Reviewed, UniProtKB/Swiss-Prot Q9IGQ6 (NRAM_I18A0)

Names and origin

Protein names

Recommended name:
    Neuraminidase
    EC=3.2.1.18

Gene names

Name:

NA

Organism

Influenza A virus (strain A/Brevig Mission/1/1918 H1N1) (Influenza A virus (strain A/South Carolina/1/1918 H1N1)) [Complete proteome]

Taxonomic identifier

88776 [NCBI]

Taxonomic lineage

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

Virus host

Aves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length	469 AA.
Sequence status	Complete.
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. 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 By similarity. Unlike other strains, A/WSN/33 neuraminidase binds and activates plasminogen into plasmin in the vicinity of HA so that activated plasmin cleaves HA rendering the virus infectious 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.
Cofactor	Binds 1 calcium ion By similarity.
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 By similarity.
Subcellular location	Virion membrane. Host apical cell membrane; Single-pass type II membrane protein. 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.
Domain	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.
Post-translational modification	N-glycosylated By similarity.
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. South Carolina isolate has been sequenced from formalid fixed-lung tissues of a 21-year-old male which died in 1918 at Ft. Jackson, SC. Brevig Mission isolate has been sequenced from lung tissues of an Inuit woman buried in the permafrost in a gravesite near Brevig Mission, Alaska. This sample was recovered by John Hultin, retired pathologist.
Sequence similarities	Belongs to the glycosyl hydrolase 34 family.

Ontologies

Keywords
Cellular component	Host cell membrane Host membrane Membrane Virion
Domain	Signal-anchor Transmembrane
Ligand	Calcium Metal-binding
Molecular function	Glycosidase Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW 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 – 469

469

Neuraminidase

PRO_0000310569

Regions

Topological domain

1 – 6

6

Cytoplasmic Potential

Transmembrane

7 – 27

21

Potential

Topological domain

28 – 469

442

Extracellular Potential

Region

11 – 33

23

Involved in apical transport and lipid raft association By similarity

Region

36 – 90

55

Hypervariable stalk region By similarity

Region

91 – 469

379

Head of neuraminidase By similarity

Sites

Active site

151

1

Potential

Active site

277

1

Potential

Active site

402

1

Potential

Metal binding

294

1

Calcium; via carbonyl oxygen By similarity

Metal binding

298

1

Calcium; via carbonyl oxygen By similarity

Metal binding

324

1

Calcium By similarity

Metal binding

344

1

Calcium; via carbonyl oxygen By similarity

Binding site

118

1

Substrate Potential

Binding site

293

1

Substrate Potential

Binding site

368

1

Substrate Potential

Amino acid modifications

Glycosylation

88

1

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

Glycosylation

146

1

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

Glycosylation

235

1

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

Disulfide bond

92 ↔ 417

By similarity

Disulfide bond

124 ↔ 129

By similarity

Disulfide bond

184 ↔ 231

By similarity

Disulfide bond

233 ↔ 238

By similarity

Disulfide bond

279 ↔ 292

By similarity

Disulfide bond

281 ↔ 290

By similarity

Disulfide bond

318 ↔ 335

By similarity

Disulfide bond

421 ↔ 446

By similarity

Secondary structure

1

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469

Helix Strand Turn

Details...

Beta strand

98 – 102

5

Beta strand

115 – 124

10

Beta strand

129 – 136

8

Beta strand

138 – 142

5

Helix

143 – 145

3

Beta strand

157 – 162

6

Turn

169 – 171

3

Beta strand

173 – 177

5

Beta strand

182 – 184

3

Beta strand

191 – 193

3

Beta strand

203 – 208

6

Beta strand

212 – 217

6

Beta strand

219 – 222

4

Beta strand

228 – 230

3

Beta strand

238 – 244

7

Beta strand

252 – 258

7

Beta strand

263 – 268

6

Beta strand

277 – 283

7

Beta strand

288 – 293

6

Beta strand

303 – 306

4

Beta strand

361 – 363

3

Beta strand

365 – 367

3

Beta strand

371 – 375

5

Beta strand

388 – 394

7

Beta strand

406 – 408

3

Turn

410 – 412

3

Beta strand

417 – 428

12

Beta strand

432 – 436

5

Beta strand

441 – 446

6

Sequences

	Sequence		Length	Mass (Da)
	Q9IGQ6-1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 28888692D4394159	FASTA	469	51,406
	10 20 30 40 50 60 MNPNQKIITI GSICMVVGII SLILQIGNII SIWVSHSIQT GNQNHPETCN QSIITYENNT 70 80 90 100 110 120 WVNQTYVNIS NTNVVAGQDA TSVILTGNSS LCPISGWAIY SKDNGIRIGS KGDVFVIREP 130 140 150 160 170 180 FISCSHLECR TFFLTQGALL NDKHSNGTVK DRSPYRTLMS CPVGEAPSPY NSRFESVAWS 190 200 210 220 230 240 ASACHDGMGW LTIGISGPDN GAVAVLKYNG IITDTIKSWR NNILRTQESE CACVNGSCFT 250 260 270 280 290 300 IMTDGPSNGQ ASYKILKIEK GKVTKSIELN APNYHYEECS CYPDTGKVMC VCRDNWHGSN 310 320 330 340 350 360 RPWVSFDQNL DYQIGYICSG VFGDNPRPND GTGSCGPVSS NGANGIKGFS FRYDNGVWIG 370 380 390 400 410 420 RTKSTSSRSG FEMIWDPNGW TETDSSFSVR QDIVAITDWS GYSGSFVQHP ELTGLDCMRP 430 440 450 460 CFWVELIRGQ PKENTIWTSG SSISFCGVNS DTVGWSWPDG AELPFSIDK

References

[1]	"Characterization of the 1918 'Spanish' influenza virus neuraminidase gene." Reid A.H., Fanning T.G., Janczewski T.A., Taubenberger J.K. Proc. Natl. Acad. Sci. U.S.A. 97:6785-6790(2000) [PubMed: 10823895] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Initial genetic characterization of the 1918 'Spanish' influenza virus." Taubenberger J.K., Reid A.H., Krafft A.E., Bijwaard K.E., Fanning T.G. Science 275:1793-1796(1997) [PubMed: 9065404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 12-23. Strain: A/South Carolina/1/18.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF250356 mRNA. Translation: AAF77036.1.
U94893 Genomic DNA. Translation: AAC57065.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3B7E	X-ray	1.45	A/B	83-467	[»]
3BEQ	X-ray	1.64	A/B	83-467	[»]
3CYE	X-ray	1.65	A/B	83-469	[»]

ModBase

Search...

Protein family/group databases

CAZy

GH34. Glycoside Hydrolase Family 34.

Family and domain databases

InterPro

IPR001860. Glyco_hydro_34.
IPR011040. Neuraminidase.
[Graphical view]

Pfam

PF00064. Neur. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

NRAM_I18A0

Accession

Primary (citable) accession number: Q9IGQ6
Secondary accession number(s): O10421

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 13, 2007
Last sequence update:	October 1, 2000
Last modified:	January 19, 2010
This is version 55 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)