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Protein

Hemagglutinin-esterase-fusion glycoprotein

Gene

HE

Organism
Influenza C virus (strain C/Johannesburg/1/1966)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Enzyme and pathway databases

BRENDAi3.1.1.53. 2767.

Protein family/group databases

TCDBi1.G.14.1.1. the influenza virus hemagglutinin/fusion pore-forming protein (influenza-h/fpp) family.

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/Johannesburg/1/1966)
Taxonomic identifieri100673 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus C
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000138885 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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi71S → A: 96% loss of esterase activity. 1 Publication1
Mutagenesisi261D → A: 64% loss of esterase activity. 1 Publication1
Mutagenesisi280N → A: Complete loss of esterase activity. 1 Publication1
Mutagenesisi368H → A: Complete loss of esterase activity. 1 Publication1
Mutagenesisi369H → A: Complete loss of esterase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 14UniRule annotationAdd BLAST14
ChainiPRO_000044055515 – 655Hemagglutinin-esterase-fusion glycoproteinUniRule annotationAdd BLAST641
ChainiPRO_000003915215 – 446Hemagglutinin-esterase-fusion glycoprotein chain 1UniRule annotationAdd BLAST432
ChainiPRO_0000039153447 – 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
Disulfide bondi120 ↔ 165
Disulfide bondi140 ↔ 188
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
Disulfide bondi346 ↔ 352
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

PTM databases

SwissPalmiP07975.

Interactioni

Subunit structurei

Homotrimer of disulfide-linked HEF1-HEF2.UniRule annotation

GO - Molecular functioni

Structurei

Secondary structure

1655
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi19 – 25Combined sources7
Beta strandi39 – 48Combined sources10
Beta strandi59 – 69Combined sources11
Beta strandi71 – 73Combined sources3
Helixi80 – 83Combined sources4
Helixi88 – 92Combined sources5
Beta strandi94 – 96Combined sources3
Helixi102 – 107Combined sources6
Beta strandi110 – 112Combined sources3
Beta strandi118 – 120Combined sources3
Beta strandi122 – 126Combined sources5
Helixi130 – 132Combined sources3
Helixi134 – 136Combined sources3
Helixi146 – 160Combined sources15
Beta strandi164 – 169Combined sources6
Beta strandi186 – 188Combined sources3
Beta strandi194 – 197Combined sources4
Turni205 – 208Combined sources4
Beta strandi214 – 220Combined sources7
Beta strandi222 – 224Combined sources3
Beta strandi230 – 240Combined sources11
Helixi244 – 250Combined sources7
Beta strandi256 – 260Combined sources5
Beta strandi262 – 264Combined sources3
Beta strandi266 – 271Combined sources6
Turni272 – 274Combined sources3
Beta strandi286 – 294Combined sources9
Beta strandi296 – 303Combined sources8
Beta strandi314 – 317Combined sources4
Beta strandi325 – 328Combined sources4
Helixi341 – 347Combined sources7
Beta strandi352 – 355Combined sources4
Beta strandi364 – 366Combined sources3
Helixi372 – 377Combined sources6
Helixi378 – 382Combined sources5
Beta strandi386 – 389Combined sources4
Beta strandi392 – 394Combined sources3
Beta strandi399 – 403Combined sources5
Beta strandi407 – 412Combined sources6
Turni419 – 421Combined sources3
Beta strandi424 – 432Combined sources9
Beta strandi452 – 454Combined sources3
Beta strandi459 – 462Combined sources4
Beta strandi469 – 474Combined sources6
Turni488 – 490Combined sources3
Helixi491 – 510Combined sources20
Beta strandi519 – 521Combined sources3
Helixi528 – 569Combined sources42
Turni573 – 575Combined sources3
Turni588 – 590Combined sources3
Helixi593 – 599Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FLCX-ray3.20A/C/E15-446[»]
B/D/F447-621[»]
ProteinModelPortaliP07975.
SMRiP07975.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07975.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni15 – 40Fusion domain-1UniRule annotationAdd BLAST26
Regioni41 – 158Esterase domain-1UniRule annotationAdd BLAST118
Regioni41 – 151Esterase domain-1Add BLAST111
Regioni151 – 310N-acetyl-9-O-acetylneuraminic acid bindingAdd BLAST160
Regioni158 – 310N-acetyl-9-O-acetylneuraminic acid bindingUniRule annotationAdd BLAST153
Regioni310 – 364Esterase domain-2UniRule annotationAdd BLAST55
Regioni311 – 365Esterase domain-2Add BLAST55
Regioni365 – 650Fusion domain-2UniRule annotationAdd BLAST286
Regioni366 – 651Fusion domain-2Add BLAST286

Sequence similaritiesi

Belongs to the influenza viruses hemagglutinin family.UniRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

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.
IPR036514. SGNH_hydro_sf.
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.

P07975-1 [UniParc]FASTAAdd to basket

« Hide

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

ICRTK
Length:655
Mass (Da):72,131
Last modified:August 1, 1988 - v1
Checksum:i52C78BFCC5A24AC8
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti96F → S. 1
Natural varianti263F → S. 1
Natural varianti457V → L. 1
Natural varianti465T → A. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M17868 Genomic RNA. Translation: AAA43788.1.
AJ872181 Genomic RNA. Translation: CAI43342.1.
AY880247 mRNA. Translation: AAW73083.1.
PIRiS07412.

Similar proteinsi

Entry informationi

Entry nameiHEMA_INCJH
AccessioniPrimary (citable) accession number: P07975
Secondary accession number(s): Q5EI66, Q5JZY4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: October 25, 2017
This is version 113 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome

Documents

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