ID   ENV_MLVMS               Reviewed;         665 AA.
AC   P03385; Q77YG8;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   27-MAR-2024, entry version 152.
DE   RecName: Full=Envelope glycoprotein;
DE            Short=Pr80env;
DE   AltName: Full=Env polyprotein;
DE   Contains:
DE     RecName: Full=Surface protein;
DE              Short=SU;
DE     AltName: Full=Glycoprotein 70;
DE              Short=gp70;
DE   Contains:
DE     RecName: Full=Transmembrane protein;
DE              Short=TM;
DE     AltName: Full=Envelope protein p15E;
DE   Contains:
DE     RecName: Full=R-peptide;
DE     AltName: Full=p2E;
DE   Flags: Precursor;
GN   Name=env;
OS   Moloney murine leukemia virus (isolate Shinnick) (MoMLV).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Gammaretrovirus;
OC   Murine leukemia virus.
OX   NCBI_TaxID=928306;
OH   NCBI_TaxID=10090; Mus musculus (Mouse).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Clone pMLV-1;
RX   PubMed=6169994; DOI=10.1038/293543a0;
RA   Shinnick T.M., Lerner R.A., Sutcliffe J.G.;
RT   "Nucleotide sequence of Moloney murine leukaemia virus.";
RL   Nature 293:543-548(1981).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Chappey C.;
RL   Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 496-665.
RX   PubMed=6159543; DOI=10.1038/287801a0;
RA   Sutcliffe J.G., Shinnick T.M., Green N., Liu F.-T., Niman H.L.,
RA   Lerner R.A.;
RT   "Chemical synthesis of a polypeptide predicted from nucleotide sequence
RT   allows detection of a new retroviral gene product.";
RL   Nature 287:801-805(1980).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 484-665.
RC   STRAIN=Clone pMLV-201;
RX   PubMed=6251454; DOI=10.1073/pnas.77.6.3302;
RA   Sutcliffe J.G., Shinnick T.M., Verma I.M., Lerner R.A.;
RT   "Nucleotide sequence of Moloney leukemia virus: 3' end reveals details of
RT   replications, analogy to bacterial transposons, and an unexpected gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 77:3302-3306(1980).
RN   [5]
RP   PROTEIN SEQUENCE OF 470-489 AND 598-665.
RX   PubMed=6947213; DOI=10.1073/pnas.78.10.6023;
RA   Green N., Shinnick T.M., Witte O., Ponticelli A., Sutcliffe J.G.,
RA   Lerner R.A.;
RT   "Sequence-specific antibodies show that maturation of Moloney leukemia
RT   virus envelope polyprotein involves removal of a COOH-terminal peptide.";
RL   Proc. Natl. Acad. Sci. U.S.A. 78:6023-6027(1981).
RN   [6]
RP   IMMUNOSUPPRESSIVE REGION.
RX   PubMed=2996136; DOI=10.1126/science.2996136;
RA   Cianciolo G.J., Copeland T.D., Oroszlan S., Snyderman R.;
RT   "Inhibition of lymphocyte proliferation by a synthetic peptide homologous
RT   to retroviral envelope proteins.";
RL   Science 230:453-455(1985).
RN   [7]
RP   SUBCELLULAR LOCATION OF THE R-PEPTIDE, AND PALMITOYLATION OF THE R-PEPTIDE.
RX   PubMed=10516003; DOI=10.1128/jvi.73.11.8975-8981.1999;
RA   Olsen K.E., Andersen K.B.;
RT   "Palmitoylation of the intracytoplasmic R peptide of the transmembrane
RT   envelope protein in Moloney murine leukemia virus.";
RL   J. Virol. 73:8975-8981(1999).
RN   [8]
RP   CLEAVAGE OF THE R-PEPTIDE.
RX   PubMed=12867658; DOI=10.1099/vir.0.19126-0;
RA   Kubo Y., Amanuma H.;
RT   "Mutational analysis of the R peptide cleavage site of Moloney murine
RT   leukaemia virus envelope protein.";
RL   J. Gen. Virol. 84:2253-2257(2003).
RN   [9]
RP   INTERCHAIN DISULFIDE BOND.
RX   PubMed=14685283; DOI=10.1038/sj.emboj.7600012;
RA   Wallin M., Ekstroem M., Garoff H.;
RT   "Isomerization of the intersubunit disulphide-bond in Env controls
RT   retrovirus fusion.";
RL   EMBO J. 23:54-65(2004).
RN   [10]
RP   FUNCTION.
RX   PubMed=18800055; DOI=10.1038/emboj.2008.187;
RA   Wu S.-R., Sjoeberg M., Wallin M., Lindqvist B., Ekstroem M., Hebert H.,
RA   Koeck P.J., Garoff H.;
RT   "Turning of the receptor-binding domains opens up the murine leukaemia
RT   virus Env for membrane fusion.";
RL   EMBO J. 27:2799-2808(2008).
RN   [11]
RP   SUBUNIT.
RX   PubMed=18094169; DOI=10.1128/jvi.01931-07;
RA   Sjoberg M., Lindqvist B., Garoff H.;
RT   "Stabilization of TM trimer interactions during activation of moloney
RT   murine leukemia virus Env.";
RL   J. Virol. 82:2358-2366(2008).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 514-567.
RX   PubMed=8612078; DOI=10.1038/nsb0596-465;
RA   Fass D., Harrison S.C., Kim P.S.;
RT   "Retrovirus envelope domain at 1.7-A resolution.";
RL   Nat. Struct. Biol. 3:465-469(1996).
CC   -!- FUNCTION: The surface protein (SU) attaches the virus to the host cell
CC       by binding to its receptor. Interaction with HECT ubiquitin ligases
CC       activates a thiol in a CXXC motif of the C-terminal domain, where the
CC       other Cys residue participates in the formation of the intersubunit
CC       disulfide. The activated thiol will attack the disulfide and cause its
CC       isomerization into a disulfide isomer within the motif. This leads to
CC       SU displacement and TM refolding, and is thought to activate its
CC       fusogenic potential by unmasking its fusion peptide. Fusion occurs at
CC       the host cell plasma membrane. {ECO:0000269|PubMed:18800055}.
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.
CC       {ECO:0000269|PubMed:18094169}.
CC   -!- INTERACTION:
CC       P03385; P03385: env; NbExp=2; IntAct=EBI-8074066, EBI-8074066;
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
CC       {ECO:0000269|PubMed:10516003}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:10516003}. Note=The R-peptide is membrane-
CC       associated through its palmitate.
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.
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. {ECO:0000269|PubMed:10516003}.
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DR   EMBL; J02255; AAB59943.1; -; Genomic_RNA.
DR   EMBL; AF033811; AAC82567.1; -; Genomic_RNA.
DR   PIR; A93265; VCVWEM.
DR   RefSeq; NP_057935.1; NC_001501.1.
DR   PDB; 1MOF; X-ray; 1.70 A; A=514-567.
DR   PDBsum; 1MOF; -.
DR   SMR; P03385; -.
DR   MINT; P03385; -.
DR   GlyCosmos; P03385; 7 sites, No reported glycans.
DR   SwissPalm; P03385; -.
DR   GeneID; 34950658; -.
DR   KEGG; vg:34950657; -.
DR   EvolutionaryTrace; P03385; -.
DR   Proteomes; UP000006625; Segment.
DR   Proteomes; UP000180702; 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:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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   1: Evidence at protein level;
KW   3D-structure; Cleavage on pair of basic residues; Coiled coil;
KW   Direct protein sequencing; 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; Metal-binding; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral penetration into host cytoplasm; Virion;
KW   Virus entry into host cell; Zinc.
FT   SIGNAL          1..33
FT                   /evidence="ECO:0000255"
FT   CHAIN           34..665
FT                   /note="Envelope glycoprotein"
FT                   /id="PRO_0000239588"
FT   CHAIN           34..469
FT                   /note="Surface protein"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000040765"
FT   CHAIN           470..649
FT                   /note="Transmembrane protein"
FT                   /id="PRO_0000040766"
FT   PEPTIDE         650..665
FT                   /note="R-peptide"
FT                   /id="PRO_0000040767"
FT   TOPO_DOM        34..610
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        611..631
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        632..665
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          34..267
FT                   /note="Receptor-binding domain (RBD)"
FT                   /evidence="ECO:0000255"
FT   REGION          268..309
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          472..492
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000250"
FT   REGION          538..554
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000250"
FT   COILED          500..537
FT                   /evidence="ECO:0000255"
FT   MOTIF           336..339
FT                   /note="CXXC"
FT   MOTIF           555..563
FT                   /note="CX6CC"
FT   MOTIF           655..658
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        288..302
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         117
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   SITE            469..470
FT                   /note="Cleavage; by host"
FT   SITE            649..650
FT                   /note="Cleavage; by viral protease p14"
FT                   /evidence="ECO:0000255"
FT   LIPID           630
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        45
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        199
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        326
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        358
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        365
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        398
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        434
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   DISULFID        79..129
FT                   /evidence="ECO:0000250"
FT   DISULFID        105..118
FT                   /evidence="ECO:0000250"
FT   DISULFID        106..114
FT                   /evidence="ECO:0000250"
FT   DISULFID        152..172
FT                   /evidence="ECO:0000250"
FT   DISULFID        164..177
FT                   /evidence="ECO:0000250"
FT   DISULFID        209..215
FT                   /evidence="ECO:0000250"
FT   DISULFID        336..563
FT                   /note="Interchain (between SU and TM chains, or C-339 with
FT                   C-563); in linked form"
FT   DISULFID        336..339
FT   DISULFID        366..420
FT                   /evidence="ECO:0000250"
FT   DISULFID        385..397
FT                   /evidence="ECO:0000250"
FT   DISULFID        427..440
FT                   /evidence="ECO:0000250"
FT   DISULFID        555..562
FT                   /evidence="ECO:0000250"
FT   CONFLICT        655
FT                   /note="Y -> F (in Ref. 4)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        663
FT                   /note="Y -> C (in Ref. 4 and 5)"
FT                   /evidence="ECO:0000305"
FT   HELIX           516..547
FT                   /evidence="ECO:0007829|PDB:1MOF"
FT   HELIX           549..551
FT                   /evidence="ECO:0007829|PDB:1MOF"
FT   HELIX           554..558
FT                   /evidence="ECO:0007829|PDB:1MOF"
SQ   SEQUENCE   665 AA;  73302 MW;  12EBA09C8FB93FE2 CRC64;
     MARSTLSKPL KNKVNPRGPL IPLILLMLRG VSTASPGSSP HQVYNITWEV TNGDRETVWA
     TSGNHPLWTW WPDLTPDLCM LAHHGPSYWG LEYQSPFSSP PGPPCCSGGS SPGCSRDCEE
     PLTSLTPRCN TAWNRLKLDQ TTHKSNEGFY VCPGPHRPRE SKSCGGPDSF YCAYWGCETT
     GRAYWKPSSS WDFITVNNNL TSDQAVQVCK DNKWCNPLVI RFTDAGRRVT SWTTGHYWGL
     RLYVSGQDPG LTFGIRLRYQ NLGPRVPIGP NPVLADQQPL SKPKPVKSPS VTKPPSGTPL
     SPTQLPPAGT ENRLLNLVDG AYQALNLTSP DKTQECWLCL VAGPPYYEGV AVLGTYSNHT
     SAPANCSVAS QHKLTLSEVT GQGLCIGAVP KTHQALCNTT QTSSRGSYYL VAPTGTMWAC
     STGLTPCIST TILNLTTDYC VLVELWPRVT YHSPSYVYGL FERSNRHKRE PVSLTLALLL
     GGLTMGGIAA GIGTGTTALM ATQQFQQLQA AVQDDLREVE KSISNLEKSL TSLSEVVLQN
     RRGLDLLFLK EGGLCAALKE ECCFYADHTG LVRDSMAKLR ERLNQRQKLF ESTQGWFEGL
     FNRSPWFTTL ISTIMGPLIV LLMILLFGPC ILNRLVQFVK DRISVVQALV LTQQYHQLKP
     IEYEP
//