Q92908 (GATA6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcription factor GATA-6

Alternative name(s):
GATA-binding factor 6

Gene names

Name:

GATA6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	595 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional activator that regulates SEMA3C and PLXNA2. Thought to be important for regulating terminal differentiation and/or proliferation. Ref.9
Subunit structure	Interacts with LMCD1 By similarity.
Subcellular location	Nucleus Ref.9.
Tissue specificity	Expressed in heart, gut and gut-derived tissues.
Domain	The GATA-type zinc fingers mediate interaction with LMCD1 By similarity.
Involvement in disease	Conotruncal heart malformations (CTHM) [MIM:217095]: A group of congenital heart defects involving the outflow tracts. Examples include truncus arteriosus communis, double-outlet right ventricle and transposition of great arteries. Truncus arteriosus communis is characterized by a single outflow tract instead of a separate aorta and pulmonary artery. In transposition of the great arteries, the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In double outlet of the right ventricle, both the pulmonary artery and aorta arise from the right ventricle. Note: The disease is caused by mutations affecting the gene represented in this entry. GATA6 mutations have been found in patients with non-syndromic persistent truncus arteriosus (Ref.9). Ref.9 Atrial septal defect 9 (ASD9) [MIM:614475]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. Some patients manifest tricuspid valve disease, pulmonary valve disease, and pulmonary artery hypertension. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Tetralogy of Fallot (TOF) [MIM:187500]: A congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing cyanosis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12 Atrioventricular septal defect 5 (AVSD5) [MIM:614474]: A congenital heart malformation characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. The complete form involves underdevelopment of the lower part of the atrial septum and the upper part of the ventricular septum; the valve itself is also shared. A less severe form, known as ostium primum atrial septal defect, is characterized by separate atrioventricular valvar orifices despite a common junction. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Pancreatic agenesis and congenital heart defects (PACHD) [MIM:600001]: An autosomal dominant disease characterized by pancreatic severe hypoplasia or agenesis, diabetes mellitus, and congenital heart abonormalities including ventricular septal defect, patent ductus arteriosus, pulmonary artery stenosis, truncus arteriosus and tetralogy of Fallot. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13
Sequence similarities	Contains 2 GATA-type zinc fingers.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative initiation Polymorphism
Disease	Atrial septal defect Disease mutation
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Clara cell differentiation Inferred from electronic annotation. Source: Compara Type II pneumocyte differentiation Inferred from electronic annotation. Source: Compara apoptotic process Inferred from electronic annotation. Source: Compara blood coagulation Traceable author statement. Source: Reactome cardiac muscle cell differentiation Inferred from electronic annotation. Source: Compara cardiac vascular smooth muscle cell differentiation Inferred from mutant phenotype PubMed 11889139PubMed 12615657. Source: UniProtKB cellular response to BMP stimulus Inferred from electronic annotation. Source: Compara cellular response to gonadotropin stimulus Inferred from electronic annotation. Source: Compara cellular response to hypoxia Inferred from direct assay PubMed 21127043. Source: UniProtKB endodermal cell fate determination Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara intestinal epithelial cell differentiation Inferred from direct assay PubMed 9566909. Source: MGI liver development Inferred from electronic annotation. Source: Compara lung saccule development Inferred from electronic annotation. Source: Compara male gonad development Inferred from expression pattern PubMed 17848411. Source: UniProtKB negative regulation of apoptotic process Inferred from mutant phenotype PubMed 21127043. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 18177748. Source: UniProtKB negative regulation of transforming growth factor beta1 production Inferred from mutant phenotype PubMed 21127043. Source: UniProtKB negative regulation of transforming growth factor beta2 production Inferred from mutant phenotype PubMed 21127043. Source: UniProtKB organ formation Inferred from electronic annotation. Source: Compara outflow tract septum morphogenesis Inferred from mutant phenotype Ref.9. Source: BHF-UCL pancreatic A cell differentiation Inferred from electronic annotation. Source: Compara phospholipid metabolic process Inferred from electronic annotation. Source: Compara positive regulation of angiogenesis Inferred from direct assay PubMed 21127043. Source: UniProtKB positive regulation of cardiac muscle cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of cardioblast differentiation Inferred from electronic annotation. Source: Compara positive regulation of cell cycle arrest Inferred from direct assay PubMed 9593712. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 19497978PubMed 19497978. Source: UniProtKB response to drug Inferred from mutant phenotype PubMed 18671946. Source: UniProtKB response to estrogen stimulus Inferred from electronic annotation. Source: Compara response to growth factor stimulus Inferred from direct assay PubMed 21127043. Source: UniProtKB tube morphogenesis Inferred from electronic annotation. Source: Compara type B pancreatic cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome transcription factor complex Inferred from electronic annotation. Source: Compara
Molecular_function	RNA polymerase II core promoter sequence-specific DNA binding Inferred from electronic annotation. Source: Compara RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara chromatin binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from mutant phenotype PubMed 21127043. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 19497978PubMed 19497978. Source: UniProtKB transcription regulatory region DNA binding Inferred from direct assay PubMed 18177748PubMed 20206639. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]

Isoform 1 (identifier: Q92908-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q92908-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-146: Missing.

Note: Produced by alternative initiation at Met-147 of isoform 1.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 595	595	Transcription factor GATA-6		PRO_0000083423
Regions
	Zinc finger	390 – 414	25	GATA-type 1
	Zinc finger	444 – 468	25	GATA-type 2
	Compositional bias	173 – 183	11	Poly-Ala
	Compositional bias	324 – 333	10	Poly-His
	Compositional bias	449 – 453	5	Poly-Thr
Amino acid modifications
	Modified residue	268	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	1 – 146	146	Missing in isoform 2.		VSP_035778
	Natural variant	15	1	G → R. Ref.9 Ref.11 Ref.12 Corresponds to variant rs116262672 [ dbSNP | Ensembl ].		VAR_067380
	Natural variant	178	1	A → V in AVSD5; increased transcriptional activity. Ref.12		VAR_067381
	Natural variant	184	1	S → N in ASD9 and TOF; loss of transcriptional activity. Ref.11		VAR_067382
	Natural variant	198	1	L → V in TOF; uncertain pathological significance; does not affect transcriptional activity. Ref.12		VAR_067383
	Natural variant	452	1	T → A in PACHD. Ref.13		VAR_067384
	Natural variant	456	1	R → C in PACHD; loss of transcriptional activity. Ref.13		VAR_067385
	Natural variant	456	1	R → H in PACHD. Ref.13		VAR_067386
	Natural variant	466	1	N → D in PACHD; loss of transcriptional activity. Ref.13		VAR_067387
	Natural variant	466	1	N → H in CTHM; persistent truncus arteriosus; loss of transcriptional activity. Ref.9		VAR_067388
	Natural variant	467	1	A → T in PACHD; loss of transcriptional activity. Ref.13		VAR_067389
	Natural variant	473	1	K → Q in PACHD; loss of transcriptional activity. Ref.13		VAR_067390
Experimental info
	Sequence conflict	281	1	G → V in CAA64997. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: C4D5410916543E0B	FASTA	595	60,033
	10 20 30 40 50 60 MALTDGGWCL PKRFGAAGAD ASDSRAFPAR EPSTPPSPIS SSSSSCSRGG ERGPGGASNC 70 80 90 100 110 120 GTPQLDTEAA AGPPARSLLL SSYASHPFGA PHGPSAPGVA GPGGNLSSWE DLLLFTDLDQ 130 140 150 160 170 180 AATASKLLWS SRGAKLSPFA PEQPEEMYQT LAALSSQGPA AYDGAPGGFV HSAAAAAAAA 190 200 210 220 230 240 AAASSPVYVP TTRVGSMLPG LPYHLQGSGS GPANHAGGAG AHPGWPQASA DSPPYGSGGG 250 260 270 280 290 300 AAGGGAAGPG GAGSAAAHVS ARFPYSPSPP MANGAAREPG GYAAAGSGGA GGVSGGGSSL 310 320 330 340 350 360 AAMGGREPQY SSLSAARPLN GTYHHHHHHH HHHPSPYSPY VGAPLTPAWP AGPFETPVLH 370 380 390 400 410 420 SLQSRAGAPL PVPRGPSADL LEDLSESREC VNCGSIQTPL WRRDGTGHYL CNACGLYSKM 430 440 450 460 470 480 NGLSRPLIKP QKRVPSSRRL GLSCANCHTT TTTLWRRNAE GEPVCNACGL YMKLHGVPRP 490 500 510 520 530 540 LAMKKEGIQT RKRKPKNINK SKTCSGNSNN SIPMTPTSTS SNSDDCSKNT SPTTQPTASG 550 560 570 580 590 AGAPVMTGAG ESTNPENSEL KYSGQDGLYI GVSLASPAEV TSSVRPDSWC ALALA
	Isoform 2 [UniParc]. Checksum: 2A0C294757CC2E92	FASTA	449	45,386
	10 20 30 40 50 60 MYQTLAALSS QGPAAYDGAP GGFVHSAAAA AAAAAAASSP VYVPTTRVGS MLPGLPYHLQ 70 80 90 100 110 120 GSGSGPANHA GGAGAHPGWP QASADSPPYG SGGGAAGGGA AGPGGAGSAA AHVSARFPYS 130 140 150 160 170 180 PSPPMANGAA REPGGYAAAG SGGAGGVSGG GSSLAAMGGR EPQYSSLSAA RPLNGTYHHH 190 200 210 220 230 240 HHHHHHHPSP YSPYVGAPLT PAWPAGPFET PVLHSLQSRA GAPLPVPRGP SADLLEDLSE 250 260 270 280 290 300 SRECVNCGSI QTPLWRRDGT GHYLCNACGL YSKMNGLSRP LIKPQKRVPS SRRLGLSCAN 310 320 330 340 350 360 CHTTTTTLWR RNAEGEPVCN ACGLYMKLHG VPRPLAMKKE GIQTRKRKPK NINKSKTCSG 370 380 390 400 410 420 NSNNSIPMTP TSTSSNSDDC SKNTSPTTQP TASGAGAPVM TGAGESTNPE NSELKYSGQD 430 440 GLYIGVSLAS PAEVTSSVRP DSWCALALA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human GATA-6 gene: structure, chromosomal location, and regulation of expression by tissue-specific and mitogen-responsive signals." Suzuki E., Evans T., Lowry J., Truong L., Bell D.W., Testa J.R., Walsh K. Genomics 38:283-290(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"Molecular cloning of human GATA-6 DNA binding protein: high levels of expression in heart and gut." Huggon I.C., Davies A., Gove C., Moscoso G., Moniz C., Foss Y., Farzaneh F., Towner P. Biochim. Biophys. Acta 1353:98-102(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Heart.
[3]	"GATA-6 DNA binding protein expressed in human gastric adenocarcinoma MKN45 cells." Yoshida T., Sato R., Mahmood S., Kawasaki S., Futai M., Maeda M. FEBS Lett. 414:333-337(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"DNA sequence and analysis of human chromosome 18." Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S. Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The human and mouse GATA-6 genes utilize two promoters and two initiation codons." Brewer A., Gove C., Davies A., McNulty C., Barrow D., Koutsourakis M., Farzaneh F., Pizzey J., Bomford A., Patient R. J. Biol. Chem. 274:38004-38016(1999) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE INITIATION.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signaling." Kodo K., Nishizawa T., Furutani M., Arai S., Yamamura E., Joo K., Takahashi T., Matsuoka R., Yamagishi H. Proc. Natl. Acad. Sci. U.S.A. 106:13933-13938(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, VARIANT CTHM HIS-466, VARIANT ARG-15, CHARACTERIZATION OF VARIANT CTHM HIS-466.
[10]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[11]	"A novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect." Lin X., Huo Z., Liu X., Zhang Y., Li L., Zhao H., Yan B., Liu Y., Yang Y., Chen Y.H. J. Hum. Genet. 55:662-667(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ASD9 ASN-184, VARIANT TOF ASN-184, CHARACTERIZATION OF VARIANT ASD9 ASN-184, VARIANT ARG-15.
[12]	"Identification of GATA6 sequence variants in patients with congenital heart defects." Maitra M., Koenig S.N., Srivastava D., Garg V. Pediatr. Res. 68:281-285(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARG-15, VARIANT AVSD5 VAL-178, VARIANT TOF VAL-198, CHARACTERIZATION OF VARIANT AVSD5 VAL-178, CHARACTERIZATION OF VARIANT TOF VAL-198.
[13]	"GATA6 haploinsufficiency causes pancreatic agenesis in humans." Allen H.L., Flanagan S.E., Shaw-Smith C., De Franco E., Akerman I., Caswell R., Ferrer J., Hattersley A.T., Ellard S. Nat. Genet. 44:20-22(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PACHD ALA-452; CYS-456; HIS-456; ASP-466; THR-467 AND GLN-473, CHARACTERIZATION OF VARIANTS PACHD CYS-456; ASP-466; THR-467 AND GLN-473.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U66075 mRNA. Translation: AAC50941.1. X95701 mRNA. Translation: CAA64997.1. D87811 mRNA. Translation: BAA22621.1. EF444980 Genomic DNA. Translation: ACA05995.1. AC091588 Genomic DNA. No translation available. CH471088 Genomic DNA. Translation: EAX01137.1.
IPI	IPI00024236. IPI00915001.
RefSeq	NP_005248.2. NM_005257.4.
UniGene	Hs.514746. Hs.741506.
3D structure databases
ProteinModelPortal	Q92908.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92908. 2 interactions.
STRING	9606.ENSP00000269216.
PTM databases
PhosphoSite	Q92908.
Polymorphism databases
DMDM	215273987.
Proteomic databases
PaxDb	Q92908.
PRIDE	Q92908.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000269216; ENSP00000269216; ENSG00000141448. ENST00000581694; ENSP00000462313; ENSG00000141448.
GeneID	2627.
KEGG	hsa:2627.
UCSC	uc002ktt.1. human.
Organism-specific databases
CTD	2627.
GeneCards	GC18P019749.
H-InvDB	HIX0039732.
HGNC	HGNC:4174. GATA6.
HPA	CAB011581.
MIM	187500. phenotype. 217095. phenotype. 600001. phenotype. 601656. gene. 614474. phenotype. 614475. phenotype.
neXtProt	NX_Q92908.
Orphanet	99103. Atrial septal defect, ostium secundum type. 1329. Complete atrioventricular canal. 334. Familial atrial fibrillation. 2255. Pancreatic hypoplasia - diabetes - heart disease. 1330. Partial atrioventricular canal. 3303. Tetralogy of Fallot.
PharmGKB	PA28589.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5641.
HOGENOM	HOG000047700.
HOVERGEN	HBG051703.
InParanoid	Q92908.
KO	K09183.
OMA	GAHPGWP.
OrthoDB	EOG4TMR21.
PhylomeDB	Q92908.
Enzyme and pathway databases
Reactome	REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	Q92908.
Bgee	Q92908.
CleanEx	HS_GATA6.
Genevestigator	Q92908.
GermOnline	ENSG00000141448. Homo sapiens.
Family and domain databases
Gene3D	3.30.50.10. 2 hits.
InterPro	IPR008013. GATA_N. IPR000679. Znf_GATA. IPR013088. Znf_NHR/GATA. [Graphical view]
Pfam	PF00320. GATA. 2 hits. PF05349. GATA-N. 1 hit. [Graphical view]
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
GenomeRNAi	2627.
NextBio	10349.
SOURCE	Search...

Entry information

Entry name

GATA6_HUMAN

Accession

Primary (citable) accession number: Q92908
Secondary accession number(s): B0YJ17, P78327

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.