ID   REP_PCV2                Reviewed;         314 AA.
AC   Q8BB16; Q8BB13; Q8BB14; Q8BB15;
DT   25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   24-JAN-2024, entry version 93.
DE   RecName: Full=Replication-associated protein;
DE            EC=2.7.7.-;
DE            EC=3.1.21.-;
DE            EC=3.6.1.-;
DE   AltName: Full=ATP-dependent helicase Rep;
DE   AltName: Full=RepP;
GN   Name=Rep; ORFNames=ORF1;
OS   Porcine circovirus 2 (PCV2).
OC   Viruses; Monodnaviria; Shotokuvirae; Cressdnaviricota; Arfiviricetes;
OC   Cirlivirales; Circoviridae; Circovirus; Circovirus porcine2.
OX   NCBI_TaxID=85708;
OH   NCBI_TaxID=9823; Sus scrofa (Pig).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS REP; REP'; REP3A; REP3B AND
RP   REP3C), AND ALTERNATIVE PROMOTER USAGE.
RC   STRAIN=Isolate PCV/688;
RX   PubMed=12504550; DOI=10.1006/viro.2002.1733;
RA   Cheung A.K.;
RT   "Transcriptional analysis of porcine circovirus type 2.";
RL   Virology 305:168-180(2003).
RN   [2]
RP   FUNCTION, MUTAGENESIS OF 179-GLY-LYS-180, AND ALTERNATIVE SPLICING.
RC   STRAIN=Isolate PCV/688;
RX   PubMed=12954212; DOI=10.1016/s0042-6822(03)00373-8;
RA   Cheung A.K.;
RT   "The essential and nonessential transcription units for viral protein
RT   synthesis and DNA replication of porcine circovirus type 2.";
RL   Virology 313:452-459(2003).
RN   [3]
RP   SUBCELLULAR LOCATION, AND NUCLEAR LOCALIZATION SIGNAL.
RX   PubMed=19150331; DOI=10.1016/j.bbrc.2009.01.001;
RA   Lin W.-L., Chien M.-S., Du Y.-W., Wu P.-C., Huang C.;
RT   "The N-terminus of porcine circovirus type 2 replication protein is
RT   required for nuclear localization and ori binding activities.";
RL   Biochem. Biophys. Res. Commun. 379:1066-1071(2009).
RN   [4]
RP   REVIEW.
RX   PubMed=25011695; DOI=10.1007/s11262-014-1099-z;
RA   Lv Q.Z., Guo K.K., Zhang Y.M.;
RT   "Current understanding of genomic DNA of porcine circovirus type 2.";
RL   Virus Genes 49:1-10(2014).
RN   [5]
RP   FUNCTION.
RX   PubMed=25768890; DOI=10.1016/j.virol.2015.01.004;
RA   Cheung A.K.;
RT   "Specific functions of the Rep and Rep' proteins of porcine circovirus
RT   during copy-release and rolling-circle DNA replication.";
RL   Virology 481:43-50(2015).
RN   [6]
RP   STRUCTURE BY NMR OF 1-116, COFACTOR, AND CHARACTERIZATION.
RX   PubMed=17275023; DOI=10.1016/j.jmb.2007.01.002;
RA   Vega-Rocha S., Byeon I.-J.L., Gronenborn B., Gronenborn A.M.,
RA   Campos-Olivas R.;
RT   "Solution structure, divalent metal and DNA binding of the endonuclease
RT   domain from the replication initiation protein from porcine circovirus 2.";
RL   J. Mol. Biol. 367:473-487(2007).
CC   -!- FUNCTION: Essential for the replication of viral ssDNA. The closed
CC       circular ssDNA genome is first converted to a superhelical dsDNA. Rep
CC       and/or Rep' binds a specific hairpin at the genome origin of
CC       replication. Introduces an endonucleolytic nick within the conserved
CC       sequence 5'-AGTATTAC-3' in the intergenic region of the genome, thereby
CC       initiating the rolling circle replication (RCR). Following cleavage,
CC       binds covalently to the 5'-phosphate of DNA as a tyrosyl ester. The
CC       cleavage gives rise to a free 3'-OH that serves as a primer for the
CC       cellular DNA polymerase. The polymerase synthesizes the (+) strand DNA
CC       by rolling circle mechanism. After one round of replication, a Rep-
CC       catalyzed nucleotidyl transfer reaction releases a circular single-
CC       stranded virus genome, thereby terminating the replication. Displays
CC       origin-specific DNA cleavage, and nucleotidyl transferase.
CC       {ECO:0000269|PubMed:12954212, ECO:0000269|PubMed:25768890}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000305|PubMed:17275023};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000305|PubMed:17275023};
CC       Note=Divalent metal cations, possibly Mg(2+) or Mn(2+).
CC       {ECO:0000305|PubMed:17275023};
CC   -!- SUBUNIT: Interacts with the capsid protein; this interaction relocates
CC       Rep into the nucleus. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:19150331}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative promoter usage, Alternative splicing; Named isoforms=10;
CC       Name=Rep;
CC         IsoId=Q8BB16-1; Sequence=Displayed;
CC       Name=Rep';
CC         IsoId=Q8BB16-2; Sequence=VSP_015884, VSP_015885;
CC       Name=NS462;
CC         IsoId=Q8BB12-2; Sequence=External;
CC       Name=NS642;
CC         IsoId=Q8BB12-3; Sequence=External;
CC       Name=NS0;
CC         IsoId=Q8BB12-1; Sequence=External;
CC       Name=NS515;
CC         IsoId=Q8BB16-6; Sequence=Not described;
CC       Name=NS672;
CC         IsoId=Q8BB16-7; Sequence=Not described;
CC       Name=Rep3a;
CC         IsoId=Q8BB16-3; Sequence=VSP_015883;
CC       Name=Rep3b;
CC         IsoId=Q8BB16-4; Sequence=VSP_015882;
CC       Name=Rep3c;
CC         IsoId=Q8BB16-5; Sequence=Not described;
CC   -!- DOMAIN: There are 3 rolling circle replication (RCR) motifs. RCR-2 is
CC       probably involved in metal coordination. RCR-3 is required for
CC       phosphodiester bond cleavage for initiation of RCR.
CC   -!- MISCELLANEOUS: [Isoform Rep]: Produced by alternative promoter usage.
CC       {ECO:0000305|PubMed:12504550}.
CC   -!- MISCELLANEOUS: [Isoform Rep']: Produced by alternative splicing of
CC       isoform Rep. {ECO:0000305|PubMed:12504550}.
CC   -!- MISCELLANEOUS: [Isoform NS515]: Produced by alternative promoter usage.
CC       {ECO:0000305|PubMed:12504550}.
CC   -!- MISCELLANEOUS: [Isoform NS672]: Produced by alternative promoter usage.
CC       {ECO:0000305|PubMed:12504550}.
CC   -!- MISCELLANEOUS: [Isoform Rep3a]: Produced by alternative splicing of
CC       isoform Rep. {ECO:0000305|PubMed:12504550}.
CC   -!- MISCELLANEOUS: [Isoform Rep3b]: Produced by alternative splicing of
CC       isoform Rep. {ECO:0000305|PubMed:12504550}.
CC   -!- MISCELLANEOUS: [Isoform Rep3c]: Produced by alternative splicing of
CC       isoform Rep. {ECO:0000305|PubMed:12504550}.
CC   -!- SIMILARITY: Belongs to the nanoviruses/circoviruses replication-
CC       associated protein family. {ECO:0000305}.
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DR   EMBL; AY094619; AAM21844.1; -; Genomic_DNA.
DR   EMBL; AY094619; AAM21845.1; -; Genomic_DNA.
DR   EMBL; AY094619; AAM21846.1; -; Genomic_DNA.
DR   EMBL; AY094619; AAM21847.1; -; Genomic_DNA.
DR   PDB; 2HW0; NMR; -; A=2-116.
DR   PDB; 6WDZ; X-ray; 2.03 A; A/D/G=2-116.
DR   PDB; 8H56; X-ray; 2.33 A; A/B=1-129.
DR   PDBsum; 2HW0; -.
DR   PDBsum; 6WDZ; -.
DR   PDBsum; 8H56; -.
DR   BMRB; Q8BB16; -.
DR   SMR; Q8BB16; -.
DR   EvolutionaryTrace; Q8BB16; -.
DR   Proteomes; UP000000470; Genome.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0016888; F:endodeoxyribonuclease activity, producing 5'-phosphomonoesters; IEA:InterPro.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0016779; F:nucleotidyltransferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR   GO; GO:0003724; F:RNA helicase activity; IEA:InterPro.
DR   GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR   GO; GO:0039684; P:rolling circle single-stranded viral DNA replication; IDA:UniProtKB.
DR   Gene3D; 3.40.1310.20; -; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR000605; Helicase_SF3_ssDNA/RNA_vir.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR003365; Viral_rep_N.
DR   Pfam; PF00910; RNA_helicase; 1.
DR   Pfam; PF02407; Viral_Rep; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   PROSITE; PS52020; CRESS_DNA_REP; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative promoter usage; Alternative splicing;
KW   ATP-binding; Covalent protein-DNA linkage; DNA replication; DNA-binding;
KW   Endonuclease; Helicase; Host nucleus; Hydrolase; Metal-binding;
KW   Multifunctional enzyme; Nuclease; Nucleotide-binding;
KW   Nucleotidyltransferase; Reference proteome; Transferase.
FT   CHAIN           1..314
FT                   /note="Replication-associated protein"
FT                   /id="PRO_0000133089"
FT   DOMAIN          11..110
FT                   /note="CRESS-DNA virus Rep endonuclease"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01364"
FT   REGION          1..29
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           4..18
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000269|PubMed:19150331"
FT   MOTIF           18..21
FT                   /note="RCR-1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01364"
FT   MOTIF           57..59
FT                   /note="RCR-2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01364"
FT   MOTIF           96..99
FT                   /note="RCR-3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01364"
FT   ACT_SITE        96
FT                   /note="For DNA cleavage activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01364"
FT   BINDING         48
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000255"
FT   BINDING         57
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000255"
FT   BINDING         100
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000255"
FT   BINDING         174..181
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P27260"
FT   VAR_SEQ         16..254
FT                   /note="Missing (in isoform Rep3b)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_015882"
FT   VAR_SEQ         16..249
FT                   /note="Missing (in isoform Rep3a)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_015883"
FT   VAR_SEQ         123..178
FT                   /note="VSTLLESGSLVTVAEQHPVTFVRNFRGLAELLKVSGKMQKRDWKTNVHVIVG
FT                   PPGC -> YSDYQQSDPVGMVLLNCCPSCRSSLSEDYFLGILEECYRTIHGGRGPVRHP
FT                   FPPMP (in isoform Rep')"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_015884"
FT   VAR_SEQ         179..314
FT                   /note="Missing (in isoform Rep')"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_015885"
FT   MUTAGEN         179..180
FT                   /note="GK->DI: Complete loss of viral DNA synthesis."
FT                   /evidence="ECO:0000269|PubMed:12954212"
FT   STRAND          8..11
FT                   /evidence="ECO:0007829|PDB:2HW0"
FT   STRAND          14..23
FT                   /evidence="ECO:0007829|PDB:6WDZ"
FT   HELIX           26..33
FT                   /evidence="ECO:0007829|PDB:6WDZ"
FT   HELIX           37..39
FT                   /evidence="ECO:0007829|PDB:6WDZ"
FT   STRAND          40..48
FT                   /evidence="ECO:0007829|PDB:6WDZ"
FT   STRAND          57..68
FT                   /evidence="ECO:0007829|PDB:6WDZ"
FT   HELIX           70..77
FT                   /evidence="ECO:0007829|PDB:6WDZ"
FT   TURN            78..80
FT                   /evidence="ECO:0007829|PDB:2HW0"
FT   STRAND          82..85
FT                   /evidence="ECO:0007829|PDB:6WDZ"
FT   HELIX           90..98
FT                   /evidence="ECO:0007829|PDB:6WDZ"
FT   STRAND          103..108
FT                   /evidence="ECO:0007829|PDB:6WDZ"
FT   HELIX           123..125
FT                   /evidence="ECO:0007829|PDB:8H56"
SQ   SEQUENCE   314 AA;  35762 MW;  3FE9D85F2CD656FC CRC64;
     MPSKKNGRSG PQPHKRWVFT LNNPSEDERK KIREPPISLF DYFIVGEEGN EEGRTPHLQG
     FANFVKKQTF NKVKWYLGAR CHIEKAKGTD QQNKEYCSKE GNLLIECGAP RSQGQRSDLS
     TAVSTLLESG SLVTVAEQHP VTFVRNFRGL AELLKVSGKM QKRDWKTNVH VIVGPPGCGK
     SKWAANFADP ETTYWKPPRN KWWDGYHGEE VVVIDDFYGW LPWDDLLRLC DRYPLTVETK
     GGTVPFLARS ILITSNQTPL EWYSSTAVPA VEALYRRITS LVFWKNATEQ STEEGGQFVT
     LSPPCPEFPY EINY
//