ID   GAG_MLVAV               Reviewed;         537 AA.
AC   P03336;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   27-MAR-2024, entry version 137.
DE   RecName: Full=Gag polyprotein;
DE   AltName: Full=Core polyprotein;
DE   Contains:
DE     RecName: Full=Matrix protein p15;
DE              Short=MA;
DE   Contains:
DE     RecName: Full=RNA-binding phosphoprotein p12;
DE     AltName: Full=pp12;
DE   Contains:
DE     RecName: Full=Capsid protein p30;
DE              Short=CA;
DE   Contains:
DE     RecName: Full=Nucleocapsid protein p10-gag;
DE              Short=NC-gag;
GN   Name=gag;
OS   AKV murine leukemia virus (AKR (endogenous) murine leukemia virus).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Gammaretrovirus;
OC   Murine leukemia virus.
OX   NCBI_TaxID=11791;
OH   NCBI_TaxID=10090; Mus musculus (Mouse).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=6319746; DOI=10.1128/jvi.49.2.471-478.1984;
RA   Herr W.;
RT   "Nucleotide sequence of AKV murine leukemia virus.";
RL   J. Virol. 49:471-478(1984).
RN   [2]
RP   SUBUNIT (CAPSID PROTEIN P30).
RX   PubMed=17223564; DOI=10.1016/j.micron.2006.11.007;
RA   Nermut M.V., Mulloy B.;
RT   "Consideration of the three-dimensional structure of core shells (capsids)
RT   in spherical retroviruses.";
RL   Micron 38:462-470(2007).
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 215-345, AND SUBUNIT (CAPSID
RP   PROTEIN P30).
RX   PubMed=15386017; DOI=10.1038/nature02915;
RA   Mortuza G.B., Haire L.F., Stevens A., Smerdon S.J., Stoye J.P.,
RA   Taylor I.A.;
RT   "High-resolution structure of a retroviral capsid hexameric amino-terminal
RT   domain.";
RL   Nature 431:481-485(2004).
CC   -!- FUNCTION: [Gag polyprotein]: Plays a role in budding and is processed
CC       by the viral protease during virion maturation outside the cell. During
CC       budding, it recruits, in a PPXY-dependent or independent manner, Nedd4-
CC       like ubiquitin ligases that conjugate ubiquitin molecules to Gag, or to
CC       Gag binding host factors. Interaction with HECT ubiquitin ligases
CC       probably links the viral protein to the host ESCRT pathway and
CC       facilitates release. {ECO:0000250|UniProtKB:P03332}.
CC   -!- FUNCTION: [Matrix protein p15]: Targets Gag and gag-pol polyproteins to
CC       the plasma membrane via a multipartite membrane binding signal, that
CC       includes its myristoylated N-terminus. Also mediates nuclear
CC       localization of the pre-integration complex.
CC       {ECO:0000250|UniProtKB:P03332}.
CC   -!- FUNCTION: [RNA-binding phosphoprotein p12]: Constituent of the pre-
CC       integration complex (PIC) which tethers the latter to mitotic
CC       chromosomes. {ECO:0000250|UniProtKB:P03332}.
CC   -!- FUNCTION: [Capsid protein p30]: Forms the spherical core of the virion
CC       that encapsulates the genomic RNA-nucleocapsid complex.
CC       {ECO:0000250|UniProtKB:P03332}.
CC   -!- FUNCTION: [Nucleocapsid protein p10-gag]: Involved in the packaging and
CC       encapsidation of two copies of the genome. Binds with high affinity to
CC       conserved UCUG elements within the packaging signal, located near the
CC       5'-end of the genome. This binding is dependent on genome dimerization.
CC       {ECO:0000250|UniProtKB:P03332}.
CC   -!- SUBUNIT: [Gag polyprotein]: Interacts (via PPXY motif) with host NEDD4
CC       (By similarity). Interacts (via PSAP motif) with host TSG101 (By
CC       similarity). Interacts (via LYPX(n)L motif) with host PDCD6IP (By
CC       similarity). {ECO:0000250|UniProtKB:P03332}.
CC   -!- SUBUNIT: [Capsid protein p30]: Homohexamer. Further associates as
CC       homomultimer (PubMed:15386017, PubMed:17223564). The virus core is
CC       composed of a lattice formed from hexagonal rings, each containing six
CC       capsid monomers (PubMed:15386017, PubMed:17223564). Interacts with
CC       mouse UBE2I and mouse PIAS4 (By similarity).
CC       {ECO:0000250|UniProtKB:P03332, ECO:0000269|PubMed:15386017,
CC       ECO:0000269|PubMed:17223564}.
CC   -!- SUBCELLULAR LOCATION: [Gag polyprotein]: Virion
CC       {ECO:0000250|UniProtKB:P03332}. Host cell membrane
CC       {ECO:0000250|UniProtKB:P03332}; Lipid-anchor
CC       {ECO:0000250|UniProtKB:P03332}. Host endosome, host multivesicular body
CC       {ECO:0000250|UniProtKB:P26807}.
CC   -!- SUBCELLULAR LOCATION: [Matrix protein p15]: Virion
CC       {ECO:0000250|UniProtKB:P03332}.
CC   -!- SUBCELLULAR LOCATION: [Capsid protein p30]: Virion
CC       {ECO:0000250|UniProtKB:P03332}.
CC   -!- SUBCELLULAR LOCATION: [Nucleocapsid protein p10-gag]: Virion
CC       {ECO:0000250|UniProtKB:P03332}.
CC   -!- SUBCELLULAR LOCATION: [RNA-binding phosphoprotein p12]: Host cytoplasm
CC       {ECO:0000250|UniProtKB:P03332}. Note=Localizes to the host cytoplasm
CC       early in infection and binds to the mitotic chromosomes later on.
CC       {ECO:0000250|UniProtKB:P03332}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=Gag polyprotein;
CC         IsoId=P03336-1; Sequence=Displayed;
CC       Name=Glyco-Gag protein;
CC         IsoId=P0DOG8-1; Sequence=External;
CC   -!- DOMAIN: [Gag polyprotein]: Late-budding domains (L domains) are short
CC       sequence motifs essential for viral particle budding. They recruit
CC       proteins of the host ESCRT machinery (Endosomal Sorting Complex
CC       Required for Transport) or ESCRT-associated proteins. RNA-binding
CC       phosphoprotein p12 contains one L domain: a PPXY motif which interacts
CC       with the WW domain 3 of NEDD4 E3 ubiquitin ligase. PPXY motif is
CC       essential for virus egress. Matrix protein p15 contains one L domain: a
CC       PTAP/PSAP motif, which interacts with the UEV domain of TSG101. The
CC       junction between the matrix protein p15 and RNA-binding phosphoprotein
CC       p12 also contains one L domain: a LYPX(n)L motif which interacts with
CC       PDCD6IP. Both PSAP and LYPX(n)L domains might play little to no role in
CC       budding and possibly drive residual virus release.
CC       {ECO:0000250|UniProtKB:P03332}.
CC   -!- PTM: [Gag polyprotein]: Ubiquitinated by ITCH. Gag can recruit the
CC       ubiquitin ligase Itch in an L domain-independent manner to facilitate
CC       virus release via a mechanism that involves Gag ubiquitination.
CC       {ECO:0000250|UniProtKB:P03332}.
CC   -!- PTM: [Gag polyprotein]: Specific enzymatic cleavages by the viral
CC       protease yield mature proteins. The protease is released by
CC       autocatalytic cleavage. The polyprotein is cleaved during and after
CC       budding, this process is termed maturation.
CC       {ECO:0000250|UniProtKB:P03332}.
CC   -!- PTM: [Capsid protein p30]: Sumoylated; required for virus replication.
CC       {ECO:0000250|UniProtKB:P03332}.
CC   -!- PTM: RNA-binding phosphoprotein p12 is phosphorylated on serine
CC       residues. {ECO:0000250|UniProtKB:P03332}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; J01998; AAB03090.1; -; Genomic_RNA.
DR   PIR; A03933; FOMVGV.
DR   PDB; 1U7K; X-ray; 1.85 A; A/B/C/D/E/F=215-345.
DR   PDB; 2Y4Z; X-ray; 2.00 A; A=215-346.
DR   PDB; 3BP9; X-ray; 2.60 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/X/Y=215-346.
DR   PDB; 6HWW; EM; 6.60 A; A/B/C=230-450.
DR   PDB; 6HWX; EM; 7.20 A; A/B/C=215-450.
DR   PDB; 6HWY; EM; 8.60 A; A/B/C/D=215-450.
DR   PDBsum; 1U7K; -.
DR   PDBsum; 2Y4Z; -.
DR   PDBsum; 3BP9; -.
DR   PDBsum; 6HWW; -.
DR   PDBsum; 6HWX; -.
DR   PDBsum; 6HWY; -.
DR   SMR; P03336; -.
DR   IntAct; P03336; 1.
DR   MINT; P03336; -.
DR   EvolutionaryTrace; P03336; -.
DR   Proteomes; UP000008875; Genome.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0072494; C:host multivesicular body; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0039660; F:structural constituent of virion; IEA:UniProtKB-KW.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0039702; P:viral budding via host ESCRT complex; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.150.180; Gamma-retroviral matrix domain; 1.
DR   Gene3D; 1.10.375.10; Human Immunodeficiency Virus Type 1 Capsid Protein; 1.
DR   Gene3D; 4.10.60.10; Zinc finger, CCHC-type; 1.
DR   InterPro; IPR000840; G_retro_matrix.
DR   InterPro; IPR036946; G_retro_matrix_sf.
DR   InterPro; IPR002079; Gag_p12.
DR   InterPro; IPR003036; Gag_P30.
DR   InterPro; IPR008919; Retrov_capsid_N.
DR   InterPro; IPR010999; Retrovr_matrix.
DR   InterPro; IPR001878; Znf_CCHC.
DR   InterPro; IPR036875; Znf_CCHC_sf.
DR   PANTHER; PTHR33166:SF1; CORE SHELL PROTEIN GAG P30 DOMAIN-CONTAINING PROTEIN; 1.
DR   PANTHER; PTHR33166; GAG_P30 DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF01140; Gag_MA; 1.
DR   Pfam; PF01141; Gag_p12; 1.
DR   Pfam; PF02093; Gag_p30; 1.
DR   Pfam; PF00098; zf-CCHC; 1.
DR   SMART; SM00343; ZnF_C2HC; 1.
DR   SUPFAM; SSF47836; Retroviral matrix proteins; 1.
DR   SUPFAM; SSF47943; Retrovirus capsid protein, N-terminal core domain; 1.
DR   SUPFAM; SSF57756; Retrovirus zinc finger-like domains; 1.
DR   PROSITE; PS50158; ZF_CCHC; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative initiation; Capsid protein; Coiled coil;
KW   Host cell membrane; Host cytoplasm; Host endosome; Host membrane;
KW   Host-virus interaction; Lipoprotein; Membrane; Metal-binding; Myristate;
KW   Phosphoprotein; RNA-binding; Ubl conjugation; Viral budding;
KW   Viral budding via the host ESCRT complexes; Viral matrix protein;
KW   Viral nucleoprotein; Viral release from host cell; Virion; Zinc;
KW   Zinc-finger.
FT   INIT_MET        1
FT                   /note="Removed; by host"
FT                   /evidence="ECO:0000255"
FT   CHAIN           2..537
FT                   /note="Gag polyprotein"
FT                   /id="PRO_0000390806"
FT   CHAIN           2..129
FT                   /note="Matrix protein p15"
FT                   /id="PRO_0000040876"
FT   CHAIN           130..214
FT                   /note="RNA-binding phosphoprotein p12"
FT                   /id="PRO_0000040877"
FT   CHAIN           215..477
FT                   /note="Capsid protein p30"
FT                   /id="PRO_0000040878"
FT   CHAIN           478..537
FT                   /note="Nucleocapsid protein p10-gag"
FT                   /id="PRO_0000040879"
FT   ZN_FING         501..518
FT                   /note="CCHC-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT   REGION          107..217
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          344..392
FT                   /note="Interaction with host PIAS4"
FT                   /evidence="ECO:0000250|UniProtKB:P03332"
FT   REGION          429..434
FT                   /note="Interaction with host UBE2I"
FT                   /evidence="ECO:0000250|UniProtKB:P03332"
FT   REGION          434..537
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          437..478
FT                   /evidence="ECO:0000255"
FT   MOTIF           109..112
FT                   /note="PTAP/PSAP motif"
FT                   /evidence="ECO:0000250|UniProtKB:P03332"
FT   MOTIF           128..132
FT                   /note="LYPX(n)L motif"
FT                   /evidence="ECO:0000250|UniProtKB:P03332"
FT   MOTIF           161..164
FT                   /note="PPXY motif"
FT                   /evidence="ECO:0000250|UniProtKB:P03332"
FT   COMPBIAS        107..129
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        434..475
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        487..522
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            129..130
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000250|UniProtKB:P03332"
FT   SITE            214..215
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000250|UniProtKB:P03332"
FT   SITE            477..478
FT                   /note="Cleavage; by viral protease"
FT                   /evidence="ECO:0000250|UniProtKB:P03332"
FT   MOD_RES         191
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:P03332"
FT   LIPID           2
FT                   /note="N-myristoyl glycine; by host"
FT                   /evidence="ECO:0000255"
FT   STRAND          216..218
FT                   /evidence="ECO:0007829|PDB:1U7K"
FT   STRAND          222..226
FT                   /evidence="ECO:0007829|PDB:1U7K"
FT   HELIX           231..239
FT                   /evidence="ECO:0007829|PDB:1U7K"
FT   TURN            244..246
FT                   /evidence="ECO:0007829|PDB:1U7K"
FT   HELIX           248..261
FT                   /evidence="ECO:0007829|PDB:1U7K"
FT   HELIX           266..276
FT                   /evidence="ECO:0007829|PDB:1U7K"
FT   HELIX           279..291
FT                   /evidence="ECO:0007829|PDB:1U7K"
FT   STRAND          298..300
FT                   /evidence="ECO:0007829|PDB:1U7K"
FT   HELIX           304..310
FT                   /evidence="ECO:0007829|PDB:1U7K"
FT   HELIX           323..344
FT                   /evidence="ECO:0007829|PDB:1U7K"
SQ   SEQUENCE   537 AA;  60558 MW;  D35C4AD89B17CF93 CRC64;
     MGQTVTTPLS LTLEHWEDVQ RIASNQSVDV KKRRWVTFCS AEWPTFGVGW PQDGTFNLDI
     ILQVKSKVFS PGPHGHPDQV PYIVTWEAIA YEPPPWVKPF VSPKLSPSPT APILPSGPST
     QPPPRSALYP ALTPSIKPRP SKPQVLSDNG GPLIDLLSED PPPYGGQGLS SSDGDGDREE
     ATSTSEIPAP SPIVSRLRGK RDPPAADSTT SRAFPLRLGG NGQLQYWPFS SSDLYNWKNN
     NPSFSEDPGK LTALIESVLT THQPTWDDCQ QLLGTLLTGE EKQRVLLEAR KAVRGNDGRP
     TQLPNEVDAA FPLERPDWDY TTQRGRNHLV LYRQLLLAGL QNAGRSPTNL AKVKGITQGP
     NESPSAFLER LKEAYRRYTP YDPEDPGQET NVSMSFIWQS APDIGRKLER LEDLKSKTLG
     DLVREAERIF NKRETPEERE ERVRRETEEK EERRRAEEEQ KEKERDRRRH REMSKLLATV
     VSGQRQDRQG GERRRPQLDK DQCAYCKEKG HWAKDCPKKP RGPRGPRPQT SLLTLDD
//