NRAM_INBBE
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 03-AUG-2022, entry version 130.
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.
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 Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000269|PubMed:1740114};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_04071,
CC 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}.
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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 iPTMnet; P27907; -.
DR PRIDE; 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:0016021; C:integral component of 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 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; SSF50939; 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
