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VPX_HV2RO
ID   VPX_HV2RO               Reviewed;         112 AA.
AC   P06939;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1988, sequence version 1.
DT   29-SEP-2021, entry version 72.
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 ROD) (HIV-2).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX   NCBI_TaxID=11720;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3031510; DOI=10.1038/326662a0;
RA   Guyader M., Emerman M., Sonigo P., Clavel F., Montagnier L., Alizon M.;
RT   "Genome organization and transactivation of the human immunodeficiency
RT   virus type 2.";
RL   Nature 326:662-669(1987).
RN   [2]
RP   INTERACTION WITH GAG.
RX   PubMed=11177390; DOI=10.1089/08892220150217193;
RA   Jin L., Zhou Y., Ratner L.;
RT   "HIV type 2 Vpx interaction with Gag and incorporation into virus-like
RT   particles.";
RL   AIDS Res. Hum. Retroviruses 17:105-111(2001).
RN   [3]
RP   NUCLEAR LOCALIZATION SIGNAL.
RX   PubMed=12832198; DOI=10.1016/s0042-6822(03)00093-x;
RA   Belshan M., Ratner L.;
RT   "Identification of the nuclear localization signal of human
RT   immunodeficiency virus type 2 Vpx.";
RL   Virology 311:7-15(2003).
RN   [4]
RP   FUNCTION.
RX   PubMed=16457868; DOI=10.1016/j.virol.2005.12.023;
RA   Mahnke L.A., Belshan M., Ratner L.;
RT   "Analysis of HIV-2 Vpx by modeling and insertional mutagenesis.";
RL   Virology 348:165-174(2006).
RN   [5]
RP   MUTAGENESIS OF 63-SER--SER-65 AND 66-TYR--TYR-71.
RX   PubMed=16325220; DOI=10.1016/j.virol.2005.10.036;
RA   Belshan M., Mahnke L.A., Ratner L.;
RT   "Conserved amino acids of the human immunodeficiency virus type 2 Vpx
RT   nuclear localization signal are critical for nuclear targeting of the viral
RT   preintegration complex in non-dividing cells.";
RL   Virology 346:118-126(2006).
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, ECO:0000269|PubMed:16457868}.
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   -!- SIMILARITY: Belongs to the lentivirus VPX protein family.
CC       {ECO:0000305}.
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DR   EMBL; M15390; AAB00766.1; -; Genomic_DNA.
DR   EMBL; X05291; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   PIR; I26262; ASLJX2.
DR   SMR; P06939; -.
DR   Proteomes; UP000007426; Genome.
DR   Proteomes; UP000246871; 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..112
FT                   /note="Protein Vpx"
FT                   /id="PRO_0000085397"
FT   REGION          61..80
FT                   /note="Binds to human NUP153"
FT                   /evidence="ECO:0000250|UniProtKB:P19508"
FT   REGION          93..112
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           65..72
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000269|PubMed:12832198"
FT   COMPBIAS        98..112
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         63..65
FT                   /note="SES->AEA: No effect on non-dividing cells
FT                   infection."
FT                   /evidence="ECO:0000269|PubMed:16325220"
FT   MUTAGEN         66..71
FT                   /note="YTKYRY->ATKARA: Partial loss of non-dividing cells
FT                   infection."
FT                   /evidence="ECO:0000269|PubMed:16325220"
FT   MUTAGEN         66..71
FT                   /note="YTKYRY->ATKYRA: No effect on non-dividing cells
FT                   infection."
FT                   /evidence="ECO:0000269|PubMed:16325220"
FT   MUTAGEN         66..71
FT                   /note="YTKYRY->FTKFRF: No effect on non-dividing cells
FT                   infection."
FT                   /evidence="ECO:0000269|PubMed:16325220"
FT   MUTAGEN         66..69
FT                   /note="YTKY->ATKA: Partial loss of non-dividing cells
FT                   infection."
FT   MUTAGEN         66
FT                   /note="Y->A: No effect on non-dividing cells infection."
FT   MUTAGEN         68..70
FT                   /note="KYR->AYA: Complete loss of non-dividing cells
FT                   infection."
FT   MUTAGEN         69..71
FT                   /note="YRY->ARA: Partial loss of non-dividing cells
FT                   infection."
FT   MUTAGEN         69
FT                   /note="Y->A: Partial loss of non-dividing cells infection."
FT   MUTAGEN         71
FT                   /note="Y->A: No effect on non-dividing cells infection."
SQ   SEQUENCE   112 AA;  12815 MW;  0A677EB6BDB5F665 CRC64;
     MTDPRETVPP GNSGEETIGE AFAWLNRTVE AINREAVNHL PRELIFQVWQ RSWRYWHDEQ
     GMSESYTKYR YLCIIQKAVY MHVRKGCTCL GRGHGPGGWR PGPPPPPPPG LV
 
 
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