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Protein Vpx (Viral protein X) (X ORF protein)

 VPX_SIVSP               Reviewed;         112 AA.
P19508;
01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
01-FEB-1991, sequence version 1.
30-AUG-2017, entry version 65.
RecName: Full=Protein Vpx;
AltName: Full=Viral protein X;
AltName: Full=X ORF protein;
Name=vpx;
Simian immunodeficiency virus (isolate PBj14/BCL-3) (SIV-sm) (Simian
immunodeficiency virus sooty mangabey monkey).
Viruses; Retro-transcribing viruses; Retroviridae; Orthoretrovirinae;
Lentivirus; Primate lentivirus group.
NCBI_TaxID=11738;
NCBI_TaxID=9527; Cercopithecidae (Old World monkeys).
[1]
NUCLEOTIDE SEQUENCE [GENOMIC RNA].
PubMed=1971917; DOI=10.1038/345636a0;
Dewhurst S., Embretson J.E., Anderson D.C., Mullins J.I., Fultz P.N.;
"Sequence analysis and acute pathogenicity of molecularly cloned
SIVSMM-PBj14.";
Nature 345:636-640(1990).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC RNA].
PubMed=1503826; DOI=10.1089/aid.1992.8.1179;
Dewhurst S., Embretson J.E., Fultz P.N., Mullins J.I.;
"Molecular clones from a non-acutely pathogenic derivative of
SIVsmmPBj14: characterization and comparison to acutely pathogenic
clones.";
AIDS Res. Hum. Retroviruses 8:1179-1187(1992).
[3]
FUNCTION, AND INTERACTION WITH HUMAN DCAF1.
STRAIN=Isolate GH-1;
PubMed=19264781; DOI=10.1128/JVI.00187-09;
Bergamaschi A., Ayinde D., David A., Le Rouzic E., Morel M.,
Collin G., Descamps D., Damond F., Brun-Vezinet F., Nisole S.,
Margottin-Goguet F., Pancino G., Transy C.;
"The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-
DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in
macrophage infection.";
J. Virol. 83:4854-4860(2009).
[4]
X-RAY CRYSTALLOGRAPHY (2.47 ANGSTROMS) IN COMPLEX WITH ZINC; HUMAN
SAMHD1 AND DCAF1, FUNCTION, AND INTERACTION WITH HUMAN SAMHD1 AND
DCAF1.
PubMed=24336198; DOI=10.1038/nature12815;
Schwefel D., Groom H.C., Boucherit V.C., Christodoulou E.,
Walker P.A., Stoye J.P., Bishop K.N., Taylor I.A.;
"Structural basis of lentiviral subversion of a cellular protein
degradation pathway.";
Nature 505:234-238(2014).
-!- FUNCTION: Plays a role in nuclear translocation of the viral pre-
integration complex (PIC), thus is required for the virus to
infect non-dividing cells. Targets specific host proteins for
degradation by the 26S proteasome. Acts by associating with the
cellular CUL4A-DDB1 E3 ligase complex through direct interaction
with host VPRPB/DCAF-1. This change in the E3 ligase substrate
specificity results in the degradation of host SAMHD1. In turn,
SAMHD1 depletion allows viral replication in host myeloid cells by
preventing SAMHD1-mediated hydrolysis of intracellular dNTPs
necessary for reverse transcription. {ECO:0000269|PubMed:19264781,
ECO:0000269|PubMed:24336198}.
-!- SUBUNIT: Interacts with the P6 region of unprocessed GAG.
Interacts with host VPRBP/DCAF1, leading to change substrate
specificity of the CUL4A-DDB1 E3 ligase complex.
{ECO:0000269|PubMed:19264781, ECO:0000269|PubMed:24336198}.
-!- INTERACTION:
Q9Y4B6:DCAF1 (xeno); NbExp=2; IntAct=EBI-6558117, EBI-1996353;
-!- SUBCELLULAR LOCATION: Virion. Host nucleus. Note=Nuclear just
after virion uncoating, or if expressed in the absence of
unprocessed GAG. {ECO:0000250}.
-!- SIMILARITY: Belongs to the lentivirus VPX protein family.
{ECO:0000305}.
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EMBL; L03298; AAA47779.1; -; Genomic_RNA.
EMBL; M31325; AAA47755.1; -; Genomic_RNA.
PDB; 4CC9; X-ray; 2.47 A; B=1-112.
PDBsum; 4CC9; -.
ProteinModelPortal; P19508; -.
SMR; P19508; -.
DIP; DIP-60689N; -.
IntAct; P19508; 1.
OrthoDB; VOG090001GG; -.
Proteomes; UP000007221; Genome.
GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
GO; GO:0019012; C:virion; IEA:UniProtKB-SubCell.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
GO; GO:0019058; P:viral life cycle; IEA:InterPro.
InterPro; IPR000012; RetroV_VpR/X.
Pfam; PF00522; VPR; 1.
1: Evidence at protein level;
3D-structure; Complete proteome; Host nucleus; Host-virus interaction;
Inhibition of host innate immune response by virus; Metal-binding;
Viral immunoevasion; Virion; Zinc.
CHAIN 1 112 Protein Vpx.
/FTId=PRO_0000085407.
MOTIF 65 72 Nuclear localization signal.
{ECO:0000250}.
COMPBIAS 101 109 Poly-Pro.
METAL 39 39 Zinc; via pros nitrogen.
{ECO:0000269|PubMed:24336198}.
METAL 82 82 Zinc; via tele nitrogen.
{ECO:0000269|PubMed:24336198}.
METAL 87 87 Zinc. {ECO:0000269|PubMed:24336198}.
METAL 89 89 Zinc. {ECO:0000269|PubMed:24336198}.
HELIX 13 15 {ECO:0000244|PDB:4CC9}.
HELIX 18 36 {ECO:0000244|PDB:4CC9}.
TURN 37 39 {ECO:0000244|PDB:4CC9}.
HELIX 42 56 {ECO:0000244|PDB:4CC9}.
TURN 57 60 {ECO:0000244|PDB:4CC9}.
HELIX 64 84 {ECO:0000244|PDB:4CC9}.
SEQUENCE 112 AA; 12855 MW; 226D0BF3A0FD2713 CRC64;
MSDPRERIPP GNSGEETIGE AFDWLDRTVE EINRAAVNHL PRELIFQVWR RSWEYWHDEM
GMSVSYTKYR YLCLIQKAMF MHCKKGCRCL GGEHGAGGWR PGPPPPPPPG LA


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