ID   ENV_MLVF5               Reviewed;         675 AA.
AC   P03390;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 3.
DT   27-MAR-2024, entry version 144.
DE   RecName: Full=Envelope glycoprotein;
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   Friend murine leukemia virus (isolate 57) (FrMLV).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Gammaretrovirus;
OC   Murine leukemia virus.
OX   NCBI_TaxID=11796;
OH   NCBI_TaxID=10090; Mus musculus (Mouse).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Friedrich R.W., Koch W., von Maydell-Livonius U., Schrewe H.,
RA   Zimmermann W.;
RL   Submitted (SEP-1990) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PRELIMINARY NUCLEOTIDE SEQUENCE.
RX   PubMed=6321768; DOI=10.1128/jvi.49.3.828-840.1984;
RA   Koch W., Zimmermann W., Oliff A., Friedrich R.W.;
RT   "Molecular analysis of the envelope gene and long terminal repeat of Friend
RT   mink cell focus-inducing virus: implications for the functions of these
RT   sequences.";
RL   J. Virol. 49:828-840(1984).
RN   [3]
RP   PALMITOYLATION AT CYS-640 OF THE TRANSMEMBRANE PROTEIN, AND MUTAGENESIS OF
RP   CYS-640.
RX   PubMed=8661417; DOI=10.1006/viro.1996.0355;
RA   Yang C., Compans R.W.;
RT   "Palmitoylation of the murine leukemia virus envelope glycoprotein
RT   transmembrane subunits.";
RL   Virology 221:87-97(1996).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 43-270.
RX   PubMed=9287219; DOI=10.1126/science.277.5332.1662;
RA   Fass D., Davey R.A., Hamson C.A., Kim P.S., Cunningham J.M., Berger J.M.;
RT   "Structure of a murine leukemia virus receptor-binding glycoprotein at 2.0-
RT   A resolution.";
RL   Science 277:1662-1666(1997).
CC   -!- FUNCTION: The surface protein (SU) attaches the virus to the host cell
CC       by binding to its receptor. This interaction triggers the refolding of
CC       the transmembrane protein (TM) and is thought to activate its fusogenic
CC       potential by unmasking its fusion peptide. Fusion occurs at the host
CC       cell plasma 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.
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 {ECO:0000250};
CC       Peripheral membrane protein {ECO:0000250}. Note=The R-peptide is
CC       membrane-associated through its palmitate. {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   -!- 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   -!- 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.
CC       {ECO:0000269|PubMed:8661417}.
CC   -!- PTM: The R-peptide is palmitoylated. {ECO:0000250}.
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DR   EMBL; X02794; CAA26561.1; -; Genomic_RNA.
DR   PDB; 1AOL; X-ray; 2.00 A; A=43-270.
DR   PDBsum; 1AOL; -.
DR   SMR; P03390; -.
DR   GlyCosmos; P03390; 7 sites, No reported glycans.
DR   SwissPalm; P03390; -.
DR   EvolutionaryTrace; P03390; -.
DR   Proteomes; UP000007776; 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: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:0039588; P:suppression by virus of host antigen processing and presentation; 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   Disulfide bond; 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;
KW   Inhibition of host adaptive immune response by virus;
KW   Inhibition of host proteasome antigen processing by virus; Lipoprotein;
KW   Membrane; Metal-binding; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus entry into host cell; Zinc.
FT   SIGNAL          1..34
FT                   /evidence="ECO:0000255"
FT   CHAIN           35..675
FT                   /note="Envelope glycoprotein"
FT                   /id="PRO_0000239581"
FT   CHAIN           35..479
FT                   /note="Surface protein"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000040751"
FT   CHAIN           480..659
FT                   /note="Transmembrane protein"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000040752"
FT   PEPTIDE         660..675
FT                   /note="R-peptide"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000040753"
FT   TOPO_DOM        35..620
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        621..641
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        642..675
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          35..270
FT                   /note="Receptor-binding domain (RBD)"
FT                   /evidence="ECO:0000255"
FT   REGION          276..323
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          482..502
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000250"
FT   REGION          548..564
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000250"
FT   COILED          513..547
FT                   /evidence="ECO:0000255"
FT   MOTIF           346..349
FT                   /note="CXXC"
FT   MOTIF           565..573
FT                   /note="CX6CC"
FT   MOTIF           665..668
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000250"
FT   BINDING         89
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   BINDING         120
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT   SITE            479..480
FT                   /note="Cleavage; by host"
FT                   /evidence="ECO:0000250"
FT   SITE            659..660
FT                   /note="Cleavage; by viral protease p14"
FT                   /evidence="ECO:0000250"
FT   LIPID           640
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000269|PubMed:8661417"
FT   CARBOHYD        46
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   CARBOHYD        202
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT   CARBOHYD        336
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        368
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        375
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        408
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        444
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   DISULFID        80..132
FT   DISULFID        106..121
FT   DISULFID        107..117
FT   DISULFID        155..175
FT   DISULFID        167..180
FT   DISULFID        212..218
FT   DISULFID        346..573
FT                   /note="Interchain (between SU and TM chains, or C-349 with
FT                   C-573); in linked form"
FT   DISULFID        346..349
FT   DISULFID        376..430
FT                   /evidence="ECO:0000250"
FT   DISULFID        395..407
FT                   /evidence="ECO:0000250"
FT   DISULFID        437..450
FT                   /evidence="ECO:0000250"
FT   DISULFID        565..572
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         640
FT                   /note="C->S: Complete loss of palmitoylation."
FT                   /evidence="ECO:0000269|PubMed:8661417"
FT   STRAND          44..52
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   STRAND          58..67
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   HELIX           79..83
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   HELIX           88..90
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   HELIX           119..122
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   STRAND          130..134
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   HELIX           135..146
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   STRAND          152..156
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   HELIX           164..167
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   HELIX           170..172
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   STRAND          183..186
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   STRAND          196..203
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   HELIX           205..213
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   STRAND          220..225
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   HELIX           227..231
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   HELIX           234..236
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   STRAND          239..245
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   TURN            248..250
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   STRAND          253..263
FT                   /evidence="ECO:0007829|PDB:1AOL"
FT   HELIX           266..268
FT                   /evidence="ECO:0007829|PDB:1AOL"
SQ   SEQUENCE   675 AA;  74025 MW;  A097038E422BB3D3 CRC64;
     MACSTLPKSP KDKIDPRDLL IPLILFLSLK GARSAAPGSS PHQVYNITWE VTNGDRETVW
     AISGNHPLWT WWPVLTPDLC MLALSGPPHW GLEYQAPYSS PPGPPCCSGS SGSSAGCSRD
     CDEPLTSLTP RCNTAWNRLK LDQVTHKSSE GFYVCPGSHR PREAKSCGGP DSFYCASWGC
     ETTGRVYWKP SSSWDYITVD NNLTTSQAVQ VCKDNKWCNP LAIQFTNAGK QVTSWTTGHY
     WGLRLYVSGR DPGLTFGIRL RYQNLGPRVP IGPNPVLADQ LSLPRPNPLP KPAKSPPASN
     STPTLISPSP TPTQPPPAGT GDRLLNLVQG AYQALNLTNP DKTQECWLCL VSGPPYYEGV
     AVLGTYSNHT SAPANCSVAS QHKLTLSEVT GRGLCIGTVP KTHQALCNTT LKIDKGSYYL
     VAPTGTTWAC NTGLTPCLSA TVLNRTTDYC VLVELWPRVT YHPPSYVYSQ FEKSYRHKRE
     PVSLTLALLL GGLTMGGIAA GVGTGTTALV ATQQFQQLHA AVQDDLKEVE KSITNLEKSL
     TSLSEVVLQN RRGLDLLFLK EGGLCAALKE ECCFYADHTG LVRDSMAKLR ERLTQRQKLF
     ESSQGWFEGL FNRSPWFTTL ISTIMGPLII LLLILLFGPC ILNRLVQFVK DRISVVQALV
     LTQQYHQLKP LEYEP
//