ID NRAM_I49A1 Reviewed; 471 AA. AC P03480; Q0A445; Q6LEJ3; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 06-MAR-2007, sequence version 2. DT 29-APR-2008, entry version 64. DE Neuraminidase (EC 3.2.1.18). GN Name=NA; OS Influenza A virus (strain A/Duck/Germany/1949 H10N7). OC Viruses; ssRNA negative-strand viruses; Orthomyxoviridae; OC Influenzavirus A. OX NCBI_TaxID=382838; OH NCBI_TaxID=8782; Aves. RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=16439620; DOI=10.1126/science.1121586; RA Obenauer J.C., Denson J., Mehta P.K., Su X., Mukatira S., RA Finkelstein D.B., Xu X., Wang J., Ma J., Fan Y., Rakestraw K.M., RA Webster R.G., Hoffmann E., Krauss S., Zheng J., Zhang Z., Naeve C.W.; RT "Large-scale sequence analysis of avian influenza isolates."; RL Science 311:1576-1580(2006). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-96. RX MEDLINE=83023028; PubMed=6896994; DOI=10.1021/bi00260a015; RA Blok J., Air G.M.; RT "Variation in the membrane-insertion and 'stalk' sequences in eight RT subtypes of influenza type A virus neuraminidase."; RL Biochemistry 21:4001-4007(1982). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-96. RA Blok J.; RT "Sequence variation at the 3' end of the neuraminidase gene from 39 RT influenza type A viruses."; RL (In) Nayak D., Fox C.F. (eds.); RL Genetic variation among influenza viruses, pp.45-54, University of RL California, Los Angeles (1982). RN [4] RP REVIEW. RX PubMed=15567494; DOI=10.1016/j.virusres.2004.08.012; RA Nayak D.P., Hui E.K., Barman S.; RT "Assembly and budding of influenza virus."; RL Virus Res. 106:147-165(2004). RN [5] RP REVIEW. RX PubMed=16192481; DOI=10.1056/NEJMra050740; RA Moscona A.; RT "Neuraminidase inhibitors for influenza."; RL N. Engl. J. Med. 353:1363-1373(2005). RN [6] RP REVIEW. RX PubMed=15744059; DOI=10.1248/bpb.28.399; RA Suzuki Y.; RT "Sialobiology of influenza: molecular mechanism of host range RT variation of influenza viruses."; RL Biol. Pharm. Bull. 28:399-408(2005). CC -!- FUNCTION: Catalyzes the removal of terminal sialic acid residues CC from viral and cellular glycoconjugates. Cleaves off the terminal CC sialic acids on the glycosylated HA during virus budding to CC facilitate virus release. Additionally helps virus spread through CC the circulation by further removing sialic acids from the cell CC surface. These cleavages prevent self-aggregation and ensure the CC efficient spread of the progeny virus from cell to cell. CC Otherwise, infection would be limited to one round of replication. CC Described as a receptor-destroying enzyme because it cleaves a CC terminal sialic acid from the cellular receptors. May facilitate CC viral invasion of the upper airways by cleaving the sialic acid CC moities on the mucin of the airway epithelial cells. Likely to CC plays a role in the budding process through its association with CC lipid rafts during intracellular transport. May additionally CC display a raft-association independent effect on budding. Plays a CC role in the determination of host range restriction on replication CC and virulence. Sialidase activity in late endosome/lysosome CC traffic seems to enhance virus replication. CC -!- CATALYTIC ACTIVITY: Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, CC alpha-(2->8)- glycosidic linkages of terminal sialic acid residues CC in oligosaccharides, glycoproteins, glycolipids, colominic acid CC and synthetic substrates. CC -!- COFACTOR: Binds 1 calcium ion (By similarity). CC -!- ENZYME REGULATION: Inhibited by the neuraminidase inhibitors CC zanamivir (Relenza) and oseltamivir (Tamiflu). These drugs CC interfere with the release of progeny virus from infected cells CC and are effective against all influenza strains. Resistance to CC neuraminidase inhibitors is quite rare. CC -!- SUBUNIT: Homotetramer (By similarity). CC -!- SUBCELLULAR LOCATION: Virion membrane (By similarity). Apical cell CC membrane; Single-pass type II membrane protein (By similarity). CC Note=Preferentially accumulates at the apical plasma membrane in CC infected polarized epithelial cells, which is the virus assembly CC site. Uses lipid rafts for cell surface transport and apical CC sorting. In the virion, forms a mushroom-shaped spike on the CC surface of the membrane (By similarity). CC -!- DOMAIN: Intact N-terminus is essential for virion morphogenesis. CC Possess two apical sorting signals, one in the ectodomain, which CC is likely to be a glycan, and the other in the transmembrane CC domain. The transmembrane domain also plays a role in lipid raft CC association (By similarity). CC -!- PTM: N-glycosylated (By similarity). CC -!- MISCELLANEOUS: The influenza A genome consist of 8 RNA segments. CC Genetic variation of hemagglutinin and/or neuraminidase genes CC results in the emergence of new influenza strains. The mechanism CC of variation can be the result of point mutations or the result of CC genetic reassortment between segments of two different strains. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 34 family. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CY014673; ABI84537.1; -; Genomic_RNA. DR EMBL; J02099; AAA43391.1; -; Genomic_RNA. DR EMBL; K01022; AAA43357.1; -; Genomic_RNA. DR GO; GO:0004308; F:exo-alpha-sialidase activity; IEA:EC. PE 3: Inferred from homology; KW Calcium; Glycoprotein; Glycosidase; Hydrolase; Membrane; KW Metal-binding; Signal-anchor; Transmembrane; Virion. FT CHAIN 1 471 Neuraminidase. FT /FTId=PRO_0000078685. FT TOPO_DOM 1 6 Cytoplasmic (Potential). FT TRANSMEM 7 27 Signal-anchor for type II membrane FT protein (Potential). FT TOPO_DOM 28 471 Extracellular (Potential). FT REGION 11 33 Involved in apical transport and lipid FT raft association (By similarity). FT REGION 36 89 Hypervariable stalk region (By FT similarity). FT REGION 90 471 Head of neuraminidase (By similarity). FT ACT_SITE 150 150 Potential. FT ACT_SITE 276 276 Potential. FT ACT_SITE 405 405 Potential. FT METAL 293 293 Calcium (via carbonyl oxygen) (By FT similarity). FT METAL 297 297 Calcium (via carbonyl oxygen) (By FT similarity). FT METAL 324 324 Calcium (By similarity). FT BINDING 117 117 Substrate (Potential). FT BINDING 292 292 Substrate (Potential). FT BINDING 371 371 Substrate (Potential). FT CARBOHYD 32 32 N-linked (GlcNAc...) (Potential). FT CARBOHYD 47 47 N-linked (GlcNAc...) (Potential). FT CARBOHYD 56 56 N-linked (GlcNAc...) (Potential). FT CARBOHYD 57 57 N-linked (GlcNAc...) (Potential). FT CARBOHYD 67 67 N-linked (GlcNAc...) (Potential). FT CARBOHYD 68 68 N-linked (GlcNAc...) (Potential). FT CARBOHYD 87 87 N-linked (GlcNAc...) (Potential). FT CARBOHYD 145 145 N-linked (GlcNAc...) (Potential). FT CARBOHYD 200 200 N-linked (GlcNAc...) (Potential). FT CARBOHYD 234 234 N-linked (GlcNAc...) (Potential). FT CARBOHYD 401 401 N-linked (GlcNAc...) (Potential). FT DISULFID 91 419 By similarity. FT DISULFID 123 128 By similarity. FT DISULFID 183 230 By similarity. FT DISULFID 232 237 By similarity. FT DISULFID 278 291 By similarity. FT DISULFID 280 289 By similarity. FT DISULFID 423 450 By similarity. FT CONFLICT 88 88 K -> H (in Ref. 2; AAA43391 and 3; FT AAA43357). SQ SEQUENCE 471 AA; 51800 MW; 68F6BBACFCDD21A1 CRC64; MNPNQKLFAL SGVAIALSVM NLLIGISNVG LNVSLHLKEK GTKQEENLTC TTITQNNTTV VENTYVNNTT IITKEPDLKA PSYLLLNKSL CSVEGWVVIA KDNAIRFGES EQIIVTREPY VSCDPSGCKM YALHQGTTIR NKHSNGTIHD RTAFRGLIST PLGTPPTVSN SDFICVGWSS TSCHDGVGRM TICIQGNNDN ATATVYYNRR LTTTIKPWAR NILRTQESEC VCHNGTCAVV MTDGSASSQA YTKVMYFHKG LVIKEEPLKG SAKHIEECSC YGHNQKITCV CRDNWQGANR PIIEIDMNTL EHTSRYVCTG ILTDTSRPGD KPSGDCSNPI TGSPSAPGVK GFGFLNGDNT WLGRTISPRS RSGFEMLKIP NAGTDPNSRI AERQEIVDNN NWSGYSGSFI DYWDDDNECY NPCFYVELIR GRPEEAKYVW WTSNSLIALC GSPFPVGSGS FPDGAQIQYF S //