GATA4_HUMAN
ID GATA4_HUMAN Reviewed; 442 AA.
AC P43694; B7ZKX0; B7ZKZ4; Q3MJ45; Q5IFM8;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Transcription factor GATA-4;
DE AltName: Full=GATA-binding factor 4;
GN Name=GATA4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT LEU-39.
RC TISSUE=Heart;
RX PubMed=7721094; DOI=10.1016/0378-1119(94)00893-w;
RA Huang W.Y., Cukerman E., Liew C.C.;
RT "Identification of a GATA motif in the cardiac alpha-myosin heavy-chain-
RT encoding gene and isolation of a human GATA-4 cDNA.";
RL Gene 155:219-223(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Palaszewski I., Dame C.;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Heart, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION.
RX PubMed=15734735; DOI=10.1074/jbc.m410928200;
RA Oskouian B., Mendel J., Shocron E., Lee M.A. Jr., Fyrst H., Saba J.D.;
RT "Regulation of sphingosine-1-phosphate lyase gene expression by members of
RT the GATA family of transcription factors.";
RL J. Biol. Chem. 280:18403-18410(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP FUNCTION IN CARDIAC HYPERTROPHY, AND IDENTIFICATION IN COMPLEX WITH CCNT1;
RP EP300 AND GATA4.
RX PubMed=20081228; DOI=10.1074/jbc.m109.070458;
RA Sunagawa Y., Morimoto T., Takaya T., Kaichi S., Wada H., Kawamura T.,
RA Fujita M., Shimatsu A., Kita T., Hasegawa K.;
RT "Cyclin-dependent kinase-9 is a component of the p300/GATA4 complex
RT required for phenylephrine-induced hypertrophy in cardiomyocytes.";
RL J. Biol. Chem. 285:9556-9568(2010).
RN [8]
RP FUNCTION, AND INTERACTION WITH GLYR1.
RX PubMed=35182466; DOI=10.1016/j.cell.2022.01.021;
RA Gonzalez-Teran B., Pittman M., Felix F., Thomas R., Richmond-Buccola D.,
RA Huettenhain R., Choudhary K., Moroni E., Costa M.W., Huang Y.,
RA Padmanabhan A., Alexanian M., Lee C.Y., Maven B.E.J., Samse-Knapp K.,
RA Morton S.U., McGregor M., Gifford C.A., Seidman J.G., Seidman C.E.,
RA Gelb B.D., Colombo G., Conklin B.R., Black B.L., Bruneau B.G., Krogan N.J.,
RA Pollard K.S., Srivastava D.;
RT "Transcription factor protein interactomes reveal genetic determinants in
RT heart disease.";
RL Cell 0:0-0(2022).
RN [9]
RP STRUCTURE BY NMR OF 262-321.
RG Northeast structural genomics consortium (NESG);
RT "Solution NMR structure of a transcription factor gata-4 from Homo sapiens,
RT Northeast structural genomics consortium (NESG) target HR4783B.";
RL Submitted (JUL-2013) to the PDB data bank.
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, DNA-BINDING, INTERACTION WITH NR5A1 AND
RP ZFPM2, VARIANT TACHD ARG-221, AND CHARACTERIZATION OF VARIANT TACHD
RP ARG-221.
RX PubMed=21220346; DOI=10.1073/pnas.1010257108;
RA Lourenco D., Brauner R., Rybczynska M., Nihoul-Fekete C., McElreavey K.,
RA Bashamboo A.;
RT "Loss-of-function mutation in GATA4 causes anomalies of human testicular
RT development.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:1597-1602(2011).
RN [11]
RP INVOLVEMENT IN CMD, VARIANT SER-271, AND CHARACTERIZATION OF VARIANT
RP SER-271.
RX PubMed=24041700; DOI=10.1016/j.bbrc.2013.09.023;
RA Li R.G., Li L., Qiu X.B., Yuan F., Xu L., Li X., Xu Y.J., Jiang W.F.,
RA Jiang J.Q., Liu X., Fang W.Y., Zhang M., Peng L.Y., Qu X.K., Yang Y.Q.;
RT "GATA4 loss-of-function mutation underlies familial dilated
RT cardiomyopathy.";
RL Biochem. Biophys. Res. Commun. 439:591-596(2013).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TBX5, VARIANTS TOF PRO-9;
RP VAL-51 AND SER-285, AND CHARACTERIZATION OF VARIANTS TOF PRO-9; VAL-51 AND
RP SER-285.
RX PubMed=24000169; DOI=10.1002/humu.22434;
RA Yang Y.Q., Gharibeh L., Li R.G., Xin Y.F., Wang J., Liu Z.M., Qiu X.B.,
RA Xu Y.J., Xu L., Qu X.K., Liu X., Fang W.Y., Huang R.T., Xue S., Nemer G.;
RT "GATA4 loss-of-function mutations underlie familial tetralogy of fallot.";
RL Hum. Mutat. 34:1662-1671(2013).
RN [13]
RP INVOLVEMENT IN CMD, VARIANTS LEU-39; GLN-226 AND SER-279, AND
RP CHARACTERIZATION OF VARIANTS LEU-39; GLN-226 AND SER-279.
RX PubMed=25017055; DOI=10.1016/j.gene.2014.07.022;
RA Li J., Liu W.D., Yang Z.L., Yuan F., Xu L., Li R.G., Yang Y.Q.;
RT "Prevalence and spectrum of GATA4 mutations associated with sporadic
RT dilated cardiomyopathy.";
RL Gene 548:174-181(2014).
RN [14]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT ASD2 SER-296.
RX PubMed=27984724; DOI=10.1016/j.cell.2016.11.033;
RA Ang Y.S., Rivas R.N., Ribeiro A.J., Srivas R., Rivera J., Stone N.R.,
RA Pratt K., Mohamed T.M., Fu J.D., Spencer C.I., Tippens N.D., Li M.,
RA Narasimha A., Radzinsky E., Moon-Grady A.J., Yu H., Pruitt B.L.,
RA Snyder M.P., Srivastava D.;
RT "Disease model of GATA4 mutation reveals transcription factor cooperativity
RT in human cardiogenesis.";
RL Cell 167:1734-1749(2016).
RN [15]
RP VARIANT ASD2 SER-296.
RX PubMed=12845333; DOI=10.1038/nature01827;
RA Garg V., Kathiriya I.S., Barnes R., Schluterman M.K., King I.N.,
RA Butler C.A., Rothrock C.R., Eapen R.S., Hirayama-Yamada K., Joo K.,
RA Matsuoka R., Cohen J.C., Srivastava D.;
RT "GATA4 mutations cause human congenital heart defects and reveal an
RT interaction with TBX5.";
RL Nature 424:443-447(2003).
RN [16]
RP VARIANTS ASD2 PHE-52 AND SER-296.
RX PubMed=15810002; DOI=10.1002/ajmg.a.30684;
RA Hirayama-Yamada K., Kamisago M., Akimoto K., Aotsuka H., Nakamura Y.,
RA Tomita H., Furutani M., Imamura S., Takao A., Nakazawa M., Matsuoka R.;
RT "Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal
RT defect.";
RL Am. J. Med. Genet. A 135:47-52(2005).
RN [17]
RP VARIANTS ASD2 ALA-93 AND GLU-316, AND VARIANTS VAL-411 AND ASN-425.
RX PubMed=18055909; DOI=10.1136/jmg.2007.052183;
RA Tomita-Mitchell A., Maslen C.L., Morris C.D., Garg V., Goldmuntz E.;
RT "GATA4 sequence variants in patients with congenital heart disease.";
RL J. Med. Genet. 44:779-783(2007).
RN [18]
RP VARIANTS ASD2 CYS-296 AND MET-403, AND VARIANTS AVSD4 SER-163 AND VAL-346.
RX PubMed=17643447; DOI=10.1016/j.yjmcc.2007.06.004;
RA Rajagopal S.K., Ma Q., Obler D., Shen J., Manichaikul A.,
RA Tomita-Mitchell A., Boardman K., Briggs C., Garg V., Srivastava D.,
RA Goldmuntz E., Broman K.W., Benson D.W., Smoot L.B., Pu W.T.;
RT "Spectrum of heart disease associated with murine and human GATA4
RT mutation.";
RL J. Mol. Cell. Cardiol. 43:677-685(2007).
RN [19]
RP VARIANTS VSD1 VAL-6; SER-46 DEL; SER-163; LYS-359; THR-429 AND VAL-442, AND
RP VARIANTS TOF ALA-118 INS AND GLN-407.
RX PubMed=18672102; DOI=10.1016/j.ejmg.2008.06.005;
RA Zhang W., Li X., Shen A., Jiao W., Guan X., Li Z.;
RT "GATA4 mutations in 486 Chinese patients with congenital heart disease.";
RL Eur. J. Med. Genet. 51:527-535(2008).
RN [20]
RP VARIANT ASD2 MET-280.
RX PubMed=20659440; DOI=10.1016/j.cca.2010.07.021;
RA Chen Y., Mao J., Sun Y., Zhang Q., Cheng H.B., Yan W.H., Choy K.W., Li H.;
RT "A novel mutation of GATA4 in a familial atrial septal defect.";
RL Clin. Chim. Acta 411:1741-1745(2010).
RN [21]
RP VARIANT VSD1 GLN-407, AND VARIANT TOF SER-163.
RX PubMed=21110066; DOI=10.1007/s10709-010-9522-4;
RA Peng T., Wang L., Zhou S.F., Li X.;
RT "Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with
RT non-familial congenital heart disease.";
RL Genetica 138:1231-1240(2010).
RN [22]
RP VARIANT ASD2 VAL-310.
RX PubMed=20347099; DOI=10.1016/j.jtcvs.2010.01.013;
RA Chen Y., Han Z.Q., Yan W.D., Tang C.Z., Xie J.Y., Chen H., Hu D.Y.;
RT "A novel mutation in GATA4 gene associated with dominant inherited familial
RT atrial septal defect.";
RL J. Thorac. Cardiovasc. Surg. 140:684-687(2010).
RN [23]
RP VARIANT VSD1 ARG-296.
RX PubMed=21637914; DOI=10.3892/ijmm.2011.715;
RA Wang J., Fang M., Liu X.Y., Xin Y.F., Liu Z.M., Chen X.Z., Wang X.Z.,
RA Fang W.Y., Liu X., Yang Y.Q.;
RT "A novel GATA4 mutation responsible for congenital ventricular septal
RT defects.";
RL Int. J. Mol. Med. 28:557-564(2011).
RN [24]
RP VARIANT VSD1 TRP-43, AND CHARACTERIZATION OF VARIANT VSD1 TRP-43.
RX PubMed=22101736; DOI=10.1007/s00246-011-0146-y;
RA Yang Y.Q., Li L., Wang J., Liu X.Y., Chen X.Z., Zhang W., Wang X.Z.,
RA Jiang J.Q., Liu X., Fang W.Y.;
RT "A novel GATA4 loss-of-function mutation associated with congenital
RT ventricular septal defect.";
RL Pediatr. Cardiol. 33:539-546(2012).
RN [25]
RP VARIANT ASN-425.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
CC -!- FUNCTION: Transcriptional activator that binds to the consensus
CC sequence 5'-AGATAG-3' and plays a key role in cardiac development and
CC function (PubMed:24000169, PubMed:27984724, PubMed:35182466). In
CC cooperation with TBX5, it binds to cardiac super-enhancers and promotes
CC cardiomyocyte gene expression, while it down-regulates endocardial and
CC endothelial gene expression (PubMed:27984724). Involved in bone
CC morphogenetic protein (BMP)-mediated induction of cardiac-specific gene
CC expression. Binds to BMP response element (BMPRE) DNA sequences within
CC cardiac activating regions (By similarity). Acts as a transcriptional
CC activator of ANF in cooperation with NKX2-5 (By similarity). Promotes
CC cardiac myocyte enlargement (PubMed:20081228). Required during
CC testicular development (PubMed:21220346). May play a role in
CC sphingolipid signaling by regulating the expression of sphingosine-1-
CC phosphate degrading enzyme, sphingosine-1-phosphate lyase
CC (PubMed:15734735). {ECO:0000250|UniProtKB:P46152,
CC ECO:0000250|UniProtKB:Q08369, ECO:0000269|PubMed:15734735,
CC ECO:0000269|PubMed:20081228, ECO:0000269|PubMed:21220346,
CC ECO:0000269|PubMed:24000169, ECO:0000269|PubMed:27984724,
CC ECO:0000269|PubMed:35182466}.
CC -!- SUBUNIT: Interacts with ZNF260 (By similarity). Interacts with the
CC homeobox domain of NKX2-5 through its C-terminal zinc finger. Also
CC interacts with JARID2 which represses its ability to activate
CC transcription of ANF. Interacts (via the second Zn finger) with NFATC4
CC (By similarity). Interacts with LMCD1 (By similarity). Forms a complex
CC made of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates
CC hypertrophy in cardiomyocytes. Interacts with NR5A1, ZFPM2 and TBX5.
CC Interacts with TBX18. Interacts with GLYR1; the interaction is required
CC for a synergistic activation of GATA4 target genes transcription
CC (PubMed:35182466). {ECO:0000250|UniProtKB:Q08369,
CC ECO:0000269|PubMed:20081228, ECO:0000269|PubMed:21220346,
CC ECO:0000269|PubMed:24000169, ECO:0000269|PubMed:35182466}.
CC -!- INTERACTION:
CC P43694; Q9Y2Y9: KLF13; NbExp=3; IntAct=EBI-7049352, EBI-1255893;
CC P43694; P52952: NKX2-5; NbExp=2; IntAct=EBI-7049352, EBI-936601;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21220346,
CC ECO:0000269|PubMed:24000169}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P43694-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P43694-2; Sequence=VSP_055082;
CC -!- PTM: Methylation at Lys-300 attenuates transcriptional activity.
CC {ECO:0000250}.
CC -!- DISEASE: Atrial septal defect 2 (ASD2) [MIM:607941]: A congenital heart
CC malformation characterized by incomplete closure of the wall between
CC the atria resulting in blood flow from the left to the right atria.
CC Patients show other heart abnormalities including ventricular and
CC atrioventricular septal defects, pulmonary valve thickening or
CC insufficiency of the cardiac valves. The disease is not associated with
CC defects in the cardiac conduction system or non-cardiac abnormalities.
CC {ECO:0000269|PubMed:12845333, ECO:0000269|PubMed:15810002,
CC ECO:0000269|PubMed:17643447, ECO:0000269|PubMed:18055909,
CC ECO:0000269|PubMed:20347099, ECO:0000269|PubMed:20659440,
CC ECO:0000269|PubMed:27984724}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Ventricular septal defect 1 (VSD1) [MIM:614429]: A common form
CC of congenital cardiovascular anomaly that may occur alone or in
CC combination with other cardiac malformations. It can affect any portion
CC of the ventricular septum, resulting in abnormal communications between
CC the two lower chambers of the heart. Classification is based on
CC location of the communication, such as perimembranous, inlet, outlet
CC (infundibular), central muscular, marginal muscular, or apical muscular
CC defect. Large defects that go unrepaired may give rise to cardiac
CC enlargement, congestive heart failure, pulmonary hypertension,
CC Eisenmenger's syndrome, delayed fetal brain development, arrhythmias,
CC and even sudden cardiac death. {ECO:0000269|PubMed:18672102,
CC ECO:0000269|PubMed:21110066, ECO:0000269|PubMed:21637914,
CC ECO:0000269|PubMed:22101736}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Tetralogy of Fallot (TOF) [MIM:187500]: A congenital heart
CC anomaly which consists of pulmonary stenosis, ventricular septal
CC defect, dextroposition of the aorta (aorta is on the right side instead
CC of the left) and hypertrophy of the right ventricle. In this condition,
CC blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into
CC the body often causing cyanosis. {ECO:0000269|PubMed:18672102,
CC ECO:0000269|PubMed:21110066, ECO:0000269|PubMed:24000169}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Atrioventricular septal defect 4 (AVSD4) [MIM:614430]: A
CC congenital heart malformation characterized by a common
CC atrioventricular junction coexisting with deficient atrioventricular
CC septation. The complete form involves underdevelopment of the lower
CC part of the atrial septum and the upper part of the ventricular septum;
CC the valve itself is also shared. A less severe form, known as ostium
CC primum atrial septal defect, is characterized by separate
CC atrioventricular valvar orifices despite a common junction.
CC {ECO:0000269|PubMed:17643447}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Testicular anomalies with or without congenital heart disease
CC (TACHD) [MIM:615542]: A 46,XY disorder of sex development with variable
CC clinical presentation and defects in testicular differentiation and
CC function. Clinical features include ambiguous genitalia, fused
CC labioscrotal folds, hypospadias, microphallus, and bilateral inguinal
CC hernia containing gonads. {ECO:0000269|PubMed:21220346}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=GATA4 mutations can predispose to dilated cardiomyopathy
CC (CMD), a disorder characterized by ventricular dilation and impaired
CC systolic function, resulting in congestive heart failure and
CC arrhythmia. Patients are at risk of premature death.
CC {ECO:0000269|PubMed:24041700, ECO:0000269|PubMed:25017055}.
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DR EMBL; L34357; AAA58496.1; -; mRNA.
DR EMBL; AY740706; AAW51922.1; -; mRNA.
DR EMBL; AC069185; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090790; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC101580; AAI01581.1; -; mRNA.
DR EMBL; BC105108; AAI05109.1; -; mRNA.
DR EMBL; BC143434; AAI43435.1; -; mRNA.
DR EMBL; BC143479; AAI43480.1; -; mRNA.
DR CCDS; CCDS5983.1; -. [P43694-1]
DR CCDS; CCDS78303.1; -. [P43694-2]
DR RefSeq; NP_001295022.1; NM_001308093.1. [P43694-2]
DR RefSeq; NP_002043.2; NM_002052.4. [P43694-1]
DR RefSeq; XP_005272442.1; XM_005272385.4. [P43694-2]
DR RefSeq; XP_005272443.1; XM_005272386.1.
DR RefSeq; XP_006716311.1; XM_006716248.1.
DR RefSeq; XP_011542119.1; XM_011543817.2. [P43694-2]
DR RefSeq; XP_011542120.1; XM_011543818.2. [P43694-2]
DR RefSeq; XP_016868801.1; XM_017013312.1.
DR PDB; 2M9W; NMR; -; A=262-321.
DR PDBsum; 2M9W; -.
DR AlphaFoldDB; P43694; -.
DR SMR; P43694; -.
DR BioGRID; 108896; 59.
DR CORUM; P43694; -.
DR IntAct; P43694; 38.
DR MINT; P43694; -.
DR STRING; 9606.ENSP00000334458; -.
DR ChEMBL; CHEMBL1687679; -.
DR iPTMnet; P43694; -.
DR PhosphoSitePlus; P43694; -.
DR BioMuta; GATA4; -.
DR DMDM; 215274105; -.
DR jPOST; P43694; -.
DR MassIVE; P43694; -.
DR MaxQB; P43694; -.
DR PaxDb; P43694; -.
DR PeptideAtlas; P43694; -.
DR PRIDE; P43694; -.
DR ProteomicsDB; 55652; -. [P43694-1]
DR ProteomicsDB; 7203; -.
DR Antibodypedia; 3405; 770 antibodies from 45 providers.
DR DNASU; 2626; -.
DR Ensembl; ENST00000335135.8; ENSP00000334458.4; ENSG00000136574.19. [P43694-1]
DR Ensembl; ENST00000532059.6; ENSP00000435712.1; ENSG00000136574.19. [P43694-2]
DR Ensembl; ENST00000622443.3; ENSP00000482268.2; ENSG00000136574.19. [P43694-1]
DR Ensembl; ENST00000643249.3; ENSP00000493647.1; ENSG00000285109.3. [P43694-2]
DR Ensembl; ENST00000647274.1; ENSP00000495511.1; ENSG00000285109.3. [P43694-1]
DR GeneID; 2626; -.
DR KEGG; hsa:2626; -.
DR MANE-Select; ENST00000532059.6; ENSP00000435712.1; NM_001308093.3; NP_001295022.1. [P43694-2]
DR UCSC; uc003wuc.3; human. [P43694-1]
DR CTD; 2626; -.
DR DisGeNET; 2626; -.
DR GeneCards; GATA4; -.
DR HGNC; HGNC:4173; GATA4.
DR HPA; ENSG00000136574; Tissue enhanced (heart muscle, ovary, pancreas).
DR MalaCards; GATA4; -.
DR MIM; 187500; phenotype.
DR MIM; 600576; gene.
DR MIM; 607941; phenotype.
DR MIM; 614429; phenotype.
DR MIM; 614430; phenotype.
DR MIM; 615542; phenotype.
DR neXtProt; NX_P43694; -.
DR OpenTargets; ENSG00000136574; -.
DR Orphanet; 251510; 46,XY partial gonadal dysgenesis.
DR Orphanet; 251071; 8p23.1 microdeletion syndrome.
DR Orphanet; 99103; Atrial septal defect, ostium secundum type.
DR Orphanet; 99067; Complete atrioventricular septal defect with ventricular hypoplasia.
DR Orphanet; 99068; Complete atrioventricular septal defect-tetralogy of Fallot.
DR Orphanet; 334; Familial atrial fibrillation.
DR Orphanet; 1480; NON RARE IN EUROPE: Ventricular septal defect.
DR Orphanet; 576232; Partial atrioventricular septal defect with ventricular hypoplasia.
DR Orphanet; 3303; Tetralogy of Fallot.
DR PharmGKB; PA28587; -.
DR VEuPathDB; HostDB:ENSG00000136574; -.
DR eggNOG; KOG1601; Eukaryota.
DR GeneTree; ENSGT00940000158349; -.
DR HOGENOM; CLU_027524_0_0_1; -.
DR InParanoid; P43694; -.
DR OMA; GIMTSNH; -.
DR OrthoDB; 807790at2759; -.
DR PhylomeDB; P43694; -.
DR TreeFam; TF315391; -.
DR PathwayCommons; P43694; -.
DR Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression.
DR Reactome; R-HSA-400511; Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).
DR Reactome; R-HSA-5578768; Physiological factors.
DR Reactome; R-HSA-9690406; Transcriptional regulation of testis differentiation.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; P43694; -.
DR SIGNOR; P43694; -.
DR BioGRID-ORCS; 2626; 15 hits in 1099 CRISPR screens.
DR ChiTaRS; GATA4; human.
DR GeneWiki; GATA4; -.
DR GenomeRNAi; 2626; -.
DR Pharos; P43694; Tbio.
DR PRO; PR:P43694; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P43694; protein.
DR Bgee; ENSG00000136574; Expressed in right atrium auricular region and 60 other tissues.
DR ExpressionAtlas; P43694; baseline and differential.
DR Genevisible; P43694; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0070410; F:co-SMAD binding; IPI:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; IDA:BHF-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0051525; F:NFAT protein binding; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IGI:BHF-UCL.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0003180; P:aortic valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060413; P:atrial septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003289; P:atrial septum primum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003290; P:atrial septum secundum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0036302; P:atrioventricular canal development; NAS:BHF-UCL.
DR GO; GO:0003162; P:atrioventricular node development; NAS:BHF-UCL.
DR GO; GO:0003190; P:atrioventricular valve formation; ISS:BHF-UCL.
DR GO; GO:0061026; P:cardiac muscle tissue regeneration; ISS:BHF-UCL.
DR GO; GO:0003215; P:cardiac right ventricle morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; TAS:BHF-UCL.
DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR GO; GO:0061049; P:cell growth involved in cardiac muscle cell development; IEA:Ensembl.
DR GO; GO:0007267; P:cell-cell signaling; ISS:BHF-UCL.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0048617; P:embryonic foregut morphogenesis; ISS:BHF-UCL.
DR GO; GO:0035054; P:embryonic heart tube anterior/posterior pattern specification; ISS:BHF-UCL.
DR GO; GO:0003197; P:endocardial cushion development; IMP:BHF-UCL.
DR GO; GO:0007492; P:endoderm development; TAS:BHF-UCL.
DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR GO; GO:0060575; P:intestinal epithelial cell differentiation; IDA:MGI.
DR GO; GO:0008584; P:male gonad development; IMP:UniProtKB.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; ISS:BHF-UCL.
DR GO; GO:0010507; P:negative regulation of autophagy; IEA:Ensembl.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISS:BHF-UCL.
DR GO; GO:1903202; P:negative regulation of oxidative stress-induced cell death; ISS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:BHF-UCL.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0051891; P:positive regulation of cardioblast differentiation; ISS:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISS:BHF-UCL.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IEA:Ensembl.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; ISS:BHF-UCL.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:BHF-UCL.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:BHF-UCL.
DR GO; GO:0060290; P:transdifferentiation; IEA:Ensembl.
DR GO; GO:0003281; P:ventricular septum development; ISS:BHF-UCL.
DR GO; GO:0042060; P:wound healing; ISS:BHF-UCL.
DR CDD; cd00202; ZnF_GATA; 2.
DR Gene3D; 3.30.50.10; -; 2.
DR InterPro; IPR008013; GATA_N.
DR InterPro; IPR016375; TF_GATA_4/5/6.
DR InterPro; IPR039355; Transcription_factor_GATA.
DR InterPro; IPR000679; Znf_GATA.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR PANTHER; PTHR10071; PTHR10071; 1.
DR Pfam; PF00320; GATA; 2.
DR Pfam; PF05349; GATA-N; 1.
DR PIRSF; PIRSF003028; TF_GATA_4/5/6; 1.
DR PRINTS; PR00619; GATAZNFINGER.
DR SMART; SM00401; ZnF_GATA; 2.
DR PROSITE; PS00344; GATA_ZN_FINGER_1; 2.
DR PROSITE; PS50114; GATA_ZN_FINGER_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Atrial septal defect;
KW Cardiomyopathy; Disease variant; DNA-binding; Metal-binding; Methylation;
KW Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..442
FT /note="Transcription factor GATA-4"
FT /id="PRO_0000083413"
FT ZN_FING 217..241
FT /note="GATA-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00094"
FT ZN_FING 271..295
FT /note="GATA-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00094"
FT REGION 60..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 314..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 409..428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 64..90
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..362
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 300
FT /note="N6-methyllysine; by EZH2"
FT /evidence="ECO:0000250|UniProtKB:Q08369"
FT VAR_SEQ 205
FT /note="L -> LV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055082"
FT VARIANT 6
FT /note="A -> V (in VSD1; dbSNP:rs199922907)"
FT /evidence="ECO:0000269|PubMed:18672102"
FT /id="VAR_067605"
FT VARIANT 9
FT /note="A -> P (in TOF; slightly diminished DNA-binding
FT affinity; decreased transcriptional activity; no effect on
FT subcellular location; no effect on interaction with TBX5;
FT dbSNP:rs864321699)"
FT /evidence="ECO:0000269|PubMed:24000169"
FT /id="VAR_071514"
FT VARIANT 39
FT /note="V -> L (probable disease-associated variant found in
FT patients with dilated cardiomyopathy; results in
FT significantly reduced transactivation activity;
FT dbSNP:rs1139241)"
FT /evidence="ECO:0000269|PubMed:25017055,
FT ECO:0000269|PubMed:7721094"
FT /id="VAR_072111"
FT VARIANT 43
FT /note="R -> W (in VSD1; significantly reduced activation of
FT the NPPA promoter with the mutant protein compared to wild-
FT type; dbSNP:rs387906770)"
FT /evidence="ECO:0000269|PubMed:22101736"
FT /id="VAR_067606"
FT VARIANT 46
FT /note="Missing (in VSD1)"
FT /evidence="ECO:0000269|PubMed:18672102"
FT /id="VAR_067607"
FT VARIANT 51
FT /note="L -> V (in TOF; slightly diminished DNA-binding
FT affinity; decreased transcriptional activity; no effect on
FT subcellular location; no effect on interaction with TBX5)"
FT /evidence="ECO:0000269|PubMed:24000169"
FT /id="VAR_071515"
FT VARIANT 52
FT /note="S -> F (in ASD2; dbSNP:rs104894074)"
FT /evidence="ECO:0000269|PubMed:15810002"
FT /id="VAR_038195"
FT VARIANT 93
FT /note="G -> A (in ASD2; unknown pathological significance;
FT dbSNP:rs56191129)"
FT /evidence="ECO:0000269|PubMed:18055909"
FT /id="VAR_067608"
FT VARIANT 118
FT /note="A -> AA (in TOF)"
FT /evidence="ECO:0000269|PubMed:18672102"
FT /id="VAR_067609"
FT VARIANT 163
FT /note="P -> S (in AVSD4; also in a patient with VSD1 and a
FT patient with TOF; dbSNP:rs387906769)"
FT /evidence="ECO:0000269|PubMed:17643447,
FT ECO:0000269|PubMed:18672102, ECO:0000269|PubMed:21110066"
FT /id="VAR_067610"
FT VARIANT 221
FT /note="G -> R (in TACHD; impairs the ability to bind and
FT transactivate the promoter of AMH gene; abolishes
FT interaction with ZFPM2; dbSNP:rs398122402)"
FT /evidence="ECO:0000269|PubMed:21220346"
FT /id="VAR_070670"
FT VARIANT 226
FT /note="P -> Q (probable disease-associated variant found in
FT patients with dilated cardiomyopathy; results in
FT significantly reduced transactivation activity)"
FT /evidence="ECO:0000269|PubMed:25017055"
FT /id="VAR_072112"
FT VARIANT 271
FT /note="C -> S (probable disease-associated variant found in
FT patients with dilated cardiomyopathy; results in
FT significantly reduced transactivation activity)"
FT /evidence="ECO:0000269|PubMed:24041700"
FT /id="VAR_072113"
FT VARIANT 279
FT /note="T -> S (probable disease-associated variant found in
FT patients with dilated cardiomyopathy; results in
FT significantly reduced transactivation activity)"
FT /evidence="ECO:0000269|PubMed:25017055"
FT /id="VAR_072114"
FT VARIANT 280
FT /note="T -> M (in ASD2; dbSNP:rs387906771)"
FT /evidence="ECO:0000269|PubMed:20659440"
FT /id="VAR_067611"
FT VARIANT 285
FT /note="N -> S (in TOF; drastically diminished DNA-binding
FT affinity; decreased transcriptional activity; no effect on
FT subcellular location; completely disrupted interaction with
FT TBX5)"
FT /evidence="ECO:0000269|PubMed:24000169"
FT /id="VAR_071516"
FT VARIANT 296
FT /note="G -> C (in ASD2; dbSNP:rs104894073)"
FT /evidence="ECO:0000269|PubMed:17643447"
FT /id="VAR_067612"
FT VARIANT 296
FT /note="G -> R (in VSD1; dbSNP:rs104894073)"
FT /evidence="ECO:0000269|PubMed:21637914"
FT /id="VAR_067613"
FT VARIANT 296
FT /note="G -> S (in ASD2; decreased function resulting in
FT reduced myocardial genes expression; fails to down-regulate
FT endothelial and endocardial genes; dbSNP:rs104894073)"
FT /evidence="ECO:0000269|PubMed:12845333,
FT ECO:0000269|PubMed:15810002, ECO:0000269|PubMed:27984724"
FT /id="VAR_016204"
FT VARIANT 310
FT /note="M -> V (in ASD2; dbSNP:rs387906772)"
FT /evidence="ECO:0000269|PubMed:20347099"
FT /id="VAR_067614"
FT VARIANT 316
FT /note="Q -> E (in ASD2; unknown pathological significance;
FT dbSNP:rs56298569)"
FT /evidence="ECO:0000269|PubMed:18055909"
FT /id="VAR_067615"
FT VARIANT 346
FT /note="A -> V (in AVSD4; dbSNP:rs115372595)"
FT /evidence="ECO:0000269|PubMed:17643447"
FT /id="VAR_067616"
FT VARIANT 359
FT /note="E -> K (in VSD1; dbSNP:rs368489876)"
FT /evidence="ECO:0000269|PubMed:18672102"
FT /id="VAR_067617"
FT VARIANT 377
FT /note="S -> G (in dbSNP:rs3729856)"
FT /id="VAR_038196"
FT VARIANT 403
FT /note="L -> M (in ASD2; dbSNP:rs777778466)"
FT /evidence="ECO:0000269|PubMed:17643447"
FT /id="VAR_067618"
FT VARIANT 407
FT /note="P -> Q (in VSD1 and TOF; unknown pathological
FT significance; dbSNP:rs115099192)"
FT /evidence="ECO:0000269|PubMed:18672102,
FT ECO:0000269|PubMed:21110066"
FT /id="VAR_067619"
FT VARIANT 411
FT /note="A -> V (in dbSNP:rs55633527)"
FT /evidence="ECO:0000269|PubMed:18055909"
FT /id="VAR_067620"
FT VARIANT 425
FT /note="D -> N (in dbSNP:rs56208331)"
FT /evidence="ECO:0000269|PubMed:18055909,
FT ECO:0000269|PubMed:27535533"
FT /id="VAR_067621"
FT VARIANT 429
FT /note="S -> T (in VSD1)"
FT /evidence="ECO:0000269|PubMed:18672102"
FT /id="VAR_067622"
FT VARIANT 442
FT /note="A -> V (in VSD1; dbSNP:rs146017816)"
FT /evidence="ECO:0000269|PubMed:18672102"
FT /id="VAR_067623"
FT CONFLICT 19
FT /note="E -> Q (in Ref. 1; AAA58496)"
FT /evidence="ECO:0000305"
FT CONFLICT 25
FT /note="A -> P (in Ref. 1; AAA58496)"
FT /evidence="ECO:0000305"
FT CONFLICT 66
FT /note="A -> P (in Ref. 1; AAA58496)"
FT /evidence="ECO:0000305"
FT CONFLICT 71
FT /note="S -> P (in Ref. 1; AAA58496)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="D -> T (in Ref. 1; AAA58496)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="T -> A (in Ref. 2; AAW51922)"
FT /evidence="ECO:0000305"
FT TURN 272..274
FT /evidence="ECO:0007829|PDB:2M9W"
FT STRAND 282..284
FT /evidence="ECO:0007829|PDB:2M9W"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:2M9W"
FT HELIX 293..301
FT /evidence="ECO:0007829|PDB:2M9W"
SQ SEQUENCE 442 AA; 44565 MW; 141B8CD841E12C7B CRC64;
MYQSLAMAAN HGPPPGAYEA GGPGAFMHGA GAASSPVYVP TPRVPSSVLG LSYLQGGGAG
SASGGASGGS SGGAASGAGP GTQQGSPGWS QAGADGAAYT PPPVSPRFSF PGTTGSLAAA
AAAAAAREAA AYSSGGGAAG AGLAGREQYG RAGFAGSYSS PYPAYMADVG ASWAAAAAAS
AGPFDSPVLH SLPGRANPAA RHPNLDMFDD FSEGRECVNC GAMSTPLWRR DGTGHYLCNA
CGLYHKMNGI NRPLIKPQRR LSASRRVGLS CANCQTTTTT LWRRNAEGEP VCNACGLYMK
LHGVPRPLAM RKEGIQTRKR KPKNLNKSKT PAAPSGSESL PPASGASSNS SNATTSSSEE
MRPIKTEPGL SSHYGHSSSV SQTFSVSAMS GHGPSIHPVL SALKLSPQGY ASPVSQSPQT
SSKQDSWNSL VLADSHGDII TA
