GATA2

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GATA2
PDB 1gnf EBI.jpg
Identifiers
Aliases GATA2, DCML, IMD21, MONOMAC, NFE1B, GATA binding protein 2
External IDs MGI: 95662 HomoloGene: 32030 GeneCards: 2624
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_032638
NM_001145661
NM_001145662

NM_008090

RefSeq (protein)

NP_001139133.1
NP_001139134.1
NP_116027.2

NP_032116.4

Location (UCSC) Chr 3: 128.48 – 128.49 Mb Chr 6: 88.19 – 88.21 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

GATA2 is a human gene which makes a protein called GATA binding protein 2 - a transcription factor.[3]

Function[edit]

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.[4] 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.[5] GATA2 also plays an essential role in the negative regulation of type 2 deiodinase gene (DIO2).[6] GATA3 expression is restricted to T-lymphocyte cells and some nonhematopoietic cell types, including embryonic stem cells.[7]

Interactions[edit]

GATA2 has been shown to interact with:

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.[14] Mutations in this gene have also been associated with familial myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) and lymphedema, deafness and myelodysplasia (Emberger syndrome).[15]

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.[16]

See also[edit]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ Matsunaga, H; Sasaki, S; Suzuki, S; Matsushita, A; Nakamura, H; Nakamura, HM; Hirahara, N; Kuroda, G; Iwaki, H; Ohba, K; Morita, H; Oki, Y; Suda, T (2015). "Essential Role of GATA2 in the Negative Regulation of Type 2 Deiodinase Gene by Liganded Thyroid Hormone Receptor β2 in Thyrotroph.". PloS one. 10 (11): e0142400. doi:10.1371/journal.pone.0142400. PMID 26571013. 
  7. ^ "Entrez Gene: GATA2 GATA binding protein 2". 
  8. ^ 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. 
  9. ^ 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 40846free to read. PMID 7568177. 
  10. ^ 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. 
  11. ^ 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 86102free to read. PMID 10938104. 
  12. ^ 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 17580free to read. PMID 10411939. 
  13. ^ 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. 
  14. ^ 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. 
  15. ^ 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
  16. ^ 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[edit]

External links[edit]

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