ID   REPA_BPPHS              Reviewed;         513 AA.
AC   P03631;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   03-AUG-2022, entry version 108.
DE   RecName: Full=Replication-associated protein A;
DE            EC=3.1.21.-;
DE            EC=6.5.1.1;
DE   AltName: Full=RepA;
GN   Name=A;
OS   Enterobacteria phage phiX174 (Isolate Sanger) (Bacteriophage phi-X174).
OC   Viruses; Monodnaviria; Sangervirae; Phixviricota; Malgrandaviricetes;
OC   Petitvirales; Microviridae; Bullavirinae; Sinsheimervirus.
OX   NCBI_TaxID=1217068;
OH   NCBI_TaxID=498388; Escherichia coli C.
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=870828; DOI=10.1038/265687a0;
RA   Sanger F., Air G.M., Barrell B.G., Brown N.L., Coulson A.R., Fiddes J.C.,
RA   Hutchison C.A. III, Slocombe P.M., Smith M.;
RT   "Nucleotide sequence of bacteriophage phi X174 DNA.";
RL   Nature 265:687-695(1977).
RN   [2]
RP   SEQUENCE REVISION.
RX   PubMed=731693; DOI=10.1016/0022-2836(78)90346-7;
RA   Sanger F., Coulson A.R., Friedmann T., Air G.M., Barrell B.G., Brown N.L.,
RA   Fiddes J.C., Hutchison C.A. III, Slocombe P.M., Smith M.;
RT   "The nucleotide sequence of bacteriophage phiX174.";
RL   J. Mol. Biol. 125:225-246(1978).
RN   [3]
RP   FUNCTION OF A AND A*.
RX   PubMed=158588; DOI=10.1016/s0021-9258(19)83533-0;
RA   Ikeda J., Yudelevich A., Shimamoto N., Hurwitz J.;
RT   "Role of polymeric forms of the bacteriophage phi X174 coded gene A protein
RT   in phi XRFI DNA cleavage.";
RL   J. Biol. Chem. 254:9416-9428(1979).
RN   [4]
RP   FUNCTION OF A*.
RX   PubMed=6454113; DOI=10.1093/nar/9.8.1991;
RA   Eisenberg S., Ascarelli R.;
RT   "The A* protein of phi X174 is an inhibitor of DNA replication.";
RL   Nucleic Acids Res. 9:1991-2002(1981).
RN   [5]
RP   ACTIVE SITES TYR-343 AND TYR-347.
RX   PubMed=2940511; DOI=10.1093/nar/14.10.4229;
RA   van Mansfield A.D.M., van Teeffelen H.A.A.M., Baas P.D., Jansz H.S.;
RT   "Two juxtaposed tyrosyl-OH groups participate in phi X174 gene A protein
RT   catalysed cleavage and ligation of DNA.";
RL   Nucleic Acids Res. 14:4229-4238(1986).
RN   [6]
RP   FUNCTION, AND MUTAGENESIS OF TYR-343 AND TYR-347.
RX   PubMed=8226920; DOI=10.1016/s0021-9258(20)80460-8;
RA   Hanai R., Wang J.C.;
RT   "The mechanism of sequence-specific DNA cleavage and strand transfer by phi
RT   X174 gene A* protein.";
RL   J. Biol. Chem. 268:23830-23836(1993).
CC   -!- FUNCTION: Plays an essential role in viral DNA replication. Binds the
CC       origin of replication and cleaves the dsDNA replicative form I (RFI)
CC       and becomes covalently bound to it via phosphotyrosine bond, generating
CC       the dsDNA replicative form II (RFII). In turn, viral DNA replication
CC       initiates in the presence of host Rep and DNA polymerase III at the 3'-
CC       OH of the cleavage site. After one round of rolling circle synthesis,
CC       protein A is linked to the newly synthesized ssDNA and joins the ends
CC       of the displaced strand to generate a circular single-stranded molecule
CC       ready to be packed into a virion.
CC   -!- FUNCTION: The A* protein binds to double-stranded DNA and prevents
CC       hydrolysis by nucleases. Additionally, A* is an inhibitor of DNA
CC       replication and may have a role in the transition from semiconservative
CC       replicative form DNA replication to single-stranded DNA synthesis in
CC       the life cycle.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-
CC         (deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP +
CC         diphosphate.; EC=6.5.1.1;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=A;
CC         IsoId=P03631-1; Sequence=Displayed;
CC       Name=A*;
CC         IsoId=P03631-2; Sequence=VSP_018674;
CC   -!- SIMILARITY: Belongs to the microviridae Rep protein family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA32571.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; J02482; AAA32570.1; -; Genomic_DNA.
DR   EMBL; J02482; AAA32571.1; ALT_INIT; Genomic_DNA.
DR   PIR; A04239; ZABPF4.
DR   Proteomes; UP000005893; Genome.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0003910; F:DNA ligase (ATP) activity; IEA:UniProtKB-EC.
DR   GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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   InterPro; IPR008766; Replication_gene_A.
DR   Pfam; PF05840; Phage_GPA; 1.
PE   1: Evidence at protein level;
KW   Alternative initiation; ATP-binding; DNA replication; DNA-binding;
KW   Endonuclease; Hydrolase; Ligase; Metal-binding; Nuclease;
KW   Nucleotide-binding; Reference proteome; Viral DNA replication; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..513
FT                   /note="Replication-associated protein A"
FT                   /id="PRO_0000003317"
FT   ZN_FING         246..268
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        343
FT                   /note="O-(5'-phospho-DNA)-tyrosine intermediate"
FT                   /evidence="ECO:0000269|PubMed:2940511"
FT   ACT_SITE        347
FT                   /note="O-(5'-phospho-DNA)-tyrosine intermediate"
FT                   /evidence="ECO:0000269|PubMed:2940511"
FT   VAR_SEQ         1..172
FT                   /note="Missing (in isoform A*)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_018674"
FT   MUTAGEN         343
FT                   /note="Y->F: Completely abolishes phage viability."
FT                   /evidence="ECO:0000269|PubMed:8226920"
FT   MUTAGEN         347
FT                   /note="Y->F: Completely abolishes phage viability."
FT                   /evidence="ECO:0000269|PubMed:8226920"
SQ   SEQUENCE   513 AA;  58719 MW;  EF2D4DC9E3BC8072 CRC64;
     MVRSYYPSEC HADYFDFERI EALKPAIEAC GISTLSQSPM LGFHKQMDNR IKLLEEILSF
     RMQGVEFDNG DMYVDGHKAA SDVRDEFVSV TEKLMDELAQ CYNVLPQLDI NNTIDHRPEG
     DEKWFLENEK TVTQFCRKLA AERPLKDIRD EYNYPKKKGI KDECSRLLEA STMKSRRGFA
     IQRLMNAMRQ AHADGWFIVF DTLTLADDRL EAFYDNPNAL RDYFRDIGRM VLAAEGRKAN
     DSHADCYQYF CVPEYGTANG RLHFHAVHFM RTLPTGSVDP NFGRRVRNRR QLNSLQNTWP
     YGYSMPIAVR YTQDAFSRSG WLWPVDAKGE PLKATSYMAV GFYVAKYVNK KSDMDLAAKG
     LGAKEWNNSL KTKLSLLPKK LFRIRMSRNF GMKMLTMTNL STECLIQLTK LGYDATPFNQ
     ILKQNAKREM RLRLGKVTVA DVLAAQPVTT NLLKFMRASI KMIGVSNLQS FIASMTQKLT
     LSDISDESKN YLDKAGITTA CLRIKSKWTA GGK