Reviewed, UniProtKB/Swiss-Prot P03476 (NRAM_I71A2)

Names and origin

Protein names

Recommended name:
    Neuraminidase
    EC=3.2.1.18

Gene names

Name:

NA

Organism

Influenza A virus (strain A/Turkey/Oregon/1971 H7N3)

Taxonomic identifier

385636 [NCBI]

Taxonomic lineage

Viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A

Virus host

Aves [TaxID: 8782]

Protein attributes

Sequence length	469 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Inferred from homology.

General annotation (Comments)

Function	Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication.
Catalytic activity	Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates.
Cofactor	Binds 1 calcium ion By similarity.
Enzyme regulation	Inhibited by the neuraminidase inhibitors zanamivir (Relenza) and oseltamivir (Tamiflu). These drugs interfere with the release of progeny virus from infected cells and are effective against all influenza strains. Resistance to neuraminidase inhibitors is quite rare.
Subunit structure	Homotetramer By similarity.
Subcellular location	Virion membraneBy similarity. Apical cell membrane; Single-pass type II membrane proteinBy similarity. Note= Preferentially accumulates at the apical plasma membrane in infected polarized epithelial cells, which is the virus assembly site. Uses lipid rafts for cell surface transport and apical sorting. In the virion, forms a mushroom-shaped spike on the surface of the membrane By similarity.
Domain	Intact N-terminus is essential for virion morphogenesis. Possess two apical sorting signals, one in the ectodomain, which is likely to be a glycan, and the other in the transmembrane domain. The transmembrane domain also plays a role in lipid raft association By similarity.
Post-translational modification	N-glycosylated By similarity.
Miscellaneous	The influenza A genome consist of 8 RNA segments. Genetic variation of hemagglutinin and/or neuraminidase genes results in the emergence of new influenza strains. The mechanism of variation can be the result of point mutations or the result of genetic reassortment between segments of two different strains.
Sequence similarities	Belongs to the glycosyl hydrolase 34 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Virion
Domain	Signal-anchor Transmembrane
Ligand	Calcium Metal-binding
Molecular function	Glycosidase Hydrolase
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW exo-alpha-sialidase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 469	469	Neuraminidase		PRO_0000078719
Regions
	Topological domain	1 – 6	6	Cytoplasmic Potential
	Transmembrane	7 – 29	23	Signal-anchor for type II membrane protein Potential
	Topological domain	30 – 469	440	Extracellular Potential
	Region	11 – 33	23	Involved in apical transport and lipid raft association By similarity
	Region	39 – 90	52	Hypervariable stalk region By similarity
	Region	91 – 469	379	Head of neuraminidase By similarity
Sites
	Active site	151	1	Potential
	Active site	278	1	Potential
	Active site	405	1	Potential
	Metal binding	294	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	298	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	324	1	Calcium By similarity
	Binding site	118	1	Substrate Potential
	Binding site	293	1	Substrate Potential
	Binding site	370	1	Substrate Potential
Amino acid modifications
	Glycosylation	57	1	N-linked (GlcNAc...) Potential
	Glycosylation	66	1	N-linked (GlcNAc...) Potential
	Glycosylation	72	1	N-linked (GlcNAc...) Potential
	Glycosylation	146	1	N-linked (GlcNAc...) Potential
	Glycosylation	308	1	N-linked (GlcNAc...) Potential
	Disulfide bond	92 ↔ 416		By similarity
	Disulfide bond	124 ↔ 129		By similarity
	Disulfide bond	184 ↔ 231		By similarity
	Disulfide bond	233 ↔ 238		By similarity
	Disulfide bond	280 ↔ 292		By similarity
	Disulfide bond	282 ↔ 290		By similarity
	Disulfide bond	318 ↔ 336		By similarity
	Disulfide bond	420 ↔ 447		By similarity
Experimental info
	Sequence conflict	94	1	F → S in CAA24276. Ref.2
	Sequence conflict	94	1	F → S in AAA43361. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P03476-1 [UniParc]. Last modified March 20, 2007. Version 2. Checksum: 1758078B2ABE0F65	FASTA	469	51,790
	10 20 30 40 50 60 MNPNQKIITI GVVNTTLSTI ALLIGVGNLV FNTVIHEKIG NHQTVIHPTI TTPAVPNCSD 70 80 90 100 110 120 TIITYNNTVI NNITTTIITE AERLFKPPLP LCPFRGFFPF HKDNAIRLGE NKDVIVTREP 130 140 150 160 170 180 YVSCDNDNCW SFALAQGALL GTKHSNGTIK DRTPYRSLIR FPIGTAPVLG NYKEICIAWS 190 200 210 220 230 240 SSSCFDGKEW MHVCMTGNDN DASAQIIYAG RMTDSIKSWR KDILRTQESE CQCIGGTCVV 250 260 270 280 290 300 AVTDGPAANS ADHRVYWIRE GRIVKYENVP KTKIQHLEEC SCYVDIDVYC ICRDNWKGSN 310 320 330 340 350 360 RPWMRINNET ILETGYVCSK FHSDTPRPAD PSTVSCDSPS NINGGPGVKG FGFKAGNDVW 370 380 390 400 410 420 LGRTVSTSGR SGFEIIKVTD GWINSPNHAK SVTQTLVSNN DWSGYSGSFI VKTKGCFQPC 430 440 450 460 FYVELIRGRP NKNDDVSWTS NSIVTFCGLD NEPGSGNWPD GSNIGFMPK

References

[1]	"Establishment of gene library of all haemagglutinin (HA) and neuraminidase (NA) subtypes for the control of influenza A virus infection." Kida H., Sakoda Y. Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Variation in the membrane-insertion and 'stalk' sequences in eight subtypes of influenza type A virus neuraminidase." Blok J., Air G.M. Biochemistry 21:4001-4007(1982) [PubMed: 6896994] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-94.
[3]	"Sequence variation at the 3' end of the neuraminidase gene from 39 influenza type A viruses." Blok J., Air G.M. Virology 121:211-229(1982) [PubMed: 6927853] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-94.
[4]	"Amelioration of influenza virus pathogenesis in chickens attributed to the enhanced interferon-inducing capacity of a virus with a truncated NS1 gene." Cauthen A.N., Swayne D.E., Sekellick M.J., Marcus P.I., Suarez D.L. J. Virol. 81:1838-1847(2007) [PubMed: 17121796] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[5]	"Assembly and budding of influenza virus." Nayak D.P., Hui E.K., Barman S. Virus Res. 106:147-165(2004) [PubMed: 15567494] [Abstract] Cited for: REVIEW.
[6]	"Neuraminidase inhibitors for influenza." Moscona A. N. Engl. J. Med. 353:1363-1373(2005) [PubMed: 16192481] [Abstract] Cited for: REVIEW.
[7]	"Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses." Suzuki Y. Biol. Pharm. Bull. 28:399-408(2005) [PubMed: 15744059] [Abstract] Cited for: REVIEW.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB276110 Genomic RNA. Translation: BAF34372.1. V01092 Genomic RNA. Translation: CAA24276.1. K01011 Genomic RNA. Translation: AAA43361.1. DQ870890 Genomic RNA. Translation: ABH04381.1. DQ870896 Genomic RNA. Translation: ABH04387.1.
3D structure databases
ModBase	Search...
Family and domain databases
ProDom	PD000431. Glyco_hydro_34. 1 hit. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
ProtoNet	Search...

Entry information

Entry name

NRAM_I71A2

Accession

Primary (citable) accession number: P03476
Secondary accession number(s): Q05JI0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	March 20, 2007
Last modified:	November 4, 2008
This is version 64 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)