P03332 (GAG_MLVMS) Reviewed, UniProtKB/Swiss-Prot
Last modified October 16, 2013. Version 122. History...
Names and origin
|Protein names||Recommended name:|
|Organism||Moloney murine leukemia virus (isolate Shinnick) (MoMLV) [Reference proteome]|
|Taxonomic identifier||928306 [NCBI]|
|Taxonomic lineage||Viruses › Retro-transcribing viruses › Retroviridae › Orthoretrovirinae › Gammaretrovirus › Murine leukemia virus ›|
|Virus host||Mus musculus (Mouse) [TaxID: 10090]|
|Sequence length||538 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Gag polyprotein plays a role in budding and is processed by the viral protease during virion maturation outside the cell. During budding, it recruits, in a PPXY-dependent or independent manner, Nedd4-like ubiquitin ligases that conjugate ubiquitin molecules to Gag, or to Gag binding host factors. Interaction with HECT ubiquitin ligases probably link the viral protein to the host ESCRT pathway and facilitate release. Ref.9
Matrix protein p15 targets Gag and gag-pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex By similarity. Ref.9
Capsid protein p30 forms the spherical core of the virion that encapsulates the genomic RNA-nucleocapsid complex By similarity. Ref.9
Nucleocapsid protein p10 is involved in the packaging and encapsidation of two copies of the genome. Binds with high affinity to conserved UCUG elements within the packaging signal, located near the 5'-end of the genome. This binding is dependent on genome dimerization. Ref.9
Capsid protein p30 is a homohexamer, that further associates as homomultimer. The virus core is composed of a lattice formed from hexagonal rings, each containing six capsid monomers By similarity. Capsid protein p30 interacts with mouse UBE2I and mouse PIAS4. Gag polyprotein interacts (via PPXY motif) with host NEDD4. Gag polyprotein interacts (via PSAP motif) with host TSG101. Gag polyprotein interacts (via LYPX(n)L motif) with host PDCD6IP. Ref.6 Ref.7
Gag polyprotein: Virion By similarity. Host cell membrane; Lipid-anchor Potential. Host late endosome membrane; Lipid-anchor Potential. Host endosome › host multivesicular body By similarity. Note: These locations are probably linked to virus assembly sites By similarity.
Late-budding domains (L domains) are short sequence motifs essential for viral particle budding. They recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex Required for Transport) or ESCRT-associated proteins. RNA-binding phosphoprotein p12 contains one L domain: a PPXY motif which interacts with the WW domain 3 of NEDD4 E3 ubiquitin ligase. PPXY motif is essential for virus egress. Matrix protein p15 contains one L domain: a PTAP/PSAP motif, which interacts with the UEV domain of TSG101. The junction between the matrix protein p15 and RNA-binding phosphoprotein p12 also contains one L domain: a LYPX(n)L motif which interacts with PDCD6IP. Both PSAP and LYPX(n)L domains might play little to no role in budding and possibly drive residual virus release.
Gag polyprotein is ubiquitinated by ITCH. Gag can recruit the ubiquitin ligase Itch in an L domain-independent manner to facilitate virus release via a mechanism that involves Gag ubiquitination.
Specific enzymatic cleavages by the viral protease yield mature proteins. The protease is released by autocatalytic cleavage. The polyprotein is cleaved during and after budding, this process is termed maturation By similarity. Ref.8
Capsid protein p30 is sumoylated; which is required for virus replication. Ref.7
RNA-binding phosphoprotein p12 is phosphorylated on serine residues. Ref.5
Contains 1 CCHC-type zinc finger.
|This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]|
|Isoform Pr65gag (identifier: P03332-1) |
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Isoform Pr80gag (identifier: Q8UN02-1) |
Also known as: GlycoGag;
The sequence of this isoform can be found in the external entry Q8UN02.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
|Note: Produced by an upstream CUG initiation codon.|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed; by host Ref.3|
|Chain||2 – 538||537||Gag polyprotein||PRO_0000390815|
|Chain||2 – 131||130||Matrix protein p15 Potential||PRO_0000040912|
|Chain||132 – 215||84||RNA-binding phosphoprotein p12 Potential||PRO_0000040913|
|Chain||216 – 478||263||Capsid protein p30 Potential||PRO_0000040914|
|Chain||479 – 538||60||Nucleocapsid protein p10 Potential||PRO_0000040915|
|Zinc finger||502 – 519||18||CCHC-type|
|Region||345 – 393||49||Interaction with mouse PIAS4|
|Region||430 – 435||6||Interaction with mouse UBE2I|
|Coiled coil||438 – 478||41||Potential|
|Motif||111 – 114||4||PTAP/PSAP motif|
|Motif||130 – 134||5||LYPX(n)L motif|
|Motif||162 – 165||4||PPXY motif|
|Site||131 – 132||2||Cleavage; by viral protease p14|
|Site||215 – 216||2||Cleavage; by viral protease p14|
|Site||478 – 479||2||Cleavage; by viral protease p14|
Amino acid modifications
|Modified residue||192||1||Phosphoserine; by host Probable|
|Lipidation||2||1||N-myristoyl glycine; by host Ref.3|
|Mutagenesis||114||1||P → A: Slight reduction in the number of virus-like particles produced.|
|Mutagenesis||137||1||S → A: No effect on reverse transcription activity. Ref.5|
|Mutagenesis||148||1||S → A: No effect on reverse transcription activity; when associated with A-150. Ref.5|
|Mutagenesis||150||1||S → A: No effect on reverse transcription activity; when associated with A-148. Ref.5|
|Mutagenesis||165||1||Y → A: Drastic reduction in the number of virus-like particles produced. Ref.6|
|Mutagenesis||192||1||S → A: Complete loss of reverse transcription activity. Ref.5|
|Mutagenesis||192||1||S → D: Complete loss of reverse transcription activity. Ref.5|
|Mutagenesis||196||1||S → A: No effect on reverse transcription activity. Ref.5|
|Mutagenesis||209||1||S → A: Strongly reduced reverse transcription activity. Ref.5|
|Mutagenesis||209||1||S → D: Strongly reduced reverse transcription activity. Ref.5|
|Mutagenesis||212||1||S → A: No effect on reverse transcription activity. Ref.5|
Helix Strand Turn
|Helix||8 – 14||7|
|Helix||16 – 25||10|
|Helix||32 – 40||9|
|Helix||43 – 46||4|
|Helix||58 – 68||11|
|Helix||77 – 79||3|
|Helix||80 – 91||12|
|Turn||356 – 360||5|
|Helix||361 – 363||3|
|Helix||364 – 378||15|
|Beta strand||494 – 496||3|
|Beta strand||501 – 503||3|
|Beta strand||505 – 507||3|
|Beta strand||510 – 512||3|
|Helix||514 – 516||3|
|Beta strand||518 – 520||3|
|Beta strand||522 – 524||3|
|||"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] (CLONE PMLV-1).
Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Myristyl amino-terminal acylation of murine retrovirus proteins: an unusual post-translational proteins modification."|
Henderson L.E., Krutzsch H.C., Oroszlan S.
Proc. Natl. Acad. Sci. U.S.A. 80:339-343(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-31, MYRISTOYLATION AT GLY-2.
|||"Primary structure of the low molecular weight nucleic acid-binding proteins of murine leukemia viruses."|
Henderson L.E., Copeland T.D., Sowder R.C., Smythers G.W., Oroszlan S.
J. Biol. Chem. 256:8400-8406(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 479-529.
|||"Phosphorylated serine residues and an arginine-rich domain of the moloney murine leukemia virus p12 protein are required for early events of viral infection."|
Yueh A., Goff S.P.
J. Virol. 77:1820-1829(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-192, MUTAGENESIS OF SER-137; SER-148; SER-150; SER-192; SER-196; SER-209 AND SER-212.
|||"Tsg101 and Alix interact with murine leukemia virus Gag and cooperate with Nedd4 ubiquitin ligases during budding."|
Segura-Morales C., Pescia C., Chatellard-Causse C., Sadoul R., Bertrand E., Basyuk E.
J. Biol. Chem. 280:27004-27012(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MOUSE NEDD4; TSG101 AND PDCD6IP/ALIX, MUTAGENESIS OF TYR-165.
|||"Interaction of moloney murine leukemia virus capsid with Ubc9 and PIASy mediates SUMO-1 addition required early in infection."|
Yueh A., Leung J., Bhattacharyya S., Perrone L.A., de los Santos K., Pu S.-Y., Goff S.P.
J. Virol. 80:342-352(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBE2I AND PIAS4, SUMOYLATION.
|||"Characterization of the murine leukemia virus protease and its comparison with the human immunodeficiency virus type 1 protease."|
Feher A., Boross P., Sperka T., Miklossy G., Kadas J., Bagossi P., Oroszlan S., Weber I.T., Tozser J.
J. Gen. Virol. 87:1321-1330(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
|||"Late domain-independent rescue of a release-deficient Moloney murine leukemia virus by the ubiquitin ligase Itch."|
Jadwin J.A., Rudd V., Sette P., Challa S., Bouamr F.
J. Virol. 84:704-715(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Three-dimensional 1H NMR structure of the nucleocapsid protein NCp10 of Moloney murine leukemia virus."|
Demene H., Jullian N., Morellet N., de Rocquigny H., Cornille F., Maigret B., Roques B.P.
J. Biomol. NMR 4:153-170(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 492-531.
|||"Solution structures of human immunodeficiency virus type 1 (HIV-1) and moloney murine leukemia virus (MoMLV) capsid protein major-homology-region peptide analogs by NMR spectroscopy."|
Clish C.B., Peyton D.H., Barklis E.
Eur. J. Biochem. 257:69-77(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 352-382.
|||"Atomic resolution structure of Moloney murine leukemia virus matrix protein and its relationship to other retroviral matrix proteins."|
Riffel N., Harlos K., Iourin O., Rao Z., Kingsman A., Stuart D., Fry E.
Structure 10:1627-1636(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 1-99.
|||"Structural basis for packaging the dimeric genome of Moloney murine leukaemia virus."|
D'Souza V., Summers M.F.
Nature 431:586-590(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 479-534.
|||"Composition and sequence-dependent binding of RNA to the nucleocapsid protein of Moloney murine leukemia virus."|
Dey A., York D., Smalls-Mantey A., Summers M.F.
Biochemistry 44:3735-3744(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 479-534.
|+||Additional computationally mapped references.|
|J02255 Genomic RNA. Translation: AAB59942.1.|
AF033811 Genomic RNA. Translation: AAC82566.1.
|PIR||FOMV1M. A03930. |
|RefSeq||NP_057934.1. NC_001501.1. |
3D structure databases
|SMR||P03332. Positions 2-98, 216-347, 352-382, 479-534. |
Protein-protein interaction databases
|IntAct||P03332. 6 interactions.|
Protocols and materials databases
Genome annotation databases
Family and domain databases
|Gene3D||184.108.40.206. 1 hit. |
1.10.375.10. 1 hit.
220.127.116.11. 1 hit.
|InterPro||IPR000840. G_retro_matrix_N. |
|Pfam||PF01140. Gag_MA. 1 hit. |
PF01141. Gag_p12. 1 hit.
PF02093. Gag_p30. 1 hit.
PF00098. zf-CCHC. 1 hit.
|SMART||SM00343. ZnF_C2HC. 1 hit. |
|SUPFAM||SSF47836. SSF47836. 1 hit. |
SSF47943. SSF47943. 1 hit.
SSF57756. SSF57756. 1 hit.
|PROSITE||PS50158. ZF_CCHC. 1 hit. |
|Accession||Primary (citable) accession number: P03332|
Secondary accession number(s): Q9WJP4
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|