Reviewed, UniProtKB/Swiss-Prot P03437 (HEMA_I68A0)

Names and origin

Protein names

Recommended name:
    Hemagglutinin
Cleaved into the following 2 chains:
    1- Recommended name:
            Hemagglutinin HA1 chain
    2- Recommended name:
            Hemagglutinin HA2 chain

Gene names

Name:

HA

Organism

Influenza A virus (strain A/Aichi/2/1968 H3N2)

Taxonomic identifier

387139 [NCBI]

Taxonomic lineage

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

Virus host

Aves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]
Cetacea (whales) [TaxID: 9721]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length	566 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induce an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.
Subunit structure	Homotrimer of disulfide-linked HA1-HA2.
Subcellular location	Virion membrane; Single-pass type I membrane protein Potential. Host apical cell membrane; Single-pass type I membrane protein. Note: Targeted to the apical plasma membrane in epithelial polarized cells through a signal present in the transmembrane domain. Associated with glycosphingolipid- and cholesterol-enriched detergent-resistant lipid rafts.
Post-translational modification	In natural infection, inactive HA is matured into HA1 and HA2 outside the cell by one or more trypsin-like, arginine-specific endoprotease secreted by the bronchial epithelial cells. One identified protease that may be involved in this process is secreted in lungs by Clara cells. Palmitoylated By similarity.
Miscellaneous	Major glycoprotein, comprises over 80% of the envelope proteins present in virus particle. The extent of infection into host organism is determined by HA. Influenza viruses bud from the apical surface of polarized epithelial cells (e.g. bronchial epithelial cells) into lumen of lungs and are therefore usually pneumotropic. The reason is that HA is cleaved by tryptase clara which is restricted to lungs. However, HAs of H5 and H7 pantropic avian viruses subtypes can be cleaved by furin and subtilisin-type enzymes, allowing the virus to grow in other organs than lungs. 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.
Sequence similarities	Belongs to the influenza viruses hemagglutinin family.

Ontologies

Keywords
Biological process	Fusion protein
Cellular component	Envelope protein Host cell membrane Host membrane Membrane Virion
Domain	Signal Transmembrane
Molecular function	Hemagglutinin
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure
Gene Ontology (GO)
Biological process	viral envelope fusion with host membrane Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell viral envelope Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	host cell surface receptor binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 16

16

Chain

17 – 344

328

Hemagglutinin HA1 chain

PRO_0000038885

Chain

346 – 566

221

Hemagglutinin HA2 chain

PRO_0000038886

Regions

Topological domain

17 – 530

514

Extracellular Potential

Transmembrane

531 – 551

21

Potential

Topological domain

552 – 566

15

Cytoplasmic Potential

Sites

Site

345 – 346

2

Cleavage; by host

Amino acid modifications

Lipidation

555

1

S-palmitoyl cysteine; by host By similarity

Lipidation

562

1

S-palmitoyl cysteine; by host By similarity

Lipidation

565

1

S-palmitoyl cysteine; by host By similarity

Glycosylation

24

1

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

Glycosylation

38

1

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

Glycosylation

54

1

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

Glycosylation

97

1

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

Glycosylation

181

1

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

Glycosylation

301

1

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

Glycosylation

499

1

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

Disulfide bond

30 ↔ 482

Interchain (between HA1 and HA2 chains)

Disulfide bond

68 ↔ 293

Disulfide bond

80 ↔ 92

Disulfide bond

113 ↔ 155

Disulfide bond

297 ↔ 321

Disulfide bond

489 ↔ 493

Experimental info

Sequence conflict

14

1

A → P in AAA43239. Ref.2

Sequence conflict

15

1

L → I in BAF37221. Ref.3

Sequence conflict

160

1

G → S in BAF37221. Ref.3

Sequence conflict

198

1

I → V in BAF37221. Ref.3

Sequence conflict

240

1

R → G in BAF37221. Ref.3

Sequence conflict

477

1

E → D in BAF37221. Ref.3

Secondary structure

1

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566

Helix Strand Turn

Details...

Beta strand

27 – 34

8

Beta strand

40 – 42

3

Beta strand

48 – 53

6

Beta strand

55 – 57

3

Beta strand

65 – 72

8

Beta strand

74 – 76

3

Helix

82 – 87

6

Helix

90 – 95

6

Beta strand

101 – 105

5

Helix

121 – 131

11

Beta strand

136 – 138

3

Beta strand

152 – 157

6

Beta strand

160 – 162

3

Beta strand

167 – 169

3

Beta strand

171 – 173

3

Beta strand

180 – 185

6

Beta strand

188 – 190

3

Beta strand

192 – 200

9

Helix

204 – 211

8

Beta strand

212 – 215

4

Beta strand

218 – 221

4

Beta strand

226 – 229

4

Beta strand

245 – 253

9

Beta strand

258 – 265

8

Beta strand

267 – 270

4

Beta strand

272 – 275

4

Beta strand

282 – 285

4

Beta strand

290 – 294

5

Beta strand

308 – 311

4

Beta strand

318 – 320

3

Turn

352 – 354

3

Beta strand

366 – 372

7

Helix

383 – 449

67

Helix

458 – 470

13

Helix

491 – 499

9

Beta strand

524 – 526

3

Sequences

	Sequence		Length	Mass (Da)
	P03437-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: E395659C23CAFECA	FASTA	566	63,416
	10 20 30 40 50 60 MKTIIALSYI FCLALGQDLP GNDNSTATLC LGHHAVPNGT LVKTITDDQI EVTNATELVQ 70 80 90 100 110 120 SSSTGKICNN PHRILDGIDC TLIDALLGDP HCDVFQNETW DLFVERSKAF SNCYPYDVPD 130 140 150 160 170 180 YASLRSLVAS SGTLEFITEG FTWTGVTQNG GSNACKRGPG SGFFSRLNWL TKSGSTYPVL 190 200 210 220 230 240 NVTMPNNDNF DKLYIWGIHH PSTNQEQTSL YVQASGRVTV STRRSQQTII PNIGSRPWVR 250 260 270 280 290 300 GLSSRISIYW TIVKPGDVLV INSNGNLIAP RGYFKMRTGK SSIMRSDAPI DTCISECITP 310 320 330 340 350 360 NGSIPNDKPF QNVNKITYGA CPKYVKQNTL KLATGMRNVP EKQTRGLFGA IAGFIENGWE 370 380 390 400 410 420 GMIDGWYGFR HQNSEGTGQA ADLKSTQAAI DQINGKLNRV IEKTNEKFHQ IEKEFSEVEG 430 440 450 460 470 480 RIQDLEKYVE DTKIDLWSYN AELLVALENQ HTIDLTDSEM NKLFEKTRRQ LRENAEEMGN 490 500 510 520 530 540 GCFKIYHKCD NACIESIRNG TYDHDVYRDE ALNNRFQIKG VELKSGYKDW ILWISFAISC 550 560 FLLCVVLLGF IMWACQRGNI RCNICI

References

[1]	"Antigenic drift between the haemagglutinin of the Hong Kong influenza strains A/Aichi/2/68 and A/Victoria/3/75." Verhoeyen M., Fang R., Jou W.M., Devos R., Huylebroeck D., Saman E., Fiers W. Nature 286:771-776(1980) [PubMed: 7402351] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Shift and drift in influenza viruses." Min J.W., Verhoeyen M., Fang R.-X., Devos R., Huylebroeck D., Fiers W. (In) Carlile M.J., Collins J.F., Moseley B.E.B. (eds.); Symposium of the Society for General Microbiology, pp.285-311, Cambridge University Press, New York (1981) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]	"Effect of the addition of oligosaccharides on the biological activities and antigenicity of influenza A/H3N2 virus hemagglutinin." Abe Y., Takashita E., Sugawara K., Matsuzaki Y., Muraki Y., Hongo S. J. Virol. 78:9605-9611(2004) [PubMed: 15331693] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[4]	"Human mucus protease inhibitor in airway fluids is a potential defensive compound against infection with influenza A and Sendai viruses." Beppu Y., Imamura Y., Tashiro M., Towatari T., Ariga H., Kido H. J. Biochem. 121:309-316(1997) [PubMed: 9089405] [Abstract] Cited for: CLEAVAGE.
[5]	"Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3-A resolution." Wilson I.A., Skehel J.J., Wiley D.C. Nature 289:366-373(1981) [PubMed: 7464906] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
[6]	"Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid." Weis W.I., Brown J.H., Cusack S.C., Paulson J.C., Skehel J.J., Wiley D.C. Nature 333:426-431(1988) [PubMed: 3374584] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[7]	"The structure of a membrane fusion mutant of the influenza virus haemagglutinin." Weis W.I., Cusack S.C., Brown J.H., Daniels R.S., Skehel J.J., Wiley D.C. EMBO J. 9:17-24(1990) [PubMed: 2295311] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF A MUTANT WITH GLY-457.
[8]	"Refinement of the influenza virus hemagglutinin by simulated annealing." Weis W.I., Bruenger A.T., Skehel J.J., Wiley D.C. J. Mol. Biol. 212:737-761(1990) [PubMed: 2329580] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[9]	"Structure of influenza haemagglutinin at the pH of membrane fusion." Bullough P.A., Hughson F.M., Skehel J.J., Wiley D.C. Nature 371:37-43(1994) [PubMed: 8072525] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[10]	"Antigen distortion allows influenza virus to escape neutralization." Fleury D., Wharton S.A., Skehel J.J., Knossow M., Bizebard T. Nat. Struct. Biol. 5:119-123(1998) [PubMed: 9461077] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02090 Genomic RNA. Translation: AAA43178.1.
V01085 Genomic RNA. Translation: CAA24269.1.
M55059 Genomic RNA. Translation: AAA43239.1.
AB284320 Genomic RNA. Translation: BAF37221.1.

PIR

HMIVHA. A93231.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EO8	X-ray	2.80	A	17-344	[»]
			B	346-520	[»]
1FYT	X-ray	2.60	C	322-334	[»]
1HA0	X-ray	2.80	A	25-518	[»]
1HGD	X-ray	2.70	A/C/E	17-344	[»]
			B/D/F	346-520	[»]
1HGE	X-ray	2.60	A/C/E	17-344	[»]
			B/D/F	346-520	[»]
1HGF	X-ray	3.00	A/C/E	17-344	[»]
			B/D/F	346-520	[»]
1HGG	X-ray	2.90	A/C/E	17-344	[»]
			B/D/F	346-520	[»]
1HGH	X-ray	2.70	A/C/E	17-344	[»]
			B/D/F	346-520	[»]
1HGI	X-ray	2.70	A/C/E	17-344	[»]
			B/D/F	346-520	[»]
1HGJ	X-ray	2.70	A/C/E	17-344	[»]
			B/D/F	346-520	[»]
1HTM	X-ray	2.50	A/C/E	17-43	[»]
			B/D/F	383-520	[»]
1J8H	X-ray	2.40	C	322-334	[»]
1KEN	X-ray	3.50	A/C/E	17-344	[»]
			B/D/F	346-520	[»]
1QFU	X-ray	2.80	A	17-344	[»]
			B	346-520	[»]
1QU1	X-ray	1.90	A/B/C/D/E/F	376-530	[»]
2HMG	X-ray	3.00	A/C/E	17-344	[»]
			B/D/F	346-520	[»]
2VIR	X-ray	3.25	C	44-325	[»]
2VIS	X-ray	3.25	C	44-325	[»]
2VIT	X-ray	3.25	C	44-325	[»]
2VIU	X-ray	2.50	A	17-344	[»]
			B	346-520	[»]
3EYM	X-ray	2.80	A/C/E	25-345	[»]
			B/D/F	346-517	[»]
3HMG	X-ray	2.90	A/C/E	17-344	[»]
			B/D/F	346-520	[»]
4HMG	X-ray	3.00	A/C/E	17-344	[»]
			B/D/F	346-520	[»]
5HMG	X-ray	3.20	A/C/E	17-344	[»]
			B/D/F	346-520	[»]

ModBase

Search...

Family and domain databases

InterPro

IPR008980. Capsid_hemagglutn.
IPR000149. Hemagglutn_influenz_HA1.
IPR001364. Hemagglutn_influenz_HA1/HA2.
IPR013829. Hemagglutn_stalk.
[Graphical view]

Gene3D

G3DSA:3.90.20.10. Haemagglutn_stalk. 2 hits.

Pfam

PF00509. Hemagglutinin. 1 hit.
[Graphical view]

PRINTS

PR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.

ProtoNet

Search...

Entry information

Entry name

HEMA_I68A0

Accession

Primary (citable) accession number: P03437
Secondary accession number(s): A0PC85, Q67132

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	January 19, 2010
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Virus (Virus annotation project)