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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

Functioni

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.UniRule annotation

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.

Catalytic activityi

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.UniRule annotation

Cofactori

Ca2+UniRule annotation

Enzyme regulationi

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.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei103SubstrateUniRule annotation1
Active sitei136Proton donor/acceptorUniRule annotation1
Binding sitei137SubstrateUniRule annotation1
Binding sitei278SubstrateUniRule annotation1
Metal bindingi279Calcium; via carbonyl oxygenUniRule annotation1
Metal bindingi283Calcium; via carbonyl oxygenUniRule annotation1
Metal bindingi309CalciumUniRule annotation1
Metal bindingi329Calcium; via carbonyl oxygenUniRule annotation1
Binding sitei353SubstrateUniRule annotation1
Active sitei387NucleophileUniRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGlycosidase, Hydrolase
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-168255. Influenza Life Cycle.
R-HSA-168275. Entry of Influenza Virion into Host Cell via Endocytosis.
R-HSA-168277. Influenza Virus Induced Apoptosis.
R-HSA-168288. Fusion of the Influenza Virion to the Host Cell Endosome.
R-HSA-168298. Release.
R-HSA-168302. Budding.
R-HSA-168303. Packaging of Eight RNA Segments.
R-HSA-168316. Assembly of Viral Components at the Budding Site.
R-HSA-168336. Uncoating of the Influenza Virion.
R-HSA-168874. Transport of HA trimer, NA tetramer and M2 tetramer from the endoplasmic reticulum to the Golgi Apparatus.
R-HSA-192823. Viral mRNA Translation.
SABIO-RKiP03468.

Protein family/group databases

CAZyiGH34. Glycoside Hydrolase Family 34.

Names & Taxonomyi

Protein namesi
Recommended name:
NeuraminidaseUniRule annotation (EC:3.2.1.18UniRule annotation)
Gene namesi
Name:NAUniRule annotation
OrganismiInfluenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Taxonomic identifieri211044 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000116373 Componenti: Genome
  • UP000170967 Componenti: Genome
  • UP000009255 Componenti: Genome
  • UP000109386 Componenti: Genome

Subcellular locationi

  • Virion membrane UniRule annotation
  • Host apical cell membrane UniRule annotation; Single-pass type II membrane protein UniRule annotation

  • 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.UniRule annotation

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 6IntravirionUniRule annotation6
Transmembranei7 – 27HelicalUniRule annotationAdd BLAST21
Topological domaini28 – 454Virion surfaceUniRule annotationAdd BLAST427

GO - Cellular componenti

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2051.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000787121 – 454NeuraminidaseAdd BLAST454

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi44N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi58N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi73N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi77 ↔ 402UniRule annotation
Disulfide bondi109 ↔ 114UniRule annotation
Glycosylationi131N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi169 ↔ 216UniRule annotation
Disulfide bondi218 ↔ 223UniRule annotation
Glycosylationi220N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi264 ↔ 277UniRule annotation
Disulfide bondi266 ↔ 275UniRule annotation
Disulfide bondi303 ↔ 320UniRule annotation
Disulfide bondi406 ↔ 431UniRule annotation

Post-translational modificationi

N-glycosylated.UniRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.UniRule annotation

Protein-protein interaction databases

IntActiP03468. 20 interactors.

Chemistry databases

BindingDBiP03468.

Structurei

3D structure databases

ProteinModelPortaliP03468.
SMRiP03468.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni11 – 33Involved in apical transport and lipid raft associationUniRule annotationAdd BLAST23
Regioni36 – 75Hypervariable stalk regionUniRule annotationAdd BLAST40
Regioni76 – 454Head of neuraminidaseUniRule annotationAdd BLAST379
Regioni262 – 263Substrate bindingUniRule annotation2

Domaini

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.UniRule annotation

Sequence similaritiesi

Belongs to the glycosyl hydrolase 34 family.UniRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

KOiK19392.
OrthoDBiVOG0900006X.

Family and domain databases

CDDicd15483. Influenza_NA. 1 hit.
HAMAPiMF_04071. INFV_NRAM. 1 hit.
InterProiView protein in InterPro
IPR001860. Glyco_hydro_34.
IPR033654. Sialidase_Influenza_A/B.
IPR011040. Sialidases.
PfamiView protein in Pfam
PF00064. Neur. 1 hit.
SUPFAMiSSF50939. SSF50939. 1 hit.

Sequencei

Sequence statusi: Complete.

P03468-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNPNQKIITI GSICLVVGLI SLILQIGNII SIWISHSIQT GSQNHTGICN
60 70 80 90 100
QNIITYKNST WVKDTTSVIL TGNSSLCPIR GWAIYSKDNS IRIGSKGDVF
110 120 130 140 150
VIREPFISCS HLECRTFFLT QGALLNDKHS NGTVKDRSPY RALMSCPVGE
160 170 180 190 200
APSPYNSRFE SVAWSASACH DGMGWLTIGI SGPDNGAVAV LKYNGIITET
210 220 230 240 250
IKSWRKKILR TQESECACVN GSCFTIMTDG PSDGLASYKI FKIEKGKVTK
260 270 280 290 300
SIELNAPNSH YEECSCYPDT GKVMCVCRDN WHGSNRPWVS FDQNLDYQIG
310 320 330 340 350
YICSGVFGDN PRPEDGTGSC GPVYVDGANG VKGFSYRYGN GVWIGRTKSH
360 370 380 390 400
SSRHGFEMIW DPNGWTETDS KFSVRQDVVA MTDWSGYSGS FVQHPELTGL
410 420 430 440 450
DCMRPCFWVE LIRGRPKEKT IWTSASSISF CGVNSDTVDW SWPDGAELPF

SIDK
Length:454
Mass (Da):50,121
Last modified:March 6, 2007 - v2
Checksum:i7C52E0A9FD93A98B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8I → T in AAM75160 (PubMed:11779399).1
Sequence conflicti51Q → H in AAA43415 (PubMed:6927853).1
Sequence conflicti128K → R in AAA43412 (PubMed:7010182).1
Sequence conflicti131N → S in ABO21711 (PubMed:15163504).1
Sequence conflicti131N → S in ABD77678 (Ref. 4) 1
Sequence conflicti314E → K in AAA43412 (PubMed:7010182).1
Sequence conflicti403M → I in AAA43412 (PubMed:7010182).1
Sequence conflicti451S → T in AAA43412 (PubMed:7010182).1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02146 Genomic RNA. Translation: AAA43412.1.
AF389120 Genomic RNA. Translation: AAM75160.1.
EF467823 Genomic RNA. Translation: ABO21711.1.
CY009446 Genomic RNA. Translation: ABD77678.1.
K01031 Genomic RNA. Translation: AAA43415.1.
RefSeqiNP_040981.1. NC_002018.1.

Genome annotation databases

GeneIDi956530.
KEGGivg:956530.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiNRAM_I34A1
AccessioniPrimary (citable) accession number: P03468
Secondary accession number(s): A4GXH6
, Q20N35, Q84043, Q8JUU4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: March 6, 2007
Last modified: June 7, 2017
This is version 128 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Glycosyl hydrolases
    Classification of glycosyl hydrolase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families