ID   NS1_PAVHU               Reviewed;         671 AA.
AC   P07298;
DT   01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1988, sequence version 1.
DT   03-AUG-2022, entry version 82.
DE   RecName: Full=Initiator protein NS1 {ECO:0000250|UniProtKB:P03134};
DE            Short=NS1;
DE            EC=3.1.21.- {ECO:0000250|UniProtKB:Q9PZT1};
DE            EC=3.6.4.12 {ECO:0000250|UniProtKB:Q9PZT1};
DE   AltName: Full=NCVP1;
DE   AltName: Full=Non-capsid protein NS-1;
DE   AltName: Full=Non-structural protein 1;
DE   AltName: Full=Non-structural protein NS1;
GN   Name=NS1;
OS   Human parvovirus B19 (isolate AU) (HPV B19).
OC   Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Quintoviricetes;
OC   Piccovirales; Parvoviridae; Parvovirinae; Erythroparvovirus.
OX   NCBI_TaxID=648238;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3701931; DOI=10.1128/jvi.58.3.921-936.1986;
RA   Shade R.O., Blundell M.C., Cotmore S.F., Tattersall P., Astell C.R.;
RT   "Nucleotide sequence and genome organization of human parvovirus B19
RT   isolated from the serum of a child during aplastic crisis.";
RL   J. Virol. 58:921-936(1986).
CC   -!- FUNCTION: Multifunctional protein essential for viral DNA replication,
CC       which cooperatively interacts with the viral DNA origin of replication
CC       and transactivates several promoters including the viral p6 promoter.
CC       Binds the origin of replication and performs an endonucleolytic nick
CC       within a conserved sequence in the viral genome, thereby initiating the
CC       rolling circle replication (RCR). Participates in the transcriptional
CC       regulation the viral p6 promoter that regulates all viral transcripts
CC       and the cellular CDN1A or IL6 promoters. Transactivates several host
CC       promoters some of which induce the S cell cycle phase for the
CC       production of host replicative proteins. Up-regulates the expression of
CC       host E2F4 and E2F5 and interacts with both these factors thereby
CC       inhibiting the host cell cycle G2/M transition. This arrest promotes
CC       apoptosis for viral release. {ECO:0000250|UniProtKB:Q9PZT1}.
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         Evidence={ECO:0000250|UniProtKB:Q9PZT1};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:Q9PZT1};
CC       Note=The endonuclease active site can probably bind other divalent
CC       cations. {ECO:0000250|UniProtKB:Q9PZT1};
CC   -!- SUBUNIT: Homooligomer; when bound to DNA. Interacts with host E2F4 and
CC       E2F5; these interactions promote the nuclear import of E2F4 and E2F5
CC       and the G2/M block observed in host cells. Interacts with host
CC       transcription factor SP1; this interaction is important for NS1
CC       transcriptional regulation of p21/WAF1. Interacts with host
CC       transcription factor SP3. {ECO:0000250|UniProtKB:Q9PZT1}.
CC   -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000250|UniProtKB:Q9PZT1}.
CC   -!- DOMAIN: In the N-terminus, the endonuclease region is involved in
CC       binding to the origin of replication on the viral DNA as well as to the
CC       overlapping viral promoter p6. In the middle, there are the ATPase and
CC       helicase activities. The C-terminus probably contains a transactivation
CC       domain. {ECO:0000250|UniProtKB:Q9PZT1}.
CC   -!- SIMILARITY: Belongs to the parvoviruses initiator protein NS1 family.
CC       {ECO:0000305}.
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DR   EMBL; M13178; AAA66866.1; -; Genomic_DNA.
DR   PIR; B24299; UYPV19.
DR   SMR; P07298; -.
DR   ABCD; P07298; 1 sequenced antibody.
DR   Proteomes; UP000008027; 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:0003678; F:DNA helicase 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:0039526; P:modulation by virus of host apoptotic process; 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; 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   3: Inferred from homology;
KW   ATP-binding; DNA replication; DNA-binding; Endonuclease; Helicase;
KW   Host G2/M cell cycle arrest by virus; Host nucleus; Host-virus interaction;
KW   Hydrolase; Magnesium; Manganese; Metal-binding;
KW   Modulation of host cell apoptosis by virus;
KW   Modulation of host cell cycle by virus; Multifunctional enzyme; Nuclease;
KW   Nucleotide-binding; Transcription; Transcription regulation;
KW   Viral DNA replication.
FT   CHAIN           1..671
FT                   /note="Initiator protein NS1"
FT                   /id="PRO_0000222467"
FT   DOMAIN          302..457
FT                   /note="SF3 helicase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   REGION          1..176
FT                   /note="Endonuclease"
FT                   /evidence="ECO:0000250|UniProtKB:Q9PZT1"
FT   REGION          532..554
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           177..180
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q9PZT1"
FT   BINDING         72
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P03134"
FT   BINDING         81
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P03134"
FT   BINDING         83
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000250|UniProtKB:P03134"
FT   BINDING         328..335
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
SQ   SEQUENCE   671 AA;  74097 MW;  E8845201FDB3F208 CRC64;
     MELFRGVLQV SSNVLDCAND NWWCSLLDLD TSDWEPLTHT NRLMAIYLSS VASKLDFTGG
     PLAGCLYFFQ VECNKFEEGY HIHVVTGGPG LNPRNLTVCV EGLFNNVLYH LVTENVKLKF
     LPGMTTKGKY FRDGEQFIEN YLMKKIPLNV VWCVTNIDGY IDTCISATFR RGACHAKKPR
     ITTAINDTSS DAGESSGTGA EVVPFNGKGT KASIKFQTMV NWLCENRVFT EDKWKLVDFN
     QYTLLSSSHS GSFQIQSALK LAIYKATNLV PTSTFLLHTD FEQVMCIKDN KIVKLLLCQN
     YDPLLVGQHV LKWIDKKCGK KNTLWFYGPP STGKTNLAMA IAKSVPVYGM VNWNNENFPF
     NDVAGKSLVV WDEGIIKSTI VEAAKAILGG QPTRVDQKMR GSVAVPGVPV VITSNGDITF
     VVSGNTTTTV HAKALKERMV KLNFTVRCSP DMGLLTEADV QQWLTWCNAQ SWDHYENWAI
     NYTFDFPGIN ADALHPDLQT TPIVTDTSIS SSGGESSEEL SESSFFNLIT PGAWNTETPR
     SSTPIPGTSS GESFVGSPVS SEVVAASWEE AFYTPLADQF RELLVGVDYV WDGVRGLPVC
     CVQHINNSGG GLGLCPHCIN VGAWYNGWKF REFTPDLVRC SCHVGASNPF SVLTCKKCAY
     LSGLQSFVDY E