P03452 (HEMA_I34A1) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hemagglutinin

Cleaved into the following 2 chains:

1. Hemagglutinin HA1 chain
2. Hemagglutinin HA2 chain

Gene names

Name:

HA

Organism

Influenza A virus (strain A/Puerto Rico/8/1934 H1N1) [Reference proteome]

Taxonomic identifier

211044 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A › Influenza A virus › H1N1 subtype

Virus host

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

Protein attributes

Sequence length	565 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. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. 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 induces 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 By similarity. 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	Clathrin- and caveolin-independent endocytosis of virus by host Clathrin-mediated endocytosis of virus by host Fusion of virus membrane with host endosomal membrane Fusion of virus membrane with host membrane Host-virus interaction Viral attachment to host cell Viral penetration into host cytoplasm Virus endocytosis by host Virus entry into host cell
Cellular component	Host cell membrane Host membrane Membrane Viral envelope protein Virion
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Hemagglutinin
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular transport of viral proteins in host cell Traceable author statement. Source: Reactome uncoating of virus Traceable author statement. Source: Reactome viral attachment to host cell Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell via clathrin-mediated endocytosis Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell via membrane fusion with the plasma membrane Traceable author statement. Source: Reactome viral entry into host cell via receptor-mediated endocytosis Traceable author statement. Source: Reactome viral genome packaging Traceable author statement. Source: Reactome viral release from host cell Traceable author statement. Source: Reactome viral transcription Traceable author statement. Source: Reactome
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome endocytic vesicle membrane Traceable author statement. Source: Reactome endoplasmic reticulum membrane Traceable author statement. Source: Reactome endosome lumen Traceable author statement. Source: Reactome host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome viral envelope Inferred from electronic annotation. Source: UniProtKB-KW virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Potential

Chain

18 – 342

325

Hemagglutinin HA1 chain

PRO_0000039034

Chain

344 – 565

222

Hemagglutinin HA2 chain

PRO_0000039035

Regions

Topological domain

18 – 528

511

Extracellular Potential

Transmembrane

529 – 549

21

Helical; Potential

Topological domain

550 – 565

16

Cytoplasmic Potential

Sites

Site

343 – 344

2

Cleavage; by host By similarity

Amino acid modifications

Lipidation

554

1

S-palmitoyl cysteine; by host By similarity

Lipidation

561

1

S-palmitoyl cysteine; by host By similarity

Lipidation

564

1

S-palmitoyl cysteine; by host By similarity

Glycosylation

27

1

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

Glycosylation

28

1

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

Glycosylation

40

1

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

Glycosylation

285

1

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

Glycosylation

303

1

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

Glycosylation

497

1

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

Disulfide bond

21 ↔ 480

Interchain (between HA1 and HA2 chains) By similarity

Disulfide bond

59 ↔ 291

By similarity

Disulfide bond

72 ↔ 84

By similarity

Disulfide bond

107 ↔ 152

By similarity

Disulfide bond

295 ↔ 319

By similarity

Disulfide bond

487 ↔ 491

By similarity

Experimental info

Sequence conflict

10

1

C → S in AAM75158. Ref.2

Sequence conflict

146

1

N → TK in CAA24272. Ref.1

Sequence conflict

155

1

E → A in CAA24272. Ref.1

Sequence conflict

199

1

P → S in CAA24272. Ref.1

Sequence conflict

203

1

E → D in CAA24272. Ref.1

Sequence conflict

207

1

L → I in CAA24272. Ref.1

Sequence conflict

207

1

L → I in AAM75158. Ref.2

Sequence conflict

268

1

M → R in CAA24272. Ref.1

Sequence conflict

308

1

Y → F in CAA24272. Ref.1

Sequence conflict

337

1

I → N in ABO21709. Ref.3

Sequence conflict

397

1

T → S in CAA24272. Ref.1

Secondary structure

1

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565

Helix Strand Turn

Details...

Beta strand

19 – 25

7

Beta strand

39 – 44

6

Beta strand

46 – 48

3

Beta strand

56 – 61

6

Beta strand

67 – 70

4

Helix

74 – 79

6

Helix

82 – 87

6

Beta strand

94 – 98

5

Helix

115 – 122

8

Beta strand

125 – 134

10

Helix

136 – 139

4

Beta strand

149 – 154

6

Beta strand

157 – 159

3

Beta strand

162 – 166

5

Beta strand

177 – 182

6

Beta strand

185 – 197

13

Helix

201 – 208

8

Beta strand

215 – 218

4

Beta strand

223 – 226

4

Beta strand

242 – 250

9

Beta strand

255 – 262

8

Beta strand

264 – 275

12

Beta strand

281 – 283

3

Beta strand

288 – 297

10

Beta strand

307 – 309

3

Beta strand

315 – 319

5

Beta strand

329 – 331

3

Sequences

	Sequence		Length	Mass (Da)
	P03452 [UniParc]. Last modified March 6, 2007. Version 2. Checksum: 47F34821748F494E	FASTA	565	63,353
	10 20 30 40 50 60 MKANLLVLLC ALAAADADTI CIGYHANNST DTVDTVLEKN VTVTHSVNLL EDSHNGKLCR 70 80 90 100 110 120 LKGIAPLQLG KCNIAGWLLG NPECDPLLPV RSWSYIVETP NSENGICYPG DFIDYEELRE 130 140 150 160 170 180 QLSSVSSFER FEIFPKESSW PNHNTNGVTA ACSHEGKSSF YRNLLWLTEK EGSYPKLKNS 190 200 210 220 230 240 YVNKKGKEVL VLWGIHHPPN SKEQQNLYQN ENAYVSVVTS NYNRRFTPEI AERPKVRDQA 250 260 270 280 290 300 GRMNYYWTLL KPGDTIIFEA NGNLIAPMYA FALSRGFGSG IITSNASMHE CNTKCQTPLG 310 320 330 340 350 360 AINSSLPYQN IHPVTIGECP KYVRSAKLRM VTGLRNIPSI QSRGLFGAIA GFIEGGWTGM 370 380 390 400 410 420 IDGWYGYHHQ NEQGSGYAAD QKSTQNAING ITNKVNTVIE KMNIQFTAVG KEFNKLEKRM 430 440 450 460 470 480 ENLNKKVDDG FLDIWTYNAE LLVLLENERT LDFHDSNVKN LYEKVKSQLK NNAKEIGNGC 490 500 510 520 530 540 FEFYHKCDNE CMESVRNGTY DYPKYSEESK LNREKVDGVK LESMGIYQIL AIYSTVASSL 550 560 VLLVSLGAIS FWMCSNGSLQ CRICI

References

[1]	"Nucleotide sequence of the haemagglutinin gene of a human influenza virus H1 subtype." Winter G., Fields S., Brownlee G.G. Nature 292:72-75(1981) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Plasmid-only rescue of influenza A virus vaccine candidates." Schickli J.H., Flandorfer A., Nakaya T., Martinez-Sobrido L., Garcia-Sastre A., Palese P. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356:1965-1973(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]	"Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments." de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F., Osterhaus A.D.M.E., Fouchier R.A.M. Virus Res. 103:155-161(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], REVERSE GENETICS.
[4]	"The NIAID influenza genome sequencing project." Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V., Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H., Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y. , Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T. Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. Strain: Isolate EE12/E1.
[5]	"The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype)." Caton A.J., Brownlee G.G., Yewdell J.W., Gerhard W. Cell 31:417-427(1982) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 18-343.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

V01088 Genomic RNA. Translation: CAA24272.1.
AF389118 Genomic RNA. Translation: AAM75158.1.
EF467821 Genomic RNA. Translation: ABO21709.1.
CY009444 Genomic RNA. Translation: ABD77675.1.
J02144 Genomic RNA. Translation: AAA43194.1.

RefSeq

NP_040980.1. NC_002017.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RU7	X-ray	2.30	A/C/E/G/I/K	18-338	[»]
			B/D/F/H/J/L	344-503	[»]
1RVX	X-ray	2.20	A/C/E/G/I/K	17-338	[»]
			B/D/F/H/J/L	344-503	[»]
1RVZ	X-ray	2.25	A/C/E/G/I/K	17-338	[»]
			B/D/F/H/J/L	344-503	[»]

ProteinModelPortal

P03452.

SMR

P03452. Positions 18-339, 344-518.

ModBase

Search...

Protein-protein interaction databases

IntAct

P03452. 7 interactions.

MINT

MINT-3375119.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Family and domain databases

Gene3D

2.10.77.10. 1 hit.
3.90.20.10. 1 hit.
3.90.209.20. 1 hit.

InterPro

IPR008980. Capsid_hemagglutn.
IPR013828. Hemagglutn_HA1_a/b_dom.
IPR013827. Hemagglutn_HA1_b-rbn_dom.
IPR000149. Hemagglutn_influenz_A.
IPR001364. Hemagglutn_influenz_A/B.
IPR013829. Hemagglutn_stalk.
[Graphical view]

Pfam

PF00509. Hemagglutinin. 1 hit.
[Graphical view]

PRINTS

PR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.

SUPFAM

SSF49818. Capsid_hemag. 1 hit.

ProtoNet

Search...

Other

BindingDB

P03452.

ChEMBL

CHEMBL1075313.

EvolutionaryTrace

P03452.

Entry information

Entry name

HEMA_I34A1

Accession

Primary (citable) accession number: P03452
Secondary accession number(s): A4GXH4 , Q20N38, Q83964, Q8JUU5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	March 6, 2007
Last modified:	April 3, 2013
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program