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Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/Duck/Ukraine/1/1963 H3N8)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hemagglutinin

Keywords - Biological processi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Hemagglutinin
Cleaved into the following 2 chains:
Gene namesi
Name:HA
OrganismiInfluenza A virus (strain A/Duck/Ukraine/1/1963 H3N8)
Taxonomic identifieri385580 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Equus caballus (Horse) [TaxID: 9796]

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini17 – 530ExtracellularSequence analysisAdd BLAST514
Transmembranei531 – 551HelicalSequence analysisAdd BLAST21
Topological domaini552 – 566CytoplasmicSequence analysisAdd BLAST15

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Viral envelope protein, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
ChainiPRO_000003894617 – 344Hemagglutinin HA1 chainAdd BLAST328
ChainiPRO_0000038947346 – 566Hemagglutinin HA2 chainAdd BLAST221

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi24N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi30 ↔ 482Interchain (between HA1 and HA2 chains)By similarity
Glycosylationi38N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi54N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi68 ↔ 293By similarity
Disulfide bondi80 ↔ 92By similarity
Glycosylationi97N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi113 ↔ 155By similarity
Glycosylationi181N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi297 ↔ 321By similarity
Glycosylationi301N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi489 ↔ 493By similarity
Glycosylationi499N-linked (GlcNAc...); by hostSequence analysis1
Lipidationi555S-palmitoyl cysteine; by hostBy similarity1
Lipidationi562S-palmitoyl cysteine; by hostBy similarity1
Lipidationi565S-palmitoyl cysteine; by hostBy similarity1

Post-translational modificationi

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).By similarity
Palmitoylated.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei345 – 346Cleavage; by hostBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.

Structurei

Secondary structure

1566
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi27 – 34Combined sources8
Beta strandi40 – 42Combined sources3
Beta strandi48 – 53Combined sources6
Beta strandi55 – 57Combined sources3
Turni71 – 73Combined sources3
Beta strandi74 – 76Combined sources3
Helixi82 – 87Combined sources6
Helixi90 – 95Combined sources6
Beta strandi101 – 105Combined sources5
Helixi121 – 131Combined sources11
Beta strandi136 – 138Combined sources3
Beta strandi152 – 157Combined sources6
Beta strandi160 – 162Combined sources3
Beta strandi167 – 169Combined sources3
Beta strandi171 – 175Combined sources5
Beta strandi180 – 185Combined sources6
Beta strandi188 – 190Combined sources3
Beta strandi192 – 200Combined sources9
Helixi204 – 211Combined sources8
Beta strandi212 – 215Combined sources4
Beta strandi218 – 221Combined sources4
Beta strandi226 – 229Combined sources4
Beta strandi245 – 253Combined sources9
Beta strandi258 – 265Combined sources8
Beta strandi267 – 270Combined sources4
Beta strandi272 – 275Combined sources4
Beta strandi282 – 285Combined sources4
Beta strandi292 – 294Combined sources3
Beta strandi296 – 299Combined sources4
Beta strandi302 – 304Combined sources3
Beta strandi307 – 311Combined sources5
Beta strandi318 – 320Combined sources3
Beta strandi331 – 333Combined sources3
Turni352 – 354Combined sources3
Turni356 – 359Combined sources4
Helixi360 – 363Combined sources4
Beta strandi366 – 373Combined sources8
Beta strandi376 – 381Combined sources6
Helixi383 – 401Combined sources19
Helixi421 – 471Combined sources51
Beta strandi474 – 477Combined sources4
Beta strandi479 – 487Combined sources9
Helixi491 – 498Combined sources8
Helixi505 – 515Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IBNNMR-A346-365[»]
1IBONMR-A346-365[»]
1MQLX-ray2.90A/D/G17-345[»]
B/E/H346-566[»]
1MQMX-ray2.60A/D/G17-345[»]
B/E/H346-566[»]
1MQNX-ray3.20A/D/G17-345[»]
B/E/H346-566[»]
ProteinModelPortaliP03442.
SMRiP03442.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03442.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di2.10.77.10. 1 hit.
3.90.20.10. 1 hit.
3.90.209.20. 1 hit.
InterProiIPR008980. 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]
PfamiPF00509. Hemagglutinin. 1 hit.
[Graphical view]
PRINTSiPR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.
SUPFAMiSSF49818. SSF49818. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P03442-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKTVIALSYI LCLTFGQDLP GNDNSTATLC LGHHAVPNGT IVKTITDDQI
60 70 80 90 100
EVTNATELVQ SSSTGKICNN PHRILDGRAC TLIDALLGDP HCDVFQNETW
110 120 130 140 150
DLFVERSNAF SNCYPYDIPD YASLRSLVAS SGTLEFITEG FTWTGVTQNG
160 170 180 190 200
GSSACKRGPA NGFFSRLNWL TKSESAYPVL NVTMPNNDNF DKLYIWGVHH
210 220 230 240 250
PSTNQEQTNL YVQASGRVTV STRRSQQTII PNIGSRPWVR GQPGRISIYW
260 270 280 290 300
TIVKPGDVLV INSNGNLIAP RGYFKMRTGK SSIMRSDAPI DTCISECITP
310 320 330 340 350
NGSIPNDKPF QNVNKITYGA CPKYVKQNTL KLATGMRNVP EKQTRGLFGA
360 370 380 390 400
IAGFIENGWE GMIDGWYGFR HQNSEGTGQA ADLKSTQAAI DQINRKLNRV
410 420 430 440 450
IEKTNEKFHQ IEKEFSEVEG RIQDLEKYVE DTKIDLWSYN AELLVALENQ
460 470 480 490 500
HTIDLADSEM NKLFEKTRRQ LRENAEDMGN GCFKIYHKCD NACIESIRNG
510 520 530 540 550
TYDHDIYRDE ALNNRFQIKG VELKSGYKDW ILWISFAISC LLLCVVLLGF
560
IMWACQRGNI RCNICI
Length:566
Mass (Da):63,530
Last modified:July 21, 1986 - v1
Checksum:iE70F87F0AE1178F4
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V01087 Unassigned RNA. Translation: CAA24271.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V01087 Unassigned RNA. Translation: CAA24271.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IBNNMR-A346-365[»]
1IBONMR-A346-365[»]
1MQLX-ray2.90A/D/G17-345[»]
B/E/H346-566[»]
1MQMX-ray2.60A/D/G17-345[»]
B/E/H346-566[»]
1MQNX-ray3.20A/D/G17-345[»]
B/E/H346-566[»]
ProteinModelPortaliP03442.
SMRiP03442.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP03442.

Family and domain databases

Gene3Di2.10.77.10. 1 hit.
3.90.20.10. 1 hit.
3.90.209.20. 1 hit.
InterProiIPR008980. 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]
PfamiPF00509. Hemagglutinin. 1 hit.
[Graphical view]
PRINTSiPR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.
SUPFAMiSSF49818. SSF49818. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiHEMA_I63A3
AccessioniPrimary (citable) accession number: P03442
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 2, 2016
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.