• Tsuzuki S, Enver T (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 99 (9): 3404–10. doi:10.1182/blood.V99.9.3404. PMID 11964310.
• Hirasawa R, Shimizu R, Takahashi S, Osawa M, Takayanagi S, Kato Y, Onodera M, Minegishi N, Yamamoto M, Fukao K, Taniguchi H, Nakauchi H, Iwama A (2002). "Essential and Instructive Roles of GATA Factors in Eosinophil Development". J. Exp. Med. 195 (11): 1379–86. doi:10.1084/jem.20020170. PMC 2193540. PMID 12045236.

External links

• GATA2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook GATA2

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