NCAP_LASSJ
ID NCAP_LASSJ Reviewed; 569 AA.
AC P13699;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 110.
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};
OS Lassa virus (strain Mouse/Sierra Leone/Josiah/1976) (LASV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX NCBI_TaxID=11622;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=10112; Mastomys natalensis (African soft-furred rat) (Praomys natalensis).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2916333; DOI=10.1016/0042-6822(89)90287-0;
RA Auperin D.D., McCormick J.B.;
RT "Nucleotide sequence of the Lassa virus (Josiah strain) S genome RNA and
RT amino acid sequence comparison of the N and GPC proteins to other
RT arenaviruses.";
RL Virology 168:421-425(1989).
RN [2]
RP INTERACTION WITH PROTEIN Z.
RX PubMed=15019244; DOI=10.1016/j.virusres.2003.11.017;
RA Eichler R., Strecker T., Kolesnikova L., ter Meulen J., Weissenhorn W.,
RA Becker S., Klenk H.D., Garten W., Lenz O.;
RT "Characterization of the Lassa virus matrix protein Z: electron microscopic
RT study of virus-like particles and interaction with the nucleoprotein
RT (NP).";
RL Virus Res. 100:249-255(2004).
RN [3]
RP INTERACTION WITH HOST IKBKE.
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 [4]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH MANGANESE AND ZINC,
RP FUNCTION, AND MUTAGENESIS OF ASP-389; GLU-391 AND ASP-466.
RX PubMed=21085117; DOI=10.1038/nature09605;
RA Qi X., Lan S., Wang W., Schelde L.M., Dong H., Wallat G.D., Ly H.,
RA Liang Y., Dong C.;
RT "Cap binding and immune evasion revealed by Lassa nucleoprotein
RT structure.";
RL Nature 468:779-783(2010).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 342-569 IN COMPLEX WITH MANGANESE
RP AND ZINC, AND FUNCTION.
RX PubMed=21262835; DOI=10.1073/pnas.1016404108;
RA Hastie K.M., Kimberlin C.R., Zandonatti M.A., MacRae I.J., Saphire E.O.;
RT "Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3' to
RT 5' exonuclease activity essential for immune suppression.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:2396-2401(2011).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.91 ANGSTROMS) OF 342-569 IN COMPLEX WITH ZINC, AND
RP FUNCTION.
RX PubMed=22937163; DOI=10.1371/journal.pone.0044211;
RA Hastie K.M., King L.B., Zandonatti M.A., Saphire E.O.;
RT "Structural basis for the dsRNA specificity of the Lassa virus NP
RT exonuclease.";
RL PLoS ONE 7:E44211-E44211(2012).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) OF 364-569 IN COMPLEX WITH ZINC, AND
RP FUNCTION.
RX PubMed=23615902; DOI=10.1074/jbc.m112.420521;
RA Jiang X., Huang Q., Wang W., Dong H., Ly H., Liang Y., Dong C.;
RT "Structures of arenaviral nucleoproteins with triphosphate dsRNA reveal a
RT unique mechanism of immune suppression.";
RL J. Biol. Chem. 288:16949-16959(2013).
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:21085117, ECO:0000269|PubMed:21262835,
CC ECO:0000269|PubMed:22937163, ECO:0000269|PubMed:23615902}.
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 (PubMed:15019244). Interacts with protein L; this interaction
CC does not interfere with Z-L interaction. Interacts with host IKBKE (via
CC Protein kinase domain); the interaction inhibits IKBKE kinase activity
CC (PubMed:22532683). {ECO:0000255|HAMAP-Rule:MF_04085,
CC ECO:0000269|PubMed:15019244, ECO:0000269|PubMed:22532683}.
CC -!- INTERACTION:
CC P13699; P13699: N; NbExp=2; IntAct=EBI-15893081, EBI-15893081;
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04085}. Host
CC cytoplasm {ECO:0000255|HAMAP-Rule:MF_04085}.
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 ECO:0000269|PubMed:21085117, ECO:0000269|PubMed:21262835}.
CC -!- SIMILARITY: Belongs to the arenaviridae nucleocapsid protein family.
CC {ECO:0000255|HAMAP-Rule:MF_04085}.
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DR EMBL; J04324; AAA46285.1; -; Genomic_RNA.
DR PIR; A31294; VHXPLJ.
DR RefSeq; NP_694869.1; NC_004296.1.
DR PDB; 3MWP; X-ray; 1.80 A; A/B/C=1-569.
DR PDB; 3MWT; X-ray; 1.98 A; A/B/C=1-569.
DR PDB; 3MX2; X-ray; 1.98 A; A/B/C=1-569.
DR PDB; 3MX5; X-ray; 1.90 A; A/B/C=1-569.
DR PDB; 3Q7B; X-ray; 2.00 A; A=342-569.
DR PDB; 3Q7C; X-ray; 1.50 A; A=342-569.
DR PDB; 4FVU; X-ray; 2.91 A; A=342-569.
DR PDB; 4G9Z; X-ray; 2.03 A; A=364-569.
DR PDB; 4GV3; X-ray; 1.68 A; A=364-569.
DR PDB; 4GV6; X-ray; 1.98 A; A=364-569.
DR PDB; 4GV9; X-ray; 2.46 A; A=364-569.
DR PDB; 7V37; X-ray; 2.40 A; A/B=342-569.
DR PDB; 7V38; X-ray; 2.40 A; A/B=342-569.
DR PDB; 7V39; X-ray; 2.20 A; A/B=342-569.
DR PDB; 7V3A; X-ray; 2.10 A; A/B=342-569.
DR PDB; 7V3B; X-ray; 1.80 A; A/B=342-569.
DR PDB; 7V3C; X-ray; 1.90 A; A/B=342-569.
DR PDBsum; 3MWP; -.
DR PDBsum; 3MWT; -.
DR PDBsum; 3MX2; -.
DR PDBsum; 3MX5; -.
DR PDBsum; 3Q7B; -.
DR PDBsum; 3Q7C; -.
DR PDBsum; 4FVU; -.
DR PDBsum; 4G9Z; -.
DR PDBsum; 4GV3; -.
DR PDBsum; 4GV6; -.
DR PDBsum; 4GV9; -.
DR PDBsum; 7V37; -.
DR PDBsum; 7V38; -.
DR PDBsum; 7V39; -.
DR PDBsum; 7V3A; -.
DR PDBsum; 7V3B; -.
DR PDBsum; 7V3C; -.
DR SMR; P13699; -.
DR DIP; DIP-59217N; -.
DR GeneID; 956584; -.
DR KEGG; vg:956584; -.
DR EvolutionaryTrace; P13699; -.
DR Proteomes; UP000002473; 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:0008408; F:3'-5' exonuclease activity; IMP:CACAO.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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; ISS:UniProtKB.
DR GO; GO:0039696; P:RNA-templated viral transcription; ISS: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 GO; GO:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; IMP:CACAO.
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 InterPro; IPR001680; WD40_repeat.
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..569
FT /note="Nucleoprotein"
FT /id="PRO_0000079192"
FT REGION 54..241
FT /note="Binding site for the cap structure m7GTP"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:21085117"
FT BINDING 389
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:21085117, ECO:0000269|PubMed:21262835"
FT BINDING 391
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:21085117, ECO:0000269|PubMed:21262835"
FT BINDING 399
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:21085117, ECO:0000269|PubMed:21262835,
FT ECO:0000269|PubMed:22937163, ECO:0000269|PubMed:23615902"
FT BINDING 506
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:21085117, ECO:0000269|PubMed:21262835,
FT ECO:0000269|PubMed:22937163, ECO:0000269|PubMed:23615902"
FT BINDING 509
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:21085117, ECO:0000269|PubMed:21262835,
FT ECO:0000269|PubMed:22937163, ECO:0000269|PubMed:23615902"
FT BINDING 529
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:21085117, ECO:0000269|PubMed:21262835,
FT ECO:0000269|PubMed:22937163, ECO:0000269|PubMed:23615902"
FT BINDING 533
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:21085117, ECO:0000269|PubMed:21262835"
FT SITE 466
FT /note="Important for exonuclease activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04085,
FT ECO:0000269|PubMed:21085117"
FT MUTAGEN 389
FT /note="D->A: Loss of RNase activity."
FT /evidence="ECO:0000269|PubMed:21262835"
FT MUTAGEN 391
FT /note="E->A: Loss of RNase activity."
FT /evidence="ECO:0000269|PubMed:21262835"
FT MUTAGEN 466
FT /note="D->A: Loss of RNase activity."
FT /evidence="ECO:0000269|PubMed:21262835"
FT HELIX 8..19
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 21..23
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 28..41
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 44..55
FT /evidence="ECO:0007829|PDB:3MWP"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 61..77
FT /evidence="ECO:0007829|PDB:3MWP"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:3MWP"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 96..117
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 119..122
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 131..143
FT /evidence="ECO:0007829|PDB:3MWP"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 169..172
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 180..191
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 195..209
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 216..225
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 227..231
FT /evidence="ECO:0007829|PDB:3MWP"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:3MWP"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 248..257
FT /evidence="ECO:0007829|PDB:3MWP"
FT STRAND 258..262
FT /evidence="ECO:0007829|PDB:3MX5"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:3MWP"
FT TURN 272..274
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 275..289
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 302..312
FT /evidence="ECO:0007829|PDB:3MWP"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:3MWP"
FT TURN 318..320
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 330..333
FT /evidence="ECO:0007829|PDB:3MWP"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:3MWP"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:3Q7C"
FT HELIX 367..377
FT /evidence="ECO:0007829|PDB:3Q7C"
FT STRAND 387..392
FT /evidence="ECO:0007829|PDB:3Q7C"
FT STRAND 398..404
FT /evidence="ECO:0007829|PDB:3Q7C"
FT TURN 405..408
FT /evidence="ECO:0007829|PDB:3Q7C"
FT STRAND 409..414
FT /evidence="ECO:0007829|PDB:3Q7C"
FT HELIX 420..429
FT /evidence="ECO:0007829|PDB:3Q7C"
FT HELIX 435..438
FT /evidence="ECO:0007829|PDB:3Q7C"
FT STRAND 439..441
FT /evidence="ECO:0007829|PDB:4G9Z"
FT HELIX 445..452
FT /evidence="ECO:0007829|PDB:3Q7C"
FT STRAND 458..463
FT /evidence="ECO:0007829|PDB:3Q7C"
FT HELIX 464..473
FT /evidence="ECO:0007829|PDB:3Q7C"
FT STRAND 479..483
FT /evidence="ECO:0007829|PDB:3Q7C"
FT HELIX 488..491
FT /evidence="ECO:0007829|PDB:3Q7C"
FT TURN 492..494
FT /evidence="ECO:0007829|PDB:3Q7C"
FT HELIX 495..502
FT /evidence="ECO:0007829|PDB:3Q7C"
FT HELIX 503..505
FT /evidence="ECO:0007829|PDB:3Q7C"
FT STRAND 513..515
FT /evidence="ECO:0007829|PDB:3MWP"
FT STRAND 518..521
FT /evidence="ECO:0007829|PDB:3Q7C"
FT STRAND 523..525
FT /evidence="ECO:0007829|PDB:3MWP"
FT HELIX 530..542
FT /evidence="ECO:0007829|PDB:3Q7C"
FT STRAND 551..554
FT /evidence="ECO:0007829|PDB:3Q7C"
FT HELIX 556..559
FT /evidence="ECO:0007829|PDB:3Q7C"
FT STRAND 560..562
FT /evidence="ECO:0007829|PDB:7V3C"
SQ SEQUENCE 569 AA; 62998 MW; 852EA775034DBCFB CRC64;
MSASKEIKSF LWTQSLRREL SGYCSNIKLQ VVKDAQALLH GLDFSEVSNV QRLMRKERRD
DNDLKRLRDL NQAVNNLVEL KSTQQKSILR VGTLTSDDLL ILAADLEKLK SKVIRTERPL
SAGVYMGNLS SQQLDQRRAL LNMIGMSGGN QGARAGRDGV VRVWDVKNAE LLNNQFGTMP
SLTLACLTKQ GQVDLNDAVQ ALTDLGLIYT AKYPNTSDLD RLTQSHPILN MIDTKKSSLN
ISGYNFSLGA AVKAGACMLD GGNMLETIKV SPQTMDGILK SILKVKKALG MFISDTPGER
NPYENILYKI CLSGDGWPYI ASRTSITGRA WENTVVDLES DGKPQKADSN NSSKSLQSAG
FTAGLTYSQL MTLKDAMLQL DPNAKTWMDI EGRPEDPVEI ALYQPSSGCY IHFFREPTDL
KQFKQDAKYS HGIDVTDLFA TQPGLTSAVI DALPRNMVIT CQGSDDIRKL LESQGRKDIK
LIDIALSKTD SRKYENAVWD QYKDLCHMHT GVVVEKKKRG GKEEITPHCA LMDCIMFDAA
VSGGLNTSVL RAVLPRDMVF RTSTPRVVL
