ENH1_HUMAN
ID ENH1_HUMAN Reviewed; 584 AA.
AC Q9N2K0; O00354; Q96L63; Q9UNM3;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 25-MAY-2022, entry version 98.
DE RecName: Full=HERV-H_2q24.3 provirus ancestral Env polyprotein;
DE AltName: Full=Env protein HERV-H/p62;
DE AltName: Full=Env protein HERV-H19;
DE AltName: Full=Env protein HERV-Hcl.3;
DE AltName: Full=Envelope polyprotein;
DE AltName: Full=HERV-H/env62;
DE Contains:
DE RecName: Full=Surface protein;
DE Short=SU;
DE Contains:
DE RecName: Full=Transmembrane protein;
DE Short=TM;
DE Flags: Precursor;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-81 AND LEU-150.
RX PubMed=10366582; DOI=10.1006/viro.1999.9750;
RA Lindeskog M., Mager D.L., Blomberg J.;
RT "Isolation of a human endogenous retroviral HERV-H element with an open env
RT reading frame.";
RL Virology 258:441-450(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-81 AND LEU-150.
RX PubMed=11162811; DOI=10.1006/viro.2000.0737;
RA de Parseval N., Casella J.-F., Gressin L., Heidmann T.;
RT "Characterization of the three HERV-H proviruses with an open envelope
RT reading frame encompassing the immunosuppressive domain and evolutionary
RT history in primates.";
RL Virology 279:558-569(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-402, AND VARIANT LEU-81.
RX PubMed=12079564; DOI=10.1089/088922202760019383;
RA Jern P., Lindeskog M., Karlsson D., Blomberg J.;
RT "Full-length HERV-H elements with env SU open reading frames in the human
RT genome.";
RL AIDS Res. Hum. Retroviruses 18:671-676(2002).
RN [4]
RP FUNCTION.
RX PubMed=11562544; DOI=10.1099/0022-1317-82-10-2515;
RA Mangeney M., de Parseval N., Thomas G., Heidmann T.;
RT "The full-length envelope of an HERV-H human endogenous retrovirus has
RT immunosuppressive properties.";
RL J. Gen. Virol. 82:2515-2518(2001).
RN [5]
RP FUNCTION.
RX PubMed=14557543; DOI=10.1073/pnas.2132646100;
RA Blaise S., de Parseval N., Benit L., Heidmann T.;
RT "Genomewide screening for fusogenic human endogenous retrovirus envelopes
RT identifies syncytin 2, a gene conserved on primate evolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13013-13018(2003).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=12970426; DOI=10.1128/jvi.77.19.10414-10422.2003;
RA de Parseval N., Lazar V., Casella J.-F., Benit L., Heidmann T.;
RT "Survey of human genes of retroviral origin: identification and
RT transcriptome of the genes with coding capacity for complete envelope
RT proteins.";
RL J. Virol. 77:10414-10422(2003).
CC -!- FUNCTION: Retroviral envelope proteins mediate receptor recognition and
CC membrane fusion during early infection. Endogenous envelope proteins
CC may have kept, lost or modified their original function during
CC evolution. This endogenous envelope protein has lost its original
CC fusogenic properties but has immunosuppressive properties in vivo.
CC {ECO:0000269|PubMed:11562544, ECO:0000269|PubMed:14557543}.
CC -!- FUNCTION: SU mediates receptor recognition. {ECO:0000250}.
CC -!- FUNCTION: TM anchors the envelope heterodimer to the viral membrane
CC through one transmembrane domain. The other hydrophobic domain, called
CC fusion peptide, mediates fusion of the viral membrane with the target
CC cell membrane (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: The surface (SU) and transmembrane (TM) proteins form a
CC heterodimer. SU and TM are attached by noncovalent interactions or by a
CC labile interchain disulfide bond (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Virion.
CC -!- SUBCELLULAR LOCATION: [Transmembrane protein]: Cell membrane
CC {ECO:0000305}; Single-pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Low expression in skin and testis. No expression in
CC several cell lines. {ECO:0000269|PubMed:12970426}.
CC -!- DOMAIN: Contains the CKS-17 immunosuppressive domain present in many
CC retroviral envelope proteins. As a synthetic peptide, it inhibits
CC immune function in vitro and in vivo (By similarity). {ECO:0000250}.
CC -!- PTM: Specific enzymatic cleavages in vivo yield the mature SU and TM
CC proteins. {ECO:0000250}.
CC -!- PTM: The CXXC motif is highly conserved across a broad range of
CC retroviral envelope proteins. It is thought to participate in the
CC formation of a labile disulfide bond possibly with the CX6CC motif
CC present in the transmembrane protein. Isomerization of the intersubunit
CC disulfide bond to an SU intrachain disulfide bond is thought to occur
CC upon receptor recognition in order to allow membrane fusion (By
CC similarity). {ECO:0000250}.
CC -!- POLYMORPHISM: Envelope protein HERV-H19 and HERV-H/p62 are allelic
CC variants of the same provirus.
CC -!- MISCELLANEOUS: Ortholog in Pan troglodytes.
CC -!- MISCELLANEOUS: HERV-H family subgenomic RNAs have been observed.
CC -!- MISCELLANEOUS: This provirus is intergenic, the closest flanking genes
CC being TAIP2 and GALNT3.
CC -!- SIMILARITY: Belongs to the gamma type-C retroviral envelope protein
CC family. HERV class-I H env subfamily. {ECO:0000305}.
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DR EMBL; AF108843; AAD34324.1; -; Genomic_DNA.
DR EMBL; U88902; AAC79121.1; -; Genomic_DNA.
DR EMBL; AJ289709; CAB94192.1; -; Genomic_DNA.
DR EMBL; AY050297; AAL11491.1; -; Genomic_DNA.
DR PIR; B44282; B44282.
DR AlphaFoldDB; Q9N2K0; -.
DR SMR; Q9N2K0; -.
DR GlyGen; Q9N2K0; 8 sites.
DR BioMuta; -; -.
DR PeptideAtlas; Q9N2K0; -.
DR PRIDE; Q9N2K0; -.
DR neXtProt; NX_Q9N2K0; -.
DR PhylomeDB; Q9N2K0; -.
DR Pharos; Q9N2K0; Tdark.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; Q9N2K0; protein.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR InterPro; IPR018154; TLV/ENV_coat_polyprotein.
DR PANTHER; PTHR10424; PTHR10424; 1.
DR Pfam; PF00429; TLV_coat; 2.
PE 2: Evidence at transcript level;
KW Cell membrane; Cleavage on pair of basic residues; Disulfide bond; ERV;
KW Glycoprotein; Membrane; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Transposable element; Viral envelope protein; Virion.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..584
FT /note="HERV-H_2q24.3 provirus ancestral Env polyprotein"
FT /id="PRO_0000008460"
FT CHAIN 36..387
FT /note="Surface protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000008461"
FT CHAIN 388..584
FT /note="Transmembrane protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000008462"
FT TOPO_DOM 36..523
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 524..544
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 545..584
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 388..408
FT /note="Fusion peptide"
FT /evidence="ECO:0000250"
FT MOTIF 64..67
FT /note="CXXC"
FT /evidence="ECO:0000250"
FT MOTIF 454..470
FT /note="CKS-17"
FT /evidence="ECO:0000250"
FT MOTIF 471..479
FT /note="CX6CC"
FT /evidence="ECO:0000250"
FT SITE 387..388
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT CARBOHYD 47
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 265
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 370
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 483
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 471..478
FT /evidence="ECO:0000250"
FT VARIANT 81
FT /note="V -> L (in allele HERV-H19)"
FT /evidence="ECO:0000269|PubMed:10366582,
FT ECO:0000269|PubMed:11162811, ECO:0000269|PubMed:12079564"
FT /id="VAR_017799"
FT VARIANT 150
FT /note="F -> L (in allele HERV-H19)"
FT /evidence="ECO:0000269|PubMed:10366582,
FT ECO:0000269|PubMed:11162811"
FT /id="VAR_017800"
FT CONFLICT 80
FT /note="A -> T (in Ref. 3; AAL11491)"
FT /evidence="ECO:0000305"
FT CONFLICT 98
FT /note="F -> C (in Ref. 3; AAL11491)"
FT /evidence="ECO:0000305"
FT CONFLICT 316
FT /note="T -> A (in Ref. 3; AAL11491)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="S -> G (in Ref. 1; AAC79121)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 584 AA; 64318 MW; C03D260B5A60BDAB CRC64;
MIFAGKAPSN TSTLMKFYSL LLYSLLFSFP FLCHPLPLPS YLHHTINLTH SLLAASNPSL
VNNCWLCISL SSSAYTAVPA VQTDWATSPI SLHLRTSFNS PHLYPPEELI YFLDRSSKTS
PDISHQQAAA LLRTYLKNLS PYINSTPPIF GPLTTQTTIP VAAPLCISWQ RPTGIPLGNL
SPSRCSFTLH LRSPTTNINE TIGAFQLHIT DKPSINTDKL KNISSNYCLG RHLPCISLHP
WLSSPCSSDS PPRPSSCLLI PSPENNSERL LVDTRRFLIH HENRTFPSTQ LPHQSPLQPL
TAAALAGSLG VWVQDTPFST PSHLFTLHLQ FCLAQGLFFL CGSSTYMCLP ANWTGTCTLV
FLTPKIQFAN GTEELPVPLM TPTQQKRVIP LIPLMVGLGL SASTVALGTG IAGISTSVMT
FRSLSNDFSA SITDISQTLS VLQAQVDSLA AVVLQNRRGL DLLTAEKGGL CIFLNEECCF
YLNQSGLVYD NIKKLKDRAQ KLANQASNYA EPPWALSNWM SWVLPIVSPL IPIFLLLLFG
PCIFRLVSQF IQNRIQAITN HSIRQMFLLT SPQYHPLPQD LPSA
