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 03-AUG-2022, entry version 112.
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; DOI=10.1128/jvi.69.9.5422-5430.1995;
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; DOI=10.1128/jvi.70.2.834-842.1996;
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; DOI=10.1128/jvi.71.7.5323-5329.1997;
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; DOI=10.1128/jvi.73.1.72-80.1999;
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:0007744|PDB:3WRN, ECO:0007744|PDB:3WRO, ECO:0007744|PDB:3WRQ, ECO:0007744|PDB:3WRR, ECO:0007744|PDB:3WRS, ECO:0007744|PDB:4PP4, ECO:0007744|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};
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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 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: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: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 Gene3D; 3.40.50.300; -; 1.
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; NS1_C; 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 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 REGION 613..643
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 615..643
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 210
FT /note="For nuclease activity"
FT /evidence="ECO:0000269|PubMed:25528417"
FT BINDING 119
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:25528417"
FT BINDING 127
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:25528417"
FT BINDING 129
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:25528417"
FT BINDING 399..406
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT HELIX 8..19
FT /evidence="ECO:0007829|PDB:4PP4"
FT TURN 20..22
FT /evidence="ECO:0007829|PDB:4PP4"
FT STRAND 24..31
FT /evidence="ECO:0007829|PDB:4PP4"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:4PP4"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:4PP4"
FT HELIX 54..70
FT /evidence="ECO:0007829|PDB:4PP4"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:4PP4"
FT HELIX 81..104
FT /evidence="ECO:0007829|PDB:4PP4"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:4PP4"
FT STRAND 112..121
FT /evidence="ECO:0007829|PDB:4PP4"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:4PP4"
FT STRAND 125..134
FT /evidence="ECO:0007829|PDB:4PP4"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:4PP4"
FT HELIX 142..160
FT /evidence="ECO:0007829|PDB:4PP4"
FT HELIX 167..179
FT /evidence="ECO:0007829|PDB:4PP4"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:4PP4"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:3WRO"
FT HELIX 203..209
FT /evidence="ECO:0007829|PDB:4PP4"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:4PP4"
FT STRAND 219..221
FT /evidence="ECO:0007829|PDB:4PP4"
FT STRAND 227..232
FT /evidence="ECO:0007829|PDB:4PP4"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:4PP4"
FT HELIX 242..252
FT /evidence="ECO:0007829|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
