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Protein

Hemagglutinin-esterase-fusion glycoprotein

Gene

HE

Organism
Influenza C virus (strain C/Ann Arbor/1/1950)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Protein inferred from homologyi

Functioni

Binds to the N-acetyl-9-O-acetylneuraminic acid residues 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 HEF2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore. Displays a receptor-destroying activity which is a neuraminidate-O-acetyl esterase. This activity cleaves off any receptor on the cell surface, which would otherwise prevent virions release. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell (By similarity).By similarity

Catalytic activityi

N-acetyl-O-acetylneuraminate + H2O = N-acetylneuraminate + acetate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei71NucleophileBy similarity1
Active sitei366Charge relay systemBy similarity1
Active sitei369Charge relay systemBy similarity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hemagglutinin, Hydrolase

Keywords - Biological processi

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 entry into host cell

Names & Taxonomyi

Protein namesi
Recommended name:
Hemagglutinin-esterase-fusion glycoprotein (EC:3.1.1.53)
Short name:
HEF
Cleaved into the following 2 chains:
Gene namesi
Name:HE
OrganismiInfluenza C virus (strain C/Ann Arbor/1/1950)
Taxonomic identifieri11553 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus C
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000008286 Componenti: Genome

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini15 – 630ExtracellularSequence analysisAdd BLAST616
Transmembranei631 – 651HelicalSequence analysisAdd BLAST21
Topological domaini652 – 655CytoplasmicSequence analysis4

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 – 14By similarityAdd BLAST14
ChainiPRO_000003914215 – 446Hemagglutinin-esterase-fusion glycoprotein chain 1Add BLAST432
ChainiPRO_0000039143447 – 655Hemagglutinin-esterase-fusion glycoprotein chain 2Add BLAST209

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi20 ↔ 583Interchain (between HEF1 and HEF2 chains)By similarity
Glycosylationi26N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi61N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi120 ↔ 165By similarity
Disulfide bondi140 ↔ 188By similarity
Glycosylationi144N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi210 ↔ 252By similarity
Disulfide bondi229 ↔ 316By similarity
Disulfide bondi237 ↔ 289By similarity
Glycosylationi395N-linked (GlcNAc...); by hostSequence analysis1

Post-translational modificationi

In natural infection, inactive HEF is matured into HEF1 and HEF2 outside the cell by one or more trypsin-like, arginine-specific endoprotease.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HEF1-HEF2.By similarity

Structurei

3D structure databases

ProteinModelPortaliP68762.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni15 – 40Fusion domain-1By similarityAdd BLAST26
Regioni41 – 151Esterase domain-1By similarityAdd BLAST111
Regioni151 – 310N-acetyl-9-O-acetylneuraminic acid bindingBy similarityAdd BLAST160
Regioni311 – 365Esterase domain-2By similarityAdd BLAST55
Regioni366 – 651Fusion domain-2By similarityAdd BLAST286

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

KOiK19253.

Family and domain databases

Gene3Di3.90.20.10. 1 hit.
InterProiIPR008980. Capsid_hemagglutn.
IPR007142. Hemagglutn-estrase_core.
IPR003860. Hemagglutn-estrase_hemagglutn.
IPR013829. Hemagglutn_stalk.
IPR014831. Hemagglutn_stalk_influenz-C.
IPR013830. SGNH_hydro.
[Graphical view]
PfamiPF03996. Hema_esterase. 1 hit.
PF02710. Hema_HEFG. 1 hit.
PF08720. Hema_stalk. 1 hit.
[Graphical view]
SUPFAMiSSF49818. SSF49818. 1 hit.
SSF52266. SSF52266. 2 hits.

Sequencei

Sequence statusi: Complete.

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

P68762-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFFSLLLMLG LTEAEKIKIC LQKQVNSSFS LHNGFGGNLY ATEEKRMFEL
60 70 80 90 100
VKPKAGASVL NQSTWIGFGD SRTDKSNSAF PRSADVSAKT ADKFRSLSGG
110 120 130 140 150
SLMLSMFGPP GKVDYLYQGC GKHKVFYEGV NWSPHAAINC YRKNWTDIKL
160 170 180 190 200
NFQKNIYELA SQSHCMSLVN ALDKTIPLQA TAGVAKNCNN SFLKNPALYT
210 220 230 240 250
QEVNPSVEKC GKENLAFFTL PTQFGTYECK LHLVASCYFI YDSKEVYNKR
260 270 280 290 300
GCDNYFQVIY DSSGKVVGGL DNRVSPYTGN SGDTPTMQCD MLQLKPGRYS
310 320 330 340 350
VRSSPRFLLM PERSYCFDMK EKGPVTAVQS IWGKGRESDH AVDQACLSTP
360 370 380 390 400
GCMLIQKQKP YIGEADDHHG DQEMRELLSG LDYEARCISQ SGWVNETSPF
410 420 430 440 450
TEEYLLPPKF GRCPLAAKEE SIPKIPDGLL IPTSGTDTTV TKPKSRIFGI
460 470 480 490 500
DDLIIGLLFV AIVEAGIGGY LLGSRKVSGG GVTKESAEKG FEKIGNDIQI
510 520 530 540 550
LRSSTNIAIE KLNDRISHDE QAIRDLTLEI ENARSEALLG ELGIIRALLV
560 570 580 590 600
GNISIGLQES LWELASEITN RAGDLAVEVS PGCWVIDNNI CDQSCQNFIF
610 620 630 640 650
KFNETAPVPT IPPLDTKIDL QSDPFYWGSS LGLAITAAIS LAALVISGIA

ICRTK
Length:655
Mass (Da):71,956
Last modified:December 12, 2006 - v2
Checksum:i81869FEDA9CD8943
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti207 – 209VEK → EEI in AAA43782 (PubMed:3855244).Curated3
Sequence conflicti214N → Y in AAA43782 (PubMed:3855244).Curated1
Sequence conflicti263S → Y in AAA43782 (PubMed:3855244).Curated1
Sequence conflicti324P → L in AAA43782 (PubMed:3855244).Curated1
Sequence conflicti346C → Y in AAA43782 (PubMed:3855244).Curated1
Sequence conflicti458L → F in AAA43782 (PubMed:3855244).Curated1
Sequence conflicti477V → E in AAA43782 (PubMed:3855244).Curated1
Sequence conflicti637 – 638AA → TP in AAA43782 (PubMed:3855244).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB126194 Genomic RNA. Translation: BAD24940.1.
M11638 Genomic RNA. Translation: AAA43782.1.
RefSeqiYP_089655.1. NC_006310.1.

Genome annotation databases

GeneIDi3077359.
KEGGivg:3077359.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB126194 Genomic RNA. Translation: BAD24940.1.
M11638 Genomic RNA. Translation: AAA43782.1.
RefSeqiYP_089655.1. NC_006310.1.

3D structure databases

ProteinModelPortaliP68762.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi3077359.
KEGGivg:3077359.

Phylogenomic databases

KOiK19253.

Family and domain databases

Gene3Di3.90.20.10. 1 hit.
InterProiIPR008980. Capsid_hemagglutn.
IPR007142. Hemagglutn-estrase_core.
IPR003860. Hemagglutn-estrase_hemagglutn.
IPR013829. Hemagglutn_stalk.
IPR014831. Hemagglutn_stalk_influenz-C.
IPR013830. SGNH_hydro.
[Graphical view]
PfamiPF03996. Hema_esterase. 1 hit.
PF02710. Hema_HEFG. 1 hit.
PF08720. Hema_stalk. 1 hit.
[Graphical view]
SUPFAMiSSF49818. SSF49818. 1 hit.
SSF52266. SSF52266. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiHEMA_INCAA
AccessioniPrimary (citable) accession number: P68762
Secondary accession number(s): P07969, Q6I7C1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: December 12, 2006
Last modified: October 5, 2016
This is version 65 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.