GenomeNet

Database: UniProt
Entry: NS1_MUMIP
LinkDB: NS1_MUMIP
Original site: NS1_MUMIP 
ID   NS1_MUMIP               Reviewed;         672 AA.
AC   P03134;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   12-AUG-2020, entry version 106.
DE   RecName: Full=Initiator protein NS1 {ECO:0000303|PubMed:12050365};
DE            Short=NS1;
DE            EC=3.1.21.- {ECO:0000250|UniProtKB:Q9PZT1};
DE            EC=3.6.4.12 {ECO:0000269|PubMed:12050365, ECO:0000269|PubMed:1833878};
DE   AltName: Full=NCVP1;
DE   AltName: Full=Non-capsid protein NS-1;
DE   AltName: Full=Non-structural protein NS1;
GN   Name=NS1;
OS   Murine minute virus (strain MVM prototype) (MVM) (Murine minute virus
OS   (strain MVM(p))).
OC   Viruses; Monodnaviria; Shotokuvirae; Cossaviricota; Quintoviricetes;
OC   Piccovirales; Parvoviridae; Parvovirinae; Protoparvovirus.
OX   NCBI_TaxID=648235;
OH   NCBI_TaxID=10090; Mus musculus (Mouse).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6298737; DOI=10.1093/nar/11.4.999;
RA   Astell C.R., Thomson M., Merchlinsky M., Ward D.C.;
RT   "The complete DNA sequence of minute virus of mice, an autonomous
RT   parvovirus.";
RL   Nucleic Acids Res. 11:999-1018(1983).
RN   [2]
RP   CATALYTIC ACTIVITY.
RX   PubMed=1833878; DOI=10.1016/0042-6822(91)90757-3;
RA   Wilson G.M., Jindal H.K., Yeung D.E., Chen W., Astell C.R.;
RT   "Expression of minute virus of mice major nonstructural protein in insect
RT   cells: purification and identification of ATPase and helicase activities.";
RL   Virology 185:90-98(1991).
RN   [3]
RP   FUNCTION, AND DNA-BINDING.
RX   PubMed=7636987;
RA   Christensen J., Cotmore S.F., Tattersall P.;
RT   "Minute virus of mice transcriptional activator protein NS1 binds directly
RT   to the transactivation region of the viral P38 promoter in a strictly ATP-
RT   dependent manner.";
RL   J. Virol. 69:5422-5430(1995).
RN   [4]
RP   INTERACTION WITH HOST SP1, AND DOMAIN.
RX   PubMed=7799962; DOI=10.1128/mcb.15.1.524;
RA   Krady J.K., Ward D.C.;
RT   "Transcriptional activation by the parvoviral nonstructural protein NS-1 is
RT   mediated via a direct interaction with Sp1.";
RL   Mol. Cell. Biol. 15:524-533(1995).
RN   [5]
RP   FUNCTION, AND DNA-BINDING.
RX   PubMed=8551622;
RA   Lorson C., Burger L.R., Mouw M., Pintel D.J.;
RT   "Efficient transactivation of the minute virus of mice P38 promoter
RT   requires upstream binding of NS1.";
RL   J. Virol. 70:834-842(1996).
RN   [6]
RP   FUNCTION.
RX   PubMed=9188601;
RA   Op De Beeck A., Caillet-Fauquet P.;
RT   "The NS1 protein of the autonomous parvovirus minute virus of mice blocks
RT   cellular DNA replication: a consequence of lesions to the chromatin?";
RL   J. Virol. 71:5323-5329(1997).
RN   [7]
RP   FUNCTION.
RX   PubMed=9349487; DOI=10.1099/0022-1317-78-10-2647;
RA   Willwand K., Baldauf A.Q., Deleu L., Mumtsidu E., Costello E., Beard P.,
RA   Rommelaere J.;
RT   "The minute virus of mice (MVM) nonstructural protein NS1 induces nicking
RT   of MVM DNA at a unique site of the right-end telomere in both hairpin and
RT   duplex conformations in vitro.";
RL   J. Gen. Virol. 78:2647-2655(1997).
RN   [8]
RP   DNA-BINDING.
RX   PubMed=9813208; DOI=10.1006/viro.1998.9375;
RA   Mouw M., Pintel D.J.;
RT   "Amino acids 16-275 of minute virus of mice NS1 include a domain that
RT   specifically binds (ACCA)2-3-containing DNA.";
RL   Virology 251:123-131(1998).
RN   [9]
RP   INTERACTION WITH HOST SP1.
RX   PubMed=9454706; DOI=10.1006/viro.1997.8940;
RA   Lorson C., Pearson J., Burger L., Pintel D.J.;
RT   "An Sp1-binding site and TATA element are sufficient to support full
RT   transactivation by proximally bound NS1 protein of minute virus of mice.";
RL   Virology 240:326-337(1998).
RN   [10]
RP   INTERACTION WITH SYNCRIP.
RX   PubMed=9847309;
RA   Harris C.E., Boden R.A., Astell C.R.;
RT   "A novel heterogeneous nuclear ribonucleoprotein-like protein interacts
RT   with NS1 of the minute virus of mice.";
RL   J. Virol. 73:72-80(1999).
RN   [11]
RP   PHOSPHORYLATION.
RX   PubMed=10388664; DOI=10.1006/viro.1999.9786;
RA   Corbau R., Salom N., Rommelaere J., Nuesch J.P.;
RT   "Phosphorylation of the viral nonstructural protein NS1 during MVMp
RT   infection of A9 cells.";
RL   Virology 259:402-415(1999).
RN   [12]
RP   FUNCTION.
RX   PubMed=11602746; DOI=10.1128/jvi.75.22.11071-11078.2001;
RA   Op De Beeck A., Sobczak-Thepot J., Sirma H., Bourgain F., Brechot C.,
RA   Caillet-Fauquet P.;
RT   "NS1- and minute virus of mice-induced cell cycle arrest: involvement of
RT   p53 and p21(cip1).";
RL   J. Virol. 75:11071-11078(2001).
RN   [13]
RP   FUNCTION, AND DNA-BINDING.
RX   PubMed=11435581; DOI=10.1128/jvi.75.15.7009-7017.2001;
RA   Christensen J., Cotmore S.F., Tattersall P.;
RT   "Minute virus of mice initiator protein NS1 and a host KDWK family
RT   transcription factor must form a precise ternary complex with origin DNA
RT   for nicking to occur.";
RL   J. Virol. 75:7009-7017(2001).
RN   [14]
RP   FUNCTION, AND DNA-BINDING.
RX   PubMed=17898054; DOI=10.1128/jvi.01703-07;
RA   Cotmore S.F., Gottlieb R.L., Tattersall P.;
RT   "Replication initiator protein NS1 of the parvovirus minute virus of mice
RT   binds to modular divergent sites distributed throughout duplex viral DNA.";
RL   J. Virol. 81:13015-13027(2007).
RN   [15]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=12050365; DOI=10.1128/jvi.76.13.6518-6531.2002;
RA   Christensen J., Tattersall P.;
RT   "Parvovirus initiator protein NS1 and RPA coordinate replication fork
RT   progression in a reconstituted DNA replication system.";
RL   J. Virol. 76:6518-6531(2002).
RN   [16]
RP   FUNCTION.
RX   PubMed=21295324; DOI=10.1016/j.virol.2010.12.035;
RA   Mincberg M., Gopas J., Tal J.;
RT   "Minute virus of mice (MVMp) infection and NS1 expression induce p53
RT   independent apoptosis in transformed rat fibroblast cells.";
RL   Virology 412:233-243(2011).
RN   [17] {ECO:0000244|PDB:3WRN, ECO:0000244|PDB:3WRO, ECO:0000244|PDB:3WRQ, ECO:0000244|PDB:3WRR, ECO:0000244|PDB:3WRS, ECO:0000244|PDB:4PP4, ECO:0000244|PDB:4R94}
RP   X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 1-255 IN COMPLEX WITH COPPER;
RP   MAGNESIUM; MANGANESE AND ZINC, ACTIVE SITE, AND COFACTOR.
RX   PubMed=25528417; DOI=10.1016/j.virol.2014.11.022;
RA   Tewary S.K., Liang L., Lin Z., Lynn A., Cotmore S.F., Tattersall P.,
RA   Zhao H., Tang L.;
RT   "Structures of minute virus of mice replication initiator protein N-
RT   terminal domain: Insights into DNA nicking and origin binding.";
RL   Virology 476:61-71(2015).
CC   -!- FUNCTION: Multifunctional protein which displays endonuclease and
CC       helicase activities required for initiating and directing viral DNA
CC       replication (PubMed:12050365). Also plays a role in viral packaging and
CC       transactivation of several promoters (PubMed:7636987). Binds site-
CC       specifically to 2-3 approximate tandem copies of the tetranucleotide
CC       5'TGGT3' within the origins of replication (Ori), unwinds this hairpin
CC       region and nicks one DNA strand thereby initiating the rolling circle
CC       replication (RCR) (PubMed:17898054, PubMed:12050365, PubMed:9349487).
CC       Cooperatively binds Ori with host PIF and probably other host factors,
CC       which activate the nickase function of NS1 (PubMed:11435581,
CC       PubMed:12050365). Becomes covalently attached to the 5' end of the nick
CC       and provides a 3'OH for priming DNA synthesis (PubMed:12050365). The
CC       helicase activity unwinds DNA in a 3'-5' direction on the longer strand
CC       (PubMed:12050365). Participates in the transcriptional regulation of
CC       several promoters including the viral p38 promoter that regulates the
CC       expression of VP1 and VP2 transcripts (PubMed:7636987, PubMed:8551622).
CC       Inhibits the host cell cycle during the G1/S transition, the S-phase,
CC       and the G2/M transition (PubMed:9188601, PubMed:11602746). These
CC       arrests may provide essential cellular factors for viral DNA
CC       replication. Promotes apoptosis in host cell (PubMed:21295324).
CC       {ECO:0000269|PubMed:11435581, ECO:0000269|PubMed:11602746,
CC       ECO:0000269|PubMed:12050365, ECO:0000269|PubMed:17898054,
CC       ECO:0000269|PubMed:21295324, ECO:0000269|PubMed:7636987,
CC       ECO:0000269|PubMed:8551622, ECO:0000269|PubMed:9188601,
CC       ECO:0000269|PubMed:9349487}.
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:12050365, ECO:0000269|PubMed:1833878};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:25528417};
CC       Note=The endonuclease active site can probably bind other divalent
CC       cations. {ECO:0000269|PubMed:25528417};
CC   -!- SUBUNIT: Homooligomer; when bound to DNA (By similarity). Interacts
CC       with human SYNCRIP (PubMed:9847309). Interacts with host transcription
CC       factor SP1; this interaction allows high levels of viral P38 promoter
CC       transactivation by NS1 (PubMed:7799962, PubMed:9454706).
CC       {ECO:0000250|UniProtKB:Q9PZT1, ECO:0000269|PubMed:7799962,
CC       ECO:0000269|PubMed:9454706, ECO:0000269|PubMed:9847309}.
CC   -!- INTERACTION:
CC       P03134; P97801: Smn1; Xeno; NbExp=3; IntAct=EBI-9515229, EBI-309807;
CC   -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000250|UniProtKB:D0EZM8}.
CC   -!- DOMAIN: In the N-terminus, the endonuclease region is involved in
CC       binding to the origin of replication (By similarity). In the middle,
CC       there are the ATPase and helicase activities (By similarity). The C-
CC       terminus probably contains a transactivation domain (PubMed:7799962).
CC       {ECO:0000250|UniProtKB:Q9PZT1, ECO:0000269|PubMed:7799962}.
CC   -!- PTM: Phosphorylated. {ECO:0000269|PubMed:10388664}.
CC   -!- SIMILARITY: Belongs to the parvoviruses initiator protein NS1 family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA24309.1; Type=Erroneous initiation; Evidence={ECO:0000305};
DR   EMBL; J02275; AAA67109.1; -; Genomic_DNA.
DR   EMBL; V01115; CAA24309.1; ALT_INIT; Genomic_DNA.
DR   PIR; A03696; UYPV1M.
DR   RefSeq; NP_041242.1; NC_001510.1.
DR   RefSeq; NP_041243.1; NC_001510.1.
DR   PDB; 3WRN; X-ray; 1.52 A; A=1-255.
DR   PDB; 3WRO; X-ray; 1.48 A; A=1-255.
DR   PDB; 3WRQ; X-ray; 1.53 A; A=1-255.
DR   PDB; 3WRR; X-ray; 1.62 A; A=1-255.
DR   PDB; 3WRS; X-ray; 1.58 A; A=1-255.
DR   PDB; 4PP4; X-ray; 1.45 A; A=1-255.
DR   PDB; 4R94; X-ray; 1.67 A; A=1-255.
DR   PDBsum; 3WRN; -.
DR   PDBsum; 3WRO; -.
DR   PDBsum; 3WRQ; -.
DR   PDBsum; 3WRR; -.
DR   PDBsum; 3WRS; -.
DR   PDBsum; 4PP4; -.
DR   PDBsum; 4R94; -.
DR   SMR; P03134; -.
DR   DIP; DIP-46505N; -.
DR   IntAct; P03134; 5.
DR   PRIDE; P03134; -.
DR   GeneID; 1489590; -.
DR   KEGG; vg:1489590; -.
DR   Proteomes; UP000007019; 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: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:0004386; F:helicase 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:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0039645; P:modulation by virus of host G1/S transition checkpoint; IEA:UniProtKB-KW.
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; IEA:UniProtKB-KW.
DR   InterPro; IPR014015; Helicase_SF3_DNA-vir.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR021972; Parvovirus_NS1_C.
DR   InterPro; IPR001257; Parvovirus_NS1_helicase.
DR   InterPro; IPR021076; Parvovirus_NS1_N.
DR   Pfam; PF12117; DUF3580; 1.
DR   Pfam; PF01057; Parvo_NS1; 1.
DR   Pfam; PF12433; PV_NSP1; 1.
DR   SUPFAM; SSF52540; SSF52540; 1.
DR   PROSITE; PS51206; SF3_HELICASE_1; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Covalent protein-DNA linkage; DNA replication;
KW   DNA-binding; Endonuclease;
KW   G1/S host cell cycle checkpoint dysregulation by virus; Helicase;
KW   Host G2/M cell cycle arrest by virus; Host nucleus; Host-virus interaction;
KW   Hydrolase; Magnesium; Metal-binding;
KW   Modulation of host cell apoptosis by virus;
KW   Modulation of host cell cycle by virus; Nuclease; Nucleotide-binding;
KW   Reference proteome; Transcription; Transcription regulation;
KW   Viral DNA replication; Viral genome packaging;
KW   Viral release from host cell.
FT   CHAIN           1..672
FT                   /note="Initiator protein NS1"
FT                   /id="PRO_0000222466"
FT   DOMAIN          373..528
FT                   /note="SF3 helicase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   NP_BIND         399..406
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT   REGION          1..276
FT                   /note="DNA-binding; interaction with SYNCRIP"
FT                   /evidence="ECO:0000269|PubMed:9813208,
FT                   ECO:0000269|PubMed:9847309"
FT   REGION          191..195
FT                   /note="Ori-binding"
FT                   /evidence="ECO:0000269|PubMed:25528417"
FT   REGION          543..672
FT                   /note="Transactivation"
FT                   /evidence="ECO:0000269|PubMed:7799962"
FT   ACT_SITE        210
FT                   /note="For nuclease activity"
FT                   /evidence="ECO:0000269|PubMed:25528417"
FT   METAL           119
FT                   /note="Divalent metal cation; via tele nitrogen"
FT                   /evidence="ECO:0000269|PubMed:25528417"
FT   METAL           127
FT                   /note="Divalent metal cation; via tele nitrogen"
FT                   /evidence="ECO:0000269|PubMed:25528417"
FT   METAL           129
FT                   /note="Divalent metal cation; via tele nitrogen"
FT                   /evidence="ECO:0000269|PubMed:25528417"
FT   HELIX           8..19
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   TURN            20..22
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   STRAND          24..31
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   STRAND          35..37
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   STRAND          40..42
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   HELIX           54..70
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   STRAND          73..75
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   HELIX           81..104
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   HELIX           109..111
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   STRAND          112..121
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   TURN            122..124
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   STRAND          125..134
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   HELIX           139..141
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   HELIX           142..160
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   HELIX           167..179
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   STRAND          182..185
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   STRAND          192..194
FT                   /evidence="ECO:0000244|PDB:3WRO"
FT   HELIX           203..209
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   HELIX           211..213
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   STRAND          219..221
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   STRAND          227..232
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   STRAND          235..237
FT                   /evidence="ECO:0000244|PDB:4PP4"
FT   HELIX           242..252
FT                   /evidence="ECO:0000244|PDB:4PP4"
SQ   SEQUENCE   672 AA;  76249 MW;  50298F27662E3C1D CRC64;
     MAGNAYSDEV LGATNWLKEK SNQEVFSFVF KNENVQLNGK DIGWNSYKKE LQEDELKSLQ
     RGAETTWDQS EDMEWETTVD EMTKKQVFIF DSLVKKCLFE VLNTKNIFPG DVNWFVQHEW
     GKDQGWHCHV LIGGKDFSQA QGKWWRRQLN VYWSRWLVTA CNVQLTPAER IKLREIAEDN
     EWVTLLTYKH KQTKKDYTKC VLFGNMIAYY FLTKKKISTS PPRDGGYFLS SDSGWKTNFL
     KEGERHLVSK LYTDDMRPET VETTVTTAQE TKRGRIQTKK EVSIKTTLKE LVHKRVTSPE
     DWMMMQPDSY IEMMAQPGGE NLLKNTLEIC TLTLARTKTA FDLILEKAET SKLTNFSLPD
     TRTCRIFAFH GWNYVKVCHA ICCVLNRQGG KRNTVLFHGP ASTGKSIIAQ AIAQAVGNVG
     CYNAANVNFP FNDCTNKNLI WVEEAGNFGQ QVNQFKAICS GQTIRIDQKG KGSKQIEPTP
     VIMTTNENIT VVRIGCEERP EHTQPIRDRM LNIHLTHTLP GDFGLVDKNE WPMICAWLVK
     NGYQSTMASY CAKWGKVPDW SENWAEPKVP TPINLLGSAR SPFTTPKSTP LSQNYALTPL
     ASDLEDLALE PWSTPNTPVA GTAETQNTGE AGSKACQDGQ LSPTWSEIEE DLRACFGAEP
     LKKDFSEPLN LD
//
DBGET integrated database retrieval system