PCGF2_HUMAN
ID PCGF2_HUMAN Reviewed; 344 AA.
AC P35227; A6NGD8;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Polycomb group RING finger protein 2;
DE AltName: Full=DNA-binding protein Mel-18;
DE AltName: Full=RING finger protein 110;
DE AltName: Full=Zinc finger protein 144;
GN Name=PCGF2; Synonyms=MEL18, RNF110, ZNF144;
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].
RX PubMed=8325509; DOI=10.1016/0378-1119(93)90275-8;
RA Ishida A., Asano H., Hasegawa M., Koseki H., Ono T., Yoshida M.C.,
RA Taniguchi M., Kanno M.;
RT "Cloning and chromosome mapping of the human Mel-18 gene which encodes a
RT DNA-binding protein with a new 'RING-finger' motif.";
RL Gene 129:249-255(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon endothelium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
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].
RC TISSUE=Placenta, and Uterus;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-344, 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 [7]
RP IDENTIFICATION IN A PRC1-LIKE COMPLEX, AND INTERACTION WITH CBX8; RING1 AND
RP RNF2.
RX PubMed=19636380; DOI=10.1371/journal.pone.0006380;
RA Maertens G.N., El Messaoudi-Aubert S., Racek T., Stock J.K., Nicholls J.,
RA Rodriguez-Niedenfuhr M., Gil J., Peters G.;
RT "Several distinct polycomb complexes regulate and co-localize on the INK4a
RT tumor suppressor locus.";
RL PLoS ONE 4:E6380-E6380(2009).
RN [8]
RP IDENTIFICATION IN A PRC1-LIKE COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=21282530; DOI=10.1074/mcp.m110.002642;
RA Vandamme J., Volkel P., Rosnoblet C., Le Faou P., Angrand P.O.;
RT "Interaction proteomics analysis of polycomb proteins defines distinct PRC1
RT Complexes in mammalian cells.";
RL Mol. Cell. Proteomics 0:0-0(2011).
RN [9]
RP FUNCTION, AND SUBUNIT.
RX PubMed=26151332; DOI=10.1038/ncomms8621;
RA Taherbhoy A.M., Huang O.W., Cochran A.G.;
RT "BMI1-RING1B is an autoinhibited RING E3 ubiquitin ligase.";
RL Nat. Commun. 6:7621-7621(2015).
RN [10]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-51 AND LYS-88, AND IDENTIFICATION
RP 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 [11]
RP INVOLVEMENT IN TPFS, AND VARIANTS TPFS LEU-65 AND SER-65.
RX PubMed=30343942; DOI=10.1016/j.ajhg.2018.09.012;
RA Turnpenny P.D., Wright M.J., Sloman M., Caswell R., van Essen A.J.,
RA Gerkes E., Pfundt R., White S.M., Shaul-Lotan N., Carpenter L.,
RA Schaefer G.B., Fryer A., Innes A.M., Forbes K.P., Chung W.K.,
RA McLaughlin H., Henderson L.B., Roberts A.E., Heath K.E.,
RA Paumard-Hernandez B., Gener B., Fawcett K.A., Gjergja-Juraski R.,
RA Pilz D.T., Fry A.E.;
RT "Missense mutations of the Pro65 residue of PCGF2 cause a recognizable
RT syndrome associated with craniofacial, neurological, cardiovascular, and
RT skeletal features.";
RL Am. J. Hum. Genet. 103:786-793(2018).
CC -!- FUNCTION: Transcriptional repressor. Binds specifically to the DNA
CC sequence 5'-GACTNGACT-3'. Has tumor suppressor activity. May play a
CC role in control of cell proliferation and/or neural cell development.
CC Regulates proliferation of early T progenitor cells by maintaining
CC expression of HES1. Also plays a role in antero-posterior specification
CC of the axial skeleton and negative regulation of the self-renewal
CC activity of hematopoietic stem cells (By similarity). Component of a
CC Polycomb group (PcG) multiprotein PRC1-like complex, a complex class
CC required to maintain the transcriptionally repressive state of many
CC genes, including Hox genes, throughout development. PcG PRC1 complex
CC acts via chromatin remodeling and modification of histones; it mediates
CC monoubiquitination of histone H2A 'Lys-119', rendering chromatin
CC heritably changed in its expressibility (PubMed:26151332). Within the
CC PRC1-like complex, regulates RNF2 ubiquitin ligase activity
CC (PubMed:26151332). {ECO:0000250|UniProtKB:P23798,
CC ECO:0000269|PubMed:26151332}.
CC -!- SUBUNIT: Exists as both a monomer and homodimer (By similarity).
CC Component of a PRC1-like complex (PubMed:19636380, PubMed:21282530,
CC PubMed:26151332). Interacts with CBX8, RING1 AND RNF2
CC (PubMed:19636380). Interacts with CBX7 (By similarity). Interacts with
CC PHC2 (By similarity). {ECO:0000250|UniProtKB:P23798,
CC ECO:0000269|PubMed:19636380, ECO:0000269|PubMed:21282530}.
CC -!- INTERACTION:
CC P35227; O95503: CBX6; NbExp=3; IntAct=EBI-2129767, EBI-3951758;
CC P35227; O95931: CBX7; NbExp=6; IntAct=EBI-2129767, EBI-3923843;
CC P35227; Q9HC52: CBX8; NbExp=11; IntAct=EBI-2129767, EBI-712912;
CC P35227; Q9HCE1: MOV10; NbExp=2; IntAct=EBI-2129767, EBI-1055820;
CC P35227; Q9HAT8: PELI2; NbExp=3; IntAct=EBI-2129767, EBI-448407;
CC P35227; P78364: PHC1; NbExp=11; IntAct=EBI-2129767, EBI-725403;
CC P35227; Q8IXK0: PHC2; NbExp=8; IntAct=EBI-2129767, EBI-713786;
CC P35227; Q06587: RING1; NbExp=13; IntAct=EBI-2129767, EBI-752313;
CC P35227; Q99496: RNF2; NbExp=16; IntAct=EBI-2129767, EBI-722416;
CC P35227; P32856-2: STX2; NbExp=3; IntAct=EBI-2129767, EBI-11956649;
CC P35227; Q12933: TRAF2; NbExp=3; IntAct=EBI-2129767, EBI-355744;
CC P35227; P0CG48: UBC; NbExp=2; IntAct=EBI-2129767, EBI-3390054;
CC P35227; P51784: USP11; NbExp=5; IntAct=EBI-2129767, EBI-306876;
CC P35227; Q93009: USP7; NbExp=5; IntAct=EBI-2129767, EBI-302474;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21282530}.
CC -!- TISSUE SPECIFICITY: Detected in all tissues examined with high
CC expression found in placenta lung and kidney and low expression, in
CC liver, pancreas and skeletal muscle.
CC -!- PTM: Phosphorylated. Homodimer formation is regulated by
CC phosphorylation with only unphosphorylated proteins forming homodimers.
CC {ECO:0000250|UniProtKB:P23798}.
CC -!- DISEASE: Turnpenny-Fry syndrome (TPFS) [MIM:618371]: A syndrome
CC characterized by facial dysmorphism, intellectual disability, feeding
CC problems, impaired growth, and a range of brain, cardiovascular, and
CC skeletal abnormalities. Craniofacial features include frontal bossing,
CC sparse hair, malar hypoplasia, small palpebral fissures and oral stoma,
CC and dysplastic ears. {ECO:0000269|PubMed:30343942}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
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DR EMBL; D13969; BAA03074.1; -; mRNA.
DR EMBL; BX647429; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC006449; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471152; EAW60528.1; -; Genomic_DNA.
DR EMBL; BC004858; AAH04858.1; -; mRNA.
DR EMBL; BC024255; AAH24255.1; -; mRNA.
DR CCDS; CCDS32638.1; -.
DR PIR; JN0717; JN0717.
DR RefSeq; NP_009075.1; NM_007144.2.
DR RefSeq; XP_005257697.1; XM_005257640.2.
DR RefSeq; XP_005257698.1; XM_005257641.4.
DR RefSeq; XP_005257699.1; XM_005257642.3.
DR RefSeq; XP_016880505.1; XM_017025016.1.
DR AlphaFoldDB; P35227; -.
DR SMR; P35227; -.
DR BioGRID; 113497; 88.
DR DIP; DIP-41880N; -.
DR IntAct; P35227; 48.
DR MINT; P35227; -.
DR STRING; 9606.ENSP00000482063; -.
DR iPTMnet; P35227; -.
DR PhosphoSitePlus; P35227; -.
DR BioMuta; PCGF2; -.
DR DMDM; 462585; -.
DR EPD; P35227; -.
DR jPOST; P35227; -.
DR MassIVE; P35227; -.
DR MaxQB; P35227; -.
DR PaxDb; P35227; -.
DR PeptideAtlas; P35227; -.
DR PRIDE; P35227; -.
DR ProteomicsDB; 54992; -.
DR Antibodypedia; 72907; 258 antibodies from 34 providers.
DR DNASU; 7703; -.
DR Ensembl; ENST00000610440.1; ENSP00000478517.1; ENSG00000278644.2.
DR Ensembl; ENST00000611883.4; ENSP00000478970.1; ENSG00000277258.5.
DR Ensembl; ENST00000616199.4; ENSP00000482063.1; ENSG00000277258.5.
DR Ensembl; ENST00000620225.5; ENSP00000482815.1; ENSG00000277258.5.
DR Ensembl; ENST00000631566.1; ENSP00000488872.1; ENSG00000278644.2.
DR Ensembl; ENST00000631610.1; ENSP00000488868.1; ENSG00000278644.2.
DR GeneID; 7703; -.
DR KEGG; hsa:7703; -.
DR MANE-Select; ENST00000620225.5; ENSP00000482815.1; NM_007144.3; NP_009075.1.
DR UCSC; uc002hqp.2; human.
DR CTD; 7703; -.
DR DisGeNET; 7703; -.
DR GeneCards; PCGF2; -.
DR HGNC; HGNC:12929; PCGF2.
DR HPA; ENSG00000277258; Low tissue specificity.
DR MalaCards; PCGF2; -.
DR MIM; 600346; gene.
DR MIM; 618371; phenotype.
DR neXtProt; NX_P35227; -.
DR OpenTargets; ENSG00000277258; -.
DR PharmGKB; PA37516; -.
DR VEuPathDB; HostDB:ENSG00000277258; -.
DR eggNOG; KOG2660; Eukaryota.
DR GeneTree; ENSGT00940000159730; -.
DR HOGENOM; CLU_046427_0_0_1; -.
DR InParanoid; P35227; -.
DR OMA; MDIAYIL; -.
DR OrthoDB; 1344247at2759; -.
DR PhylomeDB; P35227; -.
DR TreeFam; TF324206; -.
DR PathwayCommons; P35227; -.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-3899300; SUMOylation of transcription cofactors.
DR Reactome; R-HSA-4551638; SUMOylation of chromatin organization proteins.
DR Reactome; R-HSA-4570464; SUMOylation of RNA binding proteins.
DR Reactome; R-HSA-4655427; SUMOylation of DNA methylation proteins.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-8953750; Transcriptional Regulation by E2F6.
DR SignaLink; P35227; -.
DR SIGNOR; P35227; -.
DR BioGRID-ORCS; 7703; 20 hits in 1125 CRISPR screens.
DR ChiTaRS; PCGF2; human.
DR GeneWiki; PCGF2; -.
DR GenomeRNAi; 7703; -.
DR Pharos; P35227; Tbio.
DR PRO; PR:P35227; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P35227; protein.
DR Bgee; ENSG00000277258; Expressed in cortical plate and 95 other tissues.
DR ExpressionAtlas; P35227; baseline and differential.
DR Genevisible; P35227; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031519; C:PcG protein complex; IDA:UniProtKB.
DR GO; GO:0035102; C:PRC1 complex; IDA:UniProtKB.
DR GO; GO:0001739; C:sex chromatin; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IBA:GO_Central.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0097190; P:apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IEA:Ensembl.
DR GO; GO:0016573; P:histone acetylation; IEA:Ensembl.
DR GO; GO:0036353; P:histone H2A-K119 monoubiquitination; IMP:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR032443; RAWUL.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF16207; RAWUL; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Disease variant; DNA-binding; Intellectual disability; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..344
FT /note="Polycomb group RING finger protein 2"
FT /id="PRO_0000055984"
FT ZN_FING 18..57
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 240..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 81..95
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 241..258
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 265..292
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 301..333
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 344
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CROSSLNK 51
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 88
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 65
FT /note="P -> L (in TPFS)"
FT /evidence="ECO:0000269|PubMed:30343942"
FT /id="VAR_082085"
FT VARIANT 65
FT /note="P -> S (in TPFS)"
FT /evidence="ECO:0000269|PubMed:30343942"
FT /id="VAR_082086"
SQ SEQUENCE 344 AA; 37788 MW; A910BCD4C0CE9927 CRC64;
MHRTTRIKIT ELNPHLMCAL CGGYFIDATT IVECLHSFCK TCIVRYLETN KYCPMCDVQV
HKTRPLLSIR SDKTLQDIVY KLVPGLFKDE MKRRRDFYAA YPLTEVPNGS NEDRGEVLEQ
EKGALSDDEI VSLSIEFYEG ARDRDEKKGP LENGDGDKEK TGVRFLRCPA AMTVMHLAKF
LRNKMDVPSK YKVEVLYEDE PLKEYYTLMD IAYIYPWRRN GPLPLKYRVQ PACKRLTLAT
VPTPSEGTNT SGASECESVS DKAPSPATLP ATSSSLPSPA TPSHGSPSSH GPPATHPTSP
TPPSTASGAT TAANGGSLNC LQTPSSTSRG RKMTVNGAPV PPLT
