Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

GATA1 (GATA binding protein 1 (globin transcription factor1))

Identity

Other namesERYF1
GF1
NFE1
HGNC (Hugo) GATA1
LocusID (NCBI) 2623
Location Xp11.23
Location_base_pair Starts at 48644982 and ends at 48652717 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

Description Genomic sequence 7,757 bases, mRNA six exons (five coding) 1497bp. Plus strand

Protein

 
  Alternative models for generation of GATA1 isoforms. The full GATA1 protein can only be translated from the full GATA1 mRNA, whereas the GATA1s protein can be translated either from the full gata-1mRNA or from the shorter splice variant in which exon 2 is skipped.
Description The full length GATA1 protein is 413 amino acids; 42.7 KDa. However two major protein isoforms are formed by alternative splicing of the mRNA and alternative translation initiation sites as shown in the figure. The shorter GATA1 protein (GATA1s) lacks the first 83 aa. ("The N-terminal activation domain AD"). GATA1s is less active in activation of megakaryocytic promoters. Both proteins contain two Zinc finger domains mediating protein interactions and DNA binding.
Expression Bone-Marrow - Erythroid, Megakaryocytic, Mast and Eosonophillic precursors.
Localisation Nuclear
Function Transcription Factor, essential for eryhtroid and megakaryocytic development
Homology A member of the family of GATA proteins.

Mutations

Germinal Implicated in germline mutations in the N- Zinc finger domain that mediates the interaction with FOG1 and/or binding to DNA, cause X-linked Dyserythropoietic anemia with thrombocytopenia. The syndrome can be also be manifested only by X-linked macrothrombocytopenia
Somatic see below

Implicated in

Entity Acquired somatic mutations in GATA1 occur in virtually all children with Down Syndrome (DS) and congenital transient myeloproliferative syndrome (TMD) or acute megakaryocytic leukemia (AMKL, M7-ANLL). The mutations have also been detected in umbilical cord blood of DS patients and in fetal liver of aborted DS embryos. The mutations occur in-utero probably during fetal liver hematopoiesis. They consist of insertions, deletions and base substitution in exon 2 and vicinity and all result in elimination of the full length GATA1 protein with preservation of the GATA1s isoform. The presence of GATA1s in the absence of full length GATA1 blocks megakaryocytic differentiation and promote proliferation of megakaryoblasts. The genes on chromosome 21 that promote this abnormality are unknown. GATA1 mutations are almost always associated with the M7 leukemia in DS although they were also described in a pair of twins with acquired trisomy 21 and in one adult non DS patient with M7. The down-regulations of genes regulated by GATA1 may explain the exquisite sensitivity of DS leukemic blasts to ACA-C.
 
Legend: Example to the distribution of the mutations in children with M7 and DS described in Rainis et al.
  

External links

Nomenclature
HGNC (Hugo)GATA1   4170
Cards
AtlasGATA1ID40689chXp11
Entrez_Gene (NCBI)GATA1  2623  GATA binding protein 1 (globin transcription factor 1)
GeneCards (Weizmann)GATA1
Ensembl (Hinxton)ENSG00000102145 [Gene_View]  chrX:48644982-48652717 [Contig_View]  GATA1 [Vega]
AceView (NCBI)GATA1
Genatlas (Paris)GATA1
WikiGenes2623
SOURCE (Princeton)NM_002049
Genomic and cartography
GoldenPath (UCSC)GATA1  -  Xp11.23   chrX:48644982-48652717 +  Xp11.23   [Description]    (hg19-Feb_2009)
EnsemblGATA1 - Xp11.23 [CytoView]
Mapping of homologs : NCBIGATA1 [Mapview]
OMIM190685   300367   300835   305371   314050   
Gene and transcription
Genbank (Entrez)AI057349 BC009797 M30601 X17254
RefSeq transcript (Entrez)NM_002049
RefSeq genomic (Entrez)AC_000155 NC_000023 NC_018934 NG_008846 NT_079573 NW_001842363 NW_004070880 NW_004929439
Consensus coding sequences : CCDS (NCBI)GATA1
Cluster EST : UnigeneHs.765 [ NCBI ]
CGAP (NCI)Hs.765
Alternative Splicing : Fast-db (Paris)GSHG0031519
Alternative Splicing GalleryENSG00000102145
Gene ExpressionGATA1 [ NCBI-GEO ]     GATA1 [ SEEK ]   GATA1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP15976 (Uniprot)
NextProtP15976  [Medical]
With graphics : InterProP15976
Splice isoforms : SwissVarP15976 (Swissvar)
Domaine pattern : Prosite (Expaxy)GATA_ZN_FINGER_1 (PS00344)    GATA_ZN_FINGER_2 (PS50114)   
Domains : Interpro (EBI)TF_GATA-1/2/3    Znf_GATA    Znf_NHR/GATA   
Related proteins : CluSTrP15976
Domain families : Pfam (Sanger)GATA (PF00320)   
Domain families : Pfam (NCBI)pfam00320   
Domain families : Smart (EMBL)ZnF_GATA (SM00401)  
DMDM Disease mutations2623
Blocks (Seattle)P15976
Human Protein AtlasENSG00000102145
Peptide AtlasP15976
HPRD02372
IPIIPI00013999   IPI01014333   IPI01018734   IPI00607766   IPI00640714   
Protein Interaction databases
DIP (DOE-UCLA)P15976
IntAct (EBI)P15976
FunCoupENSG00000102145
BioGRIDGATA1
InParanoidP15976
Interologous Interaction database P15976
IntegromeDBGATA1
STRING (EMBL)GATA1
Ontologies - Pathways
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  transcription regulatory region sequence-specific DNA binding  RNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription  RNA polymerase II transcription factor binding  enhancer sequence-specific DNA binding  in utero embryonic development  p53 binding  DNA binding  sequence-specific DNA binding transcription factor activity  protein binding  nucleus  nucleoplasm  transcription factor complex  nucleolus  transcription from RNA polymerase II promoter  cell-cell signaling  blood coagulation  zinc ion binding  negative regulation of cell proliferation  DNA binding, bending  male gonad development  regulation of glycoprotein biosynthetic process  regulation of definitive erythrocyte differentiation  transcriptional repressor complex  erythrocyte differentiation  megakaryocyte differentiation  platelet formation  basophil differentiation  eosinophil differentiation  negative regulation of bone mineralization  chromatin DNA binding  nuclear membrane  positive regulation of osteoblast proliferation  embryonic hemopoiesis  eosinophil fate commitment  negative regulation of apoptotic process  sequence-specific DNA binding  positive regulation of erythrocyte differentiation  positive regulation of transcription from RNA polymerase II promoter  erythrocyte development  positive regulation of peptidyl-tyrosine phosphorylation  platelet aggregation  C2H2 zinc finger domain binding  transcriptional activation by promoter-enhancer looping  dendritic cell differentiation  cellular response to thyroid hormone stimulus  negative regulation of transcription regulatory region DNA binding  negative regulation of extrinsic apoptotic signaling pathway in absence of ligand  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  transcription regulatory region sequence-specific DNA binding  RNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription  RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription  RNA polymerase II transcription factor binding  enhancer sequence-specific DNA binding  in utero embryonic development  p53 binding  DNA binding  sequence-specific DNA binding transcription factor activity  protein binding  nucleus  nucleoplasm  transcription factor complex  nucleolus  transcription from RNA polymerase II promoter  cell-cell signaling  blood coagulation  zinc ion binding  negative regulation of cell proliferation  DNA binding, bending  male gonad development  regulation of glycoprotein biosynthetic process  regulation of definitive erythrocyte differentiation  transcriptional repressor complex  erythrocyte differentiation  megakaryocyte differentiation  platelet formation  basophil differentiation  eosinophil differentiation  negative regulation of bone mineralization  chromatin DNA binding  nuclear membrane  positive regulation of osteoblast proliferation  embryonic hemopoiesis  eosinophil fate commitment  negative regulation of apoptotic process  sequence-specific DNA binding  positive regulation of erythrocyte differentiation  positive regulation of transcription from RNA polymerase II promoter  erythrocyte development  positive regulation of peptidyl-tyrosine phosphorylation  platelet aggregation  C2H2 zinc finger domain binding  transcriptional activation by promoter-enhancer looping  dendritic cell differentiation  cellular response to thyroid hormone stimulus  negative regulation of transcription regulatory region DNA binding  negative regulation of extrinsic apoptotic signaling pathway in absence of ligand  
Pathways : BIOCARTAHemoglobin's Chaperone [Genes]   
REACTOMEGATA1
Protein Interaction DatabaseGATA1
Wikipedia pathwaysGATA1
Gene fusion - rearrangments
Rearrangement : TICdbGATA1 [Xp11.23]  -  MYB [6q23.3]
Rearrangement : TICdbMYB [6q23.3]  -  GATA1 [Xp11.23]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)GATA1
SNP (GeneSNP Utah)GATA1
SNP : HGBaseGATA1
Genetic variants : HAPMAPGATA1
1000_GenomesGATA1 
ICGC programENSG00000102145 
Cancer Gene: CensusGATA1 
Somatic Mutations in Cancer : COSMICGATA1 
CONAN: Copy Number AnalysisGATA1 
Mutations and Diseases : HGMDGATA1
OMIM190685    300367    300835    305371    314050   
GENETestsGATA1
Disease Genetic AssociationGATA1
Huge Navigator GATA1 [HugePedia]  GATA1 [HugeCancerGEM]
Genomic VariantsGATA1  GATA1 [DGVbeta]
Exome VariantGATA1
dbVarGATA1
ClinVarGATA1
snp3D : Map Gene to Disease2623
General knowledge
Homologs : HomoloGeneGATA1
Homology/Alignments : Family Browser (UCSC)GATA1
Phylogenetic Trees/Animal Genes : TreeFamGATA1
Chemical/Protein Interactions : CTD2623
Chemical/Pharm GKB GenePA28584
Clinical trialGATA1
Cancer Resource (Charite)ENSG00000102145
Other databases
Probes
Litterature
PubMed183 Pubmed reference(s) in Entrez
CoreMineGATA1
iHOPGATA1

Bibliography

Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1.
Nichols KE, Crispino JD, Poncz M, White JG, Orkin SH, Maris JM, Weiss MJ
Nature genetics. 2000 ; 24 (3) : 266-270.
PMID 10700180
 
Different substitutions at residue D218 of the X-linked transcription factor GATA1 lead to altered clinical severity of macrothrombocytopenia and anemia and are associated with variable skewed X inactivation.
Freson K, Matthijs G, Thys C, Marił┤n P, Hoylaerts MF, Vermylen J, Van Geet C
Human molecular genetics. 2002 ; 11 (2) : 147-152.
PMID 11809723
 
A leukemogenic twist for GATA1.
Look AT
Nature genetics. 2002 ; 32 (1) : 83-84.
PMID 12172549
 
Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome.
Wechsler J, Greene M, McDevitt MA, Anastasi J, Karp JE, Le Beau MM, Crispino JD
Nature genetics. 2002 ; 32 (1) : 148-152.
PMID 12172547
 
Acquired mutations in GATA1 in neonates with Down's syndrome with transient myeloid disorder.
Groet J, McElwaine S, Spinelli M, Rinaldi A, Burtscher I, Mulligan C, Mensah A, Cavani S, Dagna-Bricarelli F, Basso G, Cotter FE, Nizetic D
Lancet. 2003 ; 361 (9369) : 1617-1620.
PMID 12747884
 
GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome.
Hitzler JK, Cheung J, Li Y, Scherer SW, Zipursky A
Blood. 2003 ; 101 (11) : 4301-4304.
PMID 12586620
 
GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome.
Hitzler JK, Cheung J, Li Y, Scherer SW, Zipursky A
Blood. 2003 ; 101 (11) : 4301-4304.
PMID 12586620
 
Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21.
Rainis L, Bercovich D, Strehl S, Teigler-Schlegel A, Stark B, Trka J, Amariglio N, Biondi A, Muler I, Rechavi G, Kempski H, Haas OA, Izraeli S
Blood. 2003 ; 102 (3) : 981-986.
PMID 12649131
 
Natural history of GATA1 mutations in Down syndrome.
Ahmed M, Sternberg A, Hall G, Thomas A, Smith O, O'Marcaigh A, Wynn R, Stevens R, Addison M, King D, Stewart B, Gibson B, Roberts I, Vyas P
Blood. 2004 ; 103 (7) : 2480-2489.
PMID 14656875
 
The role of cytidine deaminase and GATA1 mutations in the increased cytosine arabinoside sensitivity of Down syndrome myeloblasts and leukemia cell lines.
Ge Y, Jensen TL, Stout ML, Flatley RM, Grohar PJ, Ravindranath Y, Matherly LH, Taub JW
Cancer research. 2004 ; 64 (2) : 728-735.
PMID 14744791
 
Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome.
Gurbuxani S, Vyas P, Crispino JD
Blood. 2004 ; 103 (2) : 399-406.
PMID 14512321
 
The GATA1 mutation in an adult patient with acute megakaryoblastic leukemia not accompanying Down syndrome.
Harigae H, Xu G, Sugawara T, Ishikawa I, Toki T, Ito E
Blood. 2004 ; 103 (8) : 3242-3243.
PMID 15070711
 
Leukaemia -- a developmental perspective.
Izraeli S
British journal of haematology. 2004 ; 126 (1) : 3-10.
PMID 15198727
 
Leukaemia -- a developmental perspective.
Izraeli S
British journal of haematology. 2004 ; 126 (1) : 3-10.
PMID 15198727
 
Prenatal origin of GATA1 mutations may be an initiating step in the development of megakaryocytic leukemia in Down syndrome.
Taub JW, Mundschau G, Ge Y, Poulik JM, Qureshi F, Jensen T, James SJ, Matherly LH, Wechsler J, Crispino JD
Blood. 2004 ; 104 (5) : 1588-1589.
PMID 15317736
 
Origins of leukaemia in children with Down syndrome.
Hitzler JK, Zipursky A
Nature reviews. Cancer. 2005 ; 5 (1) : 11-20.
PMID 15630411
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written02-2005Shai Izraeli
Pediatric Hemato-Oncology, Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel 52621

Citation

This paper should be referenced as such :
Izraeli S . GATA1 (GATA binding protein 1 (globin transcription factor1)). Atlas Genet Cytogenet Oncol Haematol. February 2005 .
URL : http://AtlasGeneticsOncology.org/Genes/GATA1ID40689chXp11.html

The various updated versions of this paper are referenced and archived by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/38177/1/02-2005-GATA1ID40689chXp11.pdf   [ Bibliographic record ]

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Apr 18 17:37:53 CEST 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.