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Gag polyprotein (Pr65gag) (Core polyprotein) [Cleaved into: Matrix protein p15 (MA); RNA-binding phosphoprotein p12 (pp12); Capsid protein p30 (CA); Nucleocapsid protein p10-Gag (NC-gag)]

 GAG_MLVMS               Reviewed;         538 AA.
P03332; Q9WJP4;
21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
23-JAN-2007, sequence version 4.
08-MAY-2019, entry version 144.
RecName: Full=Gag polyprotein;
Short=Pr65gag;
AltName: Full=Core polyprotein;
Contains:
RecName: Full=Matrix protein p15;
Short=MA;
Contains:
RecName: Full=RNA-binding phosphoprotein p12;
AltName: Full=pp12;
Contains:
RecName: Full=Capsid protein p30;
Short=CA;
Contains:
RecName: Full=Nucleocapsid protein p10-Gag;
Short=NC-gag;
Name=gag;
Moloney murine leukemia virus (isolate Shinnick) (MoMLV).
Viruses; Ortervirales; Retroviridae; Orthoretrovirinae;
Gammaretrovirus; Murine leukemia virus.
NCBI_TaxID=928306;
NCBI_TaxID=10090; Mus musculus (Mouse).
[1]
NUCLEOTIDE SEQUENCE [GENOMIC RNA] (CLONE PMLV-1).
PubMed=6169994; DOI=10.1038/293543a0;
Shinnick T.M., Lerner R.A., Sutcliffe J.G.;
"Nucleotide sequence of Moloney murine leukaemia virus.";
Nature 293:543-548(1981).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Chappey C.;
Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
[3]
PROTEIN SEQUENCE OF 2-31, AND MYRISTOYLATION AT GLY-2.
PubMed=6340098; DOI=10.1073/pnas.80.2.339;
Henderson L.E., Krutzsch H.C., Oroszlan S.;
"Myristyl amino-terminal acylation of murine retrovirus proteins: an
unusual post-translational proteins modification.";
Proc. Natl. Acad. Sci. U.S.A. 80:339-343(1983).
[4]
PROTEIN SEQUENCE OF 479-529.
PubMed=6267042;
Henderson L.E., Copeland T.D., Sowder R.C., Smythers G.W.,
Oroszlan S.;
"Primary structure of the low molecular weight nucleic acid-binding
proteins of murine leukemia viruses.";
J. Biol. Chem. 256:8400-8406(1981).
[5]
SUBCELLULAR LOCATION (GAG POLYPROTEIN).
PubMed=8991095;
Suomalainen M., Hultenby K., Garoff H.;
"Targeting of Moloney murine leukemia virus gag precursor to the site
of virus budding.";
J. Cell Biol. 135:1841-1852(1996).
[6]
SUBUNIT (CAPSID PROTEIN P30).
PubMed=12093170;
Mayo K., McDermott J., Barklis E.;
"Hexagonal organization of Moloney murine leukemia virus capsid
proteins.";
Virology 298:30-38(2002).
[7]
PHOSPHORYLATION AT SER-192, AND MUTAGENESIS OF SER-137; SER-148;
SER-150; SER-192; SER-196; SER-209 AND SER-212.
PubMed=12525616; DOI=10.1128/JVI.77.3.1820-1829.2003;
Yueh A., Goff S.P.;
"Phosphorylated serine residues and an arginine-rich domain of the
moloney murine leukemia virus p12 protein are required for early
events of viral infection.";
J. Virol. 77:1820-1829(2003).
[8]
INTERACTION WITH MOUSE NEDD4; TSG101 AND PDCD6IP/ALIX (GAG
POLYPROTEIN), AND MUTAGENESIS OF TYR-165.
PubMed=15908698; DOI=10.1074/jbc.M413735200;
Segura-Morales C., Pescia C., Chatellard-Causse C., Sadoul R.,
Bertrand E., Basyuk E.;
"Tsg101 and Alix interact with murine leukemia virus Gag and cooperate
with Nedd4 ubiquitin ligases during budding.";
J. Biol. Chem. 280:27004-27012(2005).
[9]
INTERACTION WITH UBE2I AND PIAS4 (CAPSID PROTEIN P30), AND SUMOYLATION
(CAPSID PROTEIN P30).
PubMed=16352559; DOI=10.1128/JVI.80.1.342-352.2006;
Yueh A., Leung J., Bhattacharyya S., Perrone L.A., de los Santos K.,
Pu S.-Y., Goff S.P.;
"Interaction of moloney murine leukemia virus capsid with Ubc9 and
PIASy mediates SUMO-1 addition required early in infection.";
J. Virol. 80:342-352(2006).
[10]
PROTEOLYTIC CLEAVAGE (GAG POLYPROTEIN).
PubMed=16603535; DOI=10.1099/vir.0.81382-0;
Feher A., Boross P., Sperka T., Miklossy G., Kadas J., Bagossi P.,
Oroszlan S., Weber I.T., Tozser J.;
"Characterization of the murine leukemia virus protease and its
comparison with the human immunodeficiency virus type 1 protease.";
J. Gen. Virol. 87:1321-1330(2006).
[11]
FUNCTION (RNA-BINDING PHOSPHOPROTEIN P12), AND SUBCELLULAR LOCATION
(RNA-BINDING PHOSPHOPROTEIN P12).
PubMed=21085616; DOI=10.1371/journal.ppat.1001183;
Prizan-Ravid A., Elis E., Laham-Karam N., Selig S., Ehrlich M.,
Bacharach E.;
"The Gag cleavage product, p12, is a functional constituent of the
murine leukemia virus pre-integration complex.";
PLoS Pathog. 6:E1001183-E1001183(2010).
[12]
DOMAIN LATE-BUDDING, FUNCTION (GAG POLYPROTEIN), AND UBIQUITINATION
(GAG POLYPROTEIN).
PubMed=19864377; DOI=10.1128/JVI.01319-09;
Jadwin J.A., Rudd V., Sette P., Challa S., Bouamr F.;
"Late domain-independent rescue of a release-deficient Moloney murine
leukemia virus by the ubiquitin ligase Itch.";
J. Virol. 84:704-715(2010).
[13]
FUNCTION (RNA-BINDING PHOSPHOPROTEIN P12), SUBCELLULAR LOCATION
(RNA-BINDING PHOSPHOPROTEIN P12), AND MUTAGENESIS OF SER-192 AND
SER-196.
PubMed=23300449; DOI=10.1371/journal.ppat.1003103;
Elis E., Ehrlich M., Prizan-Ravid A., Laham-Karam N., Bacharach E.;
"p12 tethers the murine leukemia virus pre-integration complex to
mitotic chromosomes.";
PLoS Pathog. 8:E1003103-E1003103(2012).
[14]
STRUCTURE BY NMR OF 492-531.
PubMed=8019131; DOI=10.1007/BF00175244;
Demene H., Jullian N., Morellet N., de Rocquigny H., Cornille F.,
Maigret B., Roques B.P.;
"Three-dimensional 1H NMR structure of the nucleocapsid protein NCp10
of Moloney murine leukemia virus.";
J. Biomol. NMR 4:153-170(1994).
[15]
STRUCTURE BY NMR OF 352-382.
PubMed=9799104; DOI=10.1046/j.1432-1327.1998.2570069.x;
Clish C.B., Peyton D.H., Barklis E.;
"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.";
Eur. J. Biochem. 257:69-77(1998).
[16]
X-RAY CRYSTALLOGRAPHY (1.0 ANGSTROMS) OF 1-99, AND FUNCTION (MATRIX
PROTEIN P15).
PubMed=12467570; DOI=10.1016/S0969-2126(02)00896-1;
Riffel N., Harlos K., Iourin O., Rao Z., Kingsman A., Stuart D.,
Fry E.;
"Atomic resolution structure of Moloney murine leukemia virus matrix
protein and its relationship to other retroviral matrix proteins.";
Structure 10:1627-1636(2002).
[17]
STRUCTURE BY NMR OF 479-534, FUNCTION (NUCLEOCAPSID PROTEIN P10-GAG),
AND RNA-BINDING (NUCLEOCAPSID PROTEIN P10-GAG).
PubMed=15457265; DOI=10.1038/nature02944;
D'Souza V., Summers M.F.;
"Structural basis for packaging the dimeric genome of Moloney murine
leukaemia virus.";
Nature 431:586-590(2004).
[18]
STRUCTURE BY NMR OF 479-534, AND RNA-BINDING (NUCLEOCAPSID PROTEIN
P10-GAG).
PubMed=15751950; DOI=10.1021/bi047639q;
Dey A., York D., Smalls-Mantey A., Summers M.F.;
"Composition and sequence-dependent binding of RNA to the nucleocapsid
protein of Moloney murine leukemia virus.";
Biochemistry 44:3735-3744(2005).
-!- 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 links the viral
protein to the host ESCRT pathway and facilitates release.
{ECO:0000269|PubMed:19864377}.
-!- FUNCTION: 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 pre-integration complex.
{ECO:0000305|PubMed:12467570}.
-!- FUNCTION: RNA-binding phosphoprotein p12: Constituent of the pre-
integration complex (PIC) which tethers the latter to mitotic
chromosomes. {ECO:0000269|PubMed:21085616,
ECO:0000269|PubMed:23300449}.
-!- FUNCTION: Capsid protein p30: Forms the spherical core of the
virion that encapsulates the genomic RNA-nucleocapsid complex.
{ECO:0000250|UniProtKB:P03336}.
-!- FUNCTION: Nucleocapsid protein p10-Gag: 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. {ECO:0000269|PubMed:15457265}.
-!- SUBUNIT: Capsid protein p30: Homohexamer; further associates as
homomultimer (By similarity). Capsid protein p30: The virus core
is composed of a lattice formed from hexagonal rings, each
containing six capsid monomers (PubMed:12093170). Capsid protein
p30: Interacts with mouse UBE2I and mouse PIAS4. Gag polyprotein:
Interacts (via PPXY motif) with host NEDD4 (PubMed:15908698). Gag
polyprotein: Interacts (via PSAP motif) with host TSG101
(PubMed:15908698). Gag polyprotein: Interacts (via LYPX(n)L motif)
with host PDCD6IP (PubMed:15908698).
{ECO:0000250|UniProtKB:P03336, ECO:0000269|PubMed:12093170,
ECO:0000269|PubMed:15908698, ECO:0000269|PubMed:16352559}.
-!- INTERACTION:
Q9QZK7:Dok3 (xeno); NbExp=3; IntAct=EBI-935477, EBI-2906753;
Q9JKF1:Iqgap1 (xeno); NbExp=17; IntAct=EBI-935477, EBI-644633;
-!- SUBCELLULAR LOCATION: Gag polyprotein: Virion {ECO:0000305}. Host
cell membrane {ECO:0000269|PubMed:8991095}; Lipid-anchor
{ECO:0000305}. Host late endosome membrane {ECO:0000305}; Lipid-
anchor {ECO:0000305}. Host endosome, host multivesicular body
{ECO:0000250|UniProtKB:P26807}. Note=These locations are probably
linked to virus assembly sites. {ECO:0000305}.
-!- SUBCELLULAR LOCATION: Matrix protein p15: Virion {ECO:0000305}.
-!- SUBCELLULAR LOCATION: Capsid protein p30: Virion {ECO:0000305}.
-!- SUBCELLULAR LOCATION: Nucleocapsid protein p10-Gag: Virion
{ECO:0000305}.
-!- SUBCELLULAR LOCATION: RNA-binding phosphoprotein p12: Host
cytoplasm {ECO:0000269|PubMed:21085616,
ECO:0000269|PubMed:23300449}. Note=Localizes to the host cytoplasm
early in infection and binds to the mitotic chromosomes later on.
{ECO:0000269|PubMed:23300449}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative initiation; Named isoforms=2;
Name=Pr65gag;
IsoId=P03332-1; Sequence=Displayed;
Name=Pr80gag; Synonyms=GlycoGag;
IsoId=P03332-2; Sequence=Not described;
Note=Produced by an upstream CUG initiation codon.
{ECO:0000305};
-!- DOMAIN: Gag polyprotein: 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.
{ECO:0000269|PubMed:19864377}.
-!- PTM: Gag polyprotein: 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. {ECO:0000269|PubMed:19864377}.
-!- PTM: Gag polyprotein: 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.
{ECO:0000269|PubMed:16603535}.
-!- PTM: Capsid protein p30: Sumoylated; required for virus
replication. {ECO:0000269|PubMed:16352559}.
-!- PTM: RNA-binding phosphoprotein p12 is phosphorylated on serine
residues. {ECO:0000269|PubMed:12525616}.
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EMBL; J02255; AAB59942.1; -; Genomic_RNA.
EMBL; AF033811; AAC82566.1; -; Genomic_RNA.
PIR; A03930; FOMV1M.
RefSeq; NP