ENV_MLVMS
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 03-AUG-2022, entry version 148.
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 SwissPalm; P03385; -.
DR GeneID; 34950658; -.
DR KEGG; vg:34950657; -.
DR EvolutionaryTrace; P03385; -.
DR Proteomes; UP000006625; Genome.
DR Proteomes; UP000180702; 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: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 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 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
