ENV_XMRV6
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 25-MAY-2022, entry version 61.
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 unclassified Gammaretrovirus.
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 Proteomes; UP000002240; Genome.
DR Proteomes; UP000180675; Genome.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of 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 Gene3D; 3.90.310.10; -; 1.
DR InterPro; IPR008981; FMuLV_rcpt-bd.
DR InterPro; IPR018154; TLV/ENV_coat_polyprotein.
DR PANTHER; PTHR10424; PTHR10424; 1.
DR Pfam; PF00429; TLV_coat; 1.
DR SUPFAM; SSF49830; SSF49830; 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
