NS1_PAVHV
ID NS1_PAVHV Reviewed; 671 AA.
AC Q9PZT1;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Initiator protein NS1 {ECO:0000250|UniProtKB:P03134};
DE Short=NS1;
DE EC=3.1.21.- {ECO:0000269|PubMed:27809499};
DE EC=3.6.4.12 {ECO:0000269|PubMed:11853402};
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 (strain HV) (HPV B19).
OC Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Quintoviricetes;
OC Piccovirales; Parvoviridae; Parvovirinae; Erythroparvovirus.
OX NCBI_TaxID=648237;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Gallinella G., Venturoli S.;
RT "B19 genome sequence and structure analysis.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION.
RX PubMed=8970971; DOI=10.1128/jvi.70.12.8485-8491.1996;
RA Moffatt S., Tanaka N., Tada K., Nose M., Nakamura M., Muraoka O.,
RA Hirano T., Sugamura K.;
RT "A cytotoxic nonstructural protein, NS1, of human parvovirus B19 induces
RT activation of interleukin-6 gene expression.";
RL J. Virol. 70:8485-8491(1996).
RN [3]
RP FUNCTION.
RX PubMed=9525624; DOI=10.1128/jvi.72.4.3018-3028.1998;
RA Moffatt S., Yaegashi N., Tada K., Tanaka N., Sugamura K.;
RT "Human parvovirus B19 nonstructural (NS1) protein induces apoptosis in
RT erythroid lineage cells.";
RL J. Virol. 72:3018-3028(1998).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, DNA-BINDING, INTERACTION WITH HOST
RP TRANSCRIPTION FACTOR SP1, AND INTERACTION WITH HOST TRANSCRIPTION FACTOR
RP SP3.
RX PubMed=11853402; DOI=10.1006/viro.2001.1285;
RA Raab U., Beckenlehner K., Lowin T., Niller H.H., Doyle S., Modrow S.;
RT "NS1 protein of parvovirus B19 interacts directly with DNA sequences of the
RT p6 promoter and with the cellular transcription factors Sp1/Sp3.";
RL Virology 293:86-93(2002).
RN [5]
RP FUNCTION, AND INTERACTION WITH HOST SP1.
RX PubMed=15518826; DOI=10.1016/j.virol.2004.09.008;
RA Nakashima A., Morita E., Saito S., Sugamura K.;
RT "Human Parvovirus B19 nonstructural protein transactivates the p21/WAF1
RT through Sp1.";
RL Virology 329:493-504(2004).
RN [6]
RP FUNCTION, INTERACTION WITH HOST E2F4, INTERACTION WITH HOST E2F5, NUCLEAR
RP LOCALIZATION SIGNAL, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-177.
RX PubMed=20890043; DOI=10.1172/jci41805;
RA Wan Z., Zhi N., Wong S., Keyvanfar K., Liu D., Raghavachari N.,
RA Munson P.J., Su S., Malide D., Kajigaya S., Young N.S.;
RT "Human parvovirus B19 causes cell cycle arrest of human erythroid
RT progenitors via deregulation of the E2F family of transcription factors.";
RL J. Clin. Invest. 120:3530-3544(2010).
RN [7]
RP FUNCTION.
RX PubMed=24049177; DOI=10.1128/jvi.02333-13;
RA Luo Y., Kleiboeker S., Deng X., Qiu J.;
RT "Human parvovirus B19 infection causes cell cycle arrest of human erythroid
RT progenitors at late S phase that favors viral DNA replication.";
RL J. Virol. 87:12766-12775(2013).
RN [8]
RP FUNCTION.
RX PubMed=24418564; DOI=10.1016/j.virol.2013.11.031;
RA Tewary S.K., Zhao H., Deng X., Qiu J., Tang L.;
RT "The human parvovirus B19 non-structural protein 1 N-terminal domain
RT specifically binds to the origin of replication in the viral DNA.";
RL Virology 449:297-303(2014).
RN [9]
RP FUNCTION, DOMAIN, DNA-BINDING, CATALYTIC ACTIVITY, SUBUNIT,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RC STRAIN=Isolate BR-3728/9;
RX PubMed=27809499; DOI=10.1021/acs.biochem.6b00534;
RA Sanchez J.L., Romero Z., Quinones A., Torgeson K.R., Horton N.C.;
RT "DNA binding and cleavage by the human parvovirus B19 NS1 nuclease
RT domain.";
RL Biochemistry 55:6577-6593(2016).
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 (PubMed:27809499, PubMed:24418564, PubMed:11853402). Binds the origin
CC of replication and performs an endonucleolytic nick within a conserved
CC sequence in the viral genome, thereby initiating the rolling circle
CC replication (RCR) (PubMed:27809499). Participates in the
CC transcriptional regulation the viral p6 promoter that regulates all
CC viral transcripts and the cellular CDN1A or IL6 promoters
CC (PubMed:8970971, PubMed:11853402). Transactivates several host
CC promoters some of which induce the S cell cycle phase for the
CC production of host replicative proteins (PubMed:20890043,
CC PubMed:15518826, PubMed:24049177). Up-regulates the expression of host
CC E2F4 and E2F5 and interacts with both these factors thereby inhibiting
CC the host cell cycle G2/M transition (PubMed:20890043). This arrest
CC promotes apoptosis for viral release (PubMed:20890043, PubMed:9525624).
CC {ECO:0000269|PubMed:11853402, ECO:0000269|PubMed:15518826,
CC ECO:0000269|PubMed:20890043, ECO:0000269|PubMed:24049177,
CC ECO:0000269|PubMed:24418564, ECO:0000269|PubMed:27809499,
CC ECO:0000269|PubMed:8970971, ECO:0000269|PubMed:9525624}.
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:0000269|PubMed:11853402};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:27809499};
CC Note=The endonuclease active site can probably bind other divalent
CC cations. {ECO:0000269|PubMed:27809499};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.0-7.5. {ECO:0000269|PubMed:27809499};
CC -!- SUBUNIT: Homooligomer; when bound to DNA (PubMed:27809499). Interacts
CC with host E2F4 and E2F5; these interactions promote the nuclear import
CC of E2F4 and E2F5 and the G2/M block observed in host cells
CC (PubMed:20890043). Interacts with host transcription factor SP1; this
CC interaction is important for NS1 transcriptional regulation of p21/WAF1
CC (PubMed:15518826, PubMed:11853402). Interacts with host transcription
CC factor SP3 (PubMed:11853402). {ECO:0000269|PubMed:11853402,
CC ECO:0000269|PubMed:15518826, ECO:0000269|PubMed:20890043,
CC ECO:0000269|PubMed:27809499}.
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:20890043}.
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:0000269|PubMed:27809499}.
CC -!- SIMILARITY: Belongs to the parvoviruses initiator protein NS1 family.
CC {ECO:0000305}.
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DR EMBL; AF162273; AAD46613.1; -; Genomic_DNA.
DR SMR; Q9PZT1; -.
DR ABCD; Q9PZT1; 1 sequenced antibody.
DR Proteomes; UP000006624; Genome.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0019051; P:induction by virus of host apoptotic process; IDA:UniProtKB.
DR GO; GO:0019056; P:modulation by virus of host transcription; IDA:UniProtKB.
DR GO; GO:0039685; P:rolling hairpin viral DNA replication; IDA:UniProtKB.
DR GO; GO:0039592; P:suppression by virus of G2/M transition of host mitotic cell cycle; 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 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; Reference proteome; Transcription;
KW Transcription regulation; Viral DNA replication.
FT CHAIN 1..671
FT /note="Initiator protein NS1"
FT /id="PRO_0000428715"
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:0000269|PubMed:27809499"
FT REGION 532..553
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 177..180
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:20890043"
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"
FT MUTAGEN 177
FT /note="K->C: Complete loss of nuclear localization.
FT Complete loss of NS1-mediated nuclear translocation of host
FT E2F4 and E2F5, although still up-regulating their
FT expression."
FT /evidence="ECO:0000269|PubMed:20890043"
SQ SEQUENCE 671 AA; 74065 MW; 503EFCDC87A0BF74 CRC64;
MELFRGVLQV SSNVLDCAND NWWCSLLDLD TSDWEPLTHT NRLMAIYLSS VASKLDFTGG
PLAGCLYFFQ VECNKFEEGY HIHVVIGGPG LNPRNLTVCV EGLFNNVLYH LVTENVKLKF
LPGMTTKGKY FRDGEQFIEN YLMKKIPLNV VWCVTNIDGY IDTCISATFR RGACHAKKPR
ITTAINDTSS DAGESSGTGA EVVPINGKGT 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 GESFVGSSVS SEVVAASWEE AFYTPLADQF RELLVGVDYV WDGVRGLPVC
CVQHINNSGG GLGLCPHCIN VGAWYNGWKF REFTPDLVRC SCHVGASNPF SVLTCKKCAY
LSGLQSFVDY E
