P03466 (NCAP_I34A1) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nucleoprotein

Alternative name(s):
Nucleocapsid protein
Short name=Protein N

Gene names

Name:

NP

Organism

Influenza A virus (strain A/Puerto Rico/8/1934 H1N1) [Reference proteome]

Taxonomic identifier

211044 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A › Influenza A virus › H1N1 subtype

Virus host

Aves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length	498 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Encapsidates the negative strand viral RNA, protecting it from nucleases. The encapsidated genomic RNA is termed the ribonucleoprotein (RNP) and serves as template for transcription and replication. The RNP needs to be localized in the nucleus to start an infectious cycle, but is too large to diffuse through the nuclear pore complex. NP comprises at least 2 nuclear localization signals and is responsible of the active RNP import into the nucleus through the cellular importin alpha/beta pathway. Later in the infection, nucleus export of RNP are mediated through viral proteins NEP interacting with M1 which binds nucleoproteins. It is possible that the nucleoprotein binds directly exportin-1 (XPO1) and plays an active role in RNP nuclear export. M1 interaction with RNP seems to hide nucleoprotein's nuclear localization signals. Soon after a virion infects a new cell, M1 dissociates from the RNP under acidification of the virion driven by M2 protein. Dissociation of M1 from RNP unmask nucleoprotein's nuclear localization signals, targeting the RNP to the nucleus.
Subunit structure	Homomultimerizes to form the nucleocapsid. May bind human exportin-1. Binds to viral genomic RNA. Protein-RNA contacts are mediated by a combination of electrostatic interactions between positively charged residues and the phosphate backbone and planar interactions between aromatic side chains and bases. Ref.10 Ref.12
Subcellular location	Virion Potential. Host nucleus Ref.8 Ref.9.
Post-translational modification	Late in virus-infected cells, may be cleaved from a 56-kDa protein to a 53-kDa protein by a cellular caspase. This cleavage might be a marker for the onset of apoptosis in infected cells or have a specific function in virus host interaction By similarity.
Sequence similarities	Belongs to the influenza viruses nucleoprotein family.

Ontologies

Keywords
Biological process	Host-virus interaction Viral penetration into host nucleus Virus entry into host cell
Cellular component	Host nucleus Virion
Ligand	RNA-binding Viral nucleoprotein
Molecular function	Ribonucleoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular transport of viral material Traceable author statement. Source: Reactome uncoating of virus Traceable author statement. Source: Reactome viral entry into host cell via membrane fusion with the plasma membrane Traceable author statement. Source: Reactome viral entry into host cell via receptor-mediated endocytosis Traceable author statement. Source: Reactome viral genome maturation Traceable author statement. Source: Reactome viral genome packaging Traceable author statement. Source: Reactome viral penetration into host nucleus Inferred from electronic annotation. Source: UniProtKB-KW viral release from host cell Traceable author statement. Source: Reactome viral transcription Traceable author statement. Source: Reactome
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome cytosol Traceable author statement. Source: Reactome endosome lumen Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome host cell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome ribonucleoprotein complex Inferred from electronic annotation. Source: UniProtKB-KW virion Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 498	498	Nucleoprotein		PRO_0000079092
Regions
	Motif	1 – 18	18	Unconventional nuclear localization signal
	Motif	198 – 216	19	Bipartite nuclear localization signal
Experimental info
	Mutagenesis	8	1	R → A: No effect on RNA-binding activity. Ref.11
	Mutagenesis	104	1	W → A: No effect on RNA-binding activity. Ref.11
	Mutagenesis	120	1	W → A: Partial loss of RNA-binding activity. Ref.11
	Mutagenesis	139	1	W → A: Partial loss of RNA-binding activity. Ref.11
	Mutagenesis	148	1	Y → A: No effect on RNA-binding activity. Ref.11
	Mutagenesis	150	1	R → A: No effect on RNA-binding activity. Ref.11
	Mutagenesis	156	1	R → A: No effect on RNA-binding activity. Ref.11
	Mutagenesis	175	1	R → A: No effect on RNA-binding activity. Ref.11
	Mutagenesis	199	1	R → A: 60% loss of Homomultimerization affinity. No effect on RNA-binding activity. Ref.10 Ref.11
	Mutagenesis	204	1	R → A: No effect on RNA-binding activity. Ref.11
	Mutagenesis	207	1	W → A: No effect on RNA-binding activity. Ref.11
	Mutagenesis	208	1	R → A: No effect on RNA-binding activity. Ref.11
	Mutagenesis	213	1	R → A: No effect on RNA-binding activity. Ref.11
	Mutagenesis	267	1	R → A: Complete loss of RNA-binding activity. Ref.11
	Mutagenesis	330	1	W → A: Complete loss of RNA-binding activity. Ref.11
	Mutagenesis	386	1	W → A: No effect on RNA-binding activity. Ref.11
	Mutagenesis	391	1	R → A: No effect on RNA-binding activity. Ref.11
	Mutagenesis	412	1	F → A: Complete loss of RNA-binding activity. Ref.11
	Mutagenesis	416	1	R → A: Complete loss of Homomultimerization. Complete loss of RNA-binding activity. Ref.10 Ref.11
	Mutagenesis	479	1	F → A: 2-fold increase of self association. Ref.10
	Sequence conflict	135	1	H → N in CAA24268. Ref.1
	Sequence conflict	247	1	N → D in CAA24268. Ref.1
	Sequence conflict	353	1	L → V in CAA24268. Ref.1
	Sequence conflict	425	1	I → V in CAA24268. Ref.1
	Sequence conflict	430	1	N → T in CAA24268. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P03466 [UniParc]. Last modified September 11, 2007. Version 2. Checksum: 4F750FEF05D6E668	FASTA	498	56,210
	10 20 30 40 50 60 MASQGTKRSY EQMETDGERQ NATEIRASVG KMIGGIGRFY IQMCTELKLS DYEGRLIQNS 70 80 90 100 110 120 LTIERMVLSA FDERRNKYLE EHPSAGKDPK KTGGPIYRRV NGKWMRELIL YDKEEIRRIW 130 140 150 160 170 180 RQANNGDDAT AGLTHMMIWH SNLNDATYQR TRALVRTGMD PRMCSLMQGS TLPRRSGAAG 190 200 210 220 230 240 AAVKGVGTMV MELVRMIKRG INDRNFWRGE NGRKTRIAYE RMCNILKGKF QTAAQKAMMD 250 260 270 280 290 300 QVRESRNPGN AEFEDLTFLA RSALILRGSV AHKSCLPACV YGPAVASGYD FEREGYSLVG 310 320 330 340 350 360 IDPFRLLQNS QVYSLIRPNE NPAHKSQLVW MACHSAAFED LRVLSFIKGT KVLPRGKLST 370 380 390 400 410 420 RGVQIASNEN METMESSTLE LRSRYWAIRT RSGGNTNQQR ASAGQISIQP TFSVQRNLPF 430 440 450 460 470 480 DRTTIMAAFN GNTEGRTSDM RTEIIRMMES ARPEDVSFQG RGVFELSDEK AASPIVPSFD 490 MSNEGSYFFG DNAEEYDN

References

[1]	"The structure of the gene encoding the nucleoprotein of human influenza virus A/PR/8/34." Winter G., Fields S. Virology 114:423-428(1981) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Complete nucleotide sequence of the nucleoprotein gene from the human influenza strain A/PR/8/34 (HON1)." van Rompuy L., Min Jou W., Huylebroeck D., Devos R., Fiers W. Eur. J. Biochem. 116:347-353(1981) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]	Erratum van Rompuy L., Min Jou W., Huylebroeck D., Devos R., Fiers W. Eur. J. Biochem. 116:645-645(1981) Cited for: SEQUENCE REVISION.
[4]	"Plasmid-only rescue of influenza A virus vaccine candidates." Schickli J.H., Flandorfer A., Nakaya T., Martinez-Sobrido L., Garcia-Sastre A., Palese P. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356:1965-1973(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[5]	"Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments." de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F., Osterhaus A.D.M.E., Fouchier R.A.M. Virus Res. 103:155-161(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], REVERSE GENETICS.
[6]	"Fluorescent antigen-transfected target cell cytotoxic T lymphocyte assay for ex vivo detection of antigen-specific cell-mediated cytotoxicity." van Baalen C.A., Kwa D., Verschuren E.J., Reedijk M.L., Boon A.C., de Mutsert G., Rimmelzwaan G.F., Osterhaus A.D., Gruters R.A. J. Infect. Dis. 192:1183-1190(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[7]	"The NIAID influenza genome sequencing project." Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V., Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H., Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y. , Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T. Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[8]	"A classical bipartite nuclear localization signal on Thogoto and influenza A virus nucleoproteins." Weber F., Kochs G., Gruber S., Haller O. Virology 250:9-18(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Modulation of nuclear localization of the influenza virus nucleoprotein through interaction with actin filaments." Digard P., Elton D., Bishop K., Medcalf E., Weeds A., Pope B. J. Virol. 73:2222-2231(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"Oligomerization of the influenza virus nucleoprotein: identification of positive and negative sequence elements." Elton D., Medcalf E., Bishop K., Digard P. Virology 260:190-200(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, MUTAGENESIS OF ARG-199; ARG-416 AND PHE-479.
[11]	"Identification of amino acid residues of influenza virus nucleoprotein essential for RNA binding." Elton D., Medcalf L., Bishop K., Harrison D., Digard P. J. Virol. 73:7357-7367(1999) [PubMed] [Europe PMC] [Abstract] Cited for: RNA-BINDING, MUTAGENESIS OF ARG-8; TRP-104; TRP-120; TRP-139; TYR-148; ARG-150; ARG-156; ARG-175; ARG-199; ARG-204; TRP-207; ARG-208; ARG-213; ARG-267; TRP-330; TRP-386; ARG-391; PHE-412 AND ARG-416.
[12]	"Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway." Elton D., Simpson-Holley M., Archer K., Medcalf L., Hallam R., McCauley J., Digard P. J. Virol. 75:408-419(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HUMAN XPO1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

V01084 Genomic RNA. Translation: CAA24268.1.
J02147 Genomic RNA. Translation: AAA43467.1.
AF389119 Genomic RNA. Translation: AAM75159.1.
EF467822 Genomic RNA. Translation: ABO21710.1.
AY936882 Genomic RNA. Translation: AAX39501.1.
CY009447 Genomic RNA. Translation: ABD77679.1.

RefSeq

NP_040982.1. NC_002019.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BST	X-ray	2.10	C	383-391	[»]
2WFS	electron microscopy	12.00	A/B/C/D/E/F/G/H/I	8-498	[»]

ProteinModelPortal

P03466.

SMR

P03466. Positions 22-496.

ModBase

Search...

Protein-protein interaction databases

IntAct

P03466. 19 interactions.

MINT

MINT-3375097.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

956531.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Family and domain databases

InterPro

IPR002141. Flu_NP.
[Graphical view]

Pfam

PF00506. Flu_NP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P03466.

Entry information

Entry name

NCAP_I34A1

Accession

Primary (citable) accession number: P03466
Secondary accession number(s): Q20N34 , Q58NB3, Q67228, Q80AB4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	September 11, 2007
Last modified:	May 29, 2013
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program