NCAP_SINV
ID NCAP_SINV Reviewed; 428 AA.
AC Q89462;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 102.
DE RecName: Full=Nucleoprotein;
DE EC=3.1.-.- {ECO:0000269|PubMed:27261891};
DE AltName: Full=Nucleocapsid protein;
DE Short=Protein N;
GN Name=N;
OS Sin Nombre orthohantavirus (SNV) (Sin Nombre virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC Orthohantavirus.
OX NCBI_TaxID=1980491;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=10042; Peromyscus maniculatus (North American deer mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=NM H10 {ECO:0000312|EMBL:AAA75529.1};
RX PubMed=8178455; DOI=10.1006/viro.1994.1235;
RA Spiropoulou C.F., Morzunov S., Feldmann H., Sanchez A., Peters C.J.,
RA Nichol S.T.;
RT "Genome structure and variability of a virus causing hantavirus pulmonary
RT syndrome.";
RL Virology 200:715-723(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7494336; DOI=10.1128/jvi.69.12.8132-8136.1995;
RA Chizhikov V.E., Spiropoulou C.F., Morzunov S.P., Monroe M.C., Peters C.J.,
RA Nichol S.T.;
RT "Complete genetic characterization and analysis of isolation of Sin Nombre
RT virus.";
RL J. Virol. 69:8132-8136(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=1 {ECO:0000312|EMBL:AFV71286.1}, and
RC 2 {ECO:0000312|EMBL:AFV71287.1};
RX PubMed=23110096; DOI=10.1371/journal.pone.0047731;
RA Bagamian K.H., Towner J.S., Kuenzi A.J., Douglass R.J., Rollin P.E.,
RA Waller L.A., Mills J.N.;
RT "Transmission ecology of sin nombre hantavirus in naturally infected north
RT american deermouse populations in outdoor enclosures.";
RL PLoS ONE 7:E47731-E47731(2012).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=1 {ECO:0000312|EMBL:AFV71284.1};
RA Bagamian K.H.;
RT "Evolution of Sin Nombre hantavirus in Montana.";
RL Submitted (FEB-2012) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=77734 {ECO:0000312|EMBL:AIA08877.1};
RX PubMed=24778254; DOI=10.1073/pnas.1401998111;
RA Safronetz D., Prescott J., Feldmann F., Haddock E., Rosenke R., Okumura A.,
RA Brining D., Dahlstrom E., Porcella S.F., Ebihara H., Scott D.P., Hjelle B.,
RA Feldmann H.;
RT "Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:7114-7119(2014).
RN [6]
RP COILED COIL.
RX PubMed=12019266; DOI=10.1074/jbc.m203395200;
RA Alfadhli A., Steel E., Finlay L., Baechinger H.P., Barklis E.;
RT "Hantavirus nucleocapsid protein coiled-coil domains.";
RL J. Biol. Chem. 277:27103-27108(2002).
RN [7]
RP SUBUNIT, RNA-BINDING, AND FUNCTION.
RX PubMed=15254200; DOI=10.1128/jvi.78.15.8281-8288.2004;
RA Mir M.A., Panganiban A.T.;
RT "Trimeric hantavirus nucleocapsid protein binds specifically to the viral
RT RNA panhandle.";
RL J. Virol. 78:8281-8288(2004).
RN [8]
RP SUBUNIT, RNA-BINDING, AND FUNCTION.
RX PubMed=15650206; DOI=10.1128/jvi.79.3.1824-1835.2005;
RA Mir M.A., Panganiban A.T.;
RT "The hantavirus nucleocapsid protein recognizes specific features of the
RT viral RNA panhandle and is altered in conformation upon RNA binding.";
RL J. Virol. 79:1824-1835(2005).
RN [9]
RP FUNCTION.
RX PubMed=16775315; DOI=10.1128/jvi.00147-06;
RA Mir M.A., Panganiban A.T.;
RT "Characterization of the RNA chaperone activity of hantavirus nucleocapsid
RT protein.";
RL J. Virol. 80:6276-6285(2006).
RN [10]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=16971445; DOI=10.1128/jvi.00820-06;
RA Mir M.A., Brown B., Hjelle B., Duran W.A., Panganiban A.T.;
RT "Hantavirus N protein exhibits genus-specific recognition of the viral RNA
RT panhandle.";
RL J. Virol. 80:11283-11292(2006).
RN [11]
RP FUNCTION.
RX PubMed=19047634; DOI=10.1073/pnas.0807211105;
RA Mir M.A., Duran W.A., Hjelle B.L., Ye C., Panganiban A.T.;
RT "Storage of cellular 5' mRNA caps in P bodies for viral cap-snatching.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:19294-19299(2008).
RN [12]
RP FUNCTION.
RX PubMed=18971945; DOI=10.1038/emboj.2008.228;
RA Mir M.A., Panganiban A.T.;
RT "A protein that replaces the entire cellular eIF4F complex.";
RL EMBO J. 27:3129-3139(2008).
RN [13]
RP INTERACTION WITH HOST RIBOSOMAL PROTEIN RPS19, AND FUNCTION.
RX PubMed=20844026; DOI=10.1128/jvi.01388-10;
RA Haque A., Mir M.A.;
RT "Interaction of hantavirus nucleocapsid protein with ribosomal protein
RT S19.";
RL J. Virol. 84:12450-12453(2010).
RN [14]
RP DOMAIN, AND FUNCTION.
RC STRAIN=77734;
RX PubMed=20164193; DOI=10.1074/jbc.m110.102459;
RA Mir M.A., Sheema S., Haseeb A., Haque A.;
RT "Hantavirus nucleocapsid protein has distinct m7G cap- and RNA-binding
RT sites.";
RL J. Biol. Chem. 285:11357-11368(2010).
RN [15]
RP DOMAIN, FUNCTION, AND RNA-BINDING.
RX PubMed=21378500; DOI=10.4161/rna.7.6.13862;
RA Brown B.A., Panganiban A.T.;
RT "Identification of a region of hantavirus nucleocapsid protein required for
RT RNA chaperone activity.";
RL RNA Biol. 7:830-837(2010).
RN [16]
RP INTERACTION WITH VIRAL RDRP.
RX PubMed=24850733; DOI=10.1128/jvi.00405-14;
RA Cheng E., Wang Z., Mir M.A.;
RT "Interaction between hantavirus nucleocapsid protein (N) and RNA-dependent
RT RNA polymerase (RdRp) mutants reveals the requirement of an N-RdRp
RT interaction for viral RNA synthesis.";
RL J. Virol. 88:8706-8712(2014).
RN [17]
RP FUNCTION, INTERACTION WITH HOST RIBOSOMAL PROTEIN RPS19, AND SUBUNIT.
RX PubMed=25062117; DOI=10.1042/bj20140449;
RA Ganaie S.S., Haque A., Cheng E., Bonny T.S., Salim N.N., Mir M.A.;
RT "Ribosomal protein S19-binding domain provides insights into hantavirus
RT nucleocapsid protein-mediated translation initiation mechanism.";
RL Biochem. J. 464:109-121(2014).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-88 AND ASP-103, AND
RP COFACTOR.
RX PubMed=27261891; DOI=10.1016/j.virol.2016.05.009;
RA Moencke-Buchner E., Szczepek M., Bokelmann M., Heinemann P., Raftery M.J.,
RA Krueger D.H., Reuter M.;
RT "Sin Nombre hantavirus nucleocapsid protein exhibits a metal-dependent DNA-
RT specific endonucleolytic activity.";
RL Virology 496:67-76(2016).
RN [19] {ECO:0007744|PDB:2IC6, ECO:0007744|PDB:2IC9}
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) OF 1-75, DOMAIN, AND COILED COIL.
RX PubMed=17222867; DOI=10.1016/j.jmb.2006.12.046;
RA Boudko S.P., Kuhn R.J., Rossmann M.G.;
RT "The coiled-coil domain structure of the Sin Nombre virus nucleocapsid
RT protein.";
RL J. Mol. Biol. 366:1538-1544(2007).
RN [20] {ECO:0007744|PDB:5E05, ECO:0007744|PDB:5E06}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 114-397, SUBUNIT, AND MUTAGENESIS
RP OF LEU-102; VAL-104; ILE-107; LEU-405; LEU-408; LEU-412 AND ILE-415.
RX PubMed=26559827; DOI=10.1128/jvi.02523-15;
RA Guo Y., Wang W., Sun Y., Ma C., Wang X., Wang X., Liu P., Shen S., Li B.,
RA Lin J., Deng F., Wang H., Lou Z.;
RT "Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein
RT Reveals the Mechanism for Ribonucleoprotein Complex Formation.";
RL J. Virol. 90:1048-1061(2016).
CC -!- FUNCTION: Encapsidates the genome protecting it from nucleases
CC (Probable). The encapsidated genomic RNA is termed the nucleocapsid
CC (NC) and serves as template for transcription and replication
CC (Probable). The nucleocapsid has a left-handed helical structure (By
CC similarity). As a trimer, specifically binds and acts as a chaperone to
CC unwind the panhandle structure formed by the viral RNA (vRNA) termini
CC (PubMed:15650206, PubMed:15254200, PubMed:21378500, PubMed:16971445,
CC PubMed:25062117, PubMed:16775315). Involved in the transcription and
CC replication initiation of vRNA by mediating primer annealing
CC (PubMed:20164193). Plays a role in cap snatching by sequestering capped
CC RNAs in P bodies for use by the viral RdRp during transcription
CC initiation (PubMed:19047634). Substitutes for the cellular cap-binding
CC complex (eIF4F) to preferentially facilitate the translation of capped
CC mRNAs (PubMed:18971945, PubMed:25062117). Initiates the translation by
CC specifically binding to the cap and 40S ribosomal subunit
CC (PubMed:20844026, PubMed:20164193, PubMed:25062117). Prevents the viral
CC glycoprotein N (Gn) from autophagy-dependent breakdown maybe by
CC blocking autophagosome formation (By similarity). Inhibits host
CC EIF2AK2/PKR dimerization to prevent PKR-induced translational shutdown
CC in cells and thus the activation of the antiviral state (By
CC similarity). Also displays sequence-unspecific DNA endonuclease
CC activity (PubMed:27261891). {ECO:0000250|UniProtKB:O36307,
CC ECO:0000250|UniProtKB:P05133, ECO:0000269|PubMed:15254200,
CC ECO:0000269|PubMed:15650206, ECO:0000269|PubMed:16775315,
CC ECO:0000269|PubMed:16971445, ECO:0000269|PubMed:18971945,
CC ECO:0000269|PubMed:19047634, ECO:0000269|PubMed:20164193,
CC ECO:0000269|PubMed:20844026, ECO:0000269|PubMed:21378500,
CC ECO:0000269|PubMed:25062117, ECO:0000269|PubMed:27261891, ECO:0000305}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:27261891};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:27261891};
CC -!- SUBUNIT: Homotrimer (PubMed:15650206, PubMed:15254200,
CC PubMed:25062117). Homomultimer (PubMed:26559827). Homomultimerizes and
CC binds to viral genomic RNA to form the nucleocapsid (By similarity)
CC (PubMed:26559827). Interacts with host MAP1LC3B; this interaction
CC participates to the protection of Gn from virus-triggered autophagy.
CC Interacts with host SNAP29; this interaction participates to the
CC protection of glycoprotein N from virus-triggered autophagy (By
CC similarity). Interacts (via N-terminus) with host RPS19; this
CC interaction probably mediates the loading of the 40S ribosomal subunit
CC on viral capped mRNA during N-mediated translation initiation
CC (PubMed:20844026, PubMed:25062117). Interacts with the viral RdRp; this
CC interaction is required for RdRp function (PubMed:24850733). Interacts
CC with host SUMO1 (via N-terminus) (By similarity). Interacts with host
CC DAXX (By similarity). Interacts with the viral glycoprotein N (via C-
CC terminus) (By similarity). Interacts with the viral glycoprotein C (via
CC C-terminus) (By similarity). {ECO:0000250|UniProtKB:P05133,
CC ECO:0000250|UniProtKB:P27313, ECO:0000250|UniProtKB:Q88918,
CC ECO:0000269|PubMed:15254200, ECO:0000269|PubMed:15650206,
CC ECO:0000269|PubMed:20844026, ECO:0000269|PubMed:24850733,
CC ECO:0000269|PubMed:25062117, ECO:0000269|PubMed:26559827}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P05133}. Host
CC cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P05133}. Host
CC Golgi apparatus, host cis-Golgi network {ECO:0000250|UniProtKB:P05133}.
CC Note=Internal protein of virus particle.
CC {ECO:0000250|UniProtKB:P05133}.
CC -!- DOMAIN: The N-terminus is required for chaperone activity and, in
CC trimeric form, this region likely serves in high affinity vRNA
CC panhandle recognition (PubMed:21378500). The N-terminus also contains a
CC coiled coil region, which probably participates in but is insufficient
CC to initiate N trimerization (PubMed:17222867). The YxxL motif is
CC indispensable for the interaction with host MAP1LC3B (By similarity).
CC The central region is involved in specific RNA-binding (By similarity).
CC Has distinct cap- and RNA-binding sites so it can bind simultaneously
CC both the vRNA and mRNA cap (PubMed:20164193).
CC {ECO:0000250|UniProtKB:P05133, ECO:0000269|PubMed:17222867,
CC ECO:0000269|PubMed:20164193, ECO:0000269|PubMed:21378500}.
CC -!- SIMILARITY: Belongs to the hantavirus nucleocapsid protein family.
CC {ECO:0000305}.
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DR EMBL; L25784; AAA75529.1; -; Viral_cRNA.
DR EMBL; L37904; AAC42203.1; -; Genomic_RNA.
DR EMBL; JQ690281; AFV71284.1; -; Viral_cRNA.
DR EMBL; JQ690276; AFV71286.1; -; Viral_cRNA.
DR EMBL; JQ690277; AFV71287.1; -; Viral_cRNA.
DR EMBL; KF537003; AIA08877.1; -; Viral_cRNA.
DR EMBL; KF537006; AIA08880.1; -; Viral_cRNA.
DR RefSeq; NP_941975.1; NC_005216.1.
DR PDB; 2IC6; X-ray; 1.15 A; A/B=1-75.
DR PDB; 2IC9; X-ray; 2.00 A; A/B=1-93.
DR PDB; 5E05; X-ray; 2.30 A; A=114-397.
DR PDB; 5E06; X-ray; 3.00 A; A=114-397.
DR PDBsum; 2IC6; -.
DR PDBsum; 2IC9; -.
DR PDBsum; 5E05; -.
DR PDBsum; 5E06; -.
DR SMR; Q89462; -.
DR GeneID; 2943142; -.
DR KEGG; vg:2943142; -.
DR Proteomes; UP000113911; Genome.
DR Proteomes; UP000167429; Genome.
DR Proteomes; UP000204632; Genome.
DR GO; GO:0019029; C:helical viral capsid; IEA:UniProtKB-UniRule.
DR GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-UniRule.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR InterPro; IPR002214; Hanta_nucleocap.
DR Pfam; PF00846; Hanta_nucleocap; 1.
DR PIRSF; PIRSF003949; N_HantaV; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chaperone; Coiled coil; Endonuclease; Host cytoplasm;
KW Host Golgi apparatus; Hydrolase; Nuclease; Ribonucleoprotein; RNA-binding;
KW Transcription; Transcription regulation; Translation regulation;
KW Viral nucleoprotein; Virion.
FT CHAIN 1..428
FT /note="Nucleoprotein"
FT /id="PRO_0000455187"
FT REGION 1..175
FT /note="Viral panhandle binding"
FT /evidence="ECO:0000269|PubMed:21378500"
FT REGION 1..100
FT /note="Chaperone activity"
FT /evidence="ECO:0000269|PubMed:21378500"
FT REGION 1..79
FT /note="Homomultimerization"
FT /evidence="ECO:0000250|UniProtKB:Q88918"
FT REGION 1..50
FT /note="RdRP binding"
FT /evidence="ECO:0000269|PubMed:24850733"
FT REGION 80..248
FT /note="Interaction with glycoprotein N"
FT /evidence="ECO:0000250|UniProtKB:Q88918"
FT REGION 100..125
FT /note="Homomultimerization"
FT /evidence="ECO:0000250|UniProtKB:P05133"
FT REGION 150..175
FT /note="Interaction with host RPS19"
FT /evidence="ECO:0000269|PubMed:25062117"
FT REGION 175..217
FT /note="Viral RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P05133"
FT REGION 188..191
FT /note="Interaction with host UBE2I/UBC9"
FT /evidence="ECO:0000250|UniProtKB:P05133"
FT REGION 372..428
FT /note="Interaction with host DAXX"
FT /evidence="ECO:0000250|UniProtKB:P27313"
FT REGION 372..420
FT /note="Homomultimerization"
FT /evidence="ECO:0000250|UniProtKB:Q88918"
FT COILED 4..71
FT /evidence="ECO:0000269|PubMed:12019266,
FT ECO:0000269|PubMed:17222867"
FT MOTIF 178..181
FT /note="YxxL"
FT /evidence="ECO:0000250|UniProtKB:P05133"
FT SITE 88
FT /note="Important for the endonuclease activity"
FT /evidence="ECO:0000269|PubMed:27261891"
FT SITE 103
FT /note="Important for the endonuclease activity"
FT /evidence="ECO:0000269|PubMed:27261891"
FT MUTAGEN 88
FT /note="D->A: Complete loss of endonuclease activity; when
FT associated with A-103."
FT /evidence="ECO:0000269|PubMed:27261891"
FT MUTAGEN 102
FT /note="L->A: Loss of homomultimerization."
FT /evidence="ECO:0000269|PubMed:26559827"
FT MUTAGEN 103
FT /note="D->A: Complete loss of endonuclease activity; when
FT associated with A-88."
FT /evidence="ECO:0000269|PubMed:27261891"
FT MUTAGEN 104
FT /note="V->A: Loss of homomultimerization."
FT /evidence="ECO:0000269|PubMed:26559827"
FT MUTAGEN 107
FT /note="I->A: Loss of homomultimerization."
FT /evidence="ECO:0000269|PubMed:26559827"
FT MUTAGEN 405
FT /note="L->A: Loss of homomultimerization."
FT /evidence="ECO:0000269|PubMed:26559827"
FT MUTAGEN 408
FT /note="L->A: Loss of homomultimerization."
FT /evidence="ECO:0000269|PubMed:26559827"
FT MUTAGEN 412
FT /note="L->A: Loss of homomultimerization."
FT /evidence="ECO:0000269|PubMed:26559827"
FT MUTAGEN 415
FT /note="I->A: Loss of homomultimerization."
FT /evidence="ECO:0000269|PubMed:26559827"
SQ SEQUENCE 428 AA; 48177 MW; E93C4B4A8B45F477 CRC64;
MSTLKEVQDN ITLHEQQLVT ARQKLKDAER AVELDPDDVN KSTLQSRRAA VSALETKLGE
LKRELADLIA AQKLASKPVD PTGIEPDDHL KEKSSLRYGN VLDVNSIDLE EPSGQTADWK
SIGLYILSFA LPIILKALYM LSTRGRQTIK ENKGTRIRFK DDSSYEEVNG IRKPRHLYVS
MPTAQSTMKA DEITPGRFRT IACGLFPAQV KARNIISPVM GVIGFSFFVK DWMERIDDFL
AARCPFLPEQ KDPRDAALAT NRAYFITRQL QVDESKVSDI EDLIADARAE SATIFADIAT
PHSVWVFACA PDRCPPTALY VAGMPELGAF FAILQDMRNT IMASKSVGTS EEKLKKKSAF
YQSYLRRTQS MGIQLDQKII ILYMSHWGRE AVNHFHLGDD MDPELRELAQ TLVDIKVREI
SNQEPLKL
