ID   VPX_HV2G1               Reviewed;         112 AA.
AC   P18045;
DT   01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1990, sequence version 1.
DT   25-MAY-2022, 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 Ghana-1) (HIV-2).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=11717;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2611042; DOI=10.1089/aid.1989.5.593;
RA   Hasegawa A., Tsujimoto H., Maki N., Ishikawa K., Miura T., Fukasawa M.,
RA   Miki K., Hayami M.;
RT   "Genomic divergence of HIV-2 from Ghana.";
RL   AIDS Res. Hum. Retroviruses 5:593-604(1989).
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. Targets specific host proteins for degradation by
CC       the 26S proteasome. Acts by associating with the cellular CUL4A-DDB1 E3
CC       ligase complex through direct interaction with host VPRPB/DCAF-1. This
CC       change in the E3 ligase substrate specificity results in the
CC       degradation of host SAMHD1. In turn, SAMHD1 depletion allows viral
CC       replication in host myeloid cells by preventing SAMHD1-mediated
CC       hydrolysis of intracellular dNTPs necessary for reverse transcription
CC       (By similarity). {ECO:0000250}.
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 (By
CC       similarity). Interacts with host NUP153 (By similarity). {ECO:0000250,
CC       ECO:0000250|UniProtKB:P12454, ECO:0000250|UniProtKB:P18099}.
CC   -!- INTERACTION:
CC       P18045; P18045: vpx; NbExp=5; IntAct=EBI-6558105, EBI-6558105;
CC       P18045; Q9Y4B6: DCAF1; Xeno; NbExp=2; IntAct=EBI-6558105, EBI-1996353;
CC       P18045; Q16531: DDB1; Xeno; NbExp=2; IntAct=EBI-6558105, EBI-350322;
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   -!- SIMILARITY: Belongs to the lentivirus VPX protein family.
CC       {ECO:0000305}.
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DR   EMBL; M30895; AAA43935.1; -; Genomic_DNA.
DR   PIR; JS0330; ASLJGH.
DR   SMR; P18045; -.
DR   IntAct; P18045; 2.
DR   MINT; P18045; -.
DR   Proteomes; UP000007424; Genome.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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.
DR   PRINTS; PR00444; HIVVPRVPX.
PE   1: Evidence at protein level;
KW   AIDS; Host nucleus; Host-virus interaction;
KW   Inhibition of host innate immune response by virus; Viral immunoevasion;
KW   Virion.
FT   CHAIN           1..112
FT                   /note="Protein Vpx"
FT                   /id="PRO_0000085393"
FT   REGION          61..80
FT                   /note="Binds to human NUP153"
FT                   /evidence="ECO:0000250|UniProtKB:P19508"
FT   MOTIF           65..72
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   112 AA;  12820 MW;  70998DF097DAA579 CRC64;
     MTDPRERVPP GNSGEETIGE AFEWLDRTIE ALNREAVNHL PRELIFQVWQ RSWRYWHDDQ
     GMSPSYTKYR YLCLMQKAVF IHFKRGCTCL GGGHGPGGWR SGPPPPPPPG LV