ID NRAM_INBBE Reviewed; 465 AA. AC P27907; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1992, sequence version 1. DT 08-NOV-2023, entry version 135. DE RecName: Full=Neuraminidase {ECO:0000255|HAMAP-Rule:MF_04071}; DE EC=3.2.1.18 {ECO:0000255|HAMAP-Rule:MF_04071}; GN Name=NA {ECO:0000255|HAMAP-Rule:MF_04071}; OS Influenza B virus (strain B/Beijing/1/1987). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Betainfluenzavirus; OC Betainfluenzavirus influenzae; Influenza B virus. OX NCBI_TaxID=11525; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND PARTIAL PROTEIN SEQUENCE. RX PubMed=1984652; DOI=10.1016/0042-6822(91)90031-6; RA Burmeister W.P., Daniels R.S., Dayan S., Gagnon J., Cusack S., RA Ruigrok R.W.; RT "Sequence and crystallization of influenza virus B/Beijing/1/87 RT neuraminidase."; RL Virology 180:266-272(1991). RN [2] 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 [3] RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 76-465 IN COMPLEX WITH CALCIUM RP AND SIALIC ACID, GLYCOSYLATION AT ASN-283, SUBUNIT, AND COFACTOR. RX PubMed=1740114; DOI=10.1002/j.1460-2075.1992.tb05026.x; RA Burmeister W.P., Ruigrok R.W., Cusack S.; RT "The 2.2-A resolution crystal structure of influenza B neuraminidase and RT its complex with sialic acid."; RL EMBO J. 11:49-56(1992). RN [4] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 76-465. RX PubMed=9526556; DOI=10.1021/jm9703754; RA Taylor N.R., Cleasby A., Singh O., Skarzynski T., Wonacott A.J., RA Smith P.W., Sollis S.L., Howes P.D., Cherry P.C., Bethell R., Colman P., RA Varghese J.; RT "Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors RT of influenza virus sialidases. 2. Crystallographic and molecular modeling RT study of complexes of 4-amino-4H-pyran-6-carboxamides and sialidase from RT influenza virus types A and B."; RL J. Med. Chem. 41:798-807(1998). CC -!- FUNCTION: Catalyzes the removal of terminal sialic acid residues from CC viral and cellular glycoconjugates. Cleaves off the terminal sialic CC acids on the glycosylated HA during virus budding to facilitate virus CC release. Additionally helps virus spread through the circulation by CC further removing sialic acids from the cell surface. These cleavages CC prevent self-aggregation and ensure the efficient spread of the progeny CC virus from cell to cell. Otherwise, infection would be limited to one CC round of replication. Described as a receptor-destroying enzyme because CC it cleaves a terminal sialic acid from the cellular receptors. May CC facilitate viral invasion of the upper airways by cleaving the sialic CC acid moieties on the mucin of the airway epithelial cells. Likely to CC plays a role in the budding process through its association with lipid CC rafts during intracellular transport. May additionally display a raft- CC association independent effect on budding. Plays a role in the CC determination of host range restriction on replication and virulence. CC Sialidase activity in late endosome/lysosome traffic seems to enhance CC virus replication. {ECO:0000255|HAMAP-Rule:MF_04071}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha- CC (2->8)- glycosidic linkages of terminal sialic acid residues in CC oligosaccharides, glycoproteins, glycolipids, colominic acid and CC synthetic substrates.; EC=3.2.1.18; Evidence={ECO:0000255|HAMAP- CC Rule:MF_04071}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|HAMAP- CC Rule:MF_04071, ECO:0000269|PubMed:1740114}; CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:1740114}; CC -!- ACTIVITY REGULATION: Inhibited by the neuraminidase inhibitors CC zanamivir (Relenza) and oseltamivir (Tamiflu). These drugs interfere CC with the release of progeny virus from infected cells and are effective CC against all influenza strains. Resistance to neuraminidase inhibitors CC is quite rare. {ECO:0000255|HAMAP-Rule:MF_04071}. CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_04071, CC ECO:0000269|PubMed:1740114}. CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP- CC Rule:MF_04071}. Host apical cell membrane {ECO:0000255|HAMAP- CC Rule:MF_04071}; Single-pass type II membrane protein CC {ECO:0000255|HAMAP-Rule:MF_04071}. Note=Preferentially accumulates at CC the apical plasma membrane in infected polarized epithelial cells, CC which is the virus assembly site. Uses lipid rafts for cell surface CC transport and apical sorting. In the virion, forms a mushroom-shaped CC spike on the surface of the membrane. {ECO:0000255|HAMAP- CC Rule:MF_04071}. CC -!- DOMAIN: Intact N-terminus is essential for virion morphogenesis. CC Possesses two apical sorting signals, one in the ectodomain, which is CC likely to be a glycan, and the other in the transmembrane domain. The CC transmembrane domain also plays a role in lipid raft association. CC {ECO:0000255|HAMAP-Rule:MF_04071}. CC -!- PTM: N-glycosylated. {ECO:0000255|HAMAP-Rule:MF_04071, CC ECO:0000269|PubMed:1740114}. CC -!- MISCELLANEOUS: The influenza B genome consist of 8 RNA segments. CC Genetic variation of hemagglutinin and/or neuraminidase genes results CC in the emergence of new influenza strains. The mechanism of variation CC can be the result of point mutations or the result of genetic CC reassortment between segments of two different strains. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 34 family. CC {ECO:0000255|HAMAP-Rule:MF_04071}. 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; M54967; AAA43733.1; -; Genomic_RNA. DR PIR; B38520; NMIVB1. DR PDB; 1A4G; X-ray; 2.20 A; A/B=76-465. DR PDB; 1A4Q; X-ray; 1.90 A; A/B=76-465. DR PDB; 1NSB; X-ray; 2.20 A; A/B=76-465. DR PDB; 1NSC; X-ray; 1.70 A; A/B=76-465. DR PDB; 1NSD; X-ray; 1.80 A; A/B=76-465. DR PDBsum; 1A4G; -. DR PDBsum; 1A4Q; -. DR PDBsum; 1NSB; -. DR PDBsum; 1NSC; -. DR PDBsum; 1NSD; -. DR SMR; P27907; -. DR DrugBank; DB06614; Peramivir. DR DrugBank; DB00558; Zanamivir. DR CAZy; GH34; Glycoside Hydrolase Family 34. DR GlyCosmos; P27907; 4 sites, No reported glycans. DR iPTMnet; P27907; -. DR BRENDA; 3.2.1.18; 7480. DR EvolutionaryTrace; P27907; -. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0052794; F:exo-alpha-(2->3)-sialidase activity; IEA:UniProtKB-UniRule. DR GO; GO:0052795; F:exo-alpha-(2->6)-sialidase activity; IEA:UniProtKB-UniRule. DR GO; GO:0052796; F:exo-alpha-(2->8)-sialidase activity; IEA:UniProtKB-UniRule. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro. DR GO; GO:0046761; P:viral budding from plasma membrane; IEA:UniProtKB-UniRule. DR CDD; cd15483; Influenza_NA; 1. DR Gene3D; 2.120.10.10; -; 1. DR HAMAP; MF_04071; INFV_NRAM; 1. DR InterPro; IPR001860; Glyco_hydro_34. DR InterPro; IPR033654; Sialidase_Influenza_A/B. DR InterPro; IPR036278; Sialidase_sf. DR Pfam; PF00064; Neur; 1. DR SUPFAM; SSF50939; Sialidases; 1. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Glycosidase; Host cell membrane; Host membrane; Hydrolase; KW Membrane; Metal-binding; Signal-anchor; Transmembrane; Transmembrane helix; KW Virion. FT CHAIN 1..465 FT /note="Neuraminidase" FT /id="PRO_0000078730" FT TOPO_DOM 1..11 FT /note="Intravirion" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT TRANSMEM 12..34 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT TOPO_DOM 35..465 FT /note="Virion surface" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 13..35 FT /note="Involved in apical transport and lipid raft FT association" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 38..85 FT /note="Hypervariable stalk region" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT REGION 88..465 FT /note="Head of neuraminidase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 148 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT ACT_SITE 408 FT /note="Nucleophile" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 115 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 149 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 274..275 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 291 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT BINDING 292 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071, FT ECO:0000269|PubMed:1740114" FT BINDING 296 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:1740114" FT BINDING 323 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071, FT ECO:0000269|PubMed:1740114" FT BINDING 343 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:1740114" FT BINDING 345 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000269|PubMed:1740114" FT BINDING 373 FT /ligand="substrate" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 55 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 63 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 143 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT CARBOHYD 283 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071, FT ECO:0000269|PubMed:1740114" FT DISULFID 86..419 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 121..126 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 181..228 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 230..235 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 276..290 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 278..288 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 317..336 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT DISULFID 423..446 FT /evidence="ECO:0000255|HAMAP-Rule:MF_04071" FT STRAND 89..97 FT /evidence="ECO:0007829|PDB:1NSC" FT HELIX 99..102 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 111..121 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 126..140 FT /evidence="ECO:0007829|PDB:1NSC" FT TURN 143..146 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 154..159 FT /evidence="ECO:0007829|PDB:1NSC" FT TURN 166..168 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 170..174 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 176..182 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 187..194 FT /evidence="ECO:0007829|PDB:1NSC" FT HELIX 196..198 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 200..205 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 208..214 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 216..219 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 229..231 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 234..242 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 244..246 FT /evidence="ECO:0007829|PDB:1A4Q" FT STRAND 248..256 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 259..264 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 267..269 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 274..291 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 293..295 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 300..305 FT /evidence="ECO:0007829|PDB:1NSC" FT TURN 306..309 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 310..315 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 323..325 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 351..355 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 360..366 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 368..384 FT /evidence="ECO:0007829|PDB:1NSC" FT TURN 386..388 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 394..405 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 409..415 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 417..430 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 439..447 FT /evidence="ECO:0007829|PDB:1NSC" FT STRAND 449..451 FT /evidence="ECO:0007829|PDB:1NSC" SQ SEQUENCE 465 AA; 51430 MW; 2FC60B895CBD430C CRC64; MLPSTIQTLT LFLTSGGVLL SLYVSASLSY LLYSDILLKF SSKITAPTMT LDCANASNVQ AVNRSATKEM TFLLPEPEWT YPRLSCQGST FQKALLISPH RFGEARGNSA PLIIREPFIA CGPKECKHFA LTHYAAQPGG YYNGTREDRN KLRHLISVKL GKIPTVENSI FHMAAWSGSA CHDGREWTYI GVDGPDSNAL IKIKYGEAYT DTYHSYANNI LRTQESACNC IGGDCYLMIT DGSASGISKC RFLKIREGRI IKEIFPTGRV EHTEECTCGF ASNKTIECAC RDNSYTAKRP FVKLNVETDT AEIRLMCTET YLDTPRPDDG SITGPCESNG DKGRGGIKGG FVHQRMASKI GRWYSRTMSK TERMGMELYV RYDGDPWTDS DALAHSGVMV SMKEPGWYSF GFEIKDKKCD VPCIGIEMVH DGGKKTWHSA ATAIYCLMGS GQLLWDTVTG VDMAL //