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P03385 (ENV_MLVMS) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Envelope glycoprotein

Short name=Pr80env
Alternative name(s):
Env polyprotein

Cleaved into the following 3 chains:

  1. Surface protein
    Short name=SU
    Alternative name(s):
    Glycoprotein 70
    Short name=gp70
  2. Transmembrane protein
    Short name=TM
    Alternative name(s):
    Envelope protein p15E
  3. R-peptide
    Alternative name(s):
    p2E
Gene names
Name:env
OrganismMoloney murine leukemia virus (isolate Shinnick) (MoMLV) [Reference proteome]
Taxonomic identifier928306 [NCBI]
Taxonomic lineageVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeGammaretrovirusMurine leukemia virus
Virus hostMus musculus (Mouse) [TaxID: 10090]

Protein attributes

Sequence length665 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The surface protein (SU) attaches the virus to the host cell by binding to its receptor. Interaction with HECT ubiquitin ligases activates a thiol in a CXXC motif of the C-terminal domain, where the other Cys residue participates in the formation of the intersubunit disulfide. The activated thiol will attack the disulfide and cause its isomerization into a disulfide isomer within the motif. This leads to SU displacement and TM refolding, and is thought to activate its fusogenic potential by unmasking its fusion peptide. Fusion occurs at the host cell plasma membrane. Ref.10

The transmembrane protein (TM) acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm By similarity. Ref.10

Subunit structure

The mature envelope protein (Env) consists of a trimer of SU-TM heterodimers attached by a labile interchain disulfide bond. The activated Env consists of SU monomers and TM trimers. Ref.11

Subcellular location

Transmembrane protein: Virion membrane; Single-pass type I membrane protein By similarity. Host cell membrane; Single-pass type I membrane protein By similarity Ref.7.

Surface protein: Virion membrane; Peripheral membrane protein. Host cell membrane; Peripheral membrane protein By similarity. Note: The surface protein is not anchored to the viral envelope, but associates with the virion surface through its binding to TM. Both proteins are thought to be concentrated at the site of budding and incorporated into the virions possibly by contacts between the cytoplasmic tail of Env and the N-terminus of Gag By similarity. Ref.7

R-peptide: Host cell membrane; Peripheral membrane protein. Note: The R-peptide is membrane-associated through its palmitate. Ref.7

Domain

The 17 amino acids long immunosuppressive region is present in many retroviral envelope proteins. Synthetic peptides derived from this relatively conserved sequence inhibit immune function in vitro and in vivo By similarity.

The YXXL motif is involved in determining the exact site of viral release at the surface of infected mononuclear cells and promotes endocytosis.

Post-translational modification

Specific enzymatic cleavages in vivo yield mature proteins. Envelope glycoproteins are synthesized as a inactive precursor that is N-glycosylated and processed likely by host cell furin or by a furin-like protease in the Golgi to yield the mature SU and TM proteins. The cleavage site between SU and TM requires the minimal sequence [KR]-X-[KR]-R. The R-peptide is released from the C-terminus of the cytoplasmic tail of the TM protein upon particle formation as a result of proteolytic cleavage by the viral protease. Cleavage of this peptide is required for TM to become fusogenic By similarity.

The CXXC motif is highly conserved across a broad range of retroviral envelope proteins. It is thought to participate in the formation of a labile disulfide bond possibly with the CX6CC motif present in the transmembrane protein. Isomerization of the intersubunit disulfide bond to an SU intrachain disulfide bond is thought to occur upon receptor recognition in order to allow membrane fusion By similarity.

The transmembrane protein is palmitoylated By similarity. Ref.7

The R-peptide is palmitoylated. Ref.7

Ontologies

Keywords
   Biological processFusion of virus membrane with host cell membrane
Fusion of virus membrane with host membrane
Host-virus interaction
Viral attachment to host cell
Viral penetration into host cytoplasm
Virus entry into host cell
   Cellular componentHost cell membrane
Host membrane
Membrane
Viral envelope protein
Virion
   DomainCoiled coil
Signal
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Lipoprotein
Palmitate
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processfusion of virus membrane with host plasma membrane

Inferred from electronic annotation. Source: UniProtKB-KW

virion attachment to host cell

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

viral capsid

Inferred from electronic annotation. Source: InterPro

viral envelope

Inferred from electronic annotation. Source: UniProtKB-KW

virion membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionidentical protein binding

Inferred from physical interaction Ref.10. Source: IntAct

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

structural molecule activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself2EBI-8074066,EBI-8074066

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3333 Potential
Chain34 – 665632Envelope glycoprotein
PRO_0000239588
Chain34 – 469436Surface protein By similarity
PRO_0000040765
Chain470 – 649180Transmembrane protein
PRO_0000040766
Peptide650 – 66516R-peptide
PRO_0000040767

Regions

Topological domain34 – 610577Extracellular Potential
Transmembrane611 – 63121Helical; Potential
Topological domain632 – 66534Cytoplasmic Potential
Region34 – 267234Receptor-binding domain (RBD) Potential
Region472 – 49221Fusion peptide By similarity
Region538 – 55417Immunosuppression By similarity
Coiled coil500 – 53738 Potential
Motif336 – 3394CXXC
Motif555 – 5639CX6CC
Motif655 – 6584YXXL motif; contains endocytosis signal By similarity
Compositional bias264 – 30744Pro-rich

Sites

Metal binding1171Zinc By similarity
Site469 – 4702Cleavage; by host
Site649 – 6502Cleavage; by viral protease p14 Potential

Amino acid modifications

Lipidation6301S-palmitoyl cysteine; by host By similarity
Glycosylation451N-linked (GlcNAc...); by host By similarity
Glycosylation1991N-linked (GlcNAc...); by host By similarity
Glycosylation3261N-linked (GlcNAc...); by host By similarity
Glycosylation3581N-linked (GlcNAc...); by host Potential
Glycosylation3651N-linked (GlcNAc...); by host Potential
Glycosylation3981N-linked (GlcNAc...); by host Potential
Glycosylation4341N-linked (GlcNAc...); by host Potential
Disulfide bond79 ↔ 129 By similarity
Disulfide bond105 ↔ 118 By similarity
Disulfide bond106 ↔ 114 By similarity
Disulfide bond152 ↔ 172 By similarity
Disulfide bond164 ↔ 177 By similarity
Disulfide bond209 ↔ 215 By similarity
Disulfide bond336 ↔ 563Interchain (between SU and TM chains, or C-339 with C-563); alternate Ref.9
Disulfide bond336 ↔ 339Alternate Ref.9
Disulfide bond366 ↔ 420 By similarity
Disulfide bond385 ↔ 397 By similarity
Disulfide bond427 ↔ 440 By similarity
Disulfide bond555 ↔ 562 By similarity

Experimental info

Sequence conflict6551Y → F Ref.4
Sequence conflict6631Y → C Ref.4
Sequence conflict6631Y → C Ref.5

Secondary structure

....... 665
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P03385 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 12EBA09C8FB93FE2

FASTA66573,302
        10         20         30         40         50         60 
MARSTLSKPL KNKVNPRGPL IPLILLMLRG VSTASPGSSP HQVYNITWEV TNGDRETVWA 

        70         80         90        100        110        120 
TSGNHPLWTW WPDLTPDLCM LAHHGPSYWG LEYQSPFSSP PGPPCCSGGS SPGCSRDCEE 

       130        140        150        160        170        180 
PLTSLTPRCN TAWNRLKLDQ TTHKSNEGFY VCPGPHRPRE SKSCGGPDSF YCAYWGCETT 

       190        200        210        220        230        240 
GRAYWKPSSS WDFITVNNNL TSDQAVQVCK DNKWCNPLVI RFTDAGRRVT SWTTGHYWGL 

       250        260        270        280        290        300 
RLYVSGQDPG LTFGIRLRYQ NLGPRVPIGP NPVLADQQPL SKPKPVKSPS VTKPPSGTPL 

       310        320        330        340        350        360 
SPTQLPPAGT ENRLLNLVDG AYQALNLTSP DKTQECWLCL VAGPPYYEGV AVLGTYSNHT 

       370        380        390        400        410        420 
SAPANCSVAS QHKLTLSEVT GQGLCIGAVP KTHQALCNTT QTSSRGSYYL VAPTGTMWAC 

       430        440        450        460        470        480 
STGLTPCIST TILNLTTDYC VLVELWPRVT YHSPSYVYGL FERSNRHKRE PVSLTLALLL 

       490        500        510        520        530        540 
GGLTMGGIAA GIGTGTTALM ATQQFQQLQA AVQDDLREVE KSISNLEKSL TSLSEVVLQN 

       550        560        570        580        590        600 
RRGLDLLFLK EGGLCAALKE ECCFYADHTG LVRDSMAKLR ERLNQRQKLF ESTQGWFEGL 

       610        620        630        640        650        660 
FNRSPWFTTL ISTIMGPLIV LLMILLFGPC ILNRLVQFVK DRISVVQALV LTQQYHQLKP 


IEYEP 

« Hide

References

[1]"Nucleotide sequence of Moloney murine leukaemia virus."
Shinnick T.M., Lerner R.A., Sutcliffe J.G.
Nature 293:543-548(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: Clone pMLV-1.
[2]Chappey C.
Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"Chemical synthesis of a polypeptide predicted from nucleotide sequence allows detection of a new retroviral gene product."
Sutcliffe J.G., Shinnick T.M., Green N., Liu F.-T., Niman H.L., Lerner R.A.
Nature 287:801-805(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 496-665.
[4]"Nucleotide sequence of Moloney leukemia virus: 3' end reveals details of replications, analogy to bacterial transposons, and an unexpected gene."
Sutcliffe J.G., Shinnick T.M., Verma I.M., Lerner R.A.
Proc. Natl. Acad. Sci. U.S.A. 77:3302-3306(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 484-665.
Strain: Clone pMLV-201.
[5]"Sequence-specific antibodies show that maturation of Moloney leukemia virus envelope polyprotein involves removal of a COOH-terminal peptide."
Green N., Shinnick T.M., Witte O., Ponticelli A., Sutcliffe J.G., Lerner R.A.
Proc. Natl. Acad. Sci. U.S.A. 78:6023-6027(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 470-489 AND 598-665.
[6]"Inhibition of lymphocyte proliferation by a synthetic peptide homologous to retroviral envelope proteins."
Cianciolo G.J., Copeland T.D., Oroszlan S., Snyderman R.
Science 230:453-455(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: IMMUNOSUPPRESSIVE REGION.
[7]"Palmitoylation of the intracytoplasmic R peptide of the transmembrane envelope protein in Moloney murine leukemia virus."
Olsen K.E., Andersen K.B.
J. Virol. 73:8975-8981(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION OF THE R-PEPTIDE, PALMITOYLATION OF THE R-PEPTIDE.
[8]"Mutational analysis of the R peptide cleavage site of Moloney murine leukaemia virus envelope protein."
Kubo Y., Amanuma H.
J. Gen. Virol. 84:2253-2257(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE OF THE R-PEPTIDE.
[9]"Isomerization of the intersubunit disulphide-bond in Env controls retrovirus fusion."
Wallin M., Ekstroem M., Garoff H.
EMBO J. 23:54-65(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERCHAIN DISULFIDE BOND.
[10]"Turning of the receptor-binding domains opens up the murine leukaemia virus Env for membrane fusion."
Wu S.-R., Sjoeberg M., Wallin M., Lindqvist B., Ekstroem M., Hebert H., Koeck P.J., Garoff H.
EMBO J. 27:2799-2808(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Stabilization of TM trimer interactions during activation of moloney murine leukemia virus Env."
Sjoberg M., Lindqvist B., Garoff H.
J. Virol. 82:2358-2366(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[12]"Retrovirus envelope domain at 1.7-A resolution."
Fass D., Harrison S.C., Kim P.S.
Nat. Struct. Biol. 3:465-469(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 514-567.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02255 Genomic RNA. Translation: AAB59943.1.
AF033811 Genomic RNA. Translation: AAC82567.1.
PIRVCVWEM. A93265.
RefSeqNP_057935.1. NC_001501.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1MOFX-ray1.70A514-567[»]
ProteinModelPortalP03385.
SMRP03385. Positions 42-266, 515-567.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-7304679.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID2193424.

Family and domain databases

Gene3D3.90.310.10. 1 hit.
InterProIPR008981. FMuLV_rcpt-bd.
IPR018154. TLV/ENV_coat_polyprotein.
[Graphical view]
PANTHERPTHR10424. PTHR10424. 1 hit.
PfamPF00429. TLV_coat. 1 hit.
[Graphical view]
SUPFAMSSF49830. SSF49830. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP03385.

Entry information

Entry nameENV_MLVMS
AccessionPrimary (citable) accession number: P03385
Secondary accession number(s): Q77YG8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 16, 2014
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references