Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Hemagglutinin

Gene

HA

Organism
Influenza A virus (strain A/Swine/Hong Kong/81/1978 H3N2)
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 either through clathrin-dependent endocytosis or through 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.UniRule annotation

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.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHemagglutinin
Biological processClathrin- 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:
HemagglutininUniRule annotation
Cleaved into the following 2 chains:
Hemagglutinin HA1 chainUniRule annotation
Hemagglutinin HA2 chainUniRule annotation
Gene namesi
Name:HAUniRule annotation
OrganismiInfluenza A virus (strain A/Swine/Hong Kong/81/1978 H3N2)
Taxonomic identifieri384484 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
Virus hostiAves [TaxID: 8782]
Cetacea (whales) [TaxID: 9721]
Homo sapiens (Human) [TaxID: 9606]
Phocidae (true seals) [TaxID: 9709]
Sus scrofa (Pig) [TaxID: 9823]

Subcellular locationi

  • Virion membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation
  • Host apical cell membrane UniRule annotation; Single-pass type I membrane protein UniRule annotation

  • 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.UniRule annotation

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 514ExtracellularUniRule annotationAdd BLAST514
Transmembranei515 – 535HelicalUniRule annotationAdd BLAST21
Topological domaini536 – 550CytoplasmicUniRule annotationAdd BLAST15

GO - Cellular componenti

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004408421 – 329Hemagglutinin HA1 chainUniRule annotationAdd BLAST329
ChainiPRO_0000039076330 – 550Hemagglutinin HA2 chainUniRule annotationAdd BLAST221

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi8N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi14 ↔ 466Interchain (between HA1 and HA2 chains)UniRule annotation
Glycosylationi22N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi38N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi52 ↔ 277UniRule annotation
Disulfide bondi64 ↔ 76UniRule annotation
Disulfide bondi97 ↔ 139UniRule annotation
Glycosylationi165N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi281 ↔ 305UniRule annotation
Glycosylationi285N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi473 ↔ 477UniRule annotation
Glycosylationi483N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Lipidationi539S-palmitoyl cysteine; by hostUniRule annotation1
Lipidationi546S-palmitoyl cysteine; by hostUniRule annotation1
Lipidationi549S-palmitoyl cysteine; by hostUniRule annotation1

Post-translational modificationi

Palmitoylated.UniRule annotation
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.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei329 – 330Cleavage; by hostUniRule annotation2

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HA1-HA2.UniRule annotation

GO - Molecular functioni

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1R5IX-ray2.60C/G306-318[»]
ProteinModelPortaliP11133.
SMRiP11133.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11133.

Family & Domainsi

Sequence similaritiesi

Belongs to the influenza viruses hemagglutinin family.UniRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di3.90.209.20. 1 hit.
HAMAPiMF_04072. INFV_HEMA. 1 hit.
InterProiView protein in InterPro
IPR008980. Capsid_hemagglutn.
IPR013828. Hemagglutn_HA1_a/b_dom.
IPR000149. Hemagglutn_influenz_A.
IPR001364. Hemagglutn_influenz_A/B.
PfamiView protein in Pfam
PF00509. Hemagglutinin. 1 hit.
PRINTSiPR00330. HEMAGGLUTN1.
PR00329. HEMAGGLUTN12.
SUPFAMiSSF49818. SSF49818. 1 hit.

Sequencei

Sequence statusi: Fragment.

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

P11133-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
QDLPGTDNST ATLCLGHHAV PNGTIVKTIT DDQIEVTNAT ELVQSSSTGK
60 70 80 90 100
ICNNPHKILD GIDCTLIDAL LGDPHCDVFQ DETWDLFVER SNAFSNCYPY
110 120 130 140 150
DVPDYASLRS LVASSGTLEF ITEGFTWTGV TQNGGSNACK RGPANGFFSR
160 170 180 190 200
LNWLTKSGST YPVLNVTMPN NDNSDKLYIW GVHHPSTNQE QTNLYVQASG
210 220 230 240 250
RVTVSTKRSQ QTMIPNAGSR PWVRGLSSRI SIYWTIVKPG DILVINSNGN
260 270 280 290 300
LIAPRGYFKM RTGKSSIMRS DAPIGTCSSE CITPNGSIPN DKPFQNVNKI
310 320 330 340 350
TYGACPKYVK QNTLKLATGM RNVPEKQTRG LFGAIAGFIE NGWEGMIDGW
360 370 380 390 400
YGFRHQNSEG TGQAADLKST QAAIDLINGK VNRVIEKTNE KFHQIEKEFS
410 420 430 440 450
EVEGRIQDLE KYVEDTKIDL WSYNADVLVA LENQHTIDLT DSEMNKLFEK
460 470 480 490 500
TRRQLRENAE DMGNGCFKIY HKCDNACIES IRNGTYDHDI YRDEALNNRF
510 520 530 540 550
QIKGVELKSG YKDWILWISF AISCFLLCVV LLGFIMWACQ RGNIRCNICI
Length:550
Mass (Da):61,437
Last modified:July 15, 1998 - v2
Checksum:i1F2A7E758C531CE8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19057 Genomic RNA. Translation: AAA43212.1.
PIRiB29971. HMIVS3.

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.

Entry informationi

Entry nameiHEMA_I78A9
AccessioniPrimary (citable) accession number: P11133
Secondary accession number(s): Q84019, Q84020
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 15, 1998
Last modified: July 5, 2017
This is version 108 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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