ID   VPX_HV2D1               Reviewed;         112 AA.
AC   P17760;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   29-SEP-2021, entry version 68.
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 D194) (HIV-2).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=11713;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2467304; DOI=10.1073/pnas.86.7.2383;
RA   Kuehnel H., von Briesen H., Dietrich U., Adamski M., Mix D., Biesert L.,
RA   Kreutz R., Immelmann A., Henco K., Meichsner C., Andreesen R.,
RA   Gelderblom H., Ruebsamen-Waigmann H.;
RT   "Molecular cloning of two west African human immunodeficiency virus type 2
RT   isolates that replicate well in macrophages: a Gambian isolate, from a
RT   patient with neurologic acquired immunodeficiency syndrome, and a highly
RT   divergent Ghanian isolate.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:2383-2387(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2235509; DOI=10.1093/nar/18.20.6142;
RA   Kuehnel H., Kreutz R., Ruebsamen-Waigmann H.;
RT   "Nucleotide sequence of HIV-2D194, an isolate from a Gambian case of
RT   'neuro-AIDS', which showed excellent growth in macrophages.";
RL   Nucleic Acids Res. 18:6142-6142(1990).
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   -!- 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 Gambian case of 'neuro-AIDS'.
CC   -!- SIMILARITY: Belongs to the lentivirus VPX protein family.
CC       {ECO:0000305}.
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DR   EMBL; J04542; AAA76843.1; -; Genomic_DNA.
DR   EMBL; X52223; CAA36467.1; -; Genomic_DNA.
DR   PIR; S12155; S12155.
DR   SMR; P17760; -.
DR   Proteomes; UP000007422; 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   3: Inferred from homology;
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_0000085389"
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;  747AC8D908EA66B4 CRC64;
     MADPRERVPP GNSGEETIGE AFEWLDRTIE ALNREAVNHL PRELIFQVWQ RSWAYWHDEQ
     GMSTSYTKYR YLCIMQKAVY IHFKKGCTCL GRGHGPGGWR PGPPPPPPPG LV