GATA6_HUMAN
ID GATA6_HUMAN Reviewed; 595 AA.
AC Q92908; B0YJ17; P78327;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Transcription factor GATA-6;
DE AltName: Full=GATA-binding factor 6;
GN Name=GATA6;
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 2).
RX PubMed=8975704; DOI=10.1006/geno.1996.0630;
RA Suzuki E., Evans T., Lowry J., Truong L., Bell D.W., Testa J.R., Walsh K.;
RT "The human GATA-6 gene: structure, chromosomal location, and regulation of
RT expression by tissue-specific and mitogen-responsive signals.";
RL Genomics 38:283-290(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Heart;
RX PubMed=9294001; DOI=10.1016/s0167-4781(97)00049-3;
RA Huggon I.C., Davies A., Gove C., Moscoso G., Moniz C., Foss Y.,
RA Farzaneh F., Towner P.;
RT "Molecular cloning of human GATA-6 DNA binding protein: high levels of
RT expression in heart and gut.";
RL Biochim. Biophys. Acta 1353:98-102(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND FUNCTION.
RX PubMed=9315713; DOI=10.1016/s0014-5793(97)01017-x;
RA Yoshida T., Sato R., Mahmood S., Kawasaki S., Futai M., Maeda M.;
RT "GATA-6 DNA binding protein expressed in human gastric adenocarcinoma MKN45
RT cells.";
RL FEBS Lett. 414:333-337(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP ALTERNATIVE INITIATION.
RX PubMed=10608869; DOI=10.1074/jbc.274.53.38004;
RA Brewer A., Gove C., Davies A., McNulty C., Barrow D., Koutsourakis M.,
RA Farzaneh F., Pizzey J., Bomford A., Patient R.;
RT "The human and mouse GATA-6 genes utilize two promoters and two initiation
RT codons.";
RL J. Biol. Chem. 274:38004-38016(1999).
RN [8]
RP FUNCTION.
RX PubMed=16968778; DOI=10.1073/pnas.0603424103;
RA Shapira M., Hamlin B.J., Rong J., Chen K., Ronen M., Tan M.W.;
RT "A conserved role for a GATA transcription factor in regulating epithelial
RT innate immune responses.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:14086-14091(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
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 [11]
RP FUNCTION, SUBCELLULAR LOCATION, VARIANT CTHM HIS-466, VARIANT ARG-15, AND
RP CHARACTERIZATION OF VARIANT CTHM HIS-466.
RX PubMed=19666519; DOI=10.1073/pnas.0904744106;
RA Kodo K., Nishizawa T., Furutani M., Arai S., Yamamura E., Joo K.,
RA Takahashi T., Matsuoka R., Yamagishi H.;
RT "GATA6 mutations cause human cardiac outflow tract defects by disrupting
RT semaphorin-plexin signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:13933-13938(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-429; LYS-473 AND LYS-484, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [14]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY CUTIBACTERIUM ACNES.
RX PubMed=33082341; DOI=10.1038/s41467-020-18784-z;
RA Oules B., Philippeos C., Segal J., Tihy M., Vietri Rudan M., Cujba A.M.,
RA Grange P.A., Quist S., Natsuga K., Deschamps L., Dupin N., Donati G.,
RA Watt F.M.;
RT "Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit
RT and acne pathogenesis.";
RL Nat. Commun. 11:5067-5067(2020).
RN [15]
RP VARIANT ASD9 ASN-184, VARIANT TOF ASN-184, CHARACTERIZATION OF VARIANT ASD9
RP ASN-184, AND VARIANT ARG-15.
RX PubMed=20631719; DOI=10.1038/jhg.2010.84;
RA Lin X., Huo Z., Liu X., Zhang Y., Li L., Zhao H., Yan B., Liu Y., Yang Y.,
RA Chen Y.H.;
RT "A novel GATA6 mutation in patients with tetralogy of Fallot or atrial
RT septal defect.";
RL J. Hum. Genet. 55:662-667(2010).
RN [16]
RP VARIANT ARG-15, VARIANT AVSD5 VAL-178, VARIANT TOF VAL-198,
RP CHARACTERIZATION OF VARIANT AVSD5 VAL-178, AND CHARACTERIZATION OF VARIANT
RP TOF VAL-198.
RX PubMed=20581743; DOI=10.1203/pdr.0b013e3181ed17e4;
RA Maitra M., Koenig S.N., Srivastava D., Garg V.;
RT "Identification of GATA6 sequence variants in patients with congenital
RT heart defects.";
RL Pediatr. Res. 68:281-285(2010).
RN [17]
RP VARIANTS ARG-15 AND SER-235, CHARACTERIZATION OF VARIANT SER-235, AND
RP FUNCTION.
RX PubMed=22750565; DOI=10.1016/j.ejmg.2012.06.007;
RA Yang Y.Q., Li L., Wang J., Zhang X.L., Li R.G., Xu Y.J., Tan H.W.,
RA Wang X.H., Jiang J.Q., Fang W.Y., Liu X.;
RT "GATA6 loss-of-function mutation in atrial fibrillation.";
RL Eur. J. Med. Genet. 55:520-526(2012).
RN [18]
RP VARIANT VAL-469, CHARACTERIZATION OF VARIANT VAL-469, AND FUNCTION.
RX PubMed=22824924; DOI=10.3892/ijmm.2012.1068;
RA Li J., Liu W.D., Yang Z.L., Yang Y.Q.;
RT "Novel GATA6 loss-of-function mutation responsible for familial atrial
RT fibrillation.";
RL Int. J. Mol. Med. 30:783-790(2012).
RN [19]
RP VARIANTS PACHD ALA-452; CYS-456; HIS-456; ASP-466; THR-467 AND GLN-473, AND
RP CHARACTERIZATION OF VARIANTS PACHD CYS-456; ASP-466; THR-467 AND GLN-473.
RX PubMed=22158542; DOI=10.1038/ng.1035;
RA Allen H.L., Flanagan S.E., Shaw-Smith C., De Franco E., Akerman I.,
RA Caswell R., Ferrer J., Hattersley A.T., Ellard S.;
RT "GATA6 haploinsufficiency causes pancreatic agenesis in humans.";
RL Nat. Genet. 44:20-22(2012).
RN [20]
RP VARIANTS SER-91; THR-177; GLY-543 AND LEU-585, CHARACTERIZATION OF VARIANTS
RP SER-91; THR-177; GLY-543 AND LEU-585, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27756709; DOI=10.1016/j.hrthm.2016.10.014;
RA Tucker N.R., Mahida S., Ye J., Abraham E.J., Mina J.A., Parsons V.A.,
RA McLellan M.A., Shea M.A., Hanley A., Benjamin E.J., Milan D.J., Lin H.,
RA Ellinor P.T.;
RT "Gain-of-function mutations in GATA6 lead to atrial fibrillation.";
RL Heart Rhythm 14:284-291(2017).
CC -!- FUNCTION: Transcriptional activator (PubMed:19666519, PubMed:27756709,
CC PubMed:22750565, PubMed:22824924). Regulates SEMA3C and PLXNA2
CC (PubMed:19666519). Involved in gene regulation specifically in the
CC gastric epithelium (PubMed:9315713). May regulate genes that protect
CC epithelial cells from bacterial infection (PubMed:16968778). Involved
CC in bone morphogenetic protein (BMP)-mediated cardiac-specific gene
CC expression (By similarity). Binds to BMP response element (BMPRE) DNA
CC sequences within cardiac activating regions (By similarity). In human
CC skin, controls several physiological processes contributing to
CC homeostasis of the upper pilosebaceous unit. Triggers ductal and
CC sebaceous differentiation as well as limits cell proliferation and
CC lipid production to prevent hyperseborrhoea. Mediates the effects of
CC retinoic acid on sebocyte proliferation, differentiation and lipid
CC production. Also contributes to immune regulation of sebocytes and
CC antimicrobial responses by modulating the expression of anti-
CC inflammatory genes such as IL10 and pro-inflammatory genes such as IL6,
CC TLR2, TLR4, and IFNG. Activates TGFB1 signaling which controls the
CC interfollicular epidermis fate (PubMed:33082341).
CC {ECO:0000250|UniProtKB:Q61169, ECO:0000269|PubMed:16968778,
CC ECO:0000269|PubMed:19666519, ECO:0000269|PubMed:22750565,
CC ECO:0000269|PubMed:22824924, ECO:0000269|PubMed:27756709,
CC ECO:0000269|PubMed:33082341, ECO:0000269|PubMed:9315713}.
CC -!- SUBUNIT: Interacts with LMCD1. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19666519,
CC ECO:0000269|PubMed:27756709}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1;
CC IsoId=Q92908-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92908-2; Sequence=VSP_035778;
CC -!- TISSUE SPECIFICITY: Expressed in heart, gut and gut-derived tissues.
CC Expressed in skin upper pilosebaceous unit. Expression is decreased or
CC lost in acne lesions (PubMed:33082341). {ECO:0000269|PubMed:33082341}.
CC -!- INDUCTION: In sebocytes, expression is up-regulated by Cutibacterium
CC acnes. {ECO:0000269|PubMed:33082341}.
CC -!- DOMAIN: The GATA-type zinc fingers mediate interaction with LMCD1.
CC {ECO:0000250}.
CC -!- DISEASE: Note=Rare variants in GATA6 may be a cause of susceptibility
CC to atrial fibrillation, a common sustained cardiac rhythm disturbance.
CC Atrial fibrillation is characterized by disorganized atrial electrical
CC activity and ineffective atrial contraction promoting blood stasis in
CC the atria and reduces ventricular filling. It can result in
CC palpitations, syncope, thromboembolic stroke, and congestive heart
CC failure. {ECO:0000269|PubMed:22750565, ECO:0000269|PubMed:22824924,
CC ECO:0000269|PubMed:27756709}.
CC -!- DISEASE: Conotruncal heart malformations (CTHM) [MIM:217095]: A group
CC of congenital heart defects involving the outflow tracts. Examples
CC include truncus arteriosus communis, double-outlet right ventricle and
CC transposition of great arteries. Truncus arteriosus communis is
CC characterized by a single outflow tract instead of a separate aorta and
CC pulmonary artery. In transposition of the great arteries, the aorta
CC arises from the right ventricle and the pulmonary artery from the left
CC ventricle. In double outlet of the right ventricle, both the pulmonary
CC artery and aorta arise from the right ventricle.
CC {ECO:0000269|PubMed:19666519}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. GATA6 mutations have been
CC found in patients with non-syndromic persistent truncus arteriosus
CC (PubMed:19666519). {ECO:0000269|PubMed:19666519}.
CC -!- DISEASE: Atrial septal defect 9 (ASD9) [MIM:614475]: 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 Some patients manifest tricuspid valve disease, pulmonary valve
CC disease, and pulmonary artery hypertension.
CC {ECO:0000269|PubMed:20631719}. 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:20581743,
CC ECO:0000269|PubMed:20631719}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Atrioventricular septal defect 5 (AVSD5) [MIM:614474]: 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:20581743}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Pancreatic agenesis and congenital heart defects (PACHD)
CC [MIM:600001]: An autosomal dominant disease characterized by pancreatic
CC severe hypoplasia or agenesis, diabetes mellitus, and congenital heart
CC abnormalities including ventricular septal defect, patent ductus
CC arteriosus, pulmonary artery stenosis, truncus arteriosus and tetralogy
CC of Fallot. {ECO:0000269|PubMed:22158542}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative initiation at Met-
CC 147 of isoform 1. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GATA6ID40690ch18q11.html";
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DR EMBL; U66075; AAC50941.1; -; mRNA.
DR EMBL; X95701; CAA64997.1; -; mRNA.
DR EMBL; D87811; BAA22621.1; -; mRNA.
DR EMBL; EF444980; ACA05995.1; -; Genomic_DNA.
DR EMBL; AC091588; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471088; EAX01137.1; -; Genomic_DNA.
DR CCDS; CCDS11872.1; -. [Q92908-1]
DR RefSeq; NP_005248.2; NM_005257.5. [Q92908-1]
DR AlphaFoldDB; Q92908; -.
DR SMR; Q92908; -.
DR BioGRID; 108897; 18.
DR IntAct; Q92908; 7.
DR MINT; Q92908; -.
DR STRING; 9606.ENSP00000269216; -.
DR iPTMnet; Q92908; -.
DR PhosphoSitePlus; Q92908; -.
DR BioMuta; GATA6; -.
DR DMDM; 215273987; -.
DR EPD; Q92908; -.
DR jPOST; Q92908; -.
DR MassIVE; Q92908; -.
DR MaxQB; Q92908; -.
DR PaxDb; Q92908; -.
DR PeptideAtlas; Q92908; -.
DR PRIDE; Q92908; -.
DR ProteomicsDB; 75592; -. [Q92908-1]
DR ProteomicsDB; 75593; -. [Q92908-2]
DR Antibodypedia; 22009; 519 antibodies from 36 providers.
DR DNASU; 2627; -.
DR Ensembl; ENST00000269216.10; ENSP00000269216.3; ENSG00000141448.11. [Q92908-1]
DR Ensembl; ENST00000581694.1; ENSP00000462313.1; ENSG00000141448.11. [Q92908-1]
DR GeneID; 2627; -.
DR KEGG; hsa:2627; -.
DR MANE-Select; ENST00000269216.10; ENSP00000269216.3; NM_005257.6; NP_005248.2.
DR UCSC; uc002ktt.2; human. [Q92908-1]
DR CTD; 2627; -.
DR DisGeNET; 2627; -.
DR GeneCards; GATA6; -.
DR HGNC; HGNC:4174; GATA6.
DR HPA; ENSG00000141448; Tissue enhanced (adrenal gland, ovary).
DR MalaCards; GATA6; -.
DR MIM; 187500; phenotype.
DR MIM; 217095; phenotype.
DR MIM; 600001; phenotype.
DR MIM; 601656; gene.
DR MIM; 614474; phenotype.
DR MIM; 614475; phenotype.
DR neXtProt; NX_Q92908; -.
DR OpenTargets; ENSG00000141448; -.
DR Orphanet; 99103; Atrial septal defect, ostium secundum type.
DR Orphanet; 99067; Complete atrioventricular septal defect with ventricular hypoplasia.
DR Orphanet; 2140; Congenital diaphragmatic hernia.
DR Orphanet; 334; Familial atrial fibrillation.
DR Orphanet; 2255; Pancreatic hypoplasia-diabetes-congenital heart disease syndrome.
DR Orphanet; 3303; Tetralogy of Fallot.
DR PharmGKB; PA28589; -.
DR VEuPathDB; HostDB:ENSG00000141448; -.
DR eggNOG; KOG1601; Eukaryota.
DR GeneTree; ENSGT00940000160814; -.
DR HOGENOM; CLU_027524_0_0_1; -.
DR InParanoid; Q92908; -.
DR OMA; ENSMLHC; -.
DR OrthoDB; 1030296at2759; -.
DR PhylomeDB; Q92908; -.
DR TreeFam; TF315391; -.
DR PathwayCommons; Q92908; -.
DR Reactome; R-HSA-5683826; Surfactant metabolism.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; Q92908; -.
DR SIGNOR; Q92908; -.
DR BioGRID-ORCS; 2627; 30 hits in 1094 CRISPR screens.
DR ChiTaRS; GATA6; human.
DR GeneWiki; GATA6; -.
DR GenomeRNAi; 2627; -.
DR Pharos; Q92908; Tbio.
DR PRO; PR:Q92908; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q92908; protein.
DR Bgee; ENSG00000141448; Expressed in germinal epithelium of ovary and 135 other tissues.
DR Genevisible; Q92908; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0051525; F:NFAT protein binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
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:UniProtKB.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0048645; P:animal organ formation; IEA:Ensembl.
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:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IEA:Ensembl.
DR GO; GO:0060947; P:cardiac vascular smooth muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:0045165; P:cell fate commitment; IBA:GO_Central.
DR GO; GO:0071773; P:cellular response to BMP stimulus; IEA:Ensembl.
DR GO; GO:0071371; P:cellular response to gonadotropin stimulus; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0060486; P:club cell differentiation; IEA:Ensembl.
DR GO; GO:0007493; P:endodermal cell fate determination; IEA:Ensembl.
DR GO; GO:0030855; P:epithelial cell differentiation; IBA:GO_Central.
DR GO; GO:0070315; P:G1 to G0 transition involved in cell differentiation; IDA:UniProtKB.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0060047; P:heart contraction; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0060575; P:intestinal epithelial cell differentiation; IDA:MGI.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0060430; P:lung saccule development; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; IEA:Ensembl.
DR GO; GO:1904003; P:negative regulation of sebum secreting cell proliferation; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0032911; P:negative regulation of transforming growth factor beta1 production; IMP:UniProtKB.
DR GO; GO:0032912; P:negative regulation of transforming growth factor beta2 production; IMP:UniProtKB.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0003310; P:pancreatic A cell differentiation; IEA:Ensembl.
DR GO; GO:0006644; P:phospholipid metabolic process; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0110024; P:positive regulation of cardiac muscle myoblast proliferation; IDA:BHF-UCL.
DR GO; GO:0051891; P:positive regulation of cardioblast differentiation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:1901390; P:positive regulation of transforming growth factor beta activation; IDA:UniProtKB.
DR GO; GO:0002759; P:regulation of antimicrobial humoral response; IDA:UniProtKB.
DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0070848; P:response to growth factor; IDA:UniProtKB.
DR GO; GO:0032526; P:response to retinoic acid; IDA:UniProtKB.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:UniProtKB.
DR GO; GO:0001949; P:sebaceous gland cell differentiation; IDA:UniProtKB.
DR GO; GO:0003163; P:sinoatrial node development; IEA:Ensembl.
DR GO; GO:0098773; P:skin epidermis development; IDA:UniProtKB.
DR GO; GO:0051145; P:smooth muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl.
DR GO; GO:0035239; P:tube morphogenesis; IEA:Ensembl.
DR GO; GO:0003309; P:type B pancreatic cell differentiation; IEA:Ensembl.
DR GO; GO:0060510; P:type II pneumocyte differentiation; IEA:Ensembl.
DR CDD; cd00202; ZnF_GATA; 2.
DR Gene3D; 3.30.50.10; -; 2.
DR InterPro; IPR008013; GATA_N.
DR InterPro; IPR028437; TF_GATA_6.
DR InterPro; IPR039355; Transcription_factor_GATA.
DR InterPro; IPR000679; Znf_GATA.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR PANTHER; PTHR10071; PTHR10071; 1.
DR PANTHER; PTHR10071:SF23; PTHR10071:SF23; 1.
DR Pfam; PF00320; GATA; 2.
DR Pfam; PF05349; GATA-N; 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 Activator; Alternative initiation; Atrial septal defect; Disease variant;
KW DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..595
FT /note="Transcription factor GATA-6"
FT /id="PRO_0000083423"
FT ZN_FING 390..414
FT /note="GATA-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00094"
FT ZN_FING 444..468
FT /note="GATA-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00094"
FT REGION 14..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 208..255
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 286..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 482..561
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 321..335
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 500..541
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CROSSLNK 429
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 473
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 484
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..146
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8975704,
FT ECO:0000303|PubMed:9294001, ECO:0000303|PubMed:9315713"
FT /id="VSP_035778"
FT VARIANT 15
FT /note="G -> R (in dbSNP:rs116262672)"
FT /evidence="ECO:0000269|PubMed:19666519,
FT ECO:0000269|PubMed:20581743, ECO:0000269|PubMed:20631719,
FT ECO:0000269|PubMed:22750565"
FT /id="VAR_067380"
FT VARIANT 91
FT /note="P -> S (probable disease-associated variant found in
FT patients with atrial fibrillation; gain of function; no
FT effect on subcellular localization; dbSNP:rs766886560)"
FT /evidence="ECO:0000269|PubMed:27756709"
FT /id="VAR_078427"
FT VARIANT 177
FT /note="A -> T (probable disease-associated variant found in
FT patients with atrial fibrillation; gain of function; no
FT effect on subcellular localization; dbSNP:rs1263887431)"
FT /evidence="ECO:0000269|PubMed:27756709"
FT /id="VAR_078428"
FT VARIANT 178
FT /note="A -> V (in AVSD5; increased transcriptional
FT activity; dbSNP:rs387906815)"
FT /evidence="ECO:0000269|PubMed:20581743"
FT /id="VAR_067381"
FT VARIANT 184
FT /note="S -> N (in ASD9 and TOF; loss of transcriptional
FT activity; dbSNP:rs387906816)"
FT /evidence="ECO:0000269|PubMed:20631719"
FT /id="VAR_067382"
FT VARIANT 198
FT /note="L -> V (in TOF; uncertain pathological significance;
FT does not affect transcriptional activity;
FT dbSNP:rs387906814)"
FT /evidence="ECO:0000269|PubMed:20581743"
FT /id="VAR_067383"
FT VARIANT 235
FT /note="Y -> S (probable disease-associated variant found in
FT patients with atrial fibrillation; significant loss of
FT transcriptional activator activity)"
FT /evidence="ECO:0000269|PubMed:22750565"
FT /id="VAR_078429"
FT VARIANT 452
FT /note="T -> A (in PACHD; dbSNP:rs387906817)"
FT /evidence="ECO:0000269|PubMed:22158542"
FT /id="VAR_067384"
FT VARIANT 456
FT /note="R -> C (in PACHD; loss of transcriptional activity;
FT dbSNP:rs387906818)"
FT /evidence="ECO:0000269|PubMed:22158542"
FT /id="VAR_067385"
FT VARIANT 456
FT /note="R -> H (in PACHD; dbSNP:rs387906819)"
FT /evidence="ECO:0000269|PubMed:22158542"
FT /id="VAR_067386"
FT VARIANT 466
FT /note="N -> D (in PACHD; loss of transcriptional activity;
FT dbSNP:rs387906813)"
FT /evidence="ECO:0000269|PubMed:22158542"
FT /id="VAR_067387"
FT VARIANT 466
FT /note="N -> H (in CTHM; persistent truncus arteriosus; loss
FT of transcriptional activity; dbSNP:rs387906813)"
FT /evidence="ECO:0000269|PubMed:19666519"
FT /id="VAR_067388"
FT VARIANT 467
FT /note="A -> T (in PACHD; loss of transcriptional activity;
FT dbSNP:rs387906820)"
FT /evidence="ECO:0000269|PubMed:22158542"
FT /id="VAR_067389"
FT VARIANT 469
FT /note="G -> V (probable disease-associated variant found in
FT patients with atrial fibrillation; significant loss of
FT transcriptional activator activity)"
FT /evidence="ECO:0000269|PubMed:22824924"
FT /id="VAR_078430"
FT VARIANT 473
FT /note="K -> Q (in PACHD; loss of transcriptional activity)"
FT /evidence="ECO:0000269|PubMed:22158542"
FT /id="VAR_067390"
FT VARIANT 543
FT /note="A -> G (probable disease-associated variant found in
FT patients with atrial fibrillation; gain of function; no
FT effect on subcellular localization; dbSNP:rs761668180)"
FT /evidence="ECO:0000269|PubMed:27756709"
FT /id="VAR_078431"
FT VARIANT 585
FT /note="R -> L (probable disease-associated variant found in
FT patients with atrial fibrillation; gain of function; no
FT effect on subcellular localization; dbSNP:rs201707559)"
FT /evidence="ECO:0000269|PubMed:27756709"
FT /id="VAR_078432"
FT CONFLICT 281
FT /note="G -> V (in Ref. 2; CAA64997)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 595 AA; 60033 MW; C4D5410916543E0B CRC64;
MALTDGGWCL PKRFGAAGAD ASDSRAFPAR EPSTPPSPIS SSSSSCSRGG ERGPGGASNC
GTPQLDTEAA AGPPARSLLL SSYASHPFGA PHGPSAPGVA GPGGNLSSWE DLLLFTDLDQ
AATASKLLWS SRGAKLSPFA PEQPEEMYQT LAALSSQGPA AYDGAPGGFV HSAAAAAAAA
AAASSPVYVP TTRVGSMLPG LPYHLQGSGS GPANHAGGAG AHPGWPQASA DSPPYGSGGG
AAGGGAAGPG GAGSAAAHVS ARFPYSPSPP MANGAAREPG GYAAAGSGGA GGVSGGGSSL
AAMGGREPQY SSLSAARPLN GTYHHHHHHH HHHPSPYSPY VGAPLTPAWP AGPFETPVLH
SLQSRAGAPL PVPRGPSADL LEDLSESREC VNCGSIQTPL WRRDGTGHYL CNACGLYSKM
NGLSRPLIKP QKRVPSSRRL GLSCANCHTT TTTLWRRNAE GEPVCNACGL YMKLHGVPRP
LAMKKEGIQT RKRKPKNINK SKTCSGNSNN SIPMTPTSTS SNSDDCSKNT SPTTQPTASG
AGAPVMTGAG ESTNPENSEL KYSGQDGLYI GVSLASPAEV TSSVRPDSWC ALALA
