HEMA_INCJH
ID HEMA_INCJH Reviewed; 655 AA.
AC P07975; Q5EI66; Q5JZY4;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 136.
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/Johannesburg/1/1966).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Gammainfluenzavirus.
OX NCBI_TaxID=100673;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=6532004; DOI=10.1016/0168-1702(84)90017-0;
RA Pfeifer J.B., Compans R.W.;
RT "Structure of the influenza C glycoprotein gene as determined from cloned
RT DNA.";
RL Virus Res. 1:281-296(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA / MRNA].
RX PubMed=15831958; DOI=10.1099/vir.0.80788-0;
RA Hanika A., Larisch B., Steinmann E., Schwegmann-Wessels C., Herrler G.,
RA Zimmer G.;
RT "Use of influenza C virus glycoprotein HEF for generation of vesicular
RT stomatitis virus pseudotypes.";
RL J. Gen. Virol. 86:1455-1465(2005).
RN [3]
RP MUTAGENESIS OF SER-71; ASP-261; ASN-280; HIS-368 AND HIS-369.
RX PubMed=7595356; DOI=10.1099/0022-1317-76-10-2529;
RA Pleschka S., Klenk H.D., Herrler G.;
RT "The catalytic triad of the influenza C virus glycoprotein HEF esterase:
RT characterization by site-directed mutagenesis and functional analysis.";
RL J. Gen. Virol. 76:2529-2537(1995).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 15-621 AND ACTIVE SITE.
RX PubMed=9817207; DOI=10.1038/23974;
RA Rosenthal P.B., Zhang X., Formanowski F., Fitz W., Wong C.H.,
RA Meier-Ewert H., Skehel J.J., Wiley D.C.;
RT "Structure of the haemagglutinin-esterase-fusion glycoprotein of influenza
RT C virus.";
RL Nature 396:92-96(1998).
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; M17868; AAA43788.1; -; Genomic_RNA.
DR EMBL; AJ872181; CAI43342.1; -; Genomic_RNA.
DR EMBL; AY880247; AAW73083.1; -; mRNA.
DR PIR; S07412; S07412.
DR PDB; 1FLC; X-ray; 3.20 A; A/C/E=15-446, B/D/F=447-621.
DR PDB; 6WKO; X-ray; 2.40 A; A=495-586.
DR PDBsum; 1FLC; -.
DR PDBsum; 6WKO; -.
DR SMR; P07975; -.
DR TCDB; 1.G.14.1.1; the influenza virus hemagglutinin/fusion pore-forming protein (influenza-h/fpp) family.
DR SwissPalm; P07975; -.
DR BRENDA; 3.1.1.53; 2767.
DR EvolutionaryTrace; P07975; -.
DR Proteomes; UP000138885; 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 1: Evidence at protein level;
KW 3D-structure; Disulfide bond;
KW 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_0000440555"
FT CHAIN 15..446
FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000039152"
FT CHAIN 447..655
FT /note="Hemagglutinin-esterase-fusion glycoprotein chain 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT /id="PRO_0000039153"
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 41..151
FT /note="Esterase domain-1"
FT REGION 151..310
FT /note="N-acetyl-9-O-acetylneuraminic acid binding"
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 311..365
FT /note="Esterase domain-2"
FT REGION 365..650
FT /note="Fusion domain-2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04072"
FT REGION 366..651
FT /note="Fusion domain-2"
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 120..165
FT DISULFID 140..188
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 DISULFID 346..352
FT VARIANT 96
FT /note="F -> S"
FT VARIANT 263
FT /note="F -> S"
FT VARIANT 457
FT /note="V -> L"
FT VARIANT 465
FT /note="T -> A"
FT MUTAGEN 71
FT /note="S->A: 96% loss of esterase activity."
FT /evidence="ECO:0000269|PubMed:7595356"
FT MUTAGEN 261
FT /note="D->A: 64% loss of esterase activity."
FT /evidence="ECO:0000269|PubMed:7595356"
FT MUTAGEN 280
FT /note="N->A: Complete loss of esterase activity."
FT /evidence="ECO:0000269|PubMed:7595356"
FT MUTAGEN 368
FT /note="H->A: Complete loss of esterase activity."
FT /evidence="ECO:0000269|PubMed:7595356"
FT MUTAGEN 369
FT /note="H->A: Complete loss of esterase activity."
FT /evidence="ECO:0000269|PubMed:7595356"
FT STRAND 19..25
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 39..48
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 59..69
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 71..73
FT /evidence="ECO:0007829|PDB:1FLC"
FT HELIX 80..83
FT /evidence="ECO:0007829|PDB:1FLC"
FT HELIX 88..92
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:1FLC"
FT HELIX 102..107
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 110..112
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 122..126
FT /evidence="ECO:0007829|PDB:1FLC"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:1FLC"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:1FLC"
FT HELIX 146..160
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 164..169
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:1FLC"
FT TURN 205..208
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 214..220
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 230..240
FT /evidence="ECO:0007829|PDB:1FLC"
FT HELIX 244..250
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 256..260
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 266..271
FT /evidence="ECO:0007829|PDB:1FLC"
FT TURN 272..274
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 286..294
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 296..303
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 314..317
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 325..328
FT /evidence="ECO:0007829|PDB:1FLC"
FT HELIX 341..347
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 352..355
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:1FLC"
FT HELIX 372..377
FT /evidence="ECO:0007829|PDB:1FLC"
FT HELIX 378..382
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 386..389
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 399..403
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 407..412
FT /evidence="ECO:0007829|PDB:1FLC"
FT TURN 419..421
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 424..432
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 452..454
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 459..462
FT /evidence="ECO:0007829|PDB:1FLC"
FT STRAND 469..474
FT /evidence="ECO:0007829|PDB:1FLC"
FT TURN 488..490
FT /evidence="ECO:0007829|PDB:1FLC"
FT HELIX 497..549
FT /evidence="ECO:0007829|PDB:6WKO"
FT HELIX 555..571
FT /evidence="ECO:0007829|PDB:6WKO"
FT TURN 573..575
FT /evidence="ECO:0007829|PDB:1FLC"
FT TURN 588..590
FT /evidence="ECO:0007829|PDB:1FLC"
FT HELIX 593..599
FT /evidence="ECO:0007829|PDB:1FLC"
SQ SEQUENCE 655 AA; 72131 MW; 52C78BFCC5A24AC8 CRC64;
MFFSLLLVLG LTEAEKIKIC LQKQVNSSFS LHNGFGGNLY ATEEKRMFEL VKPKAGASVL
NQSTWIGFGD SRTDKSNSAF PRSADVSAKT ADKFRFLSGG SLMLSMFGPP GKVDYLYQGC
GKHKVFYEGV NWSPHAAINC YRKNWTDIKL NFQKNIYELA SQSHCMSLVN ALDKTIPLQV
TAGTAGNCNN SFLKNPALYT QEVKPSENKC GKENLAFFTL PTQFGTYECK LHLVASCYFI
YDSKEVYNKR GCDNYFQVIY DSFGKVVGGL DNRVSPYTGN SGDTPTMQCD MLQLKPGRYS
VRSSPRFLLM PERSYCFDMK EKGPVTAVQS IWGKGRESDY AVDQACLSTP GCMLIQKQKP
YIGEADDHHG DQEMRELLSG LDYEARCISQ SGWVNETSPF TEKYLLPPKF GRCPLAAKEE
SIPKIPDGLL IPTSGTDTTV TKPKSRIFGI DDLIIGVLFV AIVETGIGGY LLGSRKESGG
GVTKESAEKG FEKIGNDIQI LKSSINIAIE KLNDRISHDE QAIRDLTLEI ENARSEALLG
ELGIIRALLV GNISIGLQES LWELASEITN RAGDLAVEVS PGCWIIDNNI CDQSCQNFIF
KFNETAPVPT IPPLDTKIDL QSDPFYWGSS LGLAITATIS LAALVISGIA ICRTK
