P26803 (ENV_MLVFP) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Envelope glycoprotein

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

Friend murine leukemia virus (isolate PVC-211) (FrMLV) [Complete proteome]

Taxonomic identifier

11798 [NCBI]

Taxonomic lineage

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

Virus host

Mus musculus (Mouse) [TaxID: 10090]

Protein attributes

Sequence length	676 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. This interaction triggers the refolding of the transmembrane protein (TM) and is thought to activate its fusogenic potential by unmasking its fusion peptide. Fusion occurs at the host cell plasma membrane By similarity. 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.
Subunit structure	The mature envelope protein (Env) consists of a trimer of SU-TM heterodimers attached by a labile interchain disulfide bond By similarity.
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. 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. R-peptide: Host cell membrane; Peripheral membrane protein By similarity. Note: The R-peptide is membrane-associated through its palmitate By similarity.
Domain	The YXXL motif is involved in determining the exact site of viral release at the surface of infected mononuclear cells and promotes endocytosis. 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.
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. The R-peptide is palmitoylated By similarity.
Miscellaneous	The surface protein appears to be responsible for the neuropathogenicity of PVC-211 MuLV.

Ontologies

Keywords
Biological process	Fusion of virus membrane with host cell membrane Fusion of virus membrane with host membrane Host-virus interaction Inhibition of host adaptive immune response by virus Inhibition of host proteasome antigen processing by virus Viral attachment to host cell Viral immunoevasion 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	Complete proteome
Gene Ontology (GO)
Biological_process	suppression by virus of host antigen processing and presentation Inferred from electronic annotation. Source: UniProtKB-KW 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 – 34	34	Potential
	Chain	35 – 676	642	Envelope glycoprotein		PRO_0000239583
	Chain	35 – 479	445	Surface protein By similarity		PRO_0000040757
	Chain	480 – 659	180	Transmembrane protein By similarity		PRO_0000040758
	Peptide	660 – 676	17	R-peptide By similarity		PRO_0000040759
Regions
	Topological domain	35 – 620	586	Extracellular Potential
	Transmembrane	621 – 641	21	Helical; Potential
	Topological domain	642 – 676	35	Cytoplasmic Potential
	Region	35 – 270	236	Receptor-binding domain (RBD) Potential
	Region	482 – 502	21	Fusion peptide By similarity
	Region	548 – 564	17	Immunosuppression By similarity
	Coiled coil	513 – 547	35	Potential
	Motif	346 – 349	4	CXXC
	Motif	565 – 573	9	CX6CC
	Motif	665 – 668	4	YXXL motif; contains endocytosis signal By similarity
	Compositional bias	267 – 317	51	Pro-rich
Sites
	Metal binding	89	1	Zinc By similarity
	Metal binding	120	1	Zinc By similarity
	Site	479 – 480	2	Cleavage; by host By similarity
	Site	659 – 660	2	Cleavage; by viral protease p14 By similarity
Amino acid modifications
	Lipidation	640	1	S-palmitoyl cysteine; by host By similarity
	Glycosylation	46	1	N-linked (GlcNAc...); by host By similarity
	Glycosylation	202	1	N-linked (GlcNAc...); by host By similarity
	Glycosylation	336	1	N-linked (GlcNAc...); by host By similarity
	Glycosylation	368	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	375	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	408	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	444	1	N-linked (GlcNAc...); by host Potential
	Disulfide bond	80 ↔ 132		By similarity
	Disulfide bond	106 ↔ 121		By similarity
	Disulfide bond	107 ↔ 117		By similarity
	Disulfide bond	155 ↔ 175		By similarity
	Disulfide bond	167 ↔ 180		By similarity
	Disulfide bond	212 ↔ 218		By similarity
	Disulfide bond	346 ↔ 573		Interchain (between SU and TM chains, or C-349 with C-573); alternate
	Disulfide bond	346 ↔ 349		Alternate
	Disulfide bond	376 ↔ 430		By similarity
	Disulfide bond	395 ↔ 407		By similarity
	Disulfide bond	437 ↔ 450		By similarity
	Disulfide bond	565 ↔ 572		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P26803 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 18D8D8A7FE0A8FA4	FASTA	676	73,946
	10 20 30 40 50 60 MACSTLSKSP KDKIDPRDLL IPLILFLSLK GARSAAPGSS PHQVYNITWE VTNGDRETVW 70 80 90 100 110 120 AISGNHPLWT WWPDLTPDLC MLALSGPPHW GLEYRAPYSS PPGPPCCSGS SGNRAGCARD 130 140 150 160 170 180 CDEPLTSLTP RCNTAWNRLK LDQVTHKSSG GFYVCPGSHR PRKAKSCGGP DSFYCASWGC 190 200 210 220 230 240 ETTGRAYWKP SSSWDYITVD NNLTTNQAAQ VCKDNKWCNP LAIQFTNAGK QVTSWTIGHY 250 260 270 280 290 300 WGLRLYVSGQ DPGLTFGIRL KYQNLGPRVP IGPNPVLADQ LSFPLPNPLP KPAKSPSASN 310 320 330 340 350 360 STPTLISPSP APTQPPPAGT GDRLLNLVQG AYQALNLTNP DKTQECWLCL VSAPPYYEGV 370 380 390 400 410 420 AVLGTYSNHT SAPANCSAGS QHKLTLSEVT GQGLCIGTVP KTHQALCNTT LKTGKGSYYL 430 440 450 460 470 480 VAPAGTMWAC NTGLTPCLSA TVLNRTTDYC VLVELWPRVT YHPPSYVYSQ FEKSYRHKRE 490 500 510 520 530 540 PVSLTLALLL GGLTMGGIAA GVGTGTTALV ATQQFQQLHA AVQDDLKEVE KSITNLEKSL 550 560 570 580 590 600 TSLSEVVLQN RRGLDLLFLK EGGLCAALKE ECCFYADHTG LVRDSMAKLR ERLTQRQKLF 610 620 630 640 650 660 ESSQGWFEGL FNRSPWFTTL ISTIMGPLII LLLILLFGPC ILNRLVQFVK DRISVVQALV 670 LTQQYHQLKP LEYEPQ

References

[1]	"Molecular characterization of a neuropathogenic and nonerythroleukemogenic variant of Friend murine leukemia virus PVC-211." Masuda M., Remington M.P., Hoffman P.M., Ruscetti S.K. J. Virol. 66:2798-2806(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Complete nucleotide sequence of a neuropathogenic variant of Friend murine leukemia virus PVC-211." Remington M.P., Hoffman P.M., Ruscetti S.K., Masuda M. Nucleic Acids Res. 20:3249-3249(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	M93134 Genomic RNA. Translation: AAA46478.1.
PIR	VCMVPV. A38210.
3D structure databases
ProteinModelPortal	P26803.
SMR	P26803. Positions 43-269, 525-577.
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...

Entry information

Entry name

ENV_MLVFP

Accession

Primary (citable) accession number: P26803

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	April 3, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program