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P88838

- NRAM_I56A3

UniProt

P88838 - NRAM_I56A3

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Protein

Neuraminidase

Gene

NA

Organism
Influenza A virus (strain A/Equine/Prague/1/1956 H7N7)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli

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 By similarity.By similarity

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.

Cofactori

Binds 1 calcium ion per subunit.By similarity

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei115 – 1151SubstrateBy similarity
Active sitei148 – 1481Proton donor/acceptorBy similarity
Binding sitei149 – 1491SubstrateBy similarity
Binding sitei290 – 2901SubstrateBy similarity
Metal bindingi291 – 2911Calcium; via carbonyl oxygenBy similarity
Metal bindingi295 – 2951Calcium; via carbonyl oxygenBy similarity
Metal bindingi322 – 3221CalciumBy similarity
Binding sitei369 – 3691SubstrateBy similarity
Active sitei403 – 4031NucleophileBy similarity

GO - Molecular functioni

  1. exo-alpha-(2->3)-sialidase activity Source: UniProtKB-EC
  2. exo-alpha-(2->6)-sialidase activity Source: UniProtKB-EC
  3. exo-alpha-(2->8)-sialidase activity Source: UniProtKB-EC
  4. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. carbohydrate metabolic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Glycosidase, Hydrolase

Keywords - Ligandi

Calcium, Metal-binding

Protein family/group databases

CAZyiGH34. Glycoside Hydrolase Family 34.

Names & Taxonomyi

Protein namesi
Recommended name:
Neuraminidase (EC:3.2.1.18)
Gene namesi
Name:NA
OrganismiInfluenza A virus (strain A/Equine/Prague/1/1956 H7N7)
Taxonomic identifieri380337 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Equus caballus (Horse) [TaxID: 9796]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]

Subcellular locationi

Virion membrane By similarity. Host apical cell membrane By similarity; Single-pass type II membrane protein By 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.By similarity

GO - Cellular componenti

  1. host cell plasma membrane Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. virion membrane Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 469469NeuraminidasePRO_0000280138Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi28 – 281N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi32 – 321N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi46 – 461N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi55 – 551N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi56 – 561N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi65 – 651N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi66 – 661N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi85 – 851N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi89 ↔ 417By similarity
Disulfide bondi121 ↔ 126By similarity
Glycosylationi143 – 1431N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi173 ↔ 191By similarity
Disulfide bondi181 ↔ 228By similarity
Glycosylationi198 – 1981N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi230 ↔ 235By similarity
Glycosylationi232 – 2321N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi276 ↔ 289By similarity
Disulfide bondi278 ↔ 287By similarity
Disulfide bondi316 ↔ 334By similarity
Glycosylationi356 – 3561N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi399 – 3991N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi421 ↔ 448By similarity

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer.By similarity

Structurei

3D structure databases

ProteinModelPortaliP88838.
SMRiP88838. Positions 81-468.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66IntravirionSequence Analysis
Topological domaini28 – 469442Virion surfaceSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei7 – 2721Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft associationBy similarityAdd
BLAST
Regioni36 – 8752Hypervariable stalk regionBy similarityAdd
BLAST
Regioni88 – 469382Head of neuraminidaseBy similarityAdd
BLAST
Regioni274 – 2752Substrate bindingBy similarity

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 By similarity.By similarity

Sequence similaritiesi

Belongs to the glycosyl hydrolase 34 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di2.120.10.10. 1 hit.
InterProiIPR001860. Glyco_hydro_34.
IPR011040. Sialidases.
[Graphical view]
PfamiPF00064. Neur. 1 hit.
[Graphical view]
SUPFAMiSSF50939. SSF50939. 1 hit.

Sequencei

Sequence statusi: Complete.

P88838-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MNPNQKLFAS SGIAIALGII NLLIGISNMS LNISLYSKGE NHKSDNLTCT
60 70 80 90 100
NINQNNTTMV NTYINNTTII DKNTKMENPG YLLLNKSLCN VEGWVVIAKD
110 120 130 140 150
NAIRFGESEQ IIVTREPYVS CDPLSCKMYA LHQGTTIRNK HSNGTTHDRT
160 170 180 190 200
AFRGLISTPL GNPPTVSNSE FICVGWSSTS CHDGVSRMTI CVQGNNENAT
210 220 230 240 250
ATVYYNKRLT TTIKTWAKNI LRTQESECVC HNSTCVVVMT DGPANNQAFT
260 270 280 290 300
KVIYFHKGTI IKEEPLKGSA KHIEECSCYG HNQRVTCVCR DNWQGANRPV
310 320 330 340 350
IEIDMNNLEH TSRYICTGVL TDTSRPKDKA IGECFNPITG SPGAPGIKGF
360 370 380 390 400
GFLNENNTWL GRTISPKLRS GFEMLKIPNA GTDPDSKIKE RQEIVGNDNW
410 420 430 440 450
SGYSGSFIDY WNDNSECYNP CFYVELIRGR PEEAKYVEWT SNSLIALCGS
460
PIPVGSGSFP DGAQIKYFS
Length:469
Mass (Da):51,890
Last modified:May 1, 1997 - v1
Checksum:i38A224BA86D9ADC8
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti85 – 851N → K in AAA43411. 1 PublicationCurated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U85989 mRNA. Translation: AAC57418.1.
CY005802 Genomic RNA. Translation: ABB20501.1.
K01008 Genomic RNA. Translation: AAA43411.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U85989 mRNA. Translation: AAC57418.1 .
CY005802 Genomic RNA. Translation: ABB20501.1 .
K01008 Genomic RNA. Translation: AAA43411.1 .

3D structure databases

ProteinModelPortali P88838.
SMRi P88838. Positions 81-468.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

CAZyi GH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Miscellaneous databases

PROi P88838.

Family and domain databases

Gene3Di 2.120.10.10. 1 hit.
InterProi IPR001860. Glyco_hydro_34.
IPR011040. Sialidases.
[Graphical view ]
Pfami PF00064. Neur. 1 hit.
[Graphical view ]
SUPFAMi SSF50939. SSF50939. 1 hit.
ProtoNeti Search...

Publicationsi

  1. "Genetic characterisation of an influenza A virus of unusual subtype (H1N7) isolated from pigs in England."
    Brown I.H., Hill M.L., Harris P.A., Alexander D.J., McCauley J.W.
    Arch. Virol. 142:1045-1050(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. "Sequence variation at the 3' end of the neuraminidase gene from 39 influenza type A viruses."
    Blok J.
    (In) Nayak D., Fox C.F. (eds.); Genetic variation among influenza viruses, pp.45-54, University of California, Los Angeles (1982)
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-88.
  4. "Assembly and budding of influenza virus."
    Nayak D.P., Hui E.K., Barman S.
    Virus Res. 106:147-165(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  5. "Neuraminidase inhibitors for influenza."
    Moscona A.
    N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  6. "Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses."
    Suzuki Y.
    Biol. Pharm. Bull. 28:399-408(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.

Entry informationi

Entry nameiNRAM_I56A3
AccessioniPrimary (citable) accession number: P88838
Secondary accession number(s): Q20P40, Q83983
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: May 1, 1997
Last modified: October 29, 2014
This is version 81 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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.

Documents

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

External Data

Dasty 3