P03385 (ENV_MLVMS) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Moloney murine leukemia virus (isolate Shinnick) (MoMLV) [Reference proteome]

Taxonomic identifier

928306 [NCBI]

Taxonomic lineage

Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Gammaretrovirus › Mammalian virus group › Replication competent viruses › Murine leukemia virus › Moloney murine leukemia virus

Virus host

Mus musculus (Mouse) [TaxID: 10090]

Protein attributes

Sequence length	665 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Fusion 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 component	Host cell membrane Host membrane Membrane Viral envelope protein Virion
Domain	Coiled coil Signal Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	viral attachment to host cell Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell via membrane fusion with the plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW viral infectious cycle Inferred from electronic annotation. Source: InterPro
Cellular_component	host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to 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_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 33

33

Potential

Chain

34 – 665

632

Envelope glycoprotein

PRO_0000239588

Chain

34 – 469

436

Surface protein By similarity

PRO_0000040765

Chain

470 – 649

180

Transmembrane protein

PRO_0000040766

Peptide

650 – 665

16

R-peptide

PRO_0000040767

Regions

Topological domain

34 – 610

577

Extracellular Potential

Transmembrane

611 – 631

21

Helical; Potential

Topological domain

632 – 665

34

Cytoplasmic Potential

Region

34 – 267

234

Receptor-binding domain (RBD) Potential

Region

472 – 492

21

Fusion peptide By similarity

Region

538 – 554

17

Immunosuppression By similarity

Coiled coil

500 – 537

38

Potential

Motif

336 – 339

4

CXXC

Motif

555 – 563

9

CX6CC

Motif

655 – 658

4

YXXL motif; contains endocytosis signal By similarity

Compositional bias

264 – 307

44

Pro-rich

Sites

Metal binding

117

1

Zinc By similarity

Site

469 – 470

2

Cleavage; by host

Site

649 – 650

2

Cleavage; by viral protease p14 Potential

Amino acid modifications

Lipidation

630

1

S-palmitoyl cysteine; by host By similarity

Glycosylation

45

1

N-linked (GlcNAc...); by host By similarity

Glycosylation

199

1

N-linked (GlcNAc...); by host By similarity

Glycosylation

326

1

N-linked (GlcNAc...); by host By similarity

Glycosylation

358

1

N-linked (GlcNAc...); by host Potential

Glycosylation

365

1

N-linked (GlcNAc...); by host Potential

Glycosylation

398

1

N-linked (GlcNAc...); by host Potential

Glycosylation

434

1

N-linked (GlcNAc...); by host Potential

Disulfide bond

79 ↔ 129

By similarity

Disulfide bond

105 ↔ 118

By similarity

Disulfide bond

106 ↔ 114

By similarity

Disulfide bond

152 ↔ 172

By similarity

Disulfide bond

164 ↔ 177

By similarity

Disulfide bond

209 ↔ 215

By similarity

Disulfide bond

336 ↔ 563

Interchain (between SU and TM chains, or C-339 with C-563); alternate Ref.9

Disulfide bond

336 ↔ 339

Alternate Ref.9

Disulfide bond

366 ↔ 420

By similarity

Disulfide bond

385 ↔ 397

By similarity

Disulfide bond

427 ↔ 440

By similarity

Disulfide bond

555 ↔ 562

By similarity

Experimental info

Sequence conflict

655

1

Y → F Ref.4

Sequence conflict

663

1

Y → C Ref.4

Sequence conflict

663

1

Y → C Ref.5

Secondary structure

1

.

.

.

.

.

.

.

665

Helix Strand Turn

Details...

Helix

516 – 547

32

Helix

549 – 551

3

Helix

554 – 558

5

Sequences

	Sequence		Length	Mass (Da)
	P03385 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 12EBA09C8FB93FE2	FASTA	665	73,302
	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

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.

PIR

VCVWEM. A93265.

RefSeq

NP_057935.1. NC_001501.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MOF	X-ray	1.70	A	514-567	[»]

ProteinModelPortal

P03385.

SMR

P03385. Positions 42-266, 515-567.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

Gene3D

3.90.310.10. 1 hit.

InterPro

IPR008981. FMuLV_rcpt-bd.
IPR018154. TLV/ENV_coat_polyprotein.
[Graphical view]

PANTHER

PTHR10424. PTHR10424. 1 hit.

Pfam

PF00429. TLV_coat. 1 hit.
[Graphical view]

SUPFAM

SSF49830. FMuLVrecept-bind. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P03385.

Entry information

Entry name

ENV_MLVMS

Accession

Primary (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 3, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program