ID   GAG_XMRV6               Reviewed;         536 AA.
AC   Q27ID9;
DT   19-JAN-2010, integrated into UniProtKB/Swiss-Prot.
DT   04-APR-2006, sequence version 1.
DT   27-MAR-2024, entry version 77.
DE   RecName: Full=Gag polyprotein;
DE            Short=Pr65gag;
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;
DE              Short=NC-gag;
GN   Name=gag;
OS   Xenotropic MuLV-related virus (isolate VP62) (XMRV).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Gammaretrovirus;
OC   Murine leukemia-related retroviruses.
OX   NCBI_TaxID=373193;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND RETRACTED PAPER.
RX   PubMed=16609730; DOI=10.1371/journal.ppat.0020025;
RA   Urisman A., Molinaro R.J., Fischer N., Plummer S.J., Casey G., Klein E.A.,
RA   Malathi K., Magi-Galluzzi C., Tubbs R.R., Ganem D., Silverman R.H.,
RA   DeRisi J.L.;
RT   "Identification of a novel Gammaretrovirus in prostate tumors of patients
RT   homozygous for R462Q RNASEL variant.";
RL   PLoS Pathog. 2:E25-E25(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=17234809; DOI=10.1073/pnas.0610291104;
RA   Dong B., Kim S., Hong S., Das Gupta J., Malathi K., Klein E.A., Ganem D.,
RA   Derisi J.L., Chow S.A., Silverman R.H.;
RT   "An infectious retrovirus susceptible to an IFN antiviral pathway from
RT   human prostate tumors.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1655-1660(2007).
RN   [3]
RP   RETRACTION NOTICE OF PUBMED:16609730.
RX   PubMed=23028303;
RX   DOI=10.1371/annotation/7e2efc01-2e9b-4e9b-aef0-87ab0e4e4732;
RA   Urisman A., Molinaro R.J., Fischer N., Plummer S.J., Casey G., Klein E.A.,
RA   Malathi K., Magi-Galluzzi C., Tubbs R.R., Ganem D., Silverman R.H.,
RA   DeRisi J.L.;
RL   PLoS Pathog. 8:0-0(2012).
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 link the viral protein to the host ESCRT pathway and
CC       facilitate 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: [Capsid protein p30]: Forms the spherical core of the virion
CC       that encapsulates the genomic RNA-nucleocapsid complex.
CC       {ECO:0000250|UniProtKB:P03336}.
CC   -!- FUNCTION: [Nucleocapsid protein p10]: Involved in the packaging and
CC       encapsidation of two copies of the genome (By similarity). Binds with
CC       high affinity to conserved UCUG elements within the packaging signal,
CC       located near the 5'-end of the genome (By similarity). This binding is
CC       dependent on genome dimerization (By similarity). Acts as a nucleic
CC       acid chaperone which is involved in rearrangement of nucleic acid
CC       secondary structures during gRNA retrotranscription (By similarity).
CC       {ECO:0000250|UniProtKB:P03332, ECO:0000250|UniProtKB:P03355}.
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. The virus core is composed of a lattice formed from
CC       hexagonal rings, each containing six capsid monomers.
CC       {ECO:0000250|UniProtKB:P03332}.
CC   -!- SUBCELLULAR LOCATION: [Gag polyprotein]: Virion {ECO:0000250}. Host
CC       cell membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}. Host late
CC       endosome membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}. Host
CC       endosome, host multivesicular body {ECO:0000250}. Note=These locations
CC       are probably linked to virus assembly sites. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Matrix protein p15]: Virion {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Capsid protein p30]: Virion {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: [Nucleocapsid protein p10]: Virion {ECO:0000305}.
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]: 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: RNA-binding phosphoprotein p12 is phosphorylated on serine
CC       residues. {ECO:0000250}.
CC   -!- CAUTION: Originally thought to be characterized from prostate tumors,
CC       the described gammaretrovirus XMRV is in fact laboratory-derived and
CC       there is no association of XMRV with prostate cancer.
CC       {ECO:0000305|PubMed:16609730, ECO:0000305|PubMed:23028303}.
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DR   EMBL; DQ399707; ABD49686.1; -; Genomic_RNA.
DR   EMBL; EF185282; ABM47427.1; -; Genomic_RNA.
DR   SMR; Q27ID9; -.
DR   ELM; Q27ID9; -.
DR   Proteomes; UP000002240; Genome.
DR   Proteomes; UP000180675; Genome.
DR   GO; GO:0044185; C:host cell late endosome membrane; IEA:UniProtKB-SubCell.
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: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   3: Inferred from homology;
KW   Capsid protein; Coiled coil; Host cell membrane; Host endosome;
KW   Host membrane; Host-virus interaction; Lipoprotein; Membrane;
KW   Metal-binding; Myristate; Phosphoprotein; Reference proteome; RNA-binding;
KW   Viral budding; Viral budding via the host ESCRT complexes;
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:0000250"
FT   CHAIN           2..536
FT                   /note="Gag polyprotein"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000390845"
FT   CHAIN           2..129
FT                   /note="Matrix protein p15"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000390846"
FT   CHAIN           130..213
FT                   /note="RNA-binding phosphoprotein p12"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000390847"
FT   CHAIN           214..476
FT                   /note="Capsid protein p30"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000390848"
FT   CHAIN           477..536
FT                   /note="Nucleocapsid protein p10"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000390849"
FT   ZN_FING         500..517
FT                   /note="CCHC-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00047"
FT   REGION          108..218
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          449..469
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          481..500
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          508..536
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          436..476
FT                   /evidence="ECO:0000255"
FT   MOTIF           109..112
FT                   /note="PTAP/PSAP motif"
FT   MOTIF           128..132
FT                   /note="LYPX(n)L motif"
FT   MOTIF           161..164
FT                   /note="PPXY motif"
FT   COMPBIAS        108..123
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        164..190
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        486..500
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            129..130
FT                   /note="Cleavage; by viral protease p14"
FT                   /evidence="ECO:0000250"
FT   SITE            213..214
FT                   /note="Cleavage; by viral protease p14"
FT                   /evidence="ECO:0000250"
FT   SITE            476..477
FT                   /note="Cleavage; by viral protease p14"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         190
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000250"
FT   LIPID           2
FT                   /note="N-myristoyl glycine; by host"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   536 AA;  60446 MW;  63CD1FB1561E0836 CRC64;
     MGQTVTTPLS LTLQHWGDVQ RIASNQSVDV KKRRWVTFCS AEWPTFNVGW PQDGTFNLGV
     ISQVKSRVFC PGPHGHPDQV PYIVTWEALA YDPPPWVKPF VSPKPPPLPT APVLPPGPSA
     QPPSRSALYP ALTPSIKSKP PKPQVLPDSG GPLIDLLTED PPPYGAQPSS SARENNEEEA
     ATTSEVSPPS PMVSRLRGRR DPPAADSTTS QAFPLRMGGD GQLQYWPFSS SDLYNWKNNN
     PSFSEDPGKL TALIESVLIT HQPTWDDCQQ LLGTLLTGEE KQRVLLEARK AVRGNDGRPT
     QLPNEVNAAF PLERPDWDYT TTEGRNHLVL YRQLLLAGLQ NAGRSPTNLA KVKGITQGPN
     ESPSAFLERL KEAYRRYTPY DPEDPGQETN VSMSFIWQSA PDIGRKLERL EDLKSKTLGD
     LVREAEKIFN KRETPEEREE RIRREIEEKE ERRRAEDEQR ERERDRRRHR EMSKLLATVV
     IGQRQDRQGG ERRRPQLDKD QCAYCKEKGH WAKDCPKKPR GPRGPRPQTS LLTLGD
//