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Protein

Transcription factor GATA-4

Gene

Gata4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional activator that binds to the consensus sequence 5'-AGATAG-3' and plays a key role in cardiac development. Involved in bone morphogenetic protein (BMP)-mediated induction of cardiac-specific gene expression. Binds to BMP response element (BMPRE) DNA sequences within cardiac activating regions. Acts as a transcriptional activator of ANF in cooperation with NKX2-5. Promotes cardiac myocyte enlargement. Required during testicular development.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri216 – 24025GATA-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri270 – 29425GATA-type 2PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. chromatin binding Source: MGI
  2. co-SMAD binding Source: MGI
  3. DNA binding Source: MGI
  4. enhancer sequence-specific DNA binding Source: Ensembl
  5. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: BHF-UCL
  6. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  7. RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
  8. RNA polymerase II transcription factor binding transcription factor activity Source: UniProtKB
  9. sequence-specific DNA binding Source: MGI
  10. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: BHF-UCL
  11. sequence-specific DNA binding transcription factor activity Source: MGI
  12. transcription coactivator activity Source: MGI
  13. transcription factor binding Source: MGI
  14. transcription regulatory region DNA binding Source: MGI
  15. zinc ion binding Source: InterPro

GO - Biological processi

  1. atrial septum morphogenesis Source: MGI
  2. atrial septum primum morphogenesis Source: BHF-UCL
  3. atrial septum secundum morphogenesis Source: MGI
  4. atrioventricular canal development Source: BHF-UCL
  5. atrioventricular valve formation Source: BHF-UCL
  6. atrioventricular valve morphogenesis Source: BHF-UCL
  7. BMP signaling pathway Source: MGI
  8. canonical Wnt signaling pathway Source: MGI
  9. cardiac muscle cell differentiation Source: UniProtKB
  10. cardiac muscle hypertrophy in response to stress Source: MGI
  11. cardiac muscle tissue development Source: MGI
  12. cardiac right ventricle morphogenesis Source: BHF-UCL
  13. cardiac septum development Source: BHF-UCL
  14. cell-cell signaling Source: MGI
  15. cell growth involved in cardiac muscle cell development Source: Ensembl
  16. cellular response to follicle-stimulating hormone stimulus Source: MGI
  17. cellular response to glucose stimulus Source: Ensembl
  18. cellular response to gonadotropin stimulus Source: MGI
  19. diaphragm morphogenesis Source: BHF-UCL
  20. embryonic digestive tract morphogenesis Source: MGI
  21. embryonic foregut morphogenesis Source: MGI
  22. embryonic heart tube anterior/posterior pattern specification Source: MGI
  23. embryonic heart tube development Source: MGI
  24. embryonic morphogenesis Source: MGI
  25. endocardial cushion development Source: BHF-UCL
  26. endoderm formation Source: MGI
  27. epithelial cell fate commitment Source: MGI
  28. gastrulation with mouth forming second Source: MGI
  29. heart development Source: MGI
  30. heart looping Source: BHF-UCL
  31. heart morphogenesis Source: BHF-UCL
  32. intestinal epithelial cell differentiation Source: MGI
  33. in utero embryonic development Source: MGI
  34. lung lobe formation Source: MGI
  35. lung morphogenesis Source: BHF-UCL
  36. male gonad development Source: MGI
  37. mitral valve formation Source: BHF-UCL
  38. negative regulation of autophagy Source: Ensembl
  39. outflow tract morphogenesis Source: BHF-UCL
  40. positive regulation of angiogenesis Source: BHF-UCL
  41. positive regulation of BMP signaling pathway Source: Ensembl
  42. positive regulation of cardiac muscle cell proliferation Source: MGI
  43. positive regulation of cardioblast differentiation Source: BHF-UCL
  44. positive regulation of transcription, DNA-templated Source: UniProtKB
  45. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  46. positive regulation vascular endothelial growth factor production Source: BHF-UCL
  47. regulation of cardiac muscle cell contraction Source: Ensembl
  48. regulation of cardiac muscle cell proliferation Source: MGI
  49. regulation of gene expression Source: MGI
  50. regulation of transcription, DNA-templated Source: DFLAT
  51. regulation of transcription from RNA polymerase II promoter Source: MGI
  52. response to drug Source: MGI
  53. response to estrogen Source: MGI
  54. response to mechanical stimulus Source: Ensembl
  55. response to retinoic acid Source: BHF-UCL
  56. seminiferous tubule development Source: MGI
  57. Sertoli cell differentiation Source: MGI
  58. signal transduction involved in regulation of gene expression Source: MGI
  59. skeletal muscle cell differentiation Source: UniProtKB
  60. SMAD protein signal transduction Source: MGI
  61. spermatogenesis Source: MGI
  62. transcription from RNA polymerase II promoter Source: BHF-UCL
  63. transdifferentiation Source: Ensembl
  64. tricuspid valve formation Source: BHF-UCL
  65. tube morphogenesis Source: MGI
  66. vasculogenesis involved in coronary vascular morphogenesis Source: DFLAT
  67. ventricular cardiac muscle tissue development Source: MGI
  68. ventricular septum development Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_196516. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
REACT_198649. Factors involved in megakaryocyte development and platelet production.
REACT_253751. Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor GATA-4
Alternative name(s):
GATA-binding factor 4
Gene namesi
Name:Gata4
Synonyms:Gata-4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 14

Organism-specific databases

MGIiMGI:95664. Gata4.

Subcellular locationi

Nucleus By similarity

GO - Cellular componenti

  1. nuclear chromatin Source: BHF-UCL
  2. nucleus Source: BHF-UCL
  3. RNA polymerase II transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 441441Transcription factor GATA-4PRO_0000083414Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei299 – 2991N6-methyllysine; by EZH21 Publication

Post-translational modificationi

Methylation at Lys-299 attenuates transcriptional activity.1 Publication

Keywords - PTMi

Methylation

Proteomic databases

PaxDbiQ08369.
PRIDEiQ08369.

PTM databases

PhosphoSiteiQ08369.

Expressioni

Tissue specificityi

Heart, intestine, liver, primative endoderm and gonads.

Inductioni

By retinoic acid.

Gene expression databases

CleanExiMM_GATA4.
ExpressionAtlasiQ08369. baseline and differential.
GenevestigatoriQ08369.

Interactioni

Subunit structurei

Interacts with ZNF260 (By similarity). Interacts with the homeobox domain of NKX2-5 through its C-terminal zinc finger. Also interacts with JARID2 which represses its ability to activate transcription of ANF. Interacts with NFATC4 and LMCD1. Forms a complex made of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates hypertrophy in cardiomyocytes. Interacts with NR5A1, ZFPM2 and TBX5. Interacts with TBX18.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Jarid2Q623153EBI-297008,EBI-493592
Nkx2-5P425824EBI-297008,EBI-297021
TBX5Q995932EBI-297008,EBI-297043From a different organism.

Protein-protein interaction databases

BioGridi199841. 18 interactions.
DIPiDIP-33032N.
IntActiQ08369. 3 interactions.
MINTiMINT-206005.

Structurei

3D structure databases

ProteinModelPortaliQ08369.
SMRiQ08369. Positions 212-320.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi118 – 1269Poly-Ala
Compositional biasi174 – 1818Poly-Ala
Compositional biasi275 – 2795Poly-Thr
Compositional biasi354 – 3596Poly-Ser

Sequence similaritiesi

Contains 2 GATA-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri216 – 24025GATA-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri270 – 29425GATA-type 2PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG5641.
GeneTreeiENSGT00760000119221.
HOVERGENiHBG051703.
InParanoidiQ08369.
KOiK09183.
PhylomeDBiQ08369.

Family and domain databases

Gene3Di3.30.50.10. 2 hits.
InterProiIPR008013. GATA_N.
IPR028436. TF_GATA_4.
IPR016375. TF_GATA_4/5/6.
IPR000679. Znf_GATA.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PANTHERiPTHR10071:SF154. PTHR10071:SF154. 1 hit.
PfamiPF00320. GATA. 2 hits.
PF05349. GATA-N. 1 hit.
[Graphical view]
PIRSFiPIRSF003028. TF_GATA_4/5/6. 1 hit.
PRINTSiPR00619. GATAZNFINGER.
SMARTiSM00401. ZnF_GATA. 2 hits.
[Graphical view]
PROSITEiPS00344. GATA_ZN_FINGER_1. 2 hits.
PS50114. GATA_ZN_FINGER_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q08369-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MYQSLAMAAN HGPPPGAYEA GGPGAFMHSA GAASSPVYVP TPRVPSSVLG
60 70 80 90 100
LSYLQGGGSA AAAGTTSGGS SGAGPSGAGP GTQQGSPGWS QAGAEGAAYT
110 120 130 140 150
PPPVSPRFSF PGTTGSLAAA AAAAAAREAA AYGSGGGAAG AGLAGREQYG
160 170 180 190 200
RPGFAGSYSS PYPAYMADVG ASWAAAAAAS AGPFDSPVLH SLPGRANPGR
210 220 230 240 250
HPNLDMFDDF SEGRECVNCG AMSTPLWRRD GTGHYLCNAC GLYHKMNGIN
260 270 280 290 300
RPLIKPQRRL SASRRVGLSC ANCQTTTTTL WRRNAEGEPV CNACGLYMKL
310 320 330 340 350
HGVPRPLAMR KEGIQTRKRK PKNLNKSKTP AGPAGETLPP SSGASSGNSS
360 370 380 390 400
NATSSSSSSE EMRPIKTEPG LSSHYGHSSS MSQTFSTVSG HGPSIHPVLS
410 420 430 440
ALKLSPQGYA SPVTQTSQAS SKQDSWNSLV LADSHGDIIT A
Length:441
Mass (Da):44,580
Last modified:March 19, 2014 - v4
Checksum:iE9521771741DD08E
GO

Sequence cautioni

The sequence AAA37662.1 differs from that shown. Reason: Frameshift at positions 6, 40 and 69. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti385 – 40218FSTVS…VLSAL → SVCVRPRALHPSSAVCS in AAA37662 (PubMed:8455608).CuratedAdd
BLAST
Sequence conflicti385 – 40218FSTVS…VLSAL → SVCVRPRALHPSSAVCS in AAB42015 (Ref. 3) CuratedAdd
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M98339 mRNA. Translation: AAA37662.1. Frameshift.
U85046 mRNA. Translation: AAB42015.1.
AF179424 mRNA. Translation: AAD55266.1.
AC090654 Genomic DNA. No translation available.
AC090962 Genomic DNA. No translation available.
CH466535 Genomic DNA. Translation: EDL36067.1.
BC137824 mRNA. Translation: AAI37825.1.
CCDSiCCDS49519.1.
PIRiA48099.
RefSeqiNP_032118.2. NM_008092.3.
UniGeneiMm.247669.

Genome annotation databases

EnsembliENSMUST00000118022; ENSMUSP00000113891; ENSMUSG00000021944.
GeneIDi14463.
KEGGimmu:14463.
UCSCiuc007uhn.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M98339 mRNA. Translation: AAA37662.1. Frameshift.
U85046 mRNA. Translation: AAB42015.1.
AF179424 mRNA. Translation: AAD55266.1.
AC090654 Genomic DNA. No translation available.
AC090962 Genomic DNA. No translation available.
CH466535 Genomic DNA. Translation: EDL36067.1.
BC137824 mRNA. Translation: AAI37825.1.
CCDSiCCDS49519.1.
PIRiA48099.
RefSeqiNP_032118.2. NM_008092.3.
UniGeneiMm.247669.

3D structure databases

ProteinModelPortaliQ08369.
SMRiQ08369. Positions 212-320.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199841. 18 interactions.
DIPiDIP-33032N.
IntActiQ08369. 3 interactions.
MINTiMINT-206005.

Chemistry

ChEMBLiCHEMBL1687680.

PTM databases

PhosphoSiteiQ08369.

Proteomic databases

PaxDbiQ08369.
PRIDEiQ08369.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000118022; ENSMUSP00000113891; ENSMUSG00000021944.
GeneIDi14463.
KEGGimmu:14463.
UCSCiuc007uhn.1. mouse.

Organism-specific databases

CTDi2626.
MGIiMGI:95664. Gata4.

Phylogenomic databases

eggNOGiCOG5641.
GeneTreeiENSGT00760000119221.
HOVERGENiHBG051703.
InParanoidiQ08369.
KOiK09183.
PhylomeDBiQ08369.

Enzyme and pathway databases

ReactomeiREACT_196516. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
REACT_198649. Factors involved in megakaryocyte development and platelet production.
REACT_253751. Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).

Miscellaneous databases

NextBioi286104.
PROiQ08369.
SOURCEiSearch...

Gene expression databases

CleanExiMM_GATA4.
ExpressionAtlasiQ08369. baseline and differential.
GenevestigatoriQ08369.

Family and domain databases

Gene3Di3.30.50.10. 2 hits.
InterProiIPR008013. GATA_N.
IPR028436. TF_GATA_4.
IPR016375. TF_GATA_4/5/6.
IPR000679. Znf_GATA.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PANTHERiPTHR10071:SF154. PTHR10071:SF154. 1 hit.
PfamiPF00320. GATA. 2 hits.
PF05349. GATA-N. 1 hit.
[Graphical view]
PIRSFiPIRSF003028. TF_GATA_4/5/6. 1 hit.
PRINTSiPR00619. GATAZNFINGER.
SMARTiSM00401. ZnF_GATA. 2 hits.
[Graphical view]
PROSITEiPS00344. GATA_ZN_FINGER_1. 2 hits.
PS50114. GATA_ZN_FINGER_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart."
    Arceci R.J., King A.A., Simon M.C., Orkin S.H., Wilson D.B.
    Mol. Cell. Biol. 13:2235-2246(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut."
    Laverriere A.C., Macneill C., Mueller C., Poelmann R.E., Burch J.B.E., Evans T.
    J. Biol. Chem. 269:23177-23184(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION OF PROBABLE FRAMESHIFTS.
  3. "Murine GATA-4 is expressed in heart and gut tissues."
    Morrisey E.E., Parmacek M.S.
    Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. Katsuoka F., Motohashi H., Yamamoto M.
    Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6 X DBA/2.
    Tissue: Heart.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  6. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  8. "Regulation of J6 gene expression by transcription factor GATA-4."
    Bielinska M., Wilson D.B.
    Biochem. J. 307:183-189(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.
  9. "A calcineurin-dependent transcriptional pathway for cardiac hypertrophy."
    Molkentin J.D., Lu J.-R., Antos C.L., Markham B., Richardson J., Robbins J., Grant S.R., Olson E.N.
    Cell 93:215-228(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NFATC4.
  10. "The cardiac tissue-restricted homeobox protein Csx/Nkx2.5 physically associates with the zinc finger protein GATA4 and cooperatively activates atrial natriuretic factor gene expression."
    Lee Y., Shioi T., Kasahara H., Jobe S.M., Wiese R.J., Markham B.E., Izumo S.
    Mol. Cell. Biol. 18:3120-3129(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH NKX2-5.
  11. "Jumonji represses atrial natriuretic factor gene expression by inhibiting transcriptional activities of cardiac transcription factors."
    Kim T.-G., Chen J., Sadoshima J., Lee Y.
    Mol. Cell. Biol. 24:10151-10160(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH JARID2.
  12. "LMCD1/Dyxin is a novel transcriptional cofactor that restricts GATA6 function by inhibiting DNA binding."
    Rath N., Wang Z., Lu M.M., Morrisey E.E.
    Mol. Cell. Biol. 25:8864-8873(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH LMCD1.
  13. "Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors."
    Farin H.F., Bussen M., Schmidt M.K., Singh M.K., Schuster-Gossler K., Kispert A.
    J. Biol. Chem. 282:25748-25759(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TBX18.
  14. "PRC2 directly methylates GATA4 and represses its transcriptional activity."
    He A., Shen X., Ma Q., Cao J., von Gise A., Zhou P., Wang G., Marquez V.E., Orkin S.H., Pu W.T.
    Genes Dev. 26:37-42(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: METHYLATION AT LYS-299.

Entry informationi

Entry nameiGATA4_MOUSE
AccessioniPrimary (citable) accession number: Q08369
Secondary accession number(s): B9EHF7, P97491, Q9QZK4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: March 19, 2014
Last modified: March 4, 2015
This is version 136 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.