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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.UniRule annotation

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei71NucleophileUniRule annotation1
Active sitei366Charge relay systemUniRule annotation1
Active sitei369Charge relay systemUniRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHemagglutinin, Hydrolase
Biological processFusion 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-esterase-fusion glycoproteinUniRule annotation (EC:3.1.1.53UniRule annotation)
Short name:
HEFUniRule annotation
Cleaved into the following 2 chains:
Hemagglutinin-esterase-fusion glycoprotein chain 1UniRule annotation
Short name:
HEF1UniRule annotation
Hemagglutinin-esterase-fusion glycoprotein chain 2UniRule annotation
Short name:
HEF2UniRule annotation
Gene namesi
Name:HEUniRule annotation
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

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini15 – 630ExtracellularUniRule annotationAdd BLAST616
Transmembranei631 – 651HelicalUniRule annotationAdd BLAST21
Topological domaini652 – 655CytoplasmicUniRule annotation4

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
Signal peptidei1 – 14UniRule annotationAdd BLAST14
ChainiPRO_000044055115 – 655Hemagglutinin-esterase-fusion glycoproteinUniRule annotationAdd BLAST641
ChainiPRO_000003914215 – 446Hemagglutinin-esterase-fusion glycoprotein chain 1UniRule annotationAdd BLAST432
ChainiPRO_0000039143447 – 655Hemagglutinin-esterase-fusion glycoprotein chain 2UniRule annotationAdd BLAST209

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi20 ↔ 583Interchain (between HEF1 and HEF2 chains)UniRule annotation
Glycosylationi26N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi61N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi144N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi189N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Disulfide bondi210 ↔ 252UniRule annotation
Disulfide bondi229 ↔ 316UniRule annotation
Disulfide bondi237 ↔ 289UniRule annotation
Glycosylationi395N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi552N-linked (GlcNAc...) asparagine; by hostUniRule annotation1
Glycosylationi603N-linked (GlcNAc...) asparagine; by hostUniRule annotation1

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.UniRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HEF1-HEF2.UniRule annotation

GO - Molecular functioni

Structurei

3D structure databases

ProteinModelPortaliP68762.
SMRiP68762.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni15 – 40Fusion domain-1UniRule annotationAdd BLAST26
Regioni41 – 158Esterase domain-1UniRule annotationAdd BLAST118
Regioni158 – 310N-acetyl-9-O-acetylneuraminic acid bindingUniRule annotationAdd BLAST153
Regioni310 – 364Esterase domain-2UniRule annotationAdd BLAST55
Regioni365 – 650Fusion domain-2UniRule annotationAdd BLAST286

Sequence similaritiesi

Belongs to the influenza viruses hemagglutinin family.UniRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

KOiK19253.
OrthoDBiVOG0900009Y.

Family and domain databases

HAMAPiMF_04072. INFV_HEMA. 1 hit.
InterProiView protein in InterPro
IPR008980. Capsid_hemagglutn.
IPR007142. Hemagglutn-estrase_core.
IPR003860. Hemagglutn-estrase_hemagglutn.
IPR014831. Hemagglutn_stalk_influenz-C.
IPR013830. SGNH_hydro.
PfamiView protein in Pfam
PF03996. Hema_esterase. 1 hit.
PF02710. Hema_HEFG. 1 hit.
PF08720. Hema_stalk. 1 hit.
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.
SMRiP68762.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi3077359.
KEGGivg:3077359.

Phylogenomic databases

KOiK19253.
OrthoDBiVOG0900009Y.

Family and domain databases

HAMAPiMF_04072. INFV_HEMA. 1 hit.
InterProiView protein in InterPro
IPR008980. Capsid_hemagglutn.
IPR007142. Hemagglutn-estrase_core.
IPR003860. Hemagglutn-estrase_hemagglutn.
IPR014831. Hemagglutn_stalk_influenz-C.
IPR013830. SGNH_hydro.
PfamiView protein in Pfam
PF03996. Hema_esterase. 1 hit.
PF02710. Hema_HEFG. 1 hit.
PF08720. Hema_stalk. 1 hit.
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 historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: December 12, 2006
Last modified: June 7, 2017
This is version 69 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

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.