OVOL2_HUMAN
ID OVOL2_HUMAN Reviewed; 275 AA.
AC Q9BRP0; Q5T8B4; Q9BX22; Q9HA54; Q9Y4M0;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Transcription factor Ovo-like 2;
DE Short=hOvo2;
DE AltName: Full=Zinc finger protein 339;
GN Name=OVOL2; Synonyms=ZNF339;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 59-275 (ISOFORM 1).
RG The European IMAGE consortium;
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP TISSUE SPECIFICITY, AND ALTERNATIVE SPLICING.
RX PubMed=12213202; DOI=10.1006/geno.2002.6831;
RA Li B., Dai Q., Li L., Nair M., Mackay D.R., Dai X.;
RT "Ovol2, a mammalian homolog of Drosophila ovo: gene structure, chromosomal
RT mapping, and aberrant expression in blind-sterile mice.";
RL Genomics 80:319-325(2002).
RN [8]
RP FUNCTION.
RX PubMed=19700410; DOI=10.1074/jbc.m109.008847;
RA Wells J., Lee B., Cai A.Q., Karapetyan A., Lee W.J., Rugg E., Sinha S.,
RA Nie Q., Dai X.;
RT "Ovol2 suppresses cell cycling and terminal differentiation of
RT keratinocytes by directly repressing c-Myc and Notch1.";
RL J. Biol. Chem. 284:29125-29135(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-269, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP TISSUE SPECIFICITY, AND INVOLVEMENT IN PPCD1.
RX PubMed=26749309; DOI=10.1016/j.ajhg.2015.11.018;
RA Davidson A.E., Liskova P., Evans C.J., Dudakova L., Noskova L.,
RA Pontikos N., Hartmannova H., Hodanova K., Stranecky V., Kozmik Z.,
RA Levis H.J., Idigo N., Sasai N., Maher G.J., Bellingham J., Veli N.,
RA Ebenezer N.D., Cheetham M.E., Daniels J.T., Thaung C.M., Jirsova K.,
RA Plagnol V., Filipec M., Kmoch S., Tuft S.J., Hardcastle A.J.;
RT "Autosomal-dominant corneal endothelial dystrophies CHED1 and PPCD1 are
RT allelic disorders caused by non-coding mutations in the promoter of
RT OVOL2.";
RL Am. J. Hum. Genet. 98:75-89(2016).
CC -!- FUNCTION: Zinc-finger transcription repressor factor (PubMed:19700410).
CC Plays a critical role in maintaining the identity of epithelial
CC lineages by suppressing epithelial-to mesenchymal transition (EMT)
CC mainly through the repression of ZEB1, an EMT inducer (By similarity).
CC Positively regulates neuronal differentiation (By similarity).
CC Suppresses cell cycling and terminal differentiation of keratinocytes
CC by directly repressing MYC and NOTCH1 (PubMed:19700410). Important for
CC the correct development of primordial germ cells in embryos (By
CC similarity). {ECO:0000250|UniProtKB:Q8CIV7,
CC ECO:0000269|PubMed:19700410}.
CC -!- INTERACTION:
CC Q9BRP0; Q8TF50: ZNF526; NbExp=3; IntAct=EBI-13007247, EBI-11035148;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8CIV7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BRP0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BRP0-2; Sequence=VSP_038260;
CC -!- TISSUE SPECIFICITY: Expressed in testis, ovary, heart and skeletal
CC muscle (PubMed:12213202). Expressed in the cornea, but absent from the
CC corneal endothelium (PubMed:26749309). {ECO:0000269|PubMed:12213202,
CC ECO:0000269|PubMed:26749309}.
CC -!- DISEASE: Corneal dystrophy, posterior polymorphous, 1 (PPCD1)
CC [MIM:122000]: A rare corneal disorder characterized by small aggregates
CC of apparent vesicles bordered by a gray haze at the level of Descemet
CC membrane, an altered corneal endothelial cell structure, and an unusual
CC proliferation of endothelial cells. Symptoms can range from very
CC aggressive to asymptomatic and non-progressive, even within the same
CC family. {ECO:0000269|PubMed:26749309}. Note=The disease is caused by
CC variants affecting the gene represented in this entry. Disease-causing
CC mutations in the OVOL2 promoter alter promoter activity, dysregulate
CC OVOL2 expression, and probably induce OVOL2 ectopic expression in the
CC corneal endothelium. {ECO:0000269|PubMed:26749309}.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
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DR EMBL; AK022284; BAB14002.1; -; mRNA.
DR EMBL; BT007295; AAP35959.1; -; mRNA.
DR EMBL; AL121585; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL160411; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10258.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10259.1; -; Genomic_DNA.
DR EMBL; BC006148; AAH06148.1; -; mRNA.
DR EMBL; AL079276; CAB45151.1; -; mRNA.
DR CCDS; CCDS13132.1; -. [Q9BRP0-1]
DR RefSeq; NP_001290390.1; NM_001303461.1. [Q9BRP0-2]
DR RefSeq; NP_001290391.1; NM_001303462.1. [Q9BRP0-2]
DR RefSeq; NP_067043.2; NM_021220.3. [Q9BRP0-1]
DR AlphaFoldDB; Q9BRP0; -.
DR SMR; Q9BRP0; -.
DR BioGRID; 121825; 30.
DR CORUM; Q9BRP0; -.
DR IntAct; Q9BRP0; 1.
DR STRING; 9606.ENSP00000278780; -.
DR iPTMnet; Q9BRP0; -.
DR PhosphoSitePlus; Q9BRP0; -.
DR BioMuta; OVOL2; -.
DR DMDM; 23396998; -.
DR EPD; Q9BRP0; -.
DR jPOST; Q9BRP0; -.
DR MassIVE; Q9BRP0; -.
DR MaxQB; Q9BRP0; -.
DR PaxDb; Q9BRP0; -.
DR PeptideAtlas; Q9BRP0; -.
DR PRIDE; Q9BRP0; -.
DR ProteomicsDB; 78792; -. [Q9BRP0-1]
DR ProteomicsDB; 78793; -. [Q9BRP0-2]
DR Antibodypedia; 24517; 170 antibodies from 25 providers.
DR DNASU; 58495; -.
DR Ensembl; ENST00000278780.7; ENSP00000278780.5; ENSG00000125850.11. [Q9BRP0-1]
DR GeneID; 58495; -.
DR KEGG; hsa:58495; -.
DR MANE-Select; ENST00000278780.7; ENSP00000278780.5; NM_021220.4; NP_067043.2.
DR UCSC; uc002wqi.1; human. [Q9BRP0-1]
DR CTD; 58495; -.
DR DisGeNET; 58495; -.
DR GeneCards; OVOL2; -.
DR HGNC; HGNC:15804; OVOL2.
DR HPA; ENSG00000125850; Tissue enhanced (salivary gland, stomach).
DR MalaCards; OVOL2; -.
DR MIM; 122000; phenotype.
DR MIM; 616441; gene.
DR neXtProt; NX_Q9BRP0; -.
DR OpenTargets; ENSG00000125850; -.
DR Orphanet; 98975; Congenital hereditary endothelial dystrophy type I.
DR Orphanet; 98973; Posterior polymorphous corneal dystrophy.
DR PharmGKB; PA38039; -.
DR VEuPathDB; HostDB:ENSG00000125850; -.
DR eggNOG; KOG3576; Eukaryota.
DR GeneTree; ENSGT00940000159359; -.
DR HOGENOM; CLU_087964_0_0_1; -.
DR InParanoid; Q9BRP0; -.
DR OMA; IPVSLDC; -.
DR OrthoDB; 1419156at2759; -.
DR PhylomeDB; Q9BRP0; -.
DR TreeFam; TF337552; -.
DR PathwayCommons; Q9BRP0; -.
DR SignaLink; Q9BRP0; -.
DR BioGRID-ORCS; 58495; 54 hits in 1092 CRISPR screens.
DR ChiTaRS; OVOL2; human.
DR GenomeRNAi; 58495; -.
DR Pharos; Q9BRP0; Tbio.
DR PRO; PR:Q9BRP0; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9BRP0; protein.
DR Bgee; ENSG00000125850; Expressed in pancreatic ductal cell and 130 other tissues.
DR Genevisible; Q9BRP0; HS.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:ARUK-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:BHF-UCL.
DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISS:ARUK-UCL.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IEA:Ensembl.
DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IEA:Ensembl.
DR GO; GO:0060214; P:endocardium formation; IEA:Ensembl.
DR GO; GO:0009913; P:epidermal cell differentiation; IBA:GO_Central.
DR GO; GO:0001947; P:heart looping; IEA:Ensembl.
DR GO; GO:0060347; P:heart trabecula formation; IEA:Ensembl.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IEA:Ensembl.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:ARUK-UCL.
DR GO; GO:0045617; P:negative regulation of keratinocyte differentiation; IMP:BHF-UCL.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IDA:BHF-UCL.
DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; IDA:BHF-UCL.
DR GO; GO:0001755; P:neural crest cell migration; IEA:Ensembl.
DR GO; GO:0001842; P:neural fold formation; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:ARUK-UCL.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IEA:Ensembl.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:BHF-UCL.
DR GO; GO:0010837; P:regulation of keratinocyte proliferation; IMP:BHF-UCL.
DR GO; GO:0060390; P:regulation of SMAD protein signal transduction; ISS:ARUK-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR027756; Ovo-like.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR10032; PTHR10032; 1.
DR Pfam; PF00096; zf-C2H2; 2.
DR SMART; SM00355; ZnF_C2H2; 4.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Corneal dystrophy; Developmental protein;
KW DNA-binding; Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..275
FT /note="Transcription factor Ovo-like 2"
FT /id="PRO_0000047013"
FT ZN_FING 119..141
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 147..169
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 175..198
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 214..237
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 15..101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 50..78
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT VAR_SEQ 1..132
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_038260"
FT CONFLICT 264
FT /note="E -> G (in Ref. 1; BAB14002)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 275 AA; 30438 MW; 3563EC44510E04AB CRC64;
MPKVFLVKRR SLGVSVRSWD ELPDEKRADT YIPVGLGRLL HDPPEDCRSD GGSSSGSGSS
SAGEPGGAES SSSPHAPESE TPEPGDAEGP DGHLATKQRP VARSKIKFTT GTCSDSVVHS
CDLCGKGFRL QRMLNRHLKC HNQVKRHLCT FCGKGFNDTF DLKRHVRTHT GIRPYKCNVC
NKAFTQRCSL ESHLKKIHGV QQQYAYKQRR DKLYVCEDCG YTGPTQEDLY LHVNSAHPGS
SFLKKTSKKL AALLQGKLTS AHQENTSLSE EEERK
