Q08369 (GATA4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor GATA-4

Alternative name(s):
GATA-binding factor 4

Gene names

Name:	Gata4
Synonyms:	Gata-4

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	440 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional activator. Binds to the consensus sequence 5'-AGATAG-3'. Regulates the expression of the HSP47/J6 gene in F9 cells. Acts as a transcriptional activator of ANF in cooperation with NKX2-5. Promotes cardiac myocyte enlargement By similarity. Ref.7
Subunit structure	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 By similarity. Ref.6 Ref.7 Ref.8 Ref.9
Subcellular location	Nucleus.
Tissue specificity	Heart, intestine, liver, primative endoderm and gonads.
Induction	By retinoic acid.
Post-translational modification	Methylation at Lys-299 attenuates transcriptional activity. Ref.10
Sequence similarities	Contains 2 GATA-type zinc fingers.
Sequence caution	The sequence AAA37662.1 differs from that shown. Reason: Frameshift at positions 6, 40 and 69.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
PTM	Methylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from direct assay PubMed 17360443. Source: MGI SMAD protein signal transduction Inferred from direct assay PubMed 9420335. Source: MGI Sertoli cell differentiation Inferred from mutant phenotype PubMed 21172404. Source: MGI atrial septum primum morphogenesis Inferred from mutant phenotype PubMed 17643447. Source: BHF-UCL atrioventricular canal development Inferred from genetic interaction PubMed 21330551. Source: BHF-UCL atrioventricular valve formation Inferred from genetic interaction PubMed 21330551. Source: BHF-UCL canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 17360443. Source: MGI cardiac muscle cell differentiation Inferred from expression pattern PubMed 21556048. Source: UniProtKB cardiac right ventricle morphogenesis Inferred from mutant phenotype PubMed 17643447. Source: BHF-UCL cell-cell signaling Inferred from mutant phenotype PubMed 16127717. Source: MGI cellular response to follicle-stimulating hormone stimulus Inferred from direct assay PubMed 9231805. Source: MGI diaphragm morphogenesis Traceable author statement PubMed 17643447. Source: BHF-UCL embryonic digestive tract morphogenesis Inferred from mutant phenotype PubMed 16127717. Source: MGI embryonic foregut morphogenesis Inferred from mutant phenotype PubMed 9136932PubMed 9136933. Source: MGI embryonic heart tube anterior/posterior pattern specification Inferred from mutant phenotype PubMed 9136932. Source: MGI endocardial cushion development Inferred from mutant phenotype PubMed 17643447. Source: BHF-UCL endoderm formation Inferred from mutant phenotype PubMed 8582296. Source: MGI epithelial cell fate commitment Inferred from mutant phenotype PubMed 16940177. Source: MGI gastrulation with mouth forming second Inferred from mutant phenotype PubMed 9136933. Source: MGI heart looping Inferred from mutant phenotype PubMed 15310850. Source: BHF-UCL in utero embryonic development Inferred from mutant phenotype PubMed 15310850PubMed 20123909PubMed 9136932PubMed 9136933. Source: MGI intestinal epithelial cell differentiation Inferred from sequence orthology PubMed 9566909. Source: MGI lung lobe formation Inferred from mutant phenotype PubMed 17142311. Source: MGI mitral valve formation Traceable author statement PubMed 14614148. Source: BHF-UCL outflow tract morphogenesis Traceable author statement PubMed 14614148. Source: BHF-UCL positive regulation of angiogenesis Inferred from direct assay PubMed 17975667. Source: BHF-UCL positive regulation of cardiac muscle cell proliferation Inferred from genetic interaction PubMed 19084512. Source: MGI positive regulation of cardioblast differentiation Inferred from expression pattern PubMed 16137232. Source: BHF-UCL positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 21029371. Source: BHF-UCL positive regulation vascular endothelial growth factor production Inferred from direct assay PubMed 17975667. Source: BHF-UCL response to estrogen stimulus Inferred from direct assay PubMed 9231805. Source: MGI response to retinoic acid Inferred from direct assay PubMed 18439490. Source: BHF-UCL seminiferous tubule development Inferred from mutant phenotype PubMed 21172404. Source: MGI signal transduction involved in regulation of gene expression Inferred from direct assay PubMed 18462699. Source: MGI skeletal muscle cell differentiation Inferred from expression pattern PubMed 21556048. Source: UniProtKB spermatogenesis Inferred from mutant phenotype PubMed 21172404. Source: MGI tricuspid valve formation Traceable author statement PubMed 14614148. Source: BHF-UCL vasculogenesis involved in coronary vascular morphogenesis Traceable author statement PubMed 20299672. Source: DFLAT ventricular cardiac muscle tissue development Inferred from genetic interaction PubMed 19084512. Source: MGI ventricular septum development Inferred from mutant phenotype PubMed 17643447. Source: BHF-UCL
Cellular_component	nuclear chromatin Inferred from direct assay PubMed 21029371. Source: BHF-UCL
Molecular_function	RNA polymerase II core promoter proximal region sequence-specific DNA binding Inferred from direct assay PubMed 21029371. Source: BHF-UCL RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 17975667. Source: BHF-UCL RNA polymerase II transcription factor binding transcription factor activity Inferred from direct assay PubMed 12845333. Source: UniProtKB chromatin binding Inferred from direct assay PubMed 21379568. Source: MGI zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Jarid2	Q62315	3	EBI-297008,EBI-493592
Nkx2-5	P42582	4	EBI-297008,EBI-297021
TBX5	Q99593	2	EBI-297008,EBI-297043	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 440	440	Transcription factor GATA-4		PRO_0000083414
Regions
	Zinc finger	216 – 240	25	GATA-type 1
	Zinc finger	270 – 294	25	GATA-type 2
	Compositional bias	118 – 126	9	Poly-Ala
	Compositional bias	174 – 181	8	Poly-Ala
	Compositional bias	275 – 279	5	Poly-Thr
	Compositional bias	354 – 359	6	Poly-Ser
Amino acid modifications
	Modified residue	299	1	N6-methyllysine; by EZH2 Ref.10
Experimental info
	Sequence conflict	29 – 30	2	SA → RT in AAA37662. Ref.1
	Sequence conflict	385 – 401	17	SVCVR…SAVCS → FSSVSGHGPSIHPVLSAL in AAD55266. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q08369 [UniParc]. Last modified July 15, 1998. Version 3. Checksum: BBCC694AB5AB86DC	FASTA	440	44,543
	10 20 30 40 50 60 MYQSLAMAAN HGPPPGAYEA GGPGAFMHSA GAASSPVYVP TPRVPSSVLG LSYLQGGGSA 70 80 90 100 110 120 AAAGTTSGGS SGAGPSGAGP GTQQGSPGWS QAGAEGAAYT PPPVSPRFSF PGTTGSLAAA 130 140 150 160 170 180 AAAAAAREAA AYGSGGGAAG AGLAGREQYG RPGFAGSYSS PYPAYMADVG ASWAAAAAAS 190 200 210 220 230 240 AGPFDSPVLH SLPGRANPGR HPNLDMFDDF SEGRECVNCG AMSTPLWRRD GTGHYLCNAC 250 260 270 280 290 300 GLYHKMNGIN RPLIKPQRRL SASRRVGLSC ANCQTTTTTL WRRNAEGEPV CNACGLYMKL 310 320 330 340 350 360 HGVPRPLAMR KEGIQTRKRK PKNLNKSKTP AGPAGETLPP SSGASSGNSS NATSSSSSSE 370 380 390 400 410 420 EMRPIKTEPG LSSHYGHSSS MSQTSVCVRP RALHPSSAVC SKLSPQGYAS PVTQTSQASS 430 440 KQDSWNSLVL ADSHGDIITA

References

[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]	"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.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M98339 mRNA. Translation: AAA37662.1. Frameshift. U85046 mRNA. Translation: AAB42015.1. AF179424 mRNA. Translation: AAD55266.1.
IPI	IPI00894774.
PIR	A48099.
RefSeq	NP_032118.2. NM_008092.3.
UniGene	Mm.247669.
3D structure databases
ProteinModelPortal	Q08369.
SMR	Q08369. Positions 212-317.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-33032N.
IntAct	Q08369. 3 interactions.
MINT	MINT-206005.
PTM databases
PhosphoSite	Q08369.
Proteomic databases
PaxDb	Q08369.
PRIDE	Q08369.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	14463.
KEGG	mmu:14463.
Organism-specific databases
CTD	2626.
MGI	MGI:95664. Gata4.
Phylogenomic databases
eggNOG	COG5641.
HOVERGEN	HBG051703.
KO	K09183.
OrthoDB	EOG4PK28S.
Gene expression databases
CleanEx	MM_GATA4.
Genevestigator	Q08369.
GermOnline	ENSMUSG00000021944. Mus musculus.
Family and domain databases
Gene3D	3.30.50.10. 2 hits.
InterPro	IPR008013. GATA_N. IPR016375. TF_GATA_4/5/6. IPR000679. Znf_GATA. IPR013088. Znf_NHR/GATA. [Graphical view]
Pfam	PF00320. GATA. 2 hits. PF05349. GATA-N. 1 hit. [Graphical view]
PIRSF	PIRSF003028. TF_GATA_4/5/6. 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
ChEMBL	CHEMBL1687680.
NextBio	286104.
SOURCE	Search...

Entry information

Entry name

GATA4_MOUSE

Accession

Primary (citable) accession number: Q08369
Secondary accession number(s): P97491, Q9QZK4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	July 15, 1998
Last modified:	May 1, 2013
This is version 116 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program