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P03332 (GAG_MLVMS) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gag polyprotein

Short name=Pr65gag
Alternative name(s):
Core polyprotein

Cleaved into the following 4 chains:

  1. Matrix protein p15
    Short name=MA
  2. RNA-binding phosphoprotein p12
    Alternative name(s):
    pp12
  3. Capsid protein p30
    Short name=CA
  4. Nucleocapsid protein p10
    Short name=NC-gag
Gene names
Name:gag
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 length538 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

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

Subcellular location

Gag polyprotein: Virion By similarity. Host cell membrane; Lipid-anchor Potential. Host late endosome membrane; Lipid-anchor Potential. Host endosomehost multivesicular body By similarity. Note: These locations are probably linked to virus assembly sites By similarity.

Matrix protein p15: Virion Potential.

Capsid protein p30: Virion Potential.

Nucleocapsid protein p10: Virion Potential.

Domain

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.

Post-translational modification

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

Sequence similarities

Contains 1 CCHC-type zinc finger.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Dok3Q9QZK73EBI-935477,EBI-2906753From a different organism.
Iqgap1Q9JKF117EBI-935477,EBI-644633From a different organism.

Alternative products

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed; by host Ref.3
Chain2 – 538537Gag polyprotein
PRO_0000390815
Chain2 – 131130Matrix protein p15 Potential
PRO_0000040912
Chain132 – 21584RNA-binding phosphoprotein p12 Potential
PRO_0000040913
Chain216 – 478263Capsid protein p30 Potential
PRO_0000040914
Chain479 – 53860Nucleocapsid protein p10 Potential
PRO_0000040915

Regions

Zinc finger502 – 51918CCHC-type
Region345 – 39349Interaction with mouse PIAS4
Region430 – 4356Interaction with mouse UBE2I
Coiled coil438 – 47841 Potential
Motif111 – 1144PTAP/PSAP motif
Motif130 – 1345LYPX(n)L motif
Motif162 – 1654PPXY motif

Sites

Site131 – 1322Cleavage; by viral protease p14
Site215 – 2162Cleavage; by viral protease p14
Site478 – 4792Cleavage; by viral protease p14

Amino acid modifications

Modified residue1921Phosphoserine; by host Probable
Lipidation21N-myristoyl glycine; by host Ref.3

Experimental info

Mutagenesis1141P → A: Slight reduction in the number of virus-like particles produced.
Mutagenesis1371S → A: No effect on reverse transcription activity. Ref.5
Mutagenesis1481S → A: No effect on reverse transcription activity; when associated with A-150. Ref.5
Mutagenesis1501S → A: No effect on reverse transcription activity; when associated with A-148. Ref.5
Mutagenesis1651Y → A: Drastic reduction in the number of virus-like particles produced. Ref.6
Mutagenesis1921S → A: Complete loss of reverse transcription activity. Ref.5
Mutagenesis1921S → D: Complete loss of reverse transcription activity. Ref.5
Mutagenesis1961S → A: No effect on reverse transcription activity. Ref.5
Mutagenesis2091S → A: Strongly reduced reverse transcription activity. Ref.5
Mutagenesis2091S → D: Strongly reduced reverse transcription activity. Ref.5
Mutagenesis2121S → A: No effect on reverse transcription activity. Ref.5

Secondary structure

................................ 538
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Pr65gag [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 8A7652439B464495

FASTA53860,858
        10         20         30         40         50         60 
MGQTVTTPLS LTLGHWKDVE RIAHNQSVDV KKRRWVTFCS AEWPTFNVGW PRDGTFNRDL 

        70         80         90        100        110        120 
ITQVKIKVFS PGPHGHPDQV PYIVTWEALA FDPPPWVKPF VHPKPPPPLP PSAPSLPLEP 

       130        140        150        160        170        180 
PRSTPPRSSL YPALTPSLGA KPKPQVLSDS GGPLIDLLTE DPPPYRDPRP PPSDRDGNGG 

       190        200        210        220        230        240 
EATPAGEAPD PSPMASRLRG RREPPVADST TSQAFPLRAG GNGQLQYWPF SSSDLYNWKN 

       250        260        270        280        290        300 
NNPSFSEDPG KLTALIESVL ITHQPTWDDC QQLLGTLLTG EEKQRVLLEA RKAVRGDDGR 

       310        320        330        340        350        360 
PTQLPNEVDA AFPLERPDWD YTTQAGRNHL VHYRQLLLAG LQNAGRSPTN LAKVKGITQG 

       370        380        390        400        410        420 
PNESPSAFLE RLKEAYRRYT PYDPEDPGQE TNVSMSFIWQ SAPDIGRKLE RLEDLKNKTL 

       430        440        450        460        470        480 
GDLVREAEKI FNKRETPEER EERIRRETEE KEERRRTEDE QKEKERDRRR HREMSKLLAT 

       490        500        510        520        530 
VVSGQKQDRQ GGERRRSQLD RDQCAYCKEK GHWAKDCPKK PRGPRGPRPQ TSLLTLDD 

« Hide

Isoform Pr80gag (GlycoGag) [UniParc].

See Q8UN02.

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] (CLONE PMLV-1).
[2]Chappey C.
Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"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.
[4]"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.
[5]"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.
[6]"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.
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02255 Genomic RNA. Translation: AAB59942.1.
AF033811 Genomic RNA. Translation: AAC82566.1.
PIRFOMV1M. A03930.
RefSeqNP_057934.1. NC_001501.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A6BNMR-B492-531[»]
1BM4NMR-A352-382[»]
1MN8X-ray1.00A/B/C/D1-99[»]
1U6PNMR-A479-534[»]
1WWDNMR-A479-534[»]
1WWENMR-A479-534[»]
1WWFNMR-A479-534[»]
1WWGNMR-A479-534[»]
ProteinModelPortalP03332.
SMRP03332. Positions 2-98, 216-347, 352-382, 479-534.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP03332. 6 interactions.
MINTMINT-2490859.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID1491870.

Family and domain databases

Gene3D1.10.150.180. 1 hit.
1.10.375.10. 1 hit.
4.10.60.10. 1 hit.
InterProIPR000840. G_retro_matrix_N.
IPR002079. Gag_p12.
IPR003036. Gag_P30.
IPR008919. Retrov_capsid_N.
IPR010999. Retrovr_matrix_N.
IPR001878. Znf_CCHC.
[Graphical view]
PfamPF01140. Gag_MA. 1 hit.
PF01141. Gag_p12. 1 hit.
PF02093. Gag_p30. 1 hit.
PF00098. zf-CCHC. 1 hit.
[Graphical view]
SMARTSM00343. ZnF_C2HC. 1 hit.
[Graphical view]
SUPFAMSSF47836. SSF47836. 1 hit.
SSF47943. SSF47943. 1 hit.
SSF57756. SSF57756. 1 hit.
PROSITEPS50158. ZF_CCHC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP03332.

Entry information

Entry nameGAG_MLVMS
AccessionPrimary (citable) accession number: P03332
Secondary accession number(s): Q9WJP4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: February 19, 2014
This is version 123 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references