P15976 (GATA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 128.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Erythroid transcription factor Alternative name(s): Eryf1 GATA-binding factor 1 Short name=GATA-1 Short name=GF-1 NF-E1 DNA-binding protein | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 413 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Transcriptional activator which probably serves as a general switch factor for erythroid development. It binds to DNA sites with the consensus sequence [AT]GATA[AG] within regulatory regions of globin genes and of other genes expressed in erythroid cells. |
| Subunit structure | May form homodimers or heterodimers with other isoforms. Interacts (via the N-terminal zinc finger) with ZFPM1. Interacts with GFI1B. Interacts with PIAS4; the interaction enhances sumoylation and represses the transactivational activity in a sumoylation-independent manner. Interacts with LMCD1 By similarity. Ref.5 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 |
| Subcellular location | |
| Tissue specificity | Erythrocytes. Ref.5 |
| Domain | The two fingers are functionally distinct and cooperate to achieve specific, stable DNA binding. The first finger is necessary only for full specificity and stability of binding, whereas the second one is required for binding By similarity. |
| Post-translational modification | Highly phosphorylated on serine residues. Phosphorylation on Ser-310 is enhanced on erythroid differentiation. Phosphorylation on Ser-142 promotes sumoylation on Lys-137 By similarity. Ref.7 Sumoylation on Lys-137 is enhanced by phosphorylation on Ser-142 and by interaction with PIAS4. Sumoylation by SUMO1 has no effect on transcriptional activity By similarity. |
| Involvement in disease | Defects in GATA1 are the cause of X-linked dyserythropoietic anemia and thrombocytopenia (XDAT) [MIM:300367]. XDAT is a disorder characterized by erythrocytes with abnormal size and shape, and paucity of platelets in peripheral blood. The bone marrow contains abundant and abnormally small megakaryocytes. Ref.9 Ref.10 Ref.11 Ref.13 Defects in GATA1 are the cause of X-linked thrombocytopenia with beta-thalassemia (XLTT) [MIM:314050]; also knwon as thrombocytopenia, platelet dysfunction, hemolysis, and imbalanced globin synthesis. XLTT consists of an unusual form of thrombocytopenia with beta-thalassemia. Patients have splenomegaly and petechiae, moderate thrombocytopenia, prolonged bleeding time due to platelet dysfunction, reticulocytosis and unbalanced hemoglobin chain synthesis resembling that of beta-thalassemia minor. Defects in GATA1 are the cause of anemia without thrombocytopenia X-linked (XLAWT) [MIM:300835]. XLAWT is a form of anemia characterized by abnormal morphology of erythrocytes and granulocytes in peripheral blood, bone marrow dysplasia with hypocellularity of erythroid and granulocytic lineages, and normal or increased number of megakaryocytes. Neutropenia of a variable degree is present in affected individuals. Ref.6 |
| Sequence similarities | Contains 2 GATA-type zinc fingers. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| HSPA1A | P08107 | 5 | EBI-3909284,EBI-629985 |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing and alternative initiation. [Align] [Select] | ||||||
| Isoform 1 (identifier: P15976-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P15976-2) The sequence of this isoform differs from the canonical sequence as follows: 290-413: QVNRPLTMRK...STTVVAPLSS → HQHYCGGSAQ...KSLGPRHPLA | ||||||
| Note: No experimental confirmation available. | ||||||
| Isoform 3 (identifier: P15976-3) Also known as: GATA-1s; The sequence of this isoform differs from the canonical sequence as follows: 1-83: Missing. | ||||||
| Note: Produced by alternative initiation at Met-84 of isoform 1. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 413 | 413 | Erythroid transcription factor | PRO_0000083397 | |||||
Regions | |||||||||
| Zinc finger | 204 – 228 | 25 | GATA-type 1 | ||||||
| Zinc finger | 258 – 282 | 25 | GATA-type 2 | ||||||
| Region | 203 – 222 | 20 | Required for interaction with ZFPM1 | ||||||
Amino acid modifications | |||||||||
| Modified residue | 26 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 72 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 142 | 1 | Phosphoserine Ref.7 | ||||||
| Modified residue | 178 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 187 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 310 | 1 | Phosphoserine By similarity | ||||||
| Cross-link | 137 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.7 | |||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 83 | 83 | Missing in isoform 3. | VSP_041451 | |||||
| Alternative sequence | 290 – 413 | 124 | QVNRP…APLSS → HQHYCGGSAQLMRAQSMASR GGVVSFSSCSQNSGQPKSLG PRHPLA in isoform 2. | VSP_014782 | |||||
| Natural variant | 205 | 1 | V → M in XDAT; severe impairment of ZFPM1 binding and erythroid differentiation in vitro. Ref.9 | VAR_010115 | |||||
| Natural variant | 208 | 1 | G → S in XDAT; partially disrupts the interaction with ZFPM1. Ref.11 | VAR_012706 | |||||
| Natural variant | 216 | 1 | R → Q in XLTT; does not affect ZFPM1 binding; reduced affinity to palindromic GATA sites; supports erythroid maturation less efficiently than wild-type GATA1. Ref.12 | VAR_033114 | |||||
| Natural variant | 218 | 1 | D → G in XDAT; partially disrupts the interaction with ZFPM1. Ref.10 | VAR_012707 | |||||
| Natural variant | 218 | 1 | D → Y in XDAT; stronger loss of affinity than of G-218-GATA1 for ZFPM1 and disturbed GATA1 self-association. Ref.13 | VAR_033115 | |||||
Experimental info | |||||||||
| Mutagenesis | 137 | 1 | K → R: Abolishes sumoylation. Ref.7 | ||||||
| Mutagenesis | 142 | 1 | S → A: Loss of sumoylation. Ref.7 | ||||||
| Mutagenesis | 142 | 1 | S → D: Increased sumoylation in vitro. Ref.7 | ||||||
| Mutagenesis | 204 | 1 | C → R: Increase of dissociation rate from bound DNA. Ref.9 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Structure and evolution of a human erythroid transcription factor." Trainor C.D., Evans T., Felsenfeld G., Boguski M.S. Nature 343:92-96(1990) [PubMed: 2104960] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Bone marrow. |
| [2] | "The major human erythroid DNA-binding protein (GF-1): primary sequence and localization of the gene to the X chromosome." Zon L.I., Tsai S.-F., Burgess S., Matsudaira P., Bruns G.A.P., Orkin S.H. Proc. Natl. Acad. Sci. U.S.A. 87:668-672(1990) [PubMed: 2300555] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE. Tissue: Erythrocyte. |
| [3] | "The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. Bentley D.R.Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Bone marrow. |
| [5] | "Alternative translation initiation site usage results in two functionally distinct forms of the GATA-1 transcription factor." Calligaris R., Bottardi S., Cogoi S., Apezteguia I., Santoro C. Proc. Natl. Acad. Sci. U.S.A. 92:11598-11602(1995) [PubMed: 8524811] [Abstract] Cited for: ALTERNATIVE INITIATION (ISOFORM 3), SUBUNIT, TISSUE SPECIFICITY. |
| [6] | "An inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis." Hollanda L.M., Lima C.S., Cunha A.F., Albuquerque D.M., Vassallo J., Ozelo M.C., Joazeiro P.P., Saad S.T., Costa F.F. Nat. Genet. 38:807-812(2006) [PubMed: 16783379] [Abstract] Cited for: INVOLVEMENT IN XLAWT. |
| [7] | "PDSM, a motif for phosphorylation-dependent SUMO modification." Hietakangas V., Anckar J., Blomster H.A., Fujimoto M., Palvimo J.J., Nakai A., Sistonen L. Proc. Natl. Acad. Sci. U.S.A. 103:45-50(2006) [PubMed: 16371476] [Abstract] Cited for: SUMOYLATION AT LYS-137, PHOSPHORYLATION AT SER-142, MUTAGENESIS OF LYS-137 AND SER-142. |
| [8] | "GATA-1 and Gfi-1B interplay to regulate Bcl-xL transcription." Kuo Y.-Y., Chang Z.-F. Mol. Cell. Biol. 27:4261-4272(2007) [PubMed: 17420275] [Abstract] Cited for: INTERACTION WITH GFI1B. |
| [9] | "Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1." Nichols K.E., Crispino J.D., Poncz M., White J.G., Orkin S.H., Maris J.M., Weiss M.J. Nat. Genet. 24:266-270(2000) [PubMed: 10700180] [Abstract] Cited for: VARIANT XDAT MET-205, INTERACTION WITH ZFPM1, CHARACTERIZATION OF VARIANT XDAT MET-205, MUTAGENESIS OF CYS-204. Tissue: Peripheral blood. |
| [10] | "Platelet characteristics in patients with X-linked macrothrombocytopenia because of a novel GATA1 mutation." Freson K., Devriendt K., Matthijs G., Van Hoof A., De Vos R., Thys C., Minner K., Hoylaerts M.F., Vermylen J., Van Geet C. Blood 98:85-92(2001) [PubMed: 11418466] [Abstract] Cited for: VARIANT XDAT GLY-218, INTERACTION WITH ZFPM1, CHARACTERIZATION OF VARIANT XDAT GLY-218. |
| [11] | "X-linked thrombocytopenia caused by a novel mutation of GATA-1." Mehaffey M.G., Newton A.L., Gandhi M.J., Crossley M., Drachman J.G. Blood 98:2681-2688(2001) [PubMed: 11675338] [Abstract] Cited for: VARIANT XDAT SER-208, INTERACTION WITH ZFPM1, CHARACTERIZATION OF VARIANT XDAT SER-208. |
| [12] | "X-linked thrombocytopenia with thalassemia from a mutation in the amino finger of GATA-1 affecting DNA binding rather than FOG-1 interaction." Yu C., Niakan K.K., Matsushita M., Stamatoyannopoulos G., Orkin S.H., Raskind W.H. Blood 100:2040-2045(2002) [PubMed: 12200364] [Abstract] Cited for: VARIANT XLTT GLN-216, INTERACTION WITH ZFPM1, CHARACTERIZATION OF VARIANT XLTT GLN-216. |
| [13] | "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., Marieen P., Hoylaerts M.F., Vermylen J., Van Geet C. Hum. Mol. Genet. 11:147-152(2002) [PubMed: 11809723] [Abstract] Cited for: VARIANT XDAT TYR-218, INTERACTION WITH ZFPM1, CHARACTERIZATION OF VARIANT XDAT TYR-218. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | X17254 mRNA. Translation: CAA35120.1. M30601 mRNA. Translation: AAA35885.1. AF196971 Genomic DNA. No translation available. BC009797 mRNA. Translation: AAH09797.1. |
| IPI | IPI00013999. IPI01014333. IPI01018734. |
| PIR | A34888. |
| RefSeq | NP_002040.1. NM_002049.3. |
| UniGene | Hs.765. |
3D structure databases | |
| ProteinModelPortal | P15976. |
| SMR | P15976. Positions 200-243, 252-310. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-41431N. |
| IntAct | P15976. 3 interactions. |
| MINT | MINT-247486. |
| STRING | P15976. |
PTM databases | |
| PhosphoSite | P15976. |
Polymorphism databases | |
| DMDM | 120956. |
Proteomic databases | |
| PRIDE | P15976. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000376670; ENSP00000365858; ENSG00000102145. |
| GeneID | 2623. |
| KEGG | hsa:2623. |
| UCSC | uc004dkq.2. human. |
Organism-specific databases | |
| CTD | 2623. |
| GeneCards | GC0XP048644. |
| H-InvDB | HIX0203296. |
| HGNC | HGNC:4170. GATA1. |
| HPA | CAB009195. HPA000232. HPA000233. |
| MIM | 300367. phenotype. 300835. phenotype. 305371. gene. 314050. phenotype. |
| neXtProt | NX_P15976. |
| Orphanet | 231393. Beta-thalassemia - X-linked thrombocytopenia. 67044. Dyserythropoietic anemia with thrombocytopenia. |
| PharmGKB | PA28584. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG16265. |
| GeneTree | ENSGT00550000074470. |
| HOGENOM | HBG716943. |
| HOVERGEN | HBG051705. |
| InParanoid | P15976. |
| OMA | FPTGPVP. |
| OrthoDB | EOG4QNMWM. |
| PhylomeDB | P15976. |
Enzyme and pathway databases | |
| Pathway_Interaction_DB | hdac_classi_pathway. Signaling events mediated by HDAC Class I. hdac_classii_pathway. Signaling events mediated by HDAC Class II. |
| Reactome | REACT_604. Hemostasis. |
Gene expression databases | |
| ArrayExpress | P15976. |
| Bgee | P15976. |
| CleanEx | HS_GATA1. |
| Genevestigator | P15976. |
| GermOnline | ENSG00000102145. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR016374. TF_GATA-1/2/3. IPR000679. Znf_GATA. IPR013088. Znf_NHR/GATA. [Graphical view] |
| Gene3D | G3DSA:3.30.50.10. Znf_NHR/GATA. 2 hits. |
| KO | K09182. |
| Pfam | PF00320. GATA. 2 hits. [Graphical view] |
| PIRSF | PIRSF003027. TF_GATA-1/2/3. 1 hit. |
| PRINTS | PR00619. GATAZNFINGER. |
| SMART | SM00401. ZnF_GATA. 2 hits. [Graphical view] |
| PROSITE | PS00344. GATA_ZN_FINGER_1. 2 hits. PS50114. GATA_ZN_FINGER_2. 2 hits. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 10331. |
| PMAP-CutDB | P15976. |
| SOURCE | Search... |
Entry information
| Entry name | GATA1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P15976 Secondary accession number(s): Q96GB8 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome X Human chromosome X: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with