NCAP_LYCVA
ID NCAP_LYCVA Reviewed; 558 AA.
AC P09992; Q49K86;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Nucleoprotein {ECO:0000255|HAMAP-Rule:MF_04085};
DE EC=3.1.13.- {ECO:0000255|HAMAP-Rule:MF_04085};
DE AltName: Full=Nucleocapsid protein {ECO:0000255|HAMAP-Rule:MF_04085};
DE AltName: Full=Protein N {ECO:0000255|HAMAP-Rule:MF_04085};
GN Name=N {ECO:0000255|HAMAP-Rule:MF_04085}; OrderedLocusNames=Segment S;
OS Lymphocytic choriomeningitis virus (strain Armstrong) (LCMV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX NCBI_TaxID=11624;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=10036; Mesocricetus auratus (Golden hamster).
OH NCBI_TaxID=10090; Mus musculus (Mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3824905; DOI=10.1016/0042-6822(87)90323-0;
RA Southern P.J., Singh M.K., Riviere Y., Jacoby D.R., Buchmeier M.J.,
RA Oldstone M.B.A.;
RT "Molecular characterization of the genomic S RNA segment from lymphocytic
RT choriomeningitis virus.";
RL Virology 157:145-155(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3259346; DOI=10.1016/0042-6822(88)90566-1;
RA Salvato M., Shimomaye E., Southern P.J., Oldstone M.B.A.;
RT "Virus-lymphocyte interactions. IV. Molecular characterization of LCMV
RT Armstrong (CTL+) small genomic segment and that of its variant, Clone 13
RT (CTL-).";
RL Virology 164:517-522(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate Armstrong 53b;
RX PubMed=16051837; DOI=10.1128/jvi.79.16.10451-10459.2005;
RA Grande-Perez A., Gomez-Mariano G., Lowenstein P.R., Domingo E.;
RT "Mutagenesis-induced, large fitness variations with an invariant arenavirus
RT consensus genomic nucleotide sequence.";
RL J. Virol. 79:10451-10459(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate Armstrong-derived variant Cl13;
RX PubMed=16537369; DOI=10.1073/pnas.0600652103;
RA Flatz L., Bergthaler A., de la Torre J.C., Pinschewer D.D.;
RT "Recovery of an arenavirus entirely from RNA polymerase I/II-driven cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:4663-4668(2006).
RN [5]
RP HOMOMULTIMERIZATION.
RX PubMed=6619802; DOI=10.1099/0022-1317-64-10-2157;
RA Bruns M., Lehmann-Grube F.;
RT "Lymphocytic choriomeningitis virus. V. Proposed structural arrangement of
RT proteins in the virion.";
RL J. Gen. Virol. 64:2157-2167(1983).
RN [6]
RP RNA-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=3962189; DOI=10.1016/0042-6822(86)90105-4;
RA Bruns M., Zeller W., Rohdewohld H., Lehmann-Grube F.;
RT "Lymphocytic choriomeningitis virus. IX. Properties of the nucleocapsid.";
RL Virology 151:77-85(1986).
RN [7]
RP INTERACTION WITH GLYCOPROTEIN G2.
RX PubMed=1853564; DOI=10.1016/0042-6822(91)90991-j;
RA Burns J.W., Buchmeier M.J.;
RT "Protein-protein interactions in lymphocytic choriomeningitis virus.";
RL Virology 183:620-629(1991).
RN [8]
RP FUNCTION.
RX PubMed=12610166; DOI=10.1128/jvi.77.6.3882-3887.2003;
RA Pinschewer D.D., Perez M., de la Torre J.C.;
RT "Role of the virus nucleoprotein in the regulation of lymphocytic
RT choriomeningitis virus transcription and RNA replication.";
RL J. Virol. 77:3882-3887(2003).
RN [9]
RP FUNCTION.
RX PubMed=17804508; DOI=10.1128/jvi.00882-07;
RA Martinez-Sobrido L., Giannakas P., Cubitt B., Garcia-Sastre A.,
RA de la Torre J.C.;
RT "Differential inhibition of type I interferon induction by arenavirus
RT nucleoproteins.";
RL J. Virol. 81:12696-12703(2007).
RN [10]
RP FUNCTION, INTERACTION WITH HOST IKBKE, AND MUTAGENESIS OF ASP-382; GLU-384;
RP ASP-459; HIS-517 AND ASP-522.
RX PubMed=22532683; DOI=10.1128/jvi.00187-12;
RA Pythoud C., Rodrigo W.W., Pasqual G., Rothenberger S., Martinez-Sobrido L.,
RA de la Torre J.C., Kunz S.;
RT "Arenavirus nucleoprotein targets interferon regulatory factor-activating
RT kinase IKKepsilon.";
RL J. Virol. 86:7728-7738(2012).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 341-558.
RX PubMed=24914986; DOI=10.1107/s1399004714007883;
RA West B.R., Hastie K.M., Saphire E.O.;
RT "Structure of the LCMV nucleoprotein provides a template for understanding
RT arenavirus replication and immunosuppression.";
RL Acta Crystallogr. D 70:1764-1769(2014).
CC -!- FUNCTION: Encapsidates the genome, protecting it from nucleases. The
CC encapsidated genomic RNA is termed the nucleocapsid (NC). Serves as
CC template for viral transcription and replication. The increased
CC presence of protein N in host cell does not seem to trigger the switch
CC from transcription to replication as observed in other negative strain
CC RNA viruses. Through the interaction with host IKBKE, strongly inhibits
CC the phosphorylation and nuclear translocation of host IRF3, a protein
CC involved in interferon activation pathway, leading to the inhibition of
CC interferon-beta and IRF3-dependent promoters activation. Encodes also a
CC functional 3'-5' exoribonuclease that degrades preferentially dsRNA
CC substrates and thereby participates in the suppression of interferon
CC induction. {ECO:0000255|HAMAP-Rule:MF_04085,
CC ECO:0000269|PubMed:12610166, ECO:0000269|PubMed:17804508,
CC ECO:0000269|PubMed:22532683}.
CC -!- SUBUNIT: Homomultimerizes to form the nucleocapsid. Binds to viral
CC genomic RNA. Interacts with glycoprotein G2. Interacts with protein Z;
CC this interaction probably directs the encapsidated genome to budding
CC sites. Interacts with protein L; this interaction does not interfere
CC with Z-L interaction. Interacts with host IKBKE (via Protein kinase
CC domain); the interaction inhibits IKBKE kinase activity
CC (PubMed:22532683). {ECO:0000255|HAMAP-Rule:MF_04085,
CC ECO:0000269|PubMed:1853564, ECO:0000269|PubMed:22532683}.
CC -!- INTERACTION:
CC P09992; P14240: L; NbExp=2; IntAct=EBI-6149284, EBI-26968662;
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04085,
CC ECO:0000269|PubMed:3962189}. Host cytoplasm {ECO:0000255|HAMAP-
CC Rule:MF_04085, ECO:0000269|PubMed:3962189}.
CC -!- DOMAIN: The N-terminal region is important for the cap-binding activity
CC while the C-terminal region contains the 3'-5' exoribonuclease
CC activity. A CCHE zinc binding site is present in the C-terminal region
CC and may thus contribute to the substrate binding and/or the specificity
CC of the exonuclease activity. {ECO:0000255|HAMAP-Rule:MF_04085}.
CC -!- SIMILARITY: Belongs to the arenaviridae nucleocapsid protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04085}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M20869; AAA46257.1; -; Genomic_RNA.
DR EMBL; AY847350; AAX49342.1; -; Genomic_RNA.
DR EMBL; DQ361065; ABC96002.1; -; Genomic_RNA.
DR PIR; A26345; VHXPLM.
DR RefSeq; NP_694852.1; NC_004294.1.
DR PDB; 4O6H; X-ray; 2.80 A; A/B/C/D/E/F/G/H=341-558.
DR PDB; 4O6I; X-ray; 2.00 A; A/B=341-558.
DR PDBsum; 4O6H; -.
DR PDBsum; 4O6I; -.
DR SMR; P09992; -.
DR IntAct; P09992; 12.
DR MINT; P09992; -.
DR GeneID; 956592; -.
DR KEGG; vg:956592; -.
DR Proteomes; UP000002474; Genome.
DR Proteomes; UP000121528; Genome.
DR Proteomes; UP000204492; Genome.
DR GO; GO:0019029; C:helical viral capsid; IEA:UniProtKB-UniRule.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-UniRule.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0039689; P:negative stranded viral RNA replication; IDA:UniProtKB.
DR GO; GO:0039696; P:RNA-templated viral transcription; IDA:UniProtKB.
DR GO; GO:0039724; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IKBKE activity; IEA:UniProtKB-UniRule.
DR Gene3D; 3.30.420.410; -; 1.
DR HAMAP; MF_04085; ARENA_NCAP; 1.
DR InterPro; IPR000229; Nucleocapsid_arenaviridae.
DR InterPro; IPR035084; Nucleocapsid_C_arenaviridae.
DR InterPro; IPR038115; Nucleocapsid_C_sf.
DR InterPro; IPR035083; Nucleocapsid_N_arenaviridae.
DR Pfam; PF17290; Arena_ncap_C; 1.
DR Pfam; PF00843; Arena_nucleocap; 1.
DR PIRSF; PIRSF004029; N_ArenaV; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Capsid protein; Helical capsid protein; Host cytoplasm;
KW Host-virus interaction; Hydrolase; Inhibition of host IKBKE by virus;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host RLR pathway by virus;
KW Interferon antiviral system evasion; Manganese; Metal-binding;
KW Reference proteome; Ribonucleoprotein; RNA-binding; Viral immunoevasion;
KW Viral nucleoprotein; Virion; Zinc.
FT CHAIN 1..558
FT /note="Nucleoprotein"
FT /id="PRO_0000079193"
FT REGION 54..237
FT /note="Binding site for the cap structure m7GTP"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085"
FT BINDING 382
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:24914986"
FT BINDING 382
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085"
FT BINDING 384
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:24914986"
FT BINDING 384
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085"
FT BINDING 392
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:24914986"
FT BINDING 499
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:24914986"
FT BINDING 502
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:24914986"
FT BINDING 518
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:24914986"
FT BINDING 522
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:24914986"
FT BINDING 522
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085"
FT SITE 459
FT /note="Important for exonuclease activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085"
FT MUTAGEN 382
FT /note="D->A: Decreases interaction with host IKBKE,
FT defective to inhibit IKBKE kinase activity and IRF3
FT activation."
FT /evidence="ECO:0000269|PubMed:22532683"
FT MUTAGEN 384
FT /note="E->A: Decreases interaction with host IKBKE,
FT defective to inhibit IKBKE kinase activity and IRF3
FT activation."
FT /evidence="ECO:0000269|PubMed:22532683"
FT MUTAGEN 459
FT /note="D->A: Decreases interaction with host IKBKE,
FT defective to inhibit IKBKE kinase activity and IRF3
FT activation."
FT /evidence="ECO:0000269|PubMed:22532683"
FT MUTAGEN 517
FT /note="H->A: Decreases interaction with host IKBKE,
FT defective to inhibit IKBKE kinase activity and IRF3
FT activation."
FT /evidence="ECO:0000269|PubMed:22532683"
FT MUTAGEN 522
FT /note="D->A: Decreases interaction with host IKBKE,
FT defective to inhibit IKBKE kinase activity and IRF3
FT activation."
FT /evidence="ECO:0000269|PubMed:22532683"
FT HELIX 360..369
FT /evidence="ECO:0007829|PDB:4O6I"
FT HELIX 370..372
FT /evidence="ECO:0007829|PDB:4O6I"
FT STRAND 375..377
FT /evidence="ECO:0007829|PDB:4O6H"
FT STRAND 380..386
FT /evidence="ECO:0007829|PDB:4O6I"
FT STRAND 389..396
FT /evidence="ECO:0007829|PDB:4O6I"
FT TURN 398..400
FT /evidence="ECO:0007829|PDB:4O6I"
FT STRAND 402..407
FT /evidence="ECO:0007829|PDB:4O6I"
FT HELIX 413..422
FT /evidence="ECO:0007829|PDB:4O6I"
FT HELIX 428..431
FT /evidence="ECO:0007829|PDB:4O6I"
FT HELIX 438..445
FT /evidence="ECO:0007829|PDB:4O6I"
FT STRAND 451..455
FT /evidence="ECO:0007829|PDB:4O6I"
FT HELIX 457..466
FT /evidence="ECO:0007829|PDB:4O6I"
FT STRAND 472..476
FT /evidence="ECO:0007829|PDB:4O6I"
FT HELIX 481..484
FT /evidence="ECO:0007829|PDB:4O6I"
FT TURN 485..487
FT /evidence="ECO:0007829|PDB:4O6I"
FT HELIX 488..495
FT /evidence="ECO:0007829|PDB:4O6I"
FT HELIX 496..498
FT /evidence="ECO:0007829|PDB:4O6I"
FT STRAND 509..511
FT /evidence="ECO:0007829|PDB:4O6I"
FT HELIX 519..531
FT /evidence="ECO:0007829|PDB:4O6I"
FT STRAND 541..544
FT /evidence="ECO:0007829|PDB:4O6I"
FT HELIX 546..549
FT /evidence="ECO:0007829|PDB:4O6I"
SQ SEQUENCE 558 AA; 62177 MW; 5B8CF94BB9FE1B88 CRC64;
MSLSKEVKSF QWTQALRREL QSFTSDVKAA VIKDATNLLN GLDFSEVSNV QRIMRKEKRD
DKDLQRLRSL NQTVHSLVDL KSTSKKNVLK VGRLSAEELM SLAADLEKLK AKIMRSERPQ
ASGVYMGNLT TQQLDQRSQI LQIVGMRKPQ QGASGVVRVW DVKDSSLLNN QFGTMPSLTM
ACMAKQSQTP LNDVVQALTD LGLLYTVKYP NLNDLERLKD KHPVLGVITE QQSSINISGY
NFSLGAAVKA GAALLDGGNM LESILIKPSN SEDLLKAVLG AKRKLNMFVS DQVGDRNPYE
NILYKVCLSG EGWPYIACRT SIVGRAWENT TIDLTSEKPA VNSPRPAPGA AGPPQVGLSY
SQTMLLKDLM GGIDPNAPTW IDIEGRFNDP VEIAIFQPQN GQFIHFYREP VDQKQFKQDS
KYSHGMDLAD LFNAQPGLTS SVIGALPQGM VLSCQGSDDI RKLLDSQNRK DIKLIDVEMT
REASREYEDK VWDKYGWLCK MHTGIVRDKK KKEITPHCAL MDCIIFESAS KARLPDLKTV
HNILPHDLIF RGPNVVTL
