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 24-JAN-2024, entry version 107. 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=3052499; 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}. 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; 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 KEGG; vg:2943142; -. DR OrthoDB; 2640at10239; -. DR Proteomes; UP000113911; Genome. DR Proteomes; UP000167429; Genome. DR Proteomes; UP000204632; Genome. 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:1990904; C:ribonucleoprotein complex; IEA:UniProtKB-KW. DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW. DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW. DR Gene3D; 1.20.58.90; -; 1. 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; Reference proteome; KW Ribonucleoprotein; RNA-binding; Transcription; Transcription regulation; KW Translation regulation; 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" FT HELIX 3..34 FT /evidence="ECO:0007829|PDB:2IC6" FT HELIX 38..71 FT /evidence="ECO:0007829|PDB:2IC6" FT HELIX 119..127 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 131..143 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 145..149 FT /evidence="ECO:0007829|PDB:5E05" FT STRAND 154..159 FT /evidence="ECO:0007829|PDB:5E05" FT STRAND 165..168 FT /evidence="ECO:0007829|PDB:5E05" FT STRAND 171..174 FT /evidence="ECO:0007829|PDB:5E05" FT STRAND 177..180 FT /evidence="ECO:0007829|PDB:5E05" FT STRAND 185..187 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 195..205 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 207..212 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 218..221 FT /evidence="ECO:0007829|PDB:5E05" FT TURN 222..224 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 225..229 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 232..241 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 253..259 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 261..272 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 273..275 FT /evidence="ECO:0007829|PDB:5E06" FT HELIX 278..288 FT /evidence="ECO:0007829|PDB:5E05" FT TURN 289..291 FT /evidence="ECO:0007829|PDB:5E05" FT STRAND 298..300 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 304..307 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 316..318 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 324..341 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 360..369 FT /evidence="ECO:0007829|PDB:5E05" FT HELIX 377..392 FT /evidence="ECO:0007829|PDB:5E05" 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 //