VPX_SIVSP
ID VPX_SIVSP Reviewed; 112 AA.
AC P19508;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Protein Vpx;
DE AltName: Full=Viral protein X;
DE AltName: Full=X ORF protein;
GN Name=vpx;
OS Simian immunodeficiency virus (isolate PBj14/BCL-3) (SIV-sm) (Simian
OS immunodeficiency virus sooty mangabey monkey).
OC Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus.
OX NCBI_TaxID=11738;
OH NCBI_TaxID=9527; Cercopithecidae (Old World monkeys).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1971917; DOI=10.1038/345636a0;
RA Dewhurst S., Embretson J.E., Anderson D.C., Mullins J.I., Fultz P.N.;
RT "Sequence analysis and acute pathogenicity of molecularly cloned SIVSMM-
RT PBj14.";
RL Nature 345:636-640(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1503826; DOI=10.1089/aid.1992.8.1179;
RA Dewhurst S., Embretson J.E., Fultz P.N., Mullins J.I.;
RT "Molecular clones from a non-acutely pathogenic derivative of SIVsmmPBj14:
RT characterization and comparison to acutely pathogenic clones.";
RL AIDS Res. Hum. Retroviruses 8:1179-1187(1992).
RN [3]
RP FUNCTION, AND INTERACTION WITH HUMAN DCAF1.
RC STRAIN=Isolate GH-1;
RX PubMed=19264781; DOI=10.1128/jvi.00187-09;
RA Bergamaschi A., Ayinde D., David A., Le Rouzic E., Morel M., Collin G.,
RA Descamps D., Damond F., Brun-Vezinet F., Nisole S., Margottin-Goguet F.,
RA Pancino G., Transy C.;
RT "The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1
RT DCAF1 ubiquitin ligase to overcome a postentry block in macrophage
RT infection.";
RL J. Virol. 83:4854-4860(2009).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.47 ANGSTROMS) IN COMPLEX WITH ZINC; HUMAN SAMHD1
RP AND DCAF1, FUNCTION, AND INTERACTION WITH HUMAN SAMHD1 AND DCAF1.
RX PubMed=24336198; DOI=10.1038/nature12815;
RA Schwefel D., Groom H.C., Boucherit V.C., Christodoulou E., Walker P.A.,
RA Stoye J.P., Bishop K.N., Taylor I.A.;
RT "Structural basis of lentiviral subversion of a cellular protein
RT degradation pathway.";
RL Nature 505:234-238(2014).
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 {ECO:0000269|PubMed:19264781, ECO:0000269|PubMed:24336198}.
CC -!- SUBUNIT: Interacts with the P6 region of unprocessed GAG. Interacts
CC with host VPRBP/DCAF1, leading to change substrate specificity of the
CC CUL4A-DDB1 E3 ligase complex. {ECO:0000269|PubMed:19264781,
CC ECO:0000269|PubMed:24336198}.
CC -!- INTERACTION:
CC P19508; Q9Y4B6: DCAF1; Xeno; NbExp=4; IntAct=EBI-6558117, EBI-1996353;
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; L03298; AAA47779.1; -; Genomic_RNA.
DR EMBL; M31325; AAA47755.1; -; Genomic_RNA.
DR PDB; 4CC9; X-ray; 2.47 A; B=1-112.
DR PDBsum; 4CC9; -.
DR SMR; P19508; -.
DR DIP; DIP-60689N; -.
DR IntAct; P19508; 1.
DR Proteomes; UP000007221; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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 IDEAL; IID90030; -.
DR InterPro; IPR000012; RetroV_VpR/X.
DR Pfam; PF00522; VPR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host nucleus; Host-virus interaction;
KW Inhibition of host innate immune response by virus; Metal-binding;
KW Reference proteome; Viral immunoevasion; Virion; Zinc.
FT CHAIN 1..112
FT /note="Protein Vpx"
FT /id="PRO_0000085407"
FT MOTIF 65..72
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT BINDING 39
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24336198"
FT BINDING 82
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24336198"
FT BINDING 87
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24336198"
FT BINDING 89
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:24336198"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:4CC9"
FT HELIX 18..36
FT /evidence="ECO:0007829|PDB:4CC9"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:4CC9"
FT HELIX 42..56
FT /evidence="ECO:0007829|PDB:4CC9"
FT TURN 57..60
FT /evidence="ECO:0007829|PDB:4CC9"
FT HELIX 64..84
FT /evidence="ECO:0007829|PDB:4CC9"
SQ SEQUENCE 112 AA; 12855 MW; 226D0BF3A0FD2713 CRC64;
MSDPRERIPP GNSGEETIGE AFDWLDRTVE EINRAAVNHL PRELIFQVWR RSWEYWHDEM
GMSVSYTKYR YLCLIQKAMF MHCKKGCRCL GGEHGAGGWR PGPPPPPPPG LA
