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P09573

- NRAM_I83A6

UniProt

P09573 - NRAM_I83A6

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Protein

Neuraminidase

Gene
NA
Organism
Influenza A virus (strain A/Chicken/Pennsylvania/1370/1983 H5N2)
Status
Reviewed - 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.

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 sitei98 – 981Substrate By similarity
Active sitei131 – 1311Proton donor/acceptor By similarity
Binding sitei132 – 1321Substrate By similarity
Binding sitei272 – 2721Substrate By similarity
Metal bindingi273 – 2731Calcium; via carbonyl oxygen By similarity
Metal bindingi277 – 2771Calcium; via carbonyl oxygen By similarity
Metal bindingi304 – 3041Calcium By similarity
Binding sitei351 – 3511Substrate By similarity
Active sitei386 – 3861Nucleophile By 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/Chicken/Pennsylvania/1370/1983 H5N2)
Taxonomic identifieri385617 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]

Subcellular locationi

Virion membrane By similarity. Host apical cell membrane; 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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66Intravirion Reviewed prediction
Transmembranei7 – 3529Helical; Signal-anchor for type II membrane protein; Reviewed predictionAdd
BLAST
Topological domaini36 – 449414Virion surface Reviewed predictionAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 449449NeuraminidasePRO_0000078680Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi48 – 481N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi66 – 661N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi72 ↔ 397 By similarity
Disulfide bondi104 ↔ 109 By similarity
Glycosylationi123 – 1231N-linked (GlcNAc...); by host Reviewed prediction
Glycosylationi126 – 1261N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi155 ↔ 173 By similarity
Disulfide bondi163 ↔ 210 By similarity
Glycosylationi180 – 1801N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi212 ↔ 217 By similarity
Glycosylationi214 – 2141N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi258 ↔ 271 By similarity
Disulfide bondi260 ↔ 269 By similarity
Disulfide bondi298 ↔ 317 By similarity
Glycosylationi382 – 3821N-linked (GlcNAc...); by host Reviewed prediction
Disulfide bondi401 ↔ 427 By similarity

Post-translational modificationi

N-glycosylated By similarity.

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotetramer By similarity.

Structurei

3D structure databases

ProteinModelPortaliP09573.
SMRiP09573. Positions 62-449.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni11 – 3323Involved in apical transport and lipid raft association By similarityAdd
BLAST
Regioni36 – 7035Hypervariable stalk regionAdd
BLAST
Regioni71 – 449379Head of neuraminidaseAdd
BLAST
Regioni256 – 2572Substrate binding By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi311 – 3155Poly-Ser

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.

Sequence similaritiesi

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.

P09573-1 [UniParc]FASTAAdd to Basket

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MNPNQKIITI GSVSLTIATV CFLMQIAILA TNVTLHFRQN ERSIPAYNQT    50
TPCKPIIIER NIKYRNWSKP QCQITGFAPF SKDNSIRLSA GGGIWVTREP 100
YVSCDPSKCY QFALGQGTTL DNNHSNGTIH DRTPHRTLLM NELGVPFHLG 150
TRQVCIAWSS SSCHDGKAWL HVCVTGDDRN ATASFIYNGM LVDSIGSWSQ 200
NILRTQESEC VCINGTCTVV MTDGSASGKA DIRILFIREG KIVHISPLSG 250
SAQHIEECSC YPRYPNVRCV CRDNWKGSNR PVIDINMADY SIDSSYVCSG 300
LVGDTPRNDD SSSSSNCRDP NNERGNPGVK GWAFDIGDDV WMGRTISKDS 350
RSGYETFRVI GGWATANSKS QTNRQVIVDN NNWSGYSGIF SVESKSCINR 400
CFYVELIRGR PQETRVWWTS NSIVVFCGTS GTYGTGSWPD GANINFMPL 449
Length:449
Mass (Da):49,693
Last modified:March 6, 2007 - v2
Checksum:iDC716FBFB147ADA1
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti42 – 421R → G in AAA43424. 1 Publication
Sequence conflicti122 – 1221N → H in AAA43424. 1 Publication
Sequence conflicti160 – 1601S → R in AAA43424. 1 Publication
Sequence conflicti232 – 2321I → T in AAA43424. 1 Publication
Sequence conflicti263 – 2653RYP → KSYL in AAA43424. 1 Publication
Sequence conflicti283 – 2831I → KL in AAA43424. 1 Publication
Sequence conflicti361 – 3611G → S in AAA43424. 1 Publication
Sequence conflicti420 – 4201S → T in AAA43424. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M12051 Genomic RNA. Translation: AAA43424.1.
CY015110 Genomic RNA. Translation: ABI85148.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M12051 Genomic RNA. Translation: AAA43424.1 .
CY015110 Genomic RNA. Translation: ABI85148.1 .

3D structure databases

ProteinModelPortali P09573.
SMRi P09573. Positions 62-449.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

CAZyi GH34. Glycoside Hydrolase Family 34.

Protocols and materials databases

Structural Biology Knowledgebase Search...

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. "The neuraminidases of the virulent and avirulent A/Chicken/Pennsylvania/83 (H5N2) influenza A viruses: sequence and antigenic analyses."
    Deshpande K.L., Naeve C.W., Webster R.G.
    Virology 147:49-60(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  3. "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.
  4. "Neuraminidase inhibitors for influenza."
    Moscona A.
    N. Engl. J. Med. 353:1363-1373(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  5. "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_I83A6
AccessioniPrimary (citable) accession number: P09573
Secondary accession number(s): Q0A2D4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: March 6, 2007
Last modified: September 3, 2014
This is version 98 of the entry and version 2 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