ID   ENV_XMRV6               Reviewed;         645 AA.
AC   Q27ID8; A1Z653;
DT   19-JAN-2010, integrated into UniProtKB/Swiss-Prot.
DT   04-APR-2006, sequence version 1.
DT   27-MAR-2024, entry version 65.
DE   RecName: Full=Envelope glycoprotein;
DE   AltName: Full=Env polyprotein;
DE   Contains:
DE     RecName: Full=Surface protein;
DE              Short=SU;
DE   Contains:
DE     RecName: Full=Transmembrane protein;
DE              Short=TM;
DE   Contains:
DE     RecName: Full=R-peptide;
DE   Flags: Precursor;
GN   Name=env;
OS   Xenotropic MuLV-related virus (isolate VP62) (XMRV).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Gammaretrovirus;
OC   Murine leukemia-related retroviruses.
OX   NCBI_TaxID=373193;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND RETRACTED PAPER.
RX   PubMed=16609730; DOI=10.1371/journal.ppat.0020025;
RA   Urisman A., Molinaro R.J., Fischer N., Plummer S.J., Casey G., Klein E.A.,
RA   Malathi K., Magi-Galluzzi C., Tubbs R.R., Ganem D., Silverman R.H.,
RA   DeRisi J.L.;
RT   "Identification of a novel Gammaretrovirus in prostate tumors of patients
RT   homozygous for R462Q RNASEL variant.";
RL   PLoS Pathog. 2:E25-E25(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=17234809; DOI=10.1073/pnas.0610291104;
RA   Dong B., Kim S., Hong S., Das Gupta J., Malathi K., Klein E.A., Ganem D.,
RA   Derisi J.L., Chow S.A., Silverman R.H.;
RT   "An infectious retrovirus susceptible to an IFN antiviral pathway from
RT   human prostate tumors.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1655-1660(2007).
RN   [3]
RP   RETRACTION NOTICE OF PUBMED:16609730.
RX   PubMed=23028303;
RX   DOI=10.1371/annotation/7e2efc01-2e9b-4e9b-aef0-87ab0e4e4732;
RA   Urisman A., Molinaro R.J., Fischer N., Plummer S.J., Casey G., Klein E.A.,
RA   Malathi K., Magi-Galluzzi C., Tubbs R.R., Ganem D., Silverman R.H.,
RA   DeRisi J.L.;
RL   PLoS Pathog. 8:0-0(2012).
CC   -!- FUNCTION: The surface protein (SU) attaches the virus to the host cell
CC       by binding to its receptor. This interaction activates a thiol in a
CC       CXXC motif of the C-terminal domain, where the other Cys residue
CC       participates in the formation of the intersubunit disulfide. The
CC       activated thiol will attack the disulfide and cause its isomerization
CC       into a disulfide isomer within the motif. This leads to SU displacement
CC       and TM refolding, and is thought to activate its fusogenic potential by
CC       unmasking its fusion peptide. Fusion occurs at the host cell plasma
CC       membrane (By similarity). {ECO:0000250}.
CC   -!- FUNCTION: The transmembrane protein (TM) acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During viral and
CC       target cell membrane fusion, the coiled coil regions (heptad repeats)
CC       assume a trimer-of-hairpins structure, positioning the fusion peptide
CC       in close proximity to the C-terminal region of the ectodomain. The
CC       formation of this structure appears to drive apposition and subsequent
CC       fusion of viral and target cell membranes. Membranes fusion leads to
CC       delivery of the nucleocapsid into the cytoplasm (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBUNIT: The mature envelope protein (Env) consists of a trimer of SU-
CC       TM heterodimers attached by a labile interchain disulfide bond. The
CC       activated Env consists of SU monomers and TM trimers (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein]: Virion membrane
CC       {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Host
CC       cell membrane {ECO:0000250}; Single-pass type I membrane protein
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein]: Virion membrane; Peripheral
CC       membrane protein. Host cell membrane {ECO:0000250}; Peripheral membrane
CC       protein {ECO:0000250}. Note=The surface protein is not anchored to the
CC       viral envelope, but associates with the virion surface through its
CC       binding to TM. Both proteins are thought to be concentrated at the site
CC       of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [R-peptide]: Host cell membrane; Peripheral
CC       membrane protein. Note=The R-peptide is membrane-associated through its
CC       palmitate. {ECO:0000250}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo (By similarity). {ECO:0000250}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. {ECO:0000250}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       N-glycosylated and processed likely by host cell furin or by a furin-
CC       like protease in the Golgi to yield the mature SU and TM proteins. The
CC       cleavage site between SU and TM requires the minimal sequence [KR]-X-
CC       [KR]-R. The R-peptide is released from the C-terminus of the
CC       cytoplasmic tail of the TM protein upon particle formation as a result
CC       of proteolytic cleavage by the viral protease. Cleavage of this peptide
CC       is required for TM to become fusogenic (By similarity). {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   -!- PTM: The transmembrane protein is palmitoylated. {ECO:0000250}.
CC   -!- PTM: The R-peptide is palmitoylated.
CC   -!- CAUTION: Originally thought to be characterized from prostate tumors,
CC       the described gammaretrovirus XMRV is in fact laboratory-derived and
CC       there is no association of XMRV with prostate cancer.
CC       {ECO:0000305|PubMed:16609730, ECO:0000305|PubMed:23028303}.
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DR   EMBL; DQ399707; ABD49688.1; -; Genomic_RNA.
DR   EMBL; EF185282; ABM47429.1; -; Genomic_RNA.
DR   SMR; Q27ID8; -.
DR   GlyCosmos; Q27ID8; 7 sites, No reported glycans.
DR   Proteomes; UP000002240; Genome.
DR   Proteomes; UP000180675; Genome.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-KW.
DR   GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR   CDD; cd09851; HTLV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 3.90.310.10; ENV polyprotein, receptor-binding domain; 1.
DR   InterPro; IPR008981; FMuLV_rcpt-bd.
DR   InterPro; IPR018154; TLV/ENV_coat_polyprotein.
DR   PANTHER; PTHR10424:SF77; BC035947 PROTEIN-RELATED; 1.
DR   PANTHER; PTHR10424; VIRAL ENVELOPE PROTEIN; 1.
DR   Pfam; PF00429; TLV_coat; 1.
DR   SUPFAM; SSF49830; ENV polyprotein, receptor-binding domain; 1.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host cell membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host membrane; Host-virus interaction; Lipoprotein;
KW   Membrane; Palmitate; Reference proteome; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral penetration into host cytoplasm; Virion; Virus entry into host cell.
FT   SIGNAL          1..33
FT                   /evidence="ECO:0000255"
FT   CHAIN           34..645
FT                   /note="Envelope glycoprotein"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000390831"
FT   CHAIN           34..444
FT                   /note="Surface protein"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000390832"
FT   CHAIN           445..645
FT                   /note="Transmembrane protein"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000390833"
FT   PEPTIDE         625..645
FT                   /note="R-peptide"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000390834"
FT   TOPO_DOM        34..585
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        586..606
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        607..640
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          32..237
FT                   /note="Receptor-binding domain (RBD)"
FT                   /evidence="ECO:0000255"
FT   REGION          260..285
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          447..467
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000250"
FT   REGION          513..529
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000250"
FT   COILED          490..510
FT                   /evidence="ECO:0000255"
FT   MOTIF           311..314
FT                   /note="CXXC"
FT                   /evidence="ECO:0000250"
FT   MOTIF           530..538
FT                   /note="CX6CC"
FT                   /evidence="ECO:0000250"
FT   MOTIF           630..633
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        260..281
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            444..445
FT                   /note="Cleavage; by host"
FT                   /evidence="ECO:0000250"
FT   SITE            624..625
FT                   /note="Cleavage; by viral protease p14"
FT                   /evidence="ECO:0000250"
FT   LIPID           605
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        43
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        58
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        333
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        340
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        373
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        409
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   DISULFID        113..130
FT                   /evidence="ECO:0000250"
FT   DISULFID        122..135
FT                   /evidence="ECO:0000250"
FT   DISULFID        311..538
FT                   /note="Interchain (between SU and TM chains, or C-314 with
FT                   C-538); in linked form"
FT                   /evidence="ECO:0000250"
FT   DISULFID        311..314
FT                   /evidence="ECO:0000250"
FT   DISULFID        341..395
FT                   /evidence="ECO:0000250"
FT   DISULFID        360..372
FT                   /evidence="ECO:0000250"
FT   DISULFID        402..415
FT                   /evidence="ECO:0000250"
FT   DISULFID        530..537
FT                   /evidence="ECO:0000250"
FT   CONFLICT        261
FT                   /note="T -> P (in Ref. 1; ABM47429)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        298
FT                   /note="L -> Q (in Ref. 1; ABM47429)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        568
FT                   /note="G -> R (in Ref. 1; ABM47429)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   645 AA;  69876 MW;  19ACC5E3EAF9AEC3 CRC64;
     MESPAFSKPL KDKINPWGPL IIMGILVRAG ASVQRDSPHQ VFNVTWKITN LMTGQTANAT
     SLLGTMTDTF PKLYFDLCDL VGDNWDDPEP DIGDGCRSPG GRKRTRLYDF YVCPGHTVLT
     GCGGPREGYC GKWGCETTGQ AYWKPSSSWD LISLKRGNTP KGQGPCFDSS VGSGSIQGAT
     PGGRCNPLVL EFTDAGKRAS WDAPKTWGLR LYRSTGADPV TLFSLTRQVL NVGPRVPIGP
     NPVITEQLPP SQPVQIMLPR TPRPPPSGAA SMVPGAPPPS QQPGTGDRLL NLVEGAYLAL
     NLTSPDKTQE CWLCLVSGPP YYEGVAVLGT YSNHTSAPAN CSVTSQHKLT LSEVTGQGLC
     IGAVPKTHQA LCNTTQKTSD GSYYLASPAG TIWACSTGLT PCLSTTVLNL TTDYCVLVEL
     WPKVTYHSPN YVYGQFEKKT KYKREPVSLT LALLLGGLTM GGIAAGVGTG TTALVATKQF
     EQLQAAIHTD LGALEKSVSA LEKSLTSLSE VVLQNRRGLD LLFLKEGGLC AALKEECCFY
     ADHTGVVRDS MAKLRERLNQ RQKLFESGQG WFEGLFNRSP WFTTLISTIM GPLIVLLLIL
     LFGPCILNRL VQFVKDRISV VQALVLTQQY HQLKSIDPEE VESRE
//