Q8WW38 (FOG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc finger protein ZFPM2

Alternative name(s):
Friend of GATA protein 2
Short name=FOG-2
Short name=Friend of GATA 2
Short name=hFOG-2
Zinc finger protein 89B
Zinc finger protein multitype 2

Gene names

Name:	ZFPM2
Synonyms:	FOG2, ZNF89B

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	1151 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription regulator that plays a central role in heart morphogenesis and development of coronary vessels from epicardium, by regulating genes that are essential during cardiogenesis. Essential cofactor that acts via the formation of a heterodimer with transcription factors of the GATA family GATA4, GATA5 and GATA6. Such heterodimer can both activate or repress transcriptional activity, depending on the cell and promoter context. Also required in gonadal differentiation, possibly be regulating expression of SRY. Probably acts a corepressor of NR2F2 By similarity. Ref.1
Subunit structure	Interacts with the N-terminal zinc-finger of GATA4, GATA5 and probably GATA6. Interacts with retinoid nuclear receptor RXRA when ligand bound By similarity. Interacts with corepressor CTBP2; this interaction is however not essential for corepressor activity. Able to bind GATA1 in vitro. Interacts with NR2F2 and NR2F6 By similarity. Ref.1
Subcellular location	Nucleus Ref.4.
Tissue specificity	Widely expressed at low level. Ref.1
Domain	The CCHC-type zinc fingers 1, 5, 6 and 8 directly bind to GATA-type zinc fingers. The Tyr residue adjacent to the last Cys of the CCHC-type zinc finger is essential for the interaction with GATA-type zinc fingers By similarity.
Post-translational modification	Sumoylation reduces transcriptional repression activity. Ref.4
Involvement in disease	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 may be caused by mutations affecting the gene represented in this entry. Ref.5 Diaphragmatic hernia 3 (DIH3) [MIM:610187]: Form of congenital diaphragmatic hernia (CDH). CDH refers to a group of congenital defects in the structural integrity of the diaphragm associated with often lethal pulmonary hypoplasia and pulmonary hypertension. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Belongs to the FOG (Friend of GATA) family. Contains 3 C2H2-type zinc fingers. Contains 5 C2HC-type zinc fingers.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Cardiomyopathy Disease mutation
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Repressor
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement. Source: Reactome embryonic organ development Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara lung development Inferred from electronic annotation. Source: Compara negative regulation of cell death Inferred from electronic annotation. Source: Compara negative regulation of fat cell differentiation Inferred from mutant phenotype PubMed 20705609. Source: UniProtKB negative regulation of female gonad development Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 20206639. Source: UniProtKB outflow tract septum morphogenesis Inferred from mutant phenotype PubMed 20807224. Source: BHF-UCL positive regulation of male gonad development Inferred from electronic annotation. Source: Compara right ventricular cardiac muscle tissue morphogenesis Inferred from mutant phenotype PubMed 20807224. Source: BHF-UCL vasculogenesis Inferred from electronic annotation. Source: Compara ventricular septum morphogenesis Inferred from mutant phenotype PubMed 20807224. Source: BHF-UCL
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW RNA polymerase II transcription coactivator activity Non-traceable author statement Ref.1. Source: BHF-UCL nucleic acid binding transcription factor activity Inferred from electronic annotation. Source: Compara transcription corepressor activity Inferred from direct assay Ref.1. Source: BHF-UCL zinc ion binding Non-traceable author statement Ref.1. Source: BHF-UCL
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8WW38-1)

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: Q8WW38-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-132: Missing.
     247-287: KDIFPCKSCG...REAAPVSEEN → SKCSVLCSPA...FFLQKKKKKK

Note: Sequence incomplete. No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1151	1151	Zinc finger protein ZFPM2		PRO_0000221043
Regions
	Zinc finger	250 – 273	24	C2HC-type 1
	Zinc finger	296 – 320	25	C2H2-type 1
	Zinc finger	335 – 357	23	C2H2-type 2
	Zinc finger	363 – 385	23	C2H2-type 3
	Zinc finger	548 – 571	24	C2HC-type 2
	Zinc finger	687 – 710	24	C2HC-type 3
	Zinc finger	854 – 877	24	C2HC-type 4
	Zinc finger	1119 – 1142	24	C2HC-type 5
	Region	829 – 835	7	Interaction with CTBP2 Probable
	Motif	736 – 740	5	Nuclear localization signal By similarity
Amino acid modifications
	Cross-link	324		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) Ref.4
	Cross-link	471		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) Ref.4
	Cross-link	915		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) Ref.4
	Cross-link	955		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) Ref.4
Natural variations
	Alternative sequence	1 – 132	132	Missing in isoform 2.		VSP_009701
	Alternative sequence	247 – 287	41	KDIFP…VSEEN → SKCSVLCSPALEVMGIYGRK KCLLTRNQEQTFFLQKKKKK K in isoform 2.		VSP_009702
	Natural variant	30	1	E → G in TOF; in one patient with sporadic TOF; does not affect its ability to interact with GATA4. Ref.5		VAR_017942
	Natural variant	403	1	A → G. Corresponds to variant rs11993776 [ dbSNP | Ensembl ].		VAR_024178
	Natural variant	657	1	S → G in TOF; in one patient with sporadic TOF; slightly impairs its ability to interact with GATA4. Ref.5 Corresponds to variant rs28374544 [ dbSNP | Ensembl ].		VAR_017943
	Natural variant	782	1	E → D. Corresponds to variant rs2920048 [ dbSNP | Ensembl ].		VAR_017944
	Natural variant	1055	1	A → V. Corresponds to variant rs16873741 [ dbSNP | Ensembl ].		VAR_030760
Experimental info
	Sequence conflict	198	1	F → L in CAB97541. Ref.3
	Sequence conflict	939	1	L → P in AAD49558. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 20, 2007. Version 3. Checksum: 680E31BA1D044C35	FASTA	1,151	128,159
	10 20 30 40 50 60 MSRRKQSKPR QIKRPLEDAI EDEEEECPSE ETDIISKGDF PLEESFSTEF GPENLSCEEV 70 80 90 100 110 120 EYFCNKGDDE GIQETAESDG DTQSEKPGQP GVETDDWDGP GELEVFQKDG ERKIQSRQQL 130 140 150 160 170 180 PVGTTWGPFP GKMDLNNNSL KTKAQVPMVL TAGPKWLLDV TWQGVEDNKN NCIVYSKGGQ 190 200 210 220 230 240 LWCTTTKAIS EGEELIAFVV DFDSRLQAAS QMTLTEGMYP ARLLDSIQLL PQQAAMASIL 250 260 270 280 290 300 PTAIVNKDIF PCKSCGIWYR SERNLQAHLM YYCSGRQREA APVSEENEDS AHQISSLCPF 310 320 330 340 350 360 PQCTKSFSNA RALEMHLNSH SGVKMEEFLP PGASLKCTVC SYTADSVINF HQHLFSHLTQ 370 380 390 400 410 420 AAFRCNHCHF GFQTQRELLQ HQELHVPSGK LPRESDMEHS PSATEDSLQP ATDLLTRSEL 430 440 450 460 470 480 PQSQKAMQTK DASSDTELDK CEKKTQLFLT NQRPEIQPTT NKQSFSYTKI KSEPSSPRLA 490 500 510 520 530 540 SSPVQPNIGP SFPVGPFLSQ FSFPQDITMV PQASEILAKM SELVHRRLRH GSSSYPPVIY 550 560 570 580 590 600 SPLMPKGATC FECNITFNNL DNYLVHKKHY CSSRWQQMAK SPEFPSVSEK MPEALSPNTG 610 620 630 640 650 660 QTSINLLNPA AHSADPENPL LQTSCINSST VLDLIGPNGK GHDKDFSTQT KKLSTSSNND 670 680 690 700 710 720 DKINGKPVDV KNPSVPLVDG ESDPNKTTCE ACNITFSRHE TYMVHKQYYC ATRHDPPLKR 730 740 750 760 770 780 SASNKVPAMQ RTMRTRKRRK MYEMCLPEQE QRPPLVQQRF LDVANLNNPC TSTQEPTEGL 790 800 810 820 830 840 GECYHPRCDI FPGIVSKHLE TSLTINKCVP VSKCDTTHSS VSCLEMDVPI DLSKKCLSQS 850 860 870 880 890 900 ERTTTSPKRL LDYHECTVCK ISFNKVENYL AHKQNFCPVT AHQRNDLGQL DGKVFPNPES 910 920 930 940 950 960 ERNSPDVSYE RSIIKCEKNG NLKQPSPNGN LFSSHLATLQ GLKVFSEAAQ LIATKEENRH 970 980 990 1000 1010 1020 LFLPQCLYPG AIKKAKGADQ LSPYYGIKPS DYISGSLVIH NTDIEQSRNA ENESPKGQAS 1030 1040 1050 1060 1070 1080 SNGCAALKKD SLPLLPKNRG MVIVNGGLKQ DERPAANPQQ ENISQNPQHE DDHKSPSWIS 1090 1100 1110 1120 1130 1140 ENPLAANENV SPGIPSAEEQ LSSIAKGVNG SSQAPTSGKY CRLCDIQFNN LSNFITHKKF 1150 YCSSHAAEHV K
	Isoform 2 [UniParc]. Checksum: A4365593BE3B4476	FASTA	1,019	113,229
	10 20 30 40 50 60 MDLNNNSLKT KAQVPMVLTA GPKWLLDVTW QGVEDNKNNC IVYSKGGQLW CTTTKAISEG 70 80 90 100 110 120 EELIAFVVDF DSRLQAASQM TLTEGMYPAR LLDSIQLLPQ QAAMASILPT AIVNSKCSVL 130 140 150 160 170 180 CSPALEVMGI YGRKKCLLTR NQEQTFFLQK KKKKKEDSAH QISSLCPFPQ CTKSFSNARA 190 200 210 220 230 240 LEMHLNSHSG VKMEEFLPPG ASLKCTVCSY TADSVINFHQ HLFSHLTQAA FRCNHCHFGF 250 260 270 280 290 300 QTQRELLQHQ ELHVPSGKLP RESDMEHSPS ATEDSLQPAT DLLTRSELPQ SQKAMQTKDA 310 320 330 340 350 360 SSDTELDKCE KKTQLFLTNQ RPEIQPTTNK QSFSYTKIKS EPSSPRLASS PVQPNIGPSF 370 380 390 400 410 420 PVGPFLSQFS FPQDITMVPQ ASEILAKMSE LVHRRLRHGS SSYPPVIYSP LMPKGATCFE 430 440 450 460 470 480 CNITFNNLDN YLVHKKHYCS SRWQQMAKSP EFPSVSEKMP EALSPNTGQT SINLLNPAAH 490 500 510 520 530 540 SADPENPLLQ TSCINSSTVL DLIGPNGKGH DKDFSTQTKK LSTSSNNDDK INGKPVDVKN 550 560 570 580 590 600 PSVPLVDGES DPNKTTCEAC NITFSRHETY MVHKQYYCAT RHDPPLKRSA SNKVPAMQRT 610 620 630 640 650 660 MRTRKRRKMY EMCLPEQEQR PPLVQQRFLD VANLNNPCTS TQEPTEGLGE CYHPRCDIFP 670 680 690 700 710 720 GIVSKHLETS LTINKCVPVS KCDTTHSSVS CLEMDVPIDL SKKCLSQSER TTTSPKRLLD 730 740 750 760 770 780 YHECTVCKIS FNKVENYLAH KQNFCPVTAH QRNDLGQLDG KVFPNPESER NSPDVSYERS 790 800 810 820 830 840 IIKCEKNGNL KQPSPNGNLF SSHLATLQGL KVFSEAAQLI ATKEENRHLF LPQCLYPGAI 850 860 870 880 890 900 KKAKGADQLS PYYGIKPSDY ISGSLVIHNT DIEQSRNAEN ESPKGQASSN GCAALKKDSL 910 920 930 940 950 960 PLLPKNRGMV IVNGGLKQDE RPAANPQQEN ISQNPQHEDD HKSPSWISEN PLAANENVSP 970 980 990 1000 1010 GIPSAEEQLS SIAKGVNGSS QAPTSGKYCR LCDIQFNNLS NFITHKKFYC SSHAAEHVK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"hFOG-2, a novel zinc finger protein, binds the co-repressor mCtBP2 and modulates GATA-mediated activation." Holmes M., Turner J., Fox A.H., Chisholm O., Crossley M., Chong B. J. Biol. Chem. 274:23491-23498(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH CTBP2, POSSIBLE INTERACTION WITH GATA1. Tissue: Erythroleukemia.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Prostate.
[3]	The European IMAGE consortium Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-287 (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 641-1151 (ISOFORM 1).
[4]	"SUMOylation regulates the transcriptional repression activity of FOG-2 and its association with GATA-4." Perdomo J., Jiang X.M., Carter D.R., Khachigian L.M., Chong B.H. PLoS ONE 7:E50637-E50637(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-324; LYS-471; LYS-915 AND LYS-955, SUBCELLULAR LOCATION.
[5]	"Mutations of ZFPM2/FOG2 gene in sporadic cases of tetralogy of Fallot." Pizzuti A., Sarkozy A., Newton A.L., Conti E., Flex E., Digilio M.C., Amati F., Gianni D., Tandoi C., Marino B., Crossley M., Dallapiccola B. Hum. Mutat. 22:372-377(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TOF GLY-30 AND GLY-657.
[6]	"Fog2 is required for normal diaphragm and lung development in mice and humans." Ackerman K.G., Herron B.J., Vargas S.O., Huang H., Tevosian S.G., Kochilas L., Rao C., Pober B.R., Babiuk R.P., Epstein J.A., Greer J.J., Beier D.R. PLoS Genet. 1:58-65(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN DIAPHRAGMATIC HERNIA 3.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF119334 mRNA. Translation: AAD49558.1. BC020928 mRNA. Translation: AAH20928.1. BC109222 mRNA. Translation: AAI09223.1. AL389987 mRNA. Translation: CAB97539.1. AL389989 mRNA. Translation: CAB97541.1.
IPI	IPI00015802. IPI00410662.
RefSeq	NP_036214.2. NM_012082.3.
UniGene	Hs.431009.
3D structure databases
ProteinModelPortal	Q8WW38.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8WW38. 2 interactions.
STRING	9606.ENSP00000384179.
PTM databases
PhosphoSite	Q8WW38.
Polymorphism databases
DMDM	126302543.
Proteomic databases
PaxDb	Q8WW38.
PRIDE	Q8WW38.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000407775; ENSP00000384179; ENSG00000169946.
GeneID	23414.
KEGG	hsa:23414.
UCSC	uc003ymd.3. human.
Organism-specific databases
CTD	23414.
GeneCards	GC08P106400.
HGNC	HGNC:16700. ZFPM2.
HPA	HPA004094.
MIM	187500. phenotype. 603693. gene. 610187. phenotype.
neXtProt	NX_Q8WW38.
Orphanet	2140. Congenital diaphragmatic hernia. 3303. Tetralogy of Fallot.
PharmGKB	PA134947303.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG146797.
HOGENOM	HOG000057275.
HOVERGEN	HBG048953.
InParanoid	Q8WW38.
OMA	DPNKTTC.
OrthoDB	EOG412M4R.
Enzyme and pathway databases
Reactome	REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	Q8WW38.
Bgee	Q8WW38.
CleanEx	HS_ZFPM2.
Genevestigator	Q8WW38.
GermOnline	ENSG00000169946. Homo sapiens.
Family and domain databases
Gene3D	3.30.160.60. 1 hit.
InterPro	IPR007087. Znf_C2H2. IPR015880. Znf_C2H2-like. IPR013087. Znf_C2H2/integrase_DNA-bd. [Graphical view]
Pfam	PF00096. zf-C2H2. 1 hit. [Graphical view]
SMART	SM00355. ZnF_C2H2. 8 hits. [Graphical view]
PROSITE	PS00028. ZINC_FINGER_C2H2_1. 2 hits. PS50157. ZINC_FINGER_C2H2_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ZFPM2. human.
GenomeRNAi	23414.
NextBio	45615.
SOURCE	Search...

Entry information

Entry name

FOG2_HUMAN

Accession

Primary (citable) accession number: Q8WW38
Secondary accession number(s): Q32MA6 , Q9NPL7, Q9NPS4, Q9UNI5

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	February 20, 2007
Last modified:	May 1, 2013
This is version 91 of the entry and version 3 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.