Reviewed, UniProtKB/Swiss-Prot P27907 (NRAM_INBBE)

Names and origin

Protein names

Recommended name:
    Neuraminidase
    EC=3.2.1.18

Gene names

Name:

NA

Organism

Influenza B virus (strain B/Beijing/1/1987)

Taxonomic identifier

11525 [NCBI]

Taxonomic lineage

Viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus B

Virus host

Homo sapiens (Human) [TaxID: 9606]

Protein attributes

Sequence length	465 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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 By similarity.
Catalytic activity	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.
Enzyme regulation	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.
Subunit structure	Homotetramer.
Subcellular location	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. In the virion, forms a mushroom-shaped spike on the surface of the membrane By similarity.
Post-translational modification	N-glycosylated By similarity.
Miscellaneous	The influenza B 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.
Sequence similarities	Belongs to the glycosyl hydrolase 34 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Virion
Domain	Signal-anchor Transmembrane
Molecular function	Glycosidase Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	exo-alpha-sialidase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 465

465

Neuraminidase

PRO_0000078730

Regions

Topological domain

1 – 6

6

Cytoplasmic Potential

Transmembrane

7 – 35

29

Signal-anchor for type II membrane protein Potential

Topological domain

36 – 465

430

Extracellular Potential

Region

39 – 68

30

Hypervariable stalk region

Region

69 – 465

397

Head of neuraminidase

Sites

Active site

148

1

Potential

Active site

274

1

Potential

Active site

408

1

Potential

Binding site

115

1

Substrate Potential

Binding site

291

1

Substrate Potential

Binding site

373

1

Substrate Potential

Amino acid modifications

Glycosylation

55

1

N-linked (GlcNAc...); by host Potential

Glycosylation

63

1

N-linked (GlcNAc...); by host Potential

Glycosylation

283

1

N-linked (GlcNAc...); by host

Disulfide bond

86 ↔ 419

Disulfide bond

121 ↔ 126

Disulfide bond

181 ↔ 228

Disulfide bond

230 ↔ 235

Disulfide bond

276 ↔ 290

Disulfide bond

278 ↔ 288

Disulfide bond

317 ↔ 336

Disulfide bond

423 ↔ 446

Secondary structure

1

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465

Helix Strand Turn

Details...

Beta strand

89 – 97

9

Helix

99 – 102

4

Beta strand

111 – 121

11

Beta strand

126 – 140

15

Turn

143 – 146

4

Beta strand

154 – 159

6

Turn

166 – 168

3

Beta strand

170 – 174

5

Beta strand

176 – 182

7

Beta strand

187 – 194

8

Beta strand

200 – 205

6

Beta strand

208 – 214

7

Beta strand

216 – 219

4

Beta strand

229 – 231

3

Beta strand

234 – 240

7

Beta strand

251 – 256

6

Beta strand

259 – 264

6

Beta strand

267 – 269

3

Beta strand

274 – 291

18

Beta strand

293 – 295

3

Beta strand

300 – 305

6

Turn

306 – 309

4

Beta strand

310 – 315

6

Beta strand

323 – 325

3

Beta strand

351 – 355

5

Beta strand

360 – 366

7

Beta strand

368 – 384

17

Turn

386 – 388

3

Beta strand

394 – 405

12

Beta strand

409 – 415

7

Beta strand

417 – 430

14

Beta strand

439 – 447

9

Beta strand

449 – 451

3

Sequences

	Sequence		Length	Mass (Da)
	P27907-1 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 2FC60B895CBD430C	FASTA	465	51,430
	10 20 30 40 50 60 MLPSTIQTLT LFLTSGGVLL SLYVSASLSY LLYSDILLKF SSKITAPTMT LDCANASNVQ 70 80 90 100 110 120 AVNRSATKEM TFLLPEPEWT YPRLSCQGST FQKALLISPH RFGEARGNSA PLIIREPFIA 130 140 150 160 170 180 CGPKECKHFA LTHYAAQPGG YYNGTREDRN KLRHLISVKL GKIPTVENSI FHMAAWSGSA 190 200 210 220 230 240 CHDGREWTYI GVDGPDSNAL IKIKYGEAYT DTYHSYANNI LRTQESACNC IGGDCYLMIT 250 260 270 280 290 300 DGSASGISKC RFLKIREGRI IKEIFPTGRV EHTEECTCGF ASNKTIECAC RDNSYTAKRP 310 320 330 340 350 360 FVKLNVETDT AEIRLMCTET YLDTPRPDDG SITGPCESNG DKGRGGIKGG FVHQRMASKI 370 380 390 400 410 420 GRWYSRTMSK TERMGMELYV RYDGDPWTDS DALAHSGVMV SMKEPGWYSF GFEIKDKKCD 430 440 450 460 VPCIGIEMVH DGGKKTWHSA ATAIYCLMGS GQLLWDTVTG VDMAL

References

[1]	"Sequence and crystallization of influenza virus B/Beijing/1/87 neuraminidase." Burmeister W.P., Daniels R.S., Dayan S., Gagnon J., Cusack S., Ruigrok R.W. Virology 180:266-272(1991) [PubMed: 1984652] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], PARTIAL PROTEIN SEQUENCE.
[2]	"Neuraminidase inhibitors for influenza." Moscona A. N. Engl. J. Med. 353:1363-1373(2005) [PubMed: 16192481] [Abstract] Cited for: REVIEW.
[3]	"The 2.2-A resolution crystal structure of influenza B neuraminidase and its complex with sialic acid." Burmeister W.P., Ruigrok R.W., Cusack S. EMBO J. 11:49-56(1992) [PubMed: 1740114] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 76-465.
[4]	"Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors of influenza virus sialidases. 2. Crystallographic and molecular modeling study of complexes of 4-amino-4H-pyran-6-carboxamides and sialidase from influenza virus types A and B." Taylor N.R., Cleasby A., Singh O., Skarzynski T., Wonacott A.J., Smith P.W., Sollis S.L., Howes P.D., Cherry P.C., Bethell R., Colman P., Varghese J. J. Med. Chem. 41:798-807(1998) [PubMed: 9526556] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 76-465.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M54967 Genomic RNA. Translation: AAA43733.1.

PIR

NMIVB1. B38520.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A4G	X-ray	2.20	A/B	76-465	[»]
1A4Q	X-ray	1.90	A/B	76-465	[»]
1NSB	X-ray	2.20	A/B	76-465	[»]
1NSC	X-ray	1.70	A/B	76-465	[»]
1NSD	X-ray	1.80	A/B	76-465	[»]

ModBase

Search...

Protein family/group databases

CAZy

GH34. Glycoside Hydrolase Family 34.

Family and domain databases

InterPro

IPR001860. Glyco_hydro_34.
[Graphical view]

Pfam

PF00064. Neur. 1 hit.
[Graphical view]

ProDom

PD000431. Glyco_hydro_34. 1 hit.
[Graphical view] [Entries sharing at least one domain]

ProtoNet

Search...

Entry information

Entry name

NRAM_INBBE

Accession

Primary (citable) accession number: P27907

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	June 16, 2009
This is version 73 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)