ID   VPX_HV2NZ               Reviewed;         112 AA.
AC   P05915;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   29-SEP-2021, entry version 63.
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 NIH-Z) (HIV-2).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=11719;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3261862; DOI=10.1073/pnas.85.16.5941;
RA   Zagury J.F., Franchini G., Reitz M.S. Jr., Collalti E., Starcich B.R.,
RA   Hall L., Fargnoli K.A., Jagodzinski L.L., Guo H.-G., Laure F., Arya S.K.,
RA   Josephs S.F., Zagury D., Wong-Staal F., Gallo R.C.;
RT   "Genetic variability between isolates of human immunodeficiency virus (HIV)
RT   type 2 is comparable to the variability among HIV type 1.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:5941-5945(1988).
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   -!- SIMILARITY: Belongs to the lentivirus VPX protein family.
CC       {ECO:0000305}.
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DR   EMBL; J03654; AAB00757.1; -; Genomic_DNA.
DR   SMR; P05915; -.
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_0000085396"
FT   REGION          61..80
FT                   /note="Binds to human NUP153"
FT                   /evidence="ECO:0000250|UniProtKB:P19508"
FT   REGION          90..112
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           65..72
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   112 AA;  12760 MW;  4883EFC8FB296668 CRC64;
     MTDPRETVPP GNSGEETIEE AFAWLDRTVE AINREAVNHH PRELIFQVWQ RSWRYWHDEQ
     GMSTSYTKYR YLCLIQMAMY MHAKRDGTCL GGGMGQKGGD QGPPPPPPPG LV