VPX_HV2BE
ID VPX_HV2BE Reviewed; 113 AA.
AC P18099;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 29-SEP-2021, entry version 77.
DE RecName: Full=Protein Vpx;
DE AltName: Full=Viral protein X;
DE AltName: Full=X ORF protein;
GN Name=vpx;
OS Human immunodeficiency virus type 2 subtype A (isolate BEN) (HIV-2).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11714;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2353457; DOI=10.1016/0042-6822(90)90484-9;
RA Kirchhoff F., Jentsch K., Bachmann B., Stuke A., Laloux C., Lueke W.,
RA Stahl-Henning C., Schneider J., Nieselt K., Eigen M., Hunsmann G.;
RT "A novel proviral clone of HIV-2: biological and phylogenetic relationship
RT to other primate immunodeficiency viruses.";
RL Virology 177:305-311(1990).
RN [2]
RP FUNCTION, INTERACTION WITH HOST DCAF1, AND MUTAGENESIS OF GLN-76.
RC STRAIN=Isolate GH-1;
RX PubMed=19264781; DOI=10.1128/jvi.00187-09;
RA Bergamaschi A., Ayinde D., David A., Le Rouzic E., Morel M., Collin G.,
RA Descamps D., Damond F., Brun-Vezinet F., Nisole S., Margottin-Goguet F.,
RA Pancino G., Transy C.;
RT "The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1
RT DCAF1 ubiquitin ligase to overcome a postentry block in macrophage
RT infection.";
RL J. Virol. 83:4854-4860(2009).
RN [3]
RP REVIEW.
RX PubMed=22422971; DOI=10.1126/science.1221057;
RA Schaller T., Goujon C., Malim M.H.;
RT "AIDS/HIV. HIV interplay with SAMHD1.";
RL Science 335:1313-1314(2012).
RN [4]
RP FUNCTION.
RX PubMed=21613998; DOI=10.1038/nature10117;
RA Laguette N., Sobhian B., Casartelli N., Ringeard M., Chable-Bessia C.,
RA Segeral E., Yatim A., Emiliani S., Schwartz O., Benkirane M.;
RT "SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction
RT factor counteracted by Vpx.";
RL Nature 474:654-657(2011).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF GLN-76.
RX PubMed=21720370; DOI=10.1038/nature10195;
RA Hrecka K., Hao C., Gierszewska M., Swanson S.K., Kesik-Brodacka M.,
RA Srivastava S., Florens L., Washburn M.P., Skowronski J.;
RT "Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the
RT SAMHD1 protein.";
RL Nature 474:658-661(2011).
RN [6]
RP FUNCTION.
RX PubMed=22973040; DOI=10.1128/jvi.01657-12;
RA Hofmann H., Logue E.C., Bloch N., Daddacha W., Polsky S.B., Schultz M.L.,
RA Kim B., Landau N.R.;
RT "The Vpx lentiviral accessory protein targets SAMHD1 for degradation in the
RT nucleus.";
RL J. Virol. 86:12552-12560(2012).
CC -!- FUNCTION: Plays a role in nuclear translocation of the viral pre-
CC integration complex (PIC), thus is required for the virus to infect
CC non-dividing cells (PubMed:19264781, PubMed:21613998, PubMed:21720370,
CC PubMed:22973040). Targets specific host proteins for degradation by the
CC 26S proteasome (PubMed:19264781, PubMed:21613998, PubMed:21720370,
CC PubMed:22973040). Acts by associating with the cellular CUL4A-DDB1 E3
CC ligase complex through direct interaction with host VPRPB/DCAF-1
CC (PubMed:19264781, PubMed:21613998, PubMed:21720370, PubMed:22973040).
CC This change in the E3 ligase substrate specificity results in the
CC degradation of host SAMHD1 (PubMed:19264781, PubMed:21613998,
CC PubMed:21720370, PubMed:22973040). In turn, SAMHD1 depletion allows
CC viral replication in host myeloid cells by preventing SAMHD1-mediated
CC hydrolysis of intracellular dNTPs necessary for reverse transcription
CC (PubMed:19264781, PubMed:21613998, PubMed:21720370, PubMed:22973040).
CC {ECO:0000269|PubMed:19264781, ECO:0000269|PubMed:21613998,
CC ECO:0000269|PubMed:21720370, ECO:0000269|PubMed:22973040}.
CC -!- SUBUNIT: Interacts with the P6 region of unprocessed GAG (By
CC similarity). Interacts with host VPRBP/DCAF1, leading to change
CC substrate specificity of the CUL4A-DDB1 E3 ligase complex
CC (PubMed:19264781). Interacts with host NUP153 (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P12454,
CC ECO:0000269|PubMed:19264781}.
CC -!- SUBCELLULAR LOCATION: Virion. Host nucleus. Note=Nuclear just after
CC virion uncoating, or if expressed in the absence of unprocessed GAG.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: This isolate is from a German AIDS patient (with
CC predominantly neurological complications) who was probably infected in
CC Mali.
CC -!- SIMILARITY: Belongs to the lentivirus VPX protein family.
CC {ECO:0000305}.
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DR EMBL; M30502; AAB00739.1; -; Genomic_DNA.
DR RefSeq; NP_056840.1; NC_001722.1.
DR SMR; P18099; -.
DR BioGRID; 1205550; 38.
DR PRIDE; P18099; -.
DR GeneID; 1724714; -.
DR KEGG; vg:1724714; -.
DR Proteomes; UP000002242; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0019058; P:viral life cycle; IEA:InterPro.
DR InterPro; IPR000012; RetroV_VpR/X.
DR Pfam; PF00522; VPR; 1.
PE 1: Evidence at protein level;
KW AIDS; Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus; Reference proteome;
KW Viral immunoevasion; Virion.
FT CHAIN 1..113
FT /note="Protein Vpx"
FT /id="PRO_0000085390"
FT REGION 61..80
FT /note="Binds to human NUP153"
FT /evidence="ECO:0000250|UniProtKB:P19508"
FT REGION 94..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 65..72
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MUTAGEN 76
FT /note="Q->LYS: Complete loss of interaction with host
FT DCAF1."
FT /evidence="ECO:0000269|PubMed:19264781,
FT ECO:0000269|PubMed:21720370"
SQ SEQUENCE 113 AA; 13208 MW; 2C18958819216B24 CRC64;
MTDPRERVPP GNSGEETIGE AFEWLERTIE ALNREAVNHL PRELIFQVWQ RSWRYWHDEQ
GMSASYTKYR YLCLMQKAIF THFKRGCTCW GEDMGREGLE DQGPPPPPPP GLV
