I2BPL_HUMAN
ID I2BPL_HUMAN Reviewed; 796 AA.
AC Q9H1B7; Q8NDQ2; Q96JG2; Q9H3I7;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Probable E3 ubiquitin-protein ligase IRF2BPL {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000305|PubMed:29374064};
DE AltName: Full=Enhanced at puberty protein 1;
DE AltName: Full=Interferon regulatory factor 2-binding protein-like;
GN Name=IRF2BPL; Synonyms=C14orf4, EAP1, KIAA1865; ORFNames=My039;
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 [GENOMIC DNA], TISSUE SPECIFICITY, TRIPLET REPEAT
RP EXPANSION, AND POLYMORPHISM.
RX PubMed=11095982; DOI=10.1006/bbrc.2000.3883;
RA Rampazzo A., Pivotto F., Occhi G., Tiso N., Bortoluzzi S., Rowen L.,
RA Hood L., Nava A., Danieli G.A.;
RT "Characterization of C14orf4, a novel intronless human gene containing a
RT polyglutamine repeat, mapped to the ARVD1 critical region.";
RL Biochem. Biophys. Res. Commun. 278:766-774(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 332-796.
RC TISSUE=Fetal brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 694-796.
RC TISSUE=Fetal brain;
RA Mao Y.M., Xie Y., Zheng Z.H.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [8]
RP MUTAGENESIS OF CYS-715.
RX PubMed=17627301; DOI=10.1172/jci31752;
RA Heger S., Mastronardi C., Dissen G.A., Lomniczi A., Cabrera R., Roth C.L.,
RA Jung H., Galimi F., Sippell W., Ojeda S.R.;
RT "Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the
RT female neuroendocrine reproductive axis.";
RL J. Clin. Invest. 117:2145-2154(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-547; SER-657; SER-658;
RP SER-659 AND SER-662, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-547; SER-657; SER-659 AND
RP SER-662, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-547; SER-659 AND SER-662, AND
RP IDENTIFICATION BY 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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-69; SER-519; SER-547;
RP SER-639; SER-657; SER-659 AND SER-662, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-215; SER-519; SER-547;
RP SER-657; SER-659 AND SER-662, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-79, AND IDENTIFICATION BY MASS
RP 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 [19]
RP FUNCTION, INVOLVEMENT IN NEDAMSS, VARIANTS NEDAMSS 126-GLN--PRO-796 DEL;
RP 127-GLN--PRO-796 DEL; 172-GLU--PRO-796 DEL; 188-ARG--PRO-796 DEL; VAL-195;
RP ARG-372 AND ASN-418, AND CHARACTERIZATION OF VARIANTS NEDAMSS
RP 127-GLN--PRO-796 DEL; 172-GLU--PRO-796 DEL; 188-ARG--PRO-796 DEL; ARG-372
RP AND ASN-418.
RX PubMed=30057031; DOI=10.1016/j.ajhg.2018.07.006;
RG Program for Undiagnosed Diseases (UD-PrOZA);
RG Undiagnosed Diseases Network;
RA Marcogliese P.C., Shashi V., Spillmann R.C., Stong N., Rosenfeld J.A.,
RA Koenig M.K., Martinez-Agosto J.A., Herzog M., Chen A.H., Dickson P.I.,
RA Lin H.J., Vera M.U., Salamon N., Graham J.M. Jr., Ortiz D., Infante E.,
RA Steyaert W., Dermaut B., Poppe B., Chung H.L., Zuo Z., Lee P.T., Kanca O.,
RA Xia F., Yang Y., Smith E.C., Jasien J., Kansagra S., Spiridigliozzi G.,
RA El-Dairi M., Lark R., Riley K., Koeberl D.D., Golden-Grant K., Yamamoto S.,
RA Wangler M.F., Mirzaa G., Hemelsoet D., Lee B., Nelson S.F., Goldstein D.B.,
RA Bellen H.J., Pena L.D.M.;
RT "IRF2BPL Is Associated with Neurological Phenotypes.";
RL Am. J. Hum. Genet. 103:245-260(2018).
RN [20]
RP FUNCTION, AND INTERACTION WITH CTNNB1.
RX PubMed=29374064; DOI=10.1158/0008-5472.can-17-2403;
RA Higashimori A., Dong Y., Zhang Y., Kang W., Nakatsu G., Ng S.S.M.,
RA Arakawa T., Sung J.J.Y., Chan F.K.L., Yu J.;
RT "Forkhead Box F2 Suppresses Gastric Cancer through a Novel FOXF2-IRF2BPL-
RT beta-Catenin Signaling Axis.";
RL Cancer Res. 78:1643-1656(2018).
RN [21]
RP INVOLVEMENT IN NEDAMSS.
RX PubMed=30166628; DOI=10.1038/s41436-018-0143-0;
RA Tran Mau-Them F., Guibaud L., Duplomb L., Keren B., Lindstrom K., Marey I.,
RA Mochel F., van den Boogaard M.J., Oegema R., Nava C., Masurel A., Jouan T.,
RA Jansen F.E., Au M., Chen A.H., Cho M., Duffourd Y., Lozier E.,
RA Konovalov F., Sharkov A., Korostelev S., Urteaga B., Dickson P., Vera M.,
RA Martinez-Agosto J.A., Begemann A., Zweier M., Schmitt-Mechelke T.,
RA Rauch A., Philippe C., van Gassen K., Nelson S., Graham J.M. Jr.,
RA Friedman J., Faivre L., Lin H.J., Thauvin-Robinet C., Vitobello A.;
RT "De novo truncating variants in the intronless IRF2BPL are responsible for
RT developmental epileptic encephalopathy.";
RL Genet. Med. 21:1008-1014(2019).
RN [22]
RP STRUCTURE BY NMR OF 705-786.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the ZF-C3HC4 domain of human KIAA1865.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [23]
RP 3D-STRUCTURE MODELING OF 708-771, AND RING FINGER.
RX PubMed=17334524; DOI=10.1590/s0100-879x2006005000075;
RA Scior T., Luna F., Koch W., Sanchez-Ruiz J.F.;
RT "In silico analysis identifies a C3HC4-RING finger domain of a putative E3
RT ubiquitin-protein ligase located at the C-terminus of a polyglutamine-
RT containing protein.";
RL Braz. J. Med. Biol. Res. 40:293-299(2007).
CC -!- FUNCTION: Probable E3 ubiquitin protein ligase involved in the
CC proteasome-mediated ubiquitin-dependent degradation of target proteins
CC (PubMed:29374064). Through the degradation of CTNNB1, functions
CC downstream of FOXF2 to negatively regulate the Wnt signaling pathway
CC (PubMed:29374064). Probably plays a role in the development of the
CC central nervous system and in neuronal maintenance (Probable). Also
CC acts as a transcriptional regulator of genes controlling female
CC reproductive function. May play a role in gene transcription by
CC transactivating GNRH1 promoter and repressing PENK promoter (By
CC similarity). {ECO:0000250|UniProtKB:Q5EIC4,
CC ECO:0000269|PubMed:29374064, ECO:0000305|PubMed:17334524,
CC ECO:0000305|PubMed:29374064, ECO:0000305|PubMed:30057031}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000305|PubMed:29374064};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000305|PubMed:29374064}.
CC -!- SUBUNIT: Interacts with CTNNB1. {ECO:0000269|PubMed:29374064}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q5EIC4}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the heart, moderately in
CC skeletal muscle and pancreas, and weakly in brain, kidney, liver,
CC testis, thyroid gland and lymphocytes. {ECO:0000269|PubMed:11095982}.
CC -!- POLYMORPHISM: The poly-Gln region is polymorphic; the most frequent
CC allele contained 24 Gln. Stretches of 20-31 Gln are observed in healthy
CC individuals. {ECO:0000269|PubMed:11095982}.
CC -!- DISEASE: Neurodevelopmental disorder with regression, abnormal
CC movements, loss of speech, and seizures (NEDAMSS) [MIM:618088]: An
CC autosomal dominant disorder characterized by global developmental delay
CC or neurodevelopmental regression, hypotonia, progressive ataxia,
CC intellectual disability, seizures, and abnormal movements.
CC {ECO:0000269|PubMed:30057031, ECO:0000269|PubMed:30166628}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the IRF2BP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB47494.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; AJ277365; CAC10539.1; -; Genomic_DNA.
DR EMBL; AC007686; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB058768; BAB47494.1; ALT_SEQ; mRNA.
DR EMBL; AL832320; CAD38615.1; -; mRNA.
DR EMBL; AF063597; AAG43156.1; -; mRNA.
DR CCDS; CCDS9854.1; -.
DR PIR; JC7555; JC7555.
DR RefSeq; NP_078772.1; NM_024496.3.
DR PDB; 2CS3; NMR; -; A=705-784.
DR PDBsum; 2CS3; -.
DR AlphaFoldDB; Q9H1B7; -.
DR SMR; Q9H1B7; -.
DR BioGRID; 122101; 43.
DR CORUM; Q9H1B7; -.
DR IntAct; Q9H1B7; 11.
DR MINT; Q9H1B7; -.
DR STRING; 9606.ENSP00000238647; -.
DR GlyGen; Q9H1B7; 11 sites, 2 O-linked glycans (11 sites).
DR iPTMnet; Q9H1B7; -.
DR PhosphoSitePlus; Q9H1B7; -.
DR BioMuta; IRF2BPL; -.
DR DMDM; 34395562; -.
DR EPD; Q9H1B7; -.
DR jPOST; Q9H1B7; -.
DR MassIVE; Q9H1B7; -.
DR MaxQB; Q9H1B7; -.
DR PaxDb; Q9H1B7; -.
DR PeptideAtlas; Q9H1B7; -.
DR PRIDE; Q9H1B7; -.
DR ProteomicsDB; 80395; -.
DR Antibodypedia; 54435; 16 antibodies from 8 providers.
DR DNASU; 64207; -.
DR Ensembl; ENST00000238647.5; ENSP00000238647.3; ENSG00000119669.5.
DR GeneID; 64207; -.
DR KEGG; hsa:64207; -.
DR MANE-Select; ENST00000238647.5; ENSP00000238647.3; NM_024496.4; NP_078772.1.
DR UCSC; uc001xsy.4; human.
DR CTD; 64207; -.
DR DisGeNET; 64207; -.
DR GeneCards; IRF2BPL; -.
DR HGNC; HGNC:14282; IRF2BPL.
DR HPA; ENSG00000119669; Low tissue specificity.
DR MalaCards; IRF2BPL; -.
DR MIM; 611720; gene.
DR MIM; 618088; phenotype.
DR neXtProt; NX_Q9H1B7; -.
DR OpenTargets; ENSG00000119669; -.
DR Orphanet; 597623; IRF2BPL-related regressive neurodevelopmental disorder-dystonia-seizures syndrome.
DR PharmGKB; PA25516; -.
DR VEuPathDB; HostDB:ENSG00000119669; -.
DR eggNOG; KOG3579; Eukaryota.
DR GeneTree; ENSGT00940000162596; -.
DR HOGENOM; CLU_019307_1_0_1; -.
DR InParanoid; Q9H1B7; -.
DR OMA; WASKPKM; -.
DR OrthoDB; 1156771at2759; -.
DR PhylomeDB; Q9H1B7; -.
DR TreeFam; TF317075; -.
DR PathwayCommons; Q9H1B7; -.
DR SignaLink; Q9H1B7; -.
DR SIGNOR; Q9H1B7; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 64207; 13 hits in 1087 CRISPR screens.
DR ChiTaRS; IRF2BPL; human.
DR EvolutionaryTrace; Q9H1B7; -.
DR GeneWiki; C14orf4; -.
DR GenomeRNAi; 64207; -.
DR Pharos; Q9H1B7; Tdark.
DR PRO; PR:Q9H1B7; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9H1B7; protein.
DR Bgee; ENSG00000119669; Expressed in germinal epithelium of ovary and 190 other tissues.
DR Genevisible; Q9H1B7; HS.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:ParkinsonsUK-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0046543; P:development of secondary female sexual characteristics; ISS:ParkinsonsUK-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ParkinsonsUK-UCL.
DR GO; GO:0007399; P:nervous system development; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ParkinsonsUK-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 1.10.10.1580; -; 1.
DR InterPro; IPR044882; I2BP1/2_C3HC4-RING_sf.
DR InterPro; IPR022750; Interferon_reg_fac2-bd1_2_Znf.
DR Pfam; PF11261; IRF-2BP1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Disease variant; Epilepsy;
KW Intellectual disability; Isopeptide bond; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Triplet repeat expansion;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..796
FT /note="Probable E3 ubiquitin-protein ligase IRF2BPL"
FT /id="PRO_0000056411"
FT ZN_FING 715..762
FT /note="RING-type; degenerate"
FT REGION 174..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 515..556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 585..698
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 85..132
FT /evidence="ECO:0000255"
FT COILED 335..371
FT /evidence="ECO:0000255"
FT COMPBIAS 210..226
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 268..296
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..322
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 592..608
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 638..665
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 519
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 547
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 639
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 657
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 658
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT CROSSLNK 79
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 126..796
FT /note="Missing (in NEDAMSS)"
FT /evidence="ECO:0000269|PubMed:30057031"
FT /id="VAR_081415"
FT VARIANT 127..796
FT /note="Missing (in NEDAMSS; loss of function)"
FT /evidence="ECO:0000269|PubMed:30057031"
FT /id="VAR_081416"
FT VARIANT 172..796
FT /note="Missing (in NEDAMSS; loss of function)"
FT /evidence="ECO:0000269|PubMed:30057031"
FT /id="VAR_081417"
FT VARIANT 188..796
FT /note="Missing (in NEDAMSS; loss of function)"
FT /evidence="ECO:0000269|PubMed:30057031"
FT /id="VAR_081418"
FT VARIANT 195
FT /note="G -> V (in NEDAMSS; unknown pathological
FT significance; dbSNP:rs770422700)"
FT /evidence="ECO:0000269|PubMed:30057031"
FT /id="VAR_081419"
FT VARIANT 372
FT /note="P -> R (in NEDAMSS; unknown pathological
FT significance; no effect on function; dbSNP:rs1555377336)"
FT /evidence="ECO:0000269|PubMed:30057031"
FT /id="VAR_081420"
FT VARIANT 418
FT /note="K -> N (in NEDAMSS; loss of function;
FT dbSNP:rs201073695)"
FT /evidence="ECO:0000269|PubMed:30057031"
FT /id="VAR_081421"
FT MUTAGEN 715
FT /note="C->A: Loss of transcription activity."
FT /evidence="ECO:0000269|PubMed:17627301"
FT STRAND 716..718
FT /evidence="ECO:0007829|PDB:2CS3"
FT STRAND 727..729
FT /evidence="ECO:0007829|PDB:2CS3"
FT HELIX 740..751
FT /evidence="ECO:0007829|PDB:2CS3"
FT STRAND 752..754
FT /evidence="ECO:0007829|PDB:2CS3"
FT STRAND 767..772
FT /evidence="ECO:0007829|PDB:2CS3"
FT HELIX 777..784
FT /evidence="ECO:0007829|PDB:2CS3"
SQ SEQUENCE 796 AA; 82659 MW; DCF7898F15AD6A37 CRC64;
MSAAQVSSSR RQSCYLCDLP RMPWAMIWDF SEPVCRGCVN YEGADRIEFV IETARQLKRA
HGCFQDGRSP GPPPPVGVKT VALSAKEAAA AAAAAAAAAA AAQQQQQQQQ QQQQQQQQQQ
QQQQQQQLNH VDGSSKPAVL AAPSGLERYG LSAAAAAAAA AAAAVEQRSR FEYPPPPVSL
GSSSHTARLP NGLGGPNGFP KPTPEEGPPE LNRQSPNSSS AAASVASRRG THGGLVTGLP
NPGGGGGPQL TVPPNLLPQT LLNGPASAAV LPPPPPHALG SRGPPTPAPP GAPGGPACLG
GTPGVSATSS SASSSTSSSV AEVGVGAGGK RPGSVSSTDQ ERELKEKQRN AEALAELSES
LRNRAEEWAS KPKMVRDTLL TLAGCTPYEV RFKKDHSLLG RVFAFDAVSK PGMDYELKLF
IEYPTGSGNV YSSASGVAKQ MYQDCMKDFG RGLSSGFKYL EYEKKHGSGD WRLLGDLLPE
AVRFFKEGVP GADMLPQPYL DASCPMLPTA LVSLSRAPSA PPGTGALPPA APSGRGAAAS
LRKRKASPEP PDSAEGALKL GEEQQRQQWM ANQSEALKLT MSAGGFAAPG HAAGGPPPPP
PPLGPHSNRT TPPESAPQNG PSPMAALMSV ADTLGTAHSP KDGSSVHSTT ASARRNSSSP
VSPASVPGQR RLASRNGDLN LQVAPPPPSA HPGMDQVHPQ NIPDSPMANS GPLCCTICHE
RLEDTHFVQC PSVPSHKFCF PCSRESIKAQ GATGEVYCPS GEKCPLVGSN VPWAFMQGEI
ATILAGDVKV KKERDP
