REP68_AAV2S
ID REP68_AAV2S Reviewed; 536 AA.
AC P03132; O56650;
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=Protein Rep68;
DE EC=3.6.4.12;
GN Name=Rep68;
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 FUNCTION.
RX PubMed=9882364; DOI=10.1128/jvi.73.2.1580-1590.1999;
RA Zhou X., Zolotukhin I., Im D.S., Muzyczka N.;
RT "Biochemical characterization of adeno-associated virus rep68 DNA helicase
RT and ATPase activities.";
RL J. Virol. 73:1580-1590(1999).
RN [6]
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 [7]
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).
RN [8]
RP INTERACTION WITH KCTD5.
RX PubMed=17239418; DOI=10.1016/j.virol.2006.12.010;
RA Weger S., Hammer E., Goetz A., Heilbronn R.;
RT "Identification of a cytoplasmic interaction partner of the large
RT regulatory proteins Rep78/Rep68 of adeno-associated virus type 2 (AAV-2).";
RL Virology 362:192-206(2007).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 225-490.
RX PubMed=12906833; DOI=10.1016/s0969-2126(03)00152-7;
RA James J.A., Escalante C.R., Yoon-Robarts M., Edwards T.A., Linden R.M.,
RA Aggarwal A.K.;
RT "Crystal structure of the SF3 helicase from adeno-associated virus type
RT 2.";
RL Structure 11:1025-1035(2003).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 225-490.
RX PubMed=15310852; DOI=10.1073/pnas.0403454101;
RA James J.A., Aggarwal A.K., Linden R.M., Escalante C.R.;
RT "Structure of adeno-associated virus type 2 Rep40-ADP complex: insight into
RT nucleotide recognition and catalysis by superfamily 3 helicases.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12455-12460(2004).
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 factor in site-specific integration
CC of the viral genome. Inhibits the host cell cycle G1/S and G2/M
CC transitions. These arrests may provide essential cellular factors for
CC viral DNA replication. {ECO:0000269|PubMed:9882364}.
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; EC=3.6.4.12;
CC -!- SUBUNIT: Interacts with host TOPORS. Interacts with host KCTD5.
CC {ECO:0000269|PubMed:11842245, ECO:0000269|PubMed:17239418,
CC ECO:0000269|PubMed:9847329}.
CC -!- INTERACTION:
CC P03132; P03120: E2; Xeno; NbExp=2; IntAct=EBI-7387242, EBI-1779322;
CC P03132; Q9NXV2: KCTD5; Xeno; NbExp=3; IntAct=EBI-7387242, EBI-1056857;
CC P03132; P53999: SUB1; Xeno; NbExp=3; IntAct=EBI-7387242, EBI-998260;
CC P03132; Q9NS56: TOPORS; Xeno; NbExp=3; IntAct=EBI-7387242, EBI-1996473;
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DR EMBL; J01901; AAA42372.1; -; Genomic_DNA.
DR EMBL; AF043303; AAC03774.1; -; Genomic_DNA.
DR PIR; A03694; UYAD1A.
DR RefSeq; YP_680422.1; NC_001401.2.
DR PDB; 1S9H; X-ray; 2.40 A; A/B/C=225-490.
DR PDB; 1U0J; X-ray; 2.10 A; A=225-490.
DR PDB; 4ZO0; X-ray; 2.30 A; A/B/C=1-206.
DR PDB; 4ZQ9; X-ray; 2.60 A; A/B/C=1-208.
DR PDB; 5DCX; X-ray; 2.60 A; A/B/C/D/E/F/G/H/I/J/K=1-224.
DR PDB; 6XB8; X-ray; 3.30 A; A/B/C/D=1-206.
DR PDB; 7JSE; EM; 4.60 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-536.
DR PDB; 7JSF; EM; 6.70 A; A/B/C/D/E/F/G=2-536.
DR PDB; 7JSG; EM; 5.20 A; A/B/C/D/E/F/G=2-536.
DR PDB; 7JSH; EM; 4.40 A; A/B/C/D/E/F/G=2-536.
DR PDB; 7JSI; EM; 5.01 A; A/B/C/D/E/F=1-536.
DR PDBsum; 1S9H; -.
DR PDBsum; 1U0J; -.
DR PDBsum; 4ZO0; -.
DR PDBsum; 4ZQ9; -.
DR PDBsum; 5DCX; -.
DR PDBsum; 6XB8; -.
DR PDBsum; 7JSE; -.
DR PDBsum; 7JSF; -.
DR PDBsum; 7JSG; -.
DR PDBsum; 7JSH; -.
DR PDBsum; 7JSI; -.
DR SMR; P03132; -.
DR IntAct; P03132; 4.
DR MINT; P03132; -.
DR DNASU; 4192013; -.
DR GeneID; 4192013; -.
DR KEGG; vg:4192013; -.
DR EvolutionaryTrace; P03132; -.
DR Proteomes; UP000008469; Genome.
DR Proteomes; UP000180764; Genome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
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:0039665; P:permeabilization of host organelle membrane involved in viral entry into host cell; 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 GO; GO:0099008; P:viral entry via permeabilization of inner membrane; IEA:UniProtKB-KW.
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-virus interaction; Hydrolase;
KW Modulation of host cell cycle by virus; Nucleotide-binding;
KW Reference proteome; Viral penetration into host cytoplasm;
KW Viral penetration via permeabilization of host membrane;
KW Virus entry into host cell.
FT CHAIN 1..536
FT /note="Protein Rep68"
FT /id="PRO_0000222474"
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 488..536
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 488..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 CONFLICT 17
FT /note="G -> E (in Ref. 2; AAC03774)"
FT /evidence="ECO:0000305"
FT STRAND 4..11
FT /evidence="ECO:0007829|PDB:4ZO0"
FT HELIX 15..18
FT /evidence="ECO:0007829|PDB:4ZO0"
FT HELIX 24..32
FT /evidence="ECO:0007829|PDB:4ZO0"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:4ZO0"
FT HELIX 50..71
FT /evidence="ECO:0007829|PDB:4ZO0"
FT STRAND 78..84
FT /evidence="ECO:0007829|PDB:4ZO0"
FT STRAND 89..96
FT /evidence="ECO:0007829|PDB:4ZO0"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:4ZO0"
FT HELIX 105..119
FT /evidence="ECO:0007829|PDB:4ZO0"
FT TURN 120..123
FT /evidence="ECO:0007829|PDB:4ZQ9"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:4ZO0"
FT STRAND 136..140
FT /evidence="ECO:0007829|PDB:4ZQ9"
FT HELIX 152..156
FT /evidence="ECO:0007829|PDB:4ZO0"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:4ZO0"
FT TURN 162..164
FT /evidence="ECO:0007829|PDB:4ZO0"
FT STRAND 165..170
FT /evidence="ECO:0007829|PDB:4ZO0"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:4ZO0"
FT TURN 176..180
FT /evidence="ECO:0007829|PDB:4ZO0"
FT HELIX 182..204
FT /evidence="ECO:0007829|PDB:4ZO0"
FT HELIX 225..234
FT /evidence="ECO:0007829|PDB:1U0J"
FT HELIX 239..254
FT /evidence="ECO:0007829|PDB:1U0J"
FT HELIX 260..277
FT /evidence="ECO:0007829|PDB:1U0J"
FT HELIX 280..284
FT /evidence="ECO:0007829|PDB:1U0J"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:1U0J"
FT HELIX 297..304
FT /evidence="ECO:0007829|PDB:1U0J"
FT HELIX 309..320
FT /evidence="ECO:0007829|PDB:1U0J"
FT TURN 322..326
FT /evidence="ECO:0007829|PDB:1S9H"
FT STRAND 329..333
FT /evidence="ECO:0007829|PDB:1U0J"
FT HELIX 340..350
FT /evidence="ECO:0007829|PDB:1U0J"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:1U0J"
FT TURN 360..363
FT /evidence="ECO:0007829|PDB:1S9H"
FT HELIX 367..369
FT /evidence="ECO:0007829|PDB:1U0J"
FT STRAND 373..377
FT /evidence="ECO:0007829|PDB:1U0J"
FT TURN 384..386
FT /evidence="ECO:0007829|PDB:1U0J"
FT HELIX 387..394
FT /evidence="ECO:0007829|PDB:1U0J"
FT STRAND 399..401
FT /evidence="ECO:0007829|PDB:1S9H"
FT TURN 404..406
FT /evidence="ECO:0007829|PDB:1S9H"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:1S9H"
FT STRAND 416..422
FT /evidence="ECO:0007829|PDB:1U0J"
FT STRAND 427..429
FT /evidence="ECO:0007829|PDB:1U0J"
FT STRAND 432..434
FT /evidence="ECO:0007829|PDB:1U0J"
FT HELIX 438..442
FT /evidence="ECO:0007829|PDB:1U0J"
FT STRAND 445..449
FT /evidence="ECO:0007829|PDB:1U0J"
FT HELIX 463..475
FT /evidence="ECO:0007829|PDB:1U0J"
FT STRAND 483..485
FT /evidence="ECO:0007829|PDB:1S9H"
SQ SEQUENCE 536 AA; 60754 MW; 7C1ECDD4E07703C8 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 EASINYADRL ARGHSL
