I2BP1_HUMAN
ID I2BP1_HUMAN Reviewed; 584 AA.
AC Q8IU81; Q53EL7; Q6DC95; Q9BRZ9; Q9Y4P4;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Interferon regulatory factor 2-binding protein 1;
DE Short=IRF-2-binding protein 1;
DE Short=IRF-2BP1;
DE AltName: Full=Probable E3 ubiquitin-protein ligase IRF2BP1;
DE EC=2.3.2.27;
DE AltName: Full=Probable RING-type E3 ubiquitin transferase IRF2BP1 {ECO:0000305};
GN Name=IRF2BP1;
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], FUNCTION, INTERACTION WITH IRF2, AND
RP SUBCELLULAR LOCATION.
RX PubMed=12799427; DOI=10.1093/nar/gkg431;
RA Childs K.S., Goodbourn S.;
RT "Identification of novel co-repressor molecules for interferon regulatory
RT factor-2.";
RL Nucleic Acids Res. 31:3016-3026(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-24.
RC TISSUE=Brain, Colon, Lung, 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 224-584.
RC TISSUE=Testis;
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-436, AND IDENTIFICATION BY
RP 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 FUNCTION AS E3 LIGASE, AND INTERACTION WITH JDP2.
RX PubMed=18671972; DOI=10.1016/j.febslet.2008.07.033;
RA Kimura M.;
RT "IRF2-binding protein-1 is a JDP2 ubiquitin ligase and an inhibitor of
RT ATF2-dependent transcription.";
RL FEBS Lett. 582:2833-2837(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125 AND SER-453, AND
RP IDENTIFICATION BY 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186; SER-421; SER-453 AND
RP SER-457, AND IDENTIFICATION BY 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-436, AND IDENTIFICATION BY
RP 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-66; SER-384; SER-421; SER-436
RP AND SER-453, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [12]
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-436 AND SER-453, 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-66; SER-125; SER-371;
RP SER-421; SER-436 AND SER-453, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-66; SER-421; SER-436 AND
RP SER-453, AND IDENTIFICATION BY MASS SPECTROMETRY [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 [16]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-177, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [17]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-227 AND LYS-438, AND
RP IDENTIFICATION 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).
CC -!- FUNCTION: Acts as a transcriptional corepressor in a IRF2-dependent
CC manner; this repression is not mediated by histone deacetylase
CC activities. May act as an E3 ligase towards JDP2, enhancing its
CC polyubiquitination. Represses ATF2-dependent transcriptional
CC activation. {ECO:0000269|PubMed:12799427, ECO:0000269|PubMed:18671972}.
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;
CC -!- SUBUNIT: Interacts with IRF2. Part of a corepressor complex containing
CC IRF2 and IRF2BP2. Interacts with JDP2. {ECO:0000269|PubMed:12799427,
CC ECO:0000269|PubMed:18671972}.
CC -!- INTERACTION:
CC Q8IU81; Q8WYK2: JDP2; NbExp=4; IntAct=EBI-6115514, EBI-1248415;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12799427}.
CC -!- SIMILARITY: Belongs to the IRF2BP family. {ECO:0000305}.
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DR EMBL; AY278022; AAP78943.1; -; mRNA.
DR EMBL; AK223622; BAD97342.1; -; mRNA.
DR EMBL; CH471126; EAW57396.1; -; Genomic_DNA.
DR EMBL; BC005834; AAH05834.2; -; mRNA.
DR EMBL; BC038222; AAH38222.1; -; mRNA.
DR EMBL; BC039002; AAH39002.1; -; mRNA.
DR EMBL; BC078181; AAH78181.1; -; mRNA.
DR EMBL; AL080159; CAB45750.1; -; mRNA.
DR CCDS; CCDS12678.1; -.
DR PIR; T12543; T12543.
DR RefSeq; NP_056464.1; NM_015649.2.
DR AlphaFoldDB; Q8IU81; -.
DR SMR; Q8IU81; -.
DR BioGRID; 117576; 69.
DR CORUM; Q8IU81; -.
DR IntAct; Q8IU81; 26.
DR MINT; Q8IU81; -.
DR STRING; 9606.ENSP00000307265; -.
DR GlyGen; Q8IU81; 3 sites, 2 O-linked glycans (3 sites).
DR iPTMnet; Q8IU81; -.
DR PhosphoSitePlus; Q8IU81; -.
DR BioMuta; IRF2BP1; -.
DR DMDM; 74727955; -.
DR EPD; Q8IU81; -.
DR jPOST; Q8IU81; -.
DR MassIVE; Q8IU81; -.
DR MaxQB; Q8IU81; -.
DR PaxDb; Q8IU81; -.
DR PeptideAtlas; Q8IU81; -.
DR PRIDE; Q8IU81; -.
DR ProteomicsDB; 70520; -.
DR Antibodypedia; 31408; 235 antibodies from 31 providers.
DR DNASU; 26145; -.
DR Ensembl; ENST00000302165.5; ENSP00000307265.3; ENSG00000170604.5.
DR GeneID; 26145; -.
DR KEGG; hsa:26145; -.
DR MANE-Select; ENST00000302165.5; ENSP00000307265.3; NM_015649.3; NP_056464.1.
DR UCSC; uc002pds.2; human.
DR CTD; 26145; -.
DR DisGeNET; 26145; -.
DR GeneCards; IRF2BP1; -.
DR HGNC; HGNC:21728; IRF2BP1.
DR HPA; ENSG00000170604; Low tissue specificity.
DR MIM; 615331; gene.
DR neXtProt; NX_Q8IU81; -.
DR OpenTargets; ENSG00000170604; -.
DR PharmGKB; PA134987893; -.
DR VEuPathDB; HostDB:ENSG00000170604; -.
DR eggNOG; KOG3579; Eukaryota.
DR GeneTree; ENSGT00940000162120; -.
DR HOGENOM; CLU_019307_2_0_1; -.
DR InParanoid; Q8IU81; -.
DR OMA; VEYPCGS; -.
DR OrthoDB; 1156771at2759; -.
DR PhylomeDB; Q8IU81; -.
DR TreeFam; TF317075; -.
DR PathwayCommons; Q8IU81; -.
DR SignaLink; Q8IU81; -.
DR SIGNOR; Q8IU81; -.
DR BioGRID-ORCS; 26145; 23 hits in 1120 CRISPR screens.
DR GenomeRNAi; 26145; -.
DR Pharos; Q8IU81; Tdark.
DR PRO; PR:Q8IU81; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8IU81; protein.
DR Bgee; ENSG00000170604; Expressed in olfactory bulb and 144 other tissues.
DR Genevisible; Q8IU81; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:ARUK-UCL.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:ARUK-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ARUK-UCL.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:ARUK-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 InterPro; IPR018957; Znf_C3HC4_RING-type.
DR Pfam; PF11261; IRF-2BP1_2; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Isopeptide bond; Metal-binding; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..584
FT /note="Interferon regulatory factor 2-binding protein 1"
FT /id="PRO_0000328729"
FT ZN_FING 503..550
FT /note="RING-type; degenerate"
FT REGION 60..127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 346..420
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 433..495
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 503..550
FT /note="Cys-rich"
FT COILED 197..217
FT /evidence="ECO:0000255"
FT COMPBIAS 350..373
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 66
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 125
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 177
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 421
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 436
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 457
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CROSSLNK 227
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 438
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 24
FT /note="M -> I (in dbSNP:rs11550349)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_042502"
FT CONFLICT 80
FT /note="L -> P (in Ref. 2; BAD97342)"
FT /evidence="ECO:0000305"
FT CONFLICT 250
FT /note="H -> R (in Ref. 2; BAD97342)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="R -> C (in Ref. 4; AAH78181)"
FT /evidence="ECO:0000305"
FT CONFLICT 577
FT /note="K -> E (in Ref. 2; BAD97342)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 584 AA; 61688 MW; 7E160D86C155E1D6 CRC64;
MASVQASRRQ WCYLCDLPKM PWAMVWDFSE AVCRGCVNFE GADRIELLID AARQLKRSHV
LPEGRSPGPP ALKHPATKDL AAAAAQGPQL PPPQAQPQPS GTGGGVSGQD RYDRATSSGR
LPLPSPALEY TLGSRLANGL GREEAVAEGA RRALLGSMPG LMPPGLLAAA VSGLGSRGLT
LAPGLSPARP LFGSDFEKEK QQRNADCLAE LNEAMRGRAE EWHGRPKAVR EQLLALSACA
PFNVRFKKDH GLVGRVFAFD ATARPPGYEF ELKLFTEYPC GSGNVYAGVL AVARQMFHDA
LREPGKALAS SGFKYLEYER RHGSGEWRQL GELLTDGVRS FREPAPAEAL PQQYPEPAPA
ALCGPPPRAP SRNLAPTPRR RKASPEPEGE AAGKMTTEEQ QQRHWVAPGG PYSAETPGVP
SPIAALKNVA EALGHSPKDP GGGGGPVRAG GASPAASSTA QPPTQHRLVA RNGEAEVSPT
AGAEAVSGGG SGTGATPGAP LCCTLCRERL EDTHFVQCPS VPGHKFCFPC SREFIKAQGP
AGEVYCPSGD KCPLVGSSVP WAFMQGEIAT ILAGDIKVKK ERDP
