HEMA_INCAA
ID HEMA_INCAA Reviewed; 655 AA.
AC P68762; P07969; Q6I7C1;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 2.
DT 02-JUN-2021, entry version 87.
DE RecName: Full=Hemagglutinin-esterase-fusion glycoprotein {ECO:0000255|HAMAP-Rule:MF_04072};
DE Short=HEF {ECO:0000255|HAMAP-Rule:MF_04072};
DE EC=3.1.1.53 {ECO:0000255|HAMAP-Rule:MF_04072};
DE Contains:
DE RecName: Full=Hemagglutinin-esterase-fusion glycoprotein chain 1 {ECO:0000255|HAMAP-Rule:MF_04072};
DE Short=HEF1 {ECO:0000255|HAMAP-Rule:MF_04072};
DE Contains:
DE RecName: Full=Hemagglutinin-esterase-fusion glycoprotein chain 2 {ECO:0000255|HAMAP-Rule:MF_04072};
DE Short=HEF2 {ECO:0000255|HAMAP-Rule:MF_04072};
DE Flags: Precursor;
GN Name=HE {ECO:0000255|HAMAP-Rule:MF_04072};
OS Influenza C virus (strain C/Ann Arbor/1/1950).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Gammainfluenzavirus.
OX NCBI_TaxID=11553;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=15218173; DOI=10.1099/vir.0.79937-0;
RA Muraki Y., Washioka H., Sugawara K., Matsuzaki Y., Takashita E., Hongo S.;
RT "Identification of an amino acid residue on influenza C virus M1 protein
RT responsible for formation of the cord-like structures of the virus.";
RL J. Gen. Virol. 85:1885-1893(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 14-655.
RX PubMed=3855244; DOI=10.1016/0042-6822(85)90006-6;
RA Buonagurio D.A., Nakada S., Desselberger U., Krystal M., Palese P.;
RT "Noncumulative sequence changes in the hemagglutinin genes of influenza C
RT virus isolates.";
RL Virology 146:221-232(1985).
CC -!- FUNCTION: Binds to the N-acetyl-9-O-acetylneuraminic acid residues on
CC the cell surface, bringing about the attachment of the virus particle
CC to the cell. Plays a major role in the determination of host range
CC restriction and virulence. Class I viral fusion protein. Responsible
CC for penetration of the virus into the cell cytoplasm by mediating the
CC fusion of the membrane of the endocytosed virus particle with the
CC endosomal membrane. Low pH in endosomes induce an irreversible
CC conformational change in HEF2, releasing the fusion hydrophobic
CC peptide. Several trimers are required to form a competent fusion pore.
CC Displays a receptor-destroying activity which is a neuraminidate-O-
CC acetyl esterase. This activity cleaves off any receptor on the cell
CC surface, which would otherwise prevent virions release. These cleavages
CC prevent self-aggregation and ensure the efficient spread of the progeny
CC virus from cell to cell. {ECO:0000255|HAMAP-Rule:MF_04072}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acetyl-9-O-acetylneuraminate = acetate + H(+) + N-
CC acetylneuraminate; Xref=Rhea:RHEA:22600, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28999, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:35418; EC=3.1.1.53; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_04072};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acetyl-4-O-acetylneuraminate = acetate + H(+) + N-
CC acetylneuraminate; Xref=Rhea:RHEA:25564, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29006, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:35418; EC=3.1.1.53; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_04072};
CC -!- SUBUNIT: Homotrimer of disulfide-linked HEF1-HEF2. {ECO:0000255|HAMAP-
CC Rule:MF_04072}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000255|HAMAP-
CC Rule:MF_04072}; Single-pass type I membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_04072}. Host cell membrane {ECO:0000255|HAMAP-Rule:MF_04072};
CC Single-pass type I membrane protein {ECO:0000255|HAMAP-Rule:MF_04072}.
CC -!- PTM: In natural infection, inactive HEF is matured into HEF1 and HEF2
CC outside the cell by one or more trypsin-like, arginine-specific
CC endoprotease. {ECO:0000255|HAMAP-Rule:MF_04072}.
CC -!- SIMILARITY: Belongs to the influenza viruses hemagglutinin family.
CC {ECO:0000255|HAMAP-Rule:MF_04072}.
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DR EMBL; AB126194; BAD24940.1; -; Genomic_RNA.
DR EMBL; M11638; AAA43782.1; -; Genomic_RNA.
DR RefSeq; YP_089655.1; NC_006310.1.
DR SMR; P68762; -.
DR DNASU; 3077359; -.
DR GeneID; 3077359; -.
DR KEGG; vg:3077359; -.
DR Proteomes; UP000008286; Genome.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-UniRule.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046789; F:host cell surface receptor binding; IEA:UniProtKB-UniRule.
DR GO; GO:0106331; F:sialate 4-O-acetylesterase activity; IEA:UniProtKB-EC.
DR GO; GO:0106330; F:sialate 9-O-acetylesterase activity; IEA:UniProtKB-EC.
DR GO; GO:0075509; P:endocytosis involved in viral entry into host cell; IEA:UniProtKB-KW.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:InterPro.
DR GO; GO:0046761; P:viral budding from plasma membrane; IEA:UniProtKB-UniRule.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR HAMAP; MF_04072; INFV_HEMA; 1.
DR InterPro; IPR008980; Capsid_hemagglutn.
DR InterPro; IPR007142; Hemagglutn-estrase_core.
DR InterPro; IPR003860; Hemagglutn-estrase_hemagglutn.
DR InterPro; IPR001364; Hemagglutn_influenz_A/B.
DR InterPro; IPR014831; Hemagglutn_stalk_influenz-C.
DR Pfam; PF03996; Hema_esterase; 1.
DR Pfam; PF02710; Hema_HEFG; 1.
DR Pfam; PF08720; Hema_stalk; 1.
DR SUPFAM; SSF49818; SSF49818; 1.
PE 3: Inferred from homology;
KW Disulfide bond; Fusion of virus membrane with host endosomal membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein; Hemagglutinin;
KW Host cell membrane; Host membrane; Host-virus interaction; Hydrolase;
KW Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Viral attachment to host cell; Viral envelope protein;
KW Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW Virus entry into host cell.
FT SIGNAL 1..14
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CHAIN 15..655
FT /note="Hemagglutinin-esterase-fusion glycoprotein"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000440551"
FT CHAIN 15..446
FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000039142"
FT CHAIN 447..655
FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000039143"
FT TOPO_DOM 15..630
FT /note="Extracellular"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TRANSMEM 631..651
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT TOPO_DOM 652..655
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT REGION 15..40
FT /note="Fusion domain-1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT REGION 41..158
FT /note="Esterase domain-1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT REGION 158..310
FT /note="N-acetyl-9-O-acetylneuraminic acid binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT REGION 310..364
FT /note="Esterase domain-2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT REGION 365..650
FT /note="Fusion domain-2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT ACT_SITE 71
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT ACT_SITE 366
FT /note="Charge relay system"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT ACT_SITE 369
FT /note="Charge relay system"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 26
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 395
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 552
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CARBOHYD 603
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 20..583
FT /note="Interchain (between HEF1 and HEF2 chains)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 210..252
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 229..316
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT DISULFID 237..289
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT CONFLICT 207..209
FT /note="VEK -> EEI (in Ref. 2; AAA43782)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="N -> Y (in Ref. 2; AAA43782)"
FT /evidence="ECO:0000305"
FT CONFLICT 263
FT /note="S -> Y (in Ref. 2; AAA43782)"
FT /evidence="ECO:0000305"
FT CONFLICT 324
FT /note="P -> L (in Ref. 2; AAA43782)"
FT /evidence="ECO:0000305"
FT CONFLICT 346
FT /note="C -> Y (in Ref. 2; AAA43782)"
FT /evidence="ECO:0000305"
FT CONFLICT 458
FT /note="L -> F (in Ref. 2; AAA43782)"
FT /evidence="ECO:0000305"
FT CONFLICT 477
FT /note="V -> E (in Ref. 2; AAA43782)"
FT /evidence="ECO:0000305"
FT CONFLICT 637..638
FT /note="AA -> TP (in Ref. 2; AAA43782)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 655 AA; 71956 MW; 81869FEDA9CD8943 CRC64;
MFFSLLLMLG LTEAEKIKIC LQKQVNSSFS LHNGFGGNLY ATEEKRMFEL VKPKAGASVL
NQSTWIGFGD SRTDKSNSAF PRSADVSAKT ADKFRSLSGG SLMLSMFGPP GKVDYLYQGC
GKHKVFYEGV NWSPHAAINC YRKNWTDIKL NFQKNIYELA SQSHCMSLVN ALDKTIPLQA
TAGVAKNCNN SFLKNPALYT QEVNPSVEKC GKENLAFFTL PTQFGTYECK LHLVASCYFI
YDSKEVYNKR GCDNYFQVIY DSSGKVVGGL DNRVSPYTGN SGDTPTMQCD MLQLKPGRYS
VRSSPRFLLM PERSYCFDMK EKGPVTAVQS IWGKGRESDH AVDQACLSTP GCMLIQKQKP
YIGEADDHHG DQEMRELLSG LDYEARCISQ SGWVNETSPF TEEYLLPPKF GRCPLAAKEE
SIPKIPDGLL IPTSGTDTTV TKPKSRIFGI DDLIIGLLFV AIVEAGIGGY LLGSRKVSGG
GVTKESAEKG FEKIGNDIQI LRSSTNIAIE KLNDRISHDE QAIRDLTLEI ENARSEALLG
ELGIIRALLV GNISIGLQES LWELASEITN RAGDLAVEVS PGCWVIDNNI CDQSCQNFIF
KFNETAPVPT IPPLDTKIDL QSDPFYWGSS LGLAITAAIS LAALVISGIA ICRTK
