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P07975 (HEMA_INCJH) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 89. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Hemagglutinin-esterase-fusion glycoprotein
Short name=HEF
EC=3.1.1.53

Cleaved into the following 2 chains:

  1. Hemagglutinin-esterase-fusion glycoprotein chain 1
    Short name=HEF1
  2. Hemagglutinin-esterase-fusion glycoprotein chain 2
    Short name=HEF2
Gene names
Name:HE
OrganismInfluenza C virus (strain C/Johannesburg/1/1966)
Taxonomic identifier100673 [NCBI]
Taxonomic lineageViruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus C ›
Virus hostHomo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Protein attributes

Sequence length655 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

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

Subunit structure

Homotrimer of disulfide-linked HEF1-HEF2.

Subcellular location

Virion membrane; Single-pass type I membrane protein Potential. Host cell membrane; Single-pass type I membrane protein.

Post-translational modification

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

Sequence similarities

Belongs to the influenza type C/coronaviruses hemagglutinin-esterase family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1414
Chain15 – 446432Hemagglutinin-esterase-fusion glycoprotein chain 1
PRO_0000039152
Chain447 – 655209Hemagglutinin-esterase-fusion glycoprotein chain 2
PRO_0000039153

Regions

Topological domain15 – 630616Extracellular Potential
Transmembrane631 – 65121Helical; Potential
Topological domain652 – 6554Cytoplasmic Potential
Region15 – 4026Fusion domain-1
Region41 – 151111Esterase domain-1
Region151 – 310160N-acetyl-9-O-acetylneuraminic acid binding
Region311 – 36555Esterase domain-2
Region366 – 651286Fusion domain-2

Sites

Active site711Nucleophile Ref.4
Active site3661Charge relay system Ref.4
Active site3691Charge relay system Ref.4

Amino acid modifications

Glycosylation261N-linked (GlcNAc...); by host
Glycosylation611N-linked (GlcNAc...); by host
Glycosylation1441N-linked (GlcNAc...); by host
Glycosylation3951N-linked (GlcNAc...); by host
Disulfide bond20 ↔ 583Interchain (between HEF1 and HEF2 chains)
Disulfide bond120 ↔ 165
Disulfide bond140 ↔ 188
Disulfide bond210 ↔ 252
Disulfide bond229 ↔ 316
Disulfide bond237 ↔ 289
Disulfide bond346 ↔ 352

Natural variations

Natural variant961F → S.
Natural variant2631F → S.
Natural variant4571V → L.
Natural variant4651T → A.

Experimental info

Mutagenesis711S → A: 96% loss of esterase activity. Ref.3
Mutagenesis2611D → A: 64% loss of esterase activity. Ref.3
Mutagenesis2801N → A: Complete loss of esterase activity. Ref.3
Mutagenesis3681H → A: Complete loss of esterase activity. Ref.3
Mutagenesis3691H → A: Complete loss of esterase activity. Ref.3

Secondary structure

1 .................................................................................................... 655
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P07975 [UniParc].

Last modified August 1, 1988. Version 1.
Checksum: 52C78BFCC5A24AC8

FASTA65572,131
        10         20         30         40         50         60 
MFFSLLLVLG LTEAEKIKIC LQKQVNSSFS LHNGFGGNLY ATEEKRMFEL VKPKAGASVL 

        70         80         90        100        110        120 
NQSTWIGFGD SRTDKSNSAF PRSADVSAKT ADKFRFLSGG SLMLSMFGPP GKVDYLYQGC 

       130        140        150        160        170        180 
GKHKVFYEGV NWSPHAAINC YRKNWTDIKL NFQKNIYELA SQSHCMSLVN ALDKTIPLQV 

       190        200        210        220        230        240 
TAGTAGNCNN SFLKNPALYT QEVKPSENKC GKENLAFFTL PTQFGTYECK LHLVASCYFI 

       250        260        270        280        290        300 
YDSKEVYNKR GCDNYFQVIY DSFGKVVGGL DNRVSPYTGN SGDTPTMQCD MLQLKPGRYS 

       310        320        330        340        350        360 
VRSSPRFLLM PERSYCFDMK EKGPVTAVQS IWGKGRESDY AVDQACLSTP GCMLIQKQKP 

       370        380        390        400        410        420 
YIGEADDHHG DQEMRELLSG LDYEARCISQ SGWVNETSPF TEKYLLPPKF GRCPLAAKEE 

       430        440        450        460        470        480 
SIPKIPDGLL IPTSGTDTTV TKPKSRIFGI DDLIIGVLFV AIVETGIGGY LLGSRKESGG 

       490        500        510        520        530        540 
GVTKESAEKG FEKIGNDIQI LKSSINIAIE KLNDRISHDE QAIRDLTLEI ENARSEALLG 

       550        560        570        580        590        600 
ELGIIRALLV GNISIGLQES LWELASEITN RAGDLAVEVS PGCWIIDNNI CDQSCQNFIF 

       610        620        630        640        650 
KFNETAPVPT IPPLDTKIDL QSDPFYWGSS LGLAITATIS LAALVISGIA ICRTK

« Hide

References

[1]"Structure of the influenza C glycoprotein gene as determined from cloned DNA."
Pfeifer J.B., Compans R.W.
Virus Res. 1:281-296(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Use of influenza C virus glycoprotein HEF for generation of vesicular stomatitis virus pseudotypes."
Hanika A., Larisch B., Steinmann E., Schwegmann-Wessels C., Herrler G., Zimmer G.
J. Gen. Virol. 86:1455-1465(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA / MRNA].
[3]"The catalytic triad of the influenza C virus glycoprotein HEF esterase: characterization by site-directed mutagenesis and functional analysis."
Pleschka S., Klenk H.D., Herrler G.
J. Gen. Virol. 76:2529-2537(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF SER-71; ASP-261; ASN-280; HIS-368 AND HIS-369.
[4]"Structure of the haemagglutinin-esterase-fusion glycoprotein of influenza C virus."
Rosenthal P.B., Zhang X., Formanowski F., Fitz W., Wong C.H., Meier-Ewert H., Skehel J.J., Wiley D.C.
Nature 396:92-96(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 15-621 AND ACTIVE SITE.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		M17868 Genomic RNA. Translation: AAA43788.1.
AJ872181 Genomic RNA. Translation: CAI43342.1.
AY880247 mRNA. Translation: AAW73083.1.
PIRS07412.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1FLCX-ray3.20A/C/E15-446[»]
B/D/F447-621[»]
ProteinModelPortalP07975.
SMRP07975. Positions 15-441, 450-611.
ModBaseSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D3.90.20.10. 1 hit.
InterProIPR008980. Capsid_hemagglutn.
IPR007142. Hemagglutn-estrase_core.
IPR003860. Hemagglutn-estrase_hemagglutn.
IPR013829. Hemagglutn_stalk.
IPR014831. Hemagglutn_stalk_influenz-C.
[Graphical view]
PfamPF03996. Hema_esterase. 1 hit.
PF02710. Hema_HEFG. 1 hit.
PF08720. Hema_stalk. 1 hit.
[Graphical view]
SUPFAMSSF49818. Capsid_hemag. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP07975.

Entry information

Entry nameHEMA_INCJH
AccessionPrimary (citable) accession number: P07975
Secondary accession number(s): Q5EI66, Q5JZY4
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: April 3, 2013
This is version 89 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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