GATA1

GATA1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1GNF, 1Y0J, 2L5E, 2L6Y, 2L6Z, 3VD6, 3VEK
Identifiers
Aliases	GATA1, ERYF1, GATA-1, GF-1, GF1, NF-E1, NFE1, XLANP, XLTDA, XLTT, GATA binding protein 1
External IDs	OMIM: 305371 MGI: 95661 HomoloGene: 1549 GeneCards: GATA1
Gene ontology Molecular function • C2H2 zinc finger domain binding • core promoter binding • transcription regulatory region sequence-specific DNA binding • sequence-specific DNA binding • RNA polymerase II core promoter sequence-specific DNA binding • DNA binding • p53 binding • DNA binding, bending • RNA polymerase II transcription factor binding • chromatin DNA binding • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding • enhancer sequence-specific DNA binding • RNA polymerase II regulatory region sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • protein binding • RNA polymerase II core promoter proximal region sequence-specific DNA binding • chromatin binding • RNA polymerase II transcription factor activity, sequence-specific DNA binding • transcription factor activity, sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • zinc ion binding • metal ion binding Cellular component • nucleus • nucleoplasm • transcriptional repressor complex • transcription factor complex Biological process • negative regulation of cell proliferation • negative regulation of transcription regulatory region DNA binding • tissue development • eosinophil fate commitment • in utero embryonic development • regulation of glycoprotein biosynthetic process • cellular response to thyroid hormone stimulus • blood coagulation • erythrocyte differentiation • platelet formation • positive regulation of osteoblast proliferation • transcription from RNA polymerase II promoter • erythrocyte development • platelet aggregation • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand • regulation of transcription, DNA-templated • regulation of primitive erythrocyte differentiation • positive regulation of transcription, DNA-templated • animal organ morphogenesis • regulation of definitive erythrocyte differentiation • transcriptional activation by promoter-enhancer looping • cell-cell signaling • embryonic hemopoiesis • heart development • cell development • positive regulation of erythrocyte differentiation • positive regulation of transcription from RNA polymerase II promoter • megakaryocyte differentiation • dendritic cell differentiation • positive regulation of peptidyl-tyrosine phosphorylation • negative regulation of bone mineralization • negative regulation of transcription from RNA polymerase II promoter • male gonad development • myeloid cell differentiation • eosinophil differentiation • basophil differentiation • negative regulation of apoptotic process • digestive tract development • homeostasis of number of cells within a tissue • transcription, DNA-templated Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2623	14460
Ensembl	ENSG00000102145	ENSMUSG00000031162
UniProt	P15976	P17679
RefSeq (mRNA)	NM_002049	NM_008089
RefSeq (protein)	NP_002040.1	NP_032115.1
Location (UCSC)	Chr X: 48.79 – 48.79 Mb	Chr X: 7.96 – 7.98 Mb
PubMed search	[1]	[2]
Wikidata

Erythroid transcription factor also known as GATA-binding factor 1 or GATA-1 is a protein that in humans is encoded by the GATA1 gene.^[3]

GATA-1 is a member of the GATA transcription factor family and is a key mediator of the development of specific types of blood cells from their precursor cells, termed hematopoietic progenitors or precursors.^[4][5] This protein plays a role in erythroid development by regulating a large ensemble of genes that mediate both the development and function of red blood cells. Critical functions in the developing red blood cell (erythroblast) include the establishment of the erythroid cytoskeleton, enzymes that mediate heme biosynthesis, and polypeptide chains that constitute the hemoglobin tetramer. Mutations in the gene encoding GATA-1 have been associated with X-linked dyserythropoietic anemia and thrombocytopenia.^[6]

Function

GATA1 is required for the maturation of red blood cells, megakaryocytes, mast cells and eosinophils.^[7] GATA1 mutant mice die in early embryonic development due to inability to form mature erythroid cells. GATA1 mutation in humans causes congenital anemias and thrombocytopenias.^[8][9]

GATA1 was first described as a red blood cell lineage transcription factor that activates the beta-globin gene.^[10] During red blood cell maturation, GATA1 activates nearly all erythroid-specific genes while silencing genes associated with the immature proliferative red blood cell precursor cells (erythroblasts).^[11][12] Genome-wide studies have provided evidence that GATA1 activates and represses a large number of genes.^{[11][12][13][14]} Many questions remain unanswered regarding the function of a large number of genes. By contrast, other GATA-1 target genes have established activities to control fundamental cell biological functions, including machinery that controls the ability of erythroid precursor cells to proliferate and proteins that control the capacity of the erythroid precursor cell to remodel its organelles such as mitochondria,^[15] proteins that control the RNA content of the erythroid precursor cell,^[16] and proteins that control signal transduction networks that orchestrate the many dynamic transitions of the developing erythroid precursor.^[17]

Structure

The GATA-1 protein contains multiple functional domains including the C-finger, the N-finger, and N-terminal sequences that have been suggested to constitute a transcriptional activation domain. The C-finger, named for being near the C-terminal, mediates Zinc finger sequence-specific DNA binding. The primary function of the N-finger, named for being near the N-terminal is binding to a cofactor named FOG1 (friend of GATA), although it has also been implicated in binding to naked DNA (DNA studied in the test tube that is not assembled into chromatin). The gene for GATA1 is on the X-chromosome.

Disease linkage

Mutations in GATA1 cause anemias and thrombocytopenia in human patients.^[18][19] Disease-causing GATA1 mutations are present in the zinc finger DNA binding domains as well as protein-protein interaction domains of GATA1.^[20]

Mutations in exon 2 of the GATA1 gene are present in almost all cases of Down syndrome (DS)-associated acute megakaryoblastic leukemia (AMKL).^[21][22] While AMKL is typically associated with the (1;22) translocation and expression of a mutant fusion protein, the genetic alterations that promote individuals with DS-AMKL are related to the GATA1 mutations, and the formation of a truncated transcription factor (GATA1s).

The same mutations in exon 2 of GATA1 present in almost all Down Syndrome-associated transient myeloproliferative disorder (TMD) or transient leukemia (TL), a precursor condition that evolves into AMKL in 30% of patients, that as many as 10% of Down Syndrome children may develop.^[23] The incidence for the GATA1 mutation in about 4% of Down Syndrome patients, but less than 10% of those with the mutation developed AMKL.^[24] This mutation is present in the fetus, suggesting an early role in leukemogenesis. In addition to screening for TL, a GATA1 mutation at birth might serve as a bio-marker for an increased risk of DS-related AMKL.^[25]

Interactions

GATA1 has been shown to interact with several proteins - either directly by binding the protein or indirectly (functional interaction without direct binding).

References

Further reading

External links

• Genecards
• GeneReviews/NCBI/NIH/UW entry on GATA1-Related X-Linked Cytopenia
• Geneatlas
• Infobiogen
• Nextbio
• FactorBook GATA1

PDB gallery
1gnf: SOLUTION STRUCTURE OF THE N-TERMINAL ZINC FINGER OF MURINE GATA-1, NMR, 25 STRUCTURES  1y0j: Zinc fingers as protein recognition motifs: structural basis for the GATA-1/Friend of GATA interaction