REP78_AAV2S
ID REP78_AAV2S Reviewed; 621 AA.
AC Q89268; O56651;
DT 14-MAY-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Protein Rep78;
GN Name=Rep78;
OS Adeno-associated virus 2 (isolate Srivastava/1982) (AAV-2).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Quintoviricetes;
OC Piccovirales; Parvoviridae; Parvovirinae; Dependoparvovirus.
OX NCBI_TaxID=648242;
OH NCBI_TaxID=40674; Mammalia.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6300419; DOI=10.1128/jvi.45.2.555-564.1983;
RA Srivastava A., Lusby E.W., Berns K.I.;
RT "Nucleotide sequence and organization of the adeno-associated virus 2
RT genome.";
RL J. Virol. 45:555-564(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7996133; DOI=10.1099/0022-1317-75-12-3385;
RA Ruffing M., Heid H., Kleinschmidt J.A.;
RT "Mutations in the carboxy terminus of adeno-associated virus 2 capsid
RT proteins affect viral infectivity: lack of an RGD integrin-binding motif.";
RL J. Gen. Virol. 75:3385-3392(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Berns K.I., Bohenzky R.A., Cassinotti P., Colvin D., Donahue B.A., Dull T.,
RA Horer M., Kleinschmidt J.A., Ruffing M., Snyder R.O., Tratschin J.-D.,
RA Weitz M.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=1370086; DOI=10.1128/jvi.66.1.317-324.1992;
RA Hunter L.A., Samulski R.J.;
RT "Colocalization of adeno-associated virus Rep and capsid proteins in the
RT nuclei of infected cells.";
RL J. Virol. 66:317-324(1992).
RN [5]
RP SUBUNIT.
RX PubMed=9151837; DOI=10.1128/jvi.71.6.4461-4471.1997;
RA Smith R.H., Spano A.J., Kotin R.M.;
RT "The Rep78 gene product of adeno-associated virus (AAV) self-associates to
RT form a hexameric complex in the presence of AAV ori sequences.";
RL J. Virol. 71:4461-4471(1997).
RN [6]
RP INTERACTION WITH HOST PRKX.
RX PubMed=9742109; DOI=10.1128/mcb.18.10.5921;
RA Chiorini J.A., Zimmermann B., Yang L., Smith R.H., Ahearn A., Herberg F.,
RA Kotin R.M.;
RT "Inhibition of PrKX, a novel protein kinase, and the cyclic AMP-dependent
RT protein kinase PKA by the regulatory proteins of adeno-associated virus
RT type 2.";
RL Mol. Cell. Biol. 18:5921-5929(1998).
RN [7]
RP INTERACTION WITH HOST TBP.
RX PubMed=9614873; DOI=10.1006/viro.1998.9144;
RA Hermonat P.L., Santin A.D., Batchu R.B., Zhan D.;
RT "The adeno-associated virus Rep78 major regulatory protein binds the
RT cellular TATA-binding protein in vitro and in vivo.";
RL Virology 245:120-127(1998).
RN [8]
RP INTERACTION WITH HOST SUB1/PC4.
RX PubMed=9847329; DOI=10.1128/jvi.73.1.260-269.1999;
RA Weger S., Wendland M., Kleinschmidt J.A., Heilbronn R.;
RT "The adeno-associated virus type 2 regulatory proteins rep78 and rep68
RT interact with the transcriptional coactivator PC4.";
RL J. Virol. 73:260-269(1999).
RN [9]
RP FUNCTION IN HOST CELL CYCLE ARREST.
RX PubMed=10944118; DOI=10.1093/emboj/19.16.4351;
RA Saudan P., Vlach J., Beard P.;
RT "Inhibition of S-phase progression by adeno-associated virus Rep78 protein
RT is mediated by hypophosphorylated pRb.";
RL EMBO J. 19:4351-4361(2000).
RN [10]
RP INTERACTION WITH HOST TOPORS.
RX PubMed=11842245; DOI=10.1099/0022-1317-83-3-511;
RA Weger S., Hammer E., Heilbronn R.;
RT "Topors, a p53 and topoisomerase I binding protein, interacts with the
RT adeno-associated virus (AAV-2) Rep78/68 proteins and enhances AAV-2 gene
RT expression.";
RL J. Gen. Virol. 83:511-516(2002).
CC -!- FUNCTION: Plays an essential role in the initiation of viral DNA
CC synthesis. Binds specifically to an inverted terminal repeat element
CC (ITR) on the 3' and 5' ends of the viral DNA, where it cleaves a site
CC specifically to generate a priming site for initiation of the synthesis
CC of a complementary strand. Also plays a role as transcriptional
CC regulator, DNA helicase and as key factors in site-specific integration
CC of the viral genome. Regulates host PKA activity by interacting with
CC host PRKX as a mechanism of interfering with helper virus propagation
CC and promoting its own replication. Inhibits the host cell cycle G1/S, S
CC and G2/M transitions. These arrests may provide essential cellular
CC factors for viral DNA replication. {ECO:0000269|PubMed:10944118}.
CC -!- SUBUNIT: Hexamer when associated with the viral DNA ori sequence.
CC Interacts with host PRKX. Interacts with host TOPORS. Interacts with
CC host TBP AND SUB1/PC4; these interactions play important roles in
CC transcriptional regulation. {ECO:0000269|PubMed:11842245,
CC ECO:0000269|PubMed:9151837, ECO:0000269|PubMed:9614873,
CC ECO:0000269|PubMed:9742109, ECO:0000269|PubMed:9847329}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:1370086}.
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DR EMBL; J01901; AAA42374.1; -; Genomic_DNA.
DR EMBL; AF043303; AAC03775.1; -; Genomic_DNA.
DR RefSeq; YP_680423.1; NC_001401.2.
DR PDB; 5BYG; X-ray; 2.50 A; A/B/C/D=1-210.
DR PDBsum; 5BYG; -.
DR SMR; Q89268; -.
DR IntAct; Q89268; 3.
DR DNASU; 1489608; -.
DR GeneID; 1489608; -.
DR KEGG; vg:1489608; -.
DR Proteomes; UP000008469; Genome.
DR Proteomes; UP000180764; 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:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
DR GO; GO:0039592; P:suppression by virus of G2/M transition of host mitotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0039693; P:viral DNA genome replication; IDA:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR014015; Helicase_SF3_DNA-vir.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR001257; Parvovirus_NS1_helicase.
DR InterPro; IPR014835; Rep_N.
DR Pfam; PF01057; Parvo_NS1; 1.
DR Pfam; PF08724; Rep_N; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51206; SF3_HELICASE_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; DNA replication;
KW G1/S host cell cycle checkpoint dysregulation by virus;
KW Host G2/M cell cycle arrest by virus; Host nucleus; Host-virus interaction;
KW Modulation of host cell cycle by virus; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..621
FT /note="Protein Rep78"
FT /id="PRO_0000428953"
FT DOMAIN 308..463
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT REGION 196..216
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 489..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 489..508
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 334..341
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT STRAND 4..11
FT /evidence="ECO:0007829|PDB:5BYG"
FT TURN 29..32
FT /evidence="ECO:0007829|PDB:5BYG"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:5BYG"
FT HELIX 50..71
FT /evidence="ECO:0007829|PDB:5BYG"
FT STRAND 78..84
FT /evidence="ECO:0007829|PDB:5BYG"
FT STRAND 86..96
FT /evidence="ECO:0007829|PDB:5BYG"
FT HELIX 102..119
FT /evidence="ECO:0007829|PDB:5BYG"
FT TURN 120..123
FT /evidence="ECO:0007829|PDB:5BYG"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:5BYG"
FT STRAND 136..142
FT /evidence="ECO:0007829|PDB:5BYG"
FT HELIX 152..156
FT /evidence="ECO:0007829|PDB:5BYG"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:5BYG"
FT TURN 162..164
FT /evidence="ECO:0007829|PDB:5BYG"
FT STRAND 165..170
FT /evidence="ECO:0007829|PDB:5BYG"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:5BYG"
FT TURN 176..180
FT /evidence="ECO:0007829|PDB:5BYG"
FT HELIX 182..199
FT /evidence="ECO:0007829|PDB:5BYG"
FT HELIX 202..205
FT /evidence="ECO:0007829|PDB:5BYG"
SQ SEQUENCE 621 AA; 70563 MW; FBF4F1FEAF48FF2A CRC64;
MPGFYEIVIK VPSDLDGHLP GISDSFVNWV AEKEWELPPD SDMDLNLIEQ APLTVAEKLQ
RDFLTEWRRV SKAPEALFFV QFEKGESYFH MHVLVETTGV KSMVLGRFLS QIREKLIQRI
YRGIEPTLPN WFAVTKTRNG AGGGNKVVDE CYIPNYLLPK TQPELQWAWT NMEQYLSACL
NLTERKRLVA QHLTHVSQTQ EQNKENQNPN SDAPVIRSKT SARYMELVGW LVDKGITSEK
QWIQEDQASY ISFNAASNSR SQIKAALDNA GKIMSLTKTA PDYLVGQQPV EDISSNRIYK
ILELNGYDPQ YAASVFLGWA TKKFGKRNTI WLFGPATTGK TNIAEAIAHT VPFYGCVNWT
NENFPFNDCV DKMVIWWEEG KMTAKVVESA KAILGGSKVR VDQKCKSSAQ IDPTPVIVTS
NTNMCAVIDG NSTTFEHQQP LQDRMFKFEL TRRLDHDFGK VTKQEVKDFF RWAKDHVVEV
EHEFYVKKGG AKKRPAPSDA DISEPKRVRE SVAQPSTSDA EASINYADRY QNKCSRHVGM
NLMLFPCRQC ERMNQNSNIC FTHGQKDCLE CFPVSESQPV SVVKKAYQKL CYIHHIMGKV
PDACTACDLV NVDLDDCIFE Q
