ERPG3_HUMAN
ID ERPG3_HUMAN Reviewed; 1061 AA.
AC P0DP91;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2017, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Chimeric ERCC6-PGBD3 protein;
DE AltName: Full=Chimeric CSB-PGBD3 protein;
GN Name=ERCC6 {ECO:0000312|HGNC:HGNC:3438};
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 GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LYS-850.
RC TISSUE=Testis;
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 [3]
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158, 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [6]
RP ALTERNATIVE SPLICING.
RX PubMed=18369450; DOI=10.1371/journal.pgen.1000031;
RA Newman J.C., Bailey A.D., Fan H.Y., Pavelitz T., Weiner A.M.;
RT "An abundant evolutionarily conserved CSB-PiggyBac fusion protein expressed
RT in Cockayne syndrome.";
RL PLoS Genet. 4:E1000031-E1000031(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158; SER-429 AND SER-430, AND
RP 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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158, AND IDENTIFICATION BY
RP 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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-429 AND SER-430, 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 [10]
RP FUNCTION.
RX PubMed=22483866; DOI=10.1016/j.dnarep.2012.02.004;
RA Bailey A.D., Gray L.T., Pavelitz T., Newman J.C., Horibata K., Tanaka K.,
RA Weiner A.M.;
RT "The conserved Cockayne syndrome B-piggyBac fusion protein (CSB-PGBD3)
RT affects DNA repair and induces both interferon-like and innate antiviral
RT responses in CSB-null cells.";
RL DNA Repair 11:488-501(2012).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158 AND SER-554, AND
RP IDENTIFICATION BY MASS 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 [12]
RP INVOLVEMENT IN POF11, VARIANTS POF11 ASP-746 AND ILE-1056, CHARACTERIZATION
RP OF VARIANTS POF11 ASP-746 AND ILE-1056, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=26218421; DOI=10.1371/journal.pgen.1005419;
RA Qin Y., Guo T., Li G., Tang T.S., Zhao S., Jiao X., Gong J., Gao F.,
RA Guo C., Simpson J.L., Chen Z.J.;
RT "CSB-PGBD3 mutations cause premature ovarian failure.";
RL PLoS Genet. 11:E1005419-E1005419(2015).
RN [13]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-255, 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).
CC -!- FUNCTION: Involved in repair of DNA damage following UV irradiation,
CC acting either in the absence of ERCC6 or synergistically with ERCC6.
CC Involved in the regulation of gene expression. In the absence of ERCC6,
CC induces the expression of genes characteristic of interferon-like
CC antiviral responses. This response is almost completely suppressed in
CC the presence of ERCC6. In the presence of ERCC6, regulates the
CC expression of genes involved in metabolism regulation, including IGFBP5
CC and IGFBP7. In vitro binds to PGBD3-related transposable elements,
CC called MER85s; these non-autonomous 140 bp elements are characterized
CC by the presence of PGBD3 terminal inverted repeats and the absence of
CC internal transposase ORF. {ECO:0000269|PubMed:22483866}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26218421}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=CSB-PGBD3 {ECO:0000303|PubMed:18369450};
CC IsoId=P0DP91-1, Q03468-2;
CC Sequence=Displayed;
CC Name=CSB;
CC IsoId=Q03468-1; Sequence=External;
CC Name=PGBD3;
CC IsoId=Q8N328-1; Sequence=External;
CC -!- TISSUE SPECIFICITY: Expressed in heart and oocytes, but not in
CC granulosa cells (at protein level). {ECO:0000269|PubMed:26218421}.
CC -!- DISEASE: Premature ovarian failure 11 (POF11) [MIM:616946]: An ovarian
CC disorder defined as the cessation of ovarian function under the age of
CC 40 years. It is characterized by oligomenorrhea or amenorrhea, in the
CC presence of elevated levels of serum gonadotropins and low estradiol.
CC {ECO:0000269|PubMed:26218421}. Note=The protein represented in this
CC entry is involved in disease pathogenesis. Disease-causing variants
CC affect isoform CSB-PGBD3, which is a chimeric protein between ERCC6 N-
CC terminus and the entire PGBD3 sequence. {ECO:0000269|PubMed:26218421}.
CC -!- MISCELLANEOUS: [Isoform CSB-PGBD3]: Produced by an alternative splicing
CC event that joins the first 5 exons of ERCC6 gene in frame to the entire
CC PGBD3 coding region, which is located within ERCC6 intron 5. The
CC resulting chimeric protein consists of the N-terminal 465 residues of
CC ERCC6 tethered to the entire PGBD3 sequence.
CC {ECO:0000269|PubMed:18369450}.
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DR EMBL; AL138760; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC034479; AAH34479.1; -; mRNA.
DR CCDS; CCDS60529.1; -.
DR RefSeq; NP_001263987.1; NM_001277058.1. [P0DP91-1]
DR RefSeq; NP_001263988.1; NM_001277059.1. [P0DP91-1]
DR AlphaFoldDB; P0DP91; -.
DR SMR; P0DP91; -.
DR IntAct; P0DP91; 2.
DR STRING; 9606.ENSP00000423550; -.
DR iPTMnet; P0DP91; -.
DR PhosphoSitePlus; P0DP91; -.
DR BioMuta; CSB-PGBD3; -.
DR jPOST; P0DP91; -.
DR MassIVE; P0DP91; -.
DR PeptideAtlas; P0DP91; -.
DR PRIDE; P0DP91; -.
DR Antibodypedia; 34972; 412 antibodies from 35 providers.
DR DNASU; 2074; -.
DR Ensembl; ENST00000447839.7; ENSP00000387966.2; ENSG00000225830.16. [P0DP91-1]
DR Ensembl; ENST00000515869.1; ENSP00000423550.1; ENSG00000225830.16. [P0DP91-1]
DR GeneID; 2074; -.
DR CTD; 2074; -.
DR DisGeNET; 2074; -.
DR GeneCards; ERCC6; -.
DR GeneReviews; ERCC6; -.
DR HGNC; HGNC:3438; ERCC6.
DR HPA; ENSG00000225830; Low tissue specificity.
DR MalaCards; ERCC6; -.
DR MIM; 609413; gene.
DR MIM; 616946; phenotype.
DR neXtProt; NX_P0DP91; -.
DR OpenTargets; ENSG00000225830; -.
DR VEuPathDB; HostDB:ENSG00000225830; -.
DR eggNOG; KOG0387; Eukaryota.
DR GeneTree; ENSGT00940000158057; -.
DR PathwayCommons; P0DP91; -.
DR SignaLink; P0DP91; -.
DR Pharos; P0DP91; Tbio.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P0DP91; protein.
DR Bgee; ENSG00000225830; Expressed in oocyte and 175 other tissues.
DR ExpressionAtlas; P0DP91; baseline and differential.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0033141; P:positive regulation of peptidyl-serine phosphorylation of STAT protein; IMP:UniProtKB.
DR InterPro; IPR029526; PGBD.
DR Pfam; PF13843; DDE_Tnp_1_7; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Isopeptide bond; Nucleus;
KW Phosphoprotein; Premature ovarian failure; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..1061
FT /note="Chimeric ERCC6-PGBD3 protein"
FT /id="PRO_0000441747"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 287..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 344..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 494..521
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 537..573
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 363..396
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 405..422
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 447..465
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 429
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 554
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 255
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 746
FT /note="G -> D (in POF11; weaker cellular response to DNA
FT damage as indicated by delayed recruitment of mutant
FT protein to DNA damaged sites, compared to ERCC6 isoform 1;
FT no effect on interaction with RNA polymerase II either
FT after UV or H(2)O(2) damage)"
FT /evidence="ECO:0000269|PubMed:26218421"
FT /id="VAR_079009"
FT VARIANT 850
FT /note="R -> K (in dbSNP:rs4253072)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_079010"
FT VARIANT 1056
FT /note="V -> I (in POF11; weaker cellular response to DNA
FT damage as indicated by delayed recruitment of mutant
FT protein to DNA damaged sites, compared to ERCC6 isoform 1;
FT no effect on interaction with RNA polymerase II either
FT after UV or H(2)O(2) damage)"
FT /evidence="ECO:0000269|PubMed:26218421"
FT /id="VAR_079011"
FT CONFLICT 346
FT /note="V -> A (in Ref. 2; AAH34479)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1061 AA; 119487 MW; 542A37356E38C376 CRC64;
MPNEGIPHSS QTQEQDCLQS QPVSNNEEMA IKQESGGDGE VEEYLSFRSV GDGLSTSAVG
CASAAPRRGP ALLHIDRHQI QAVEPSAQAL ELQGLGVDVY DQDVLEQGVL QQVDNAIHEA
SRASQLVDVE KEYRSVLDDL TSCTTSLRQI NKIIEQLSPQ AATSRDINRK LDSVKRQKYN
KEQQLKKITA KQKHLQAILG GAEVKIELDH ASLEEDAEPG PSSLGSMLMP VQETAWEELI
RTGQMTPFGT QIPQKQEKKP RKIMLNEASG FEKYLADQAK LSFERKKQGC NKRAARKAPA
PVTPPAPVQN KNKPNKKARV LSKKEERLKK HIKKLQKRAL QFQGKVGLPK ARRPWESDMR
PEAEGDSEGE ESEYFPTEEE EEEEDDEVEG AEADLSGDGT DYELKPLPKG GKRQKKVPVQ
EIDDDFFPSS GEEAEAASVG EGGGGGRKVG RYRDDGDEDY YKQRLSPKMP RTLSLHEITD
LLETDDSIEA SAIVIQPPEN ATAPVSDEES GDEEGGTINN LPGSLLHTAA YLIQDGSDAE
SDSDDPSYAP KDDSPDEVPS TFTVQQPPPS RRRKMTKILC KWKKADLTVQ PVAGRVTAPP
NDFFTVMRTP TEILELFLDD EVIELIVKYS NLYACSKGVH LGLTSSEFKC FLGIIFLSGY
VSVPRRRMFW EQRTDVHNVL VSAAMRRDRF ETIFSNLHVA DNANLDPVDK FSKLRPLISK
LNERCMKFVP NETYFSFDEF MVPYFGRHGC KQFIRGKPIR FGYKFWCGAT CLGYICWFQP
YQGKNPNTKH EEYGVGASLV LQFSEALTEA HPGQYHFVFN NFFTSIALLD KLSSMGHQAT
GTVRKDHIDR VPLESDVALK KKERGTFDYR IDGKGNIVCR WNDNSVVTVA SSGAGIHPLC
LVSRYSQKLK KKIQVQQPNM IKVYNQFMGG VDRADENIDK YRASIRGKKW YSSPLLFCFE
LVLQNAWQLH KTYDEKPVDF LEFRRRVVCH YLETHGHPPE PGQKGRPQKR NIDSRYDGIN
HVIVKQGKQT RCAECHKNTT FRCEKCDVAL HVKCSVEYHT E
