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Protein Vpr



Human immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli


During virus entry, plays a role in the transport of the viral pre-integration (PIC) complex to the host nucleus. This function is crucial for viral infection of non-dividing macrophages. May act directly at the nuclear pore complex, by binding nucleoporins phenylalanine-glycine (FG)-repeat regions.UniRule annotation3 Publications
During virus replication, may deplete host UNG protein, and incude G2-M cell cycle arrest. Acts by targeting specific host proteins for degradation by the 26S proteasome, through association with the cellular CUL4A-DDB1 E3 ligase complex by direct interaction with host VPRPB/DCAF-1. Cell cycle arrest reportedly occurs within hours of infection and is not blocked by antiviral agents, suggesting that it is initiated by the VPR carried into the virion. Additionally, VPR induces apoptosis in a cell cycle dependent manner suggesting that these two effects are mechanistically linked. Detected in the serum and cerebrospinal fluid of AIDS patient, VPR may also induce cell death to bystander cells.UniRule annotation8 Publications


HIV-1 lineages are divided in three main groups, M (for Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast majority of strains found worldwide belong to the group M. Group O seems to be endemic to and largely confined to Cameroon and neighboring countries in West Central Africa, where these viruses represent a small minority of HIV-1 strains. The group N is represented by a limited number of isolates from Cameroonian persons. The group M is further subdivided in 9 clades or subtypes (A to D, F to H, J and K).UniRule annotation

GO - Biological processi


Molecular functionActivator, Ion channel
Biological processApoptosis, Cell cycle, Host G2/M cell cycle arrest by virus, Host-virus interaction, Ion transport, Modulation of host cell cycle by virus, Transcription, Transcription regulation, Transport, Viral penetration into host nucleus, Virus entry into host cell

Enzyme and pathway databases

ReactomeiR-HSA-162585. Uncoating of the HIV Virion.
R-HSA-162588. Budding and maturation of HIV virion.
R-HSA-162592. Integration of provirus.
R-HSA-162594. Early Phase of HIV Life Cycle.
R-HSA-164516. Minus-strand DNA synthesis.
R-HSA-164525. Plus-strand DNA synthesis.
R-HSA-164843. 2-LTR circle formation.
R-HSA-173107. Binding and entry of HIV virion.
R-HSA-175474. Assembly Of The HIV Virion.
R-HSA-175567. Integration of viral DNA into host genomic DNA.
R-HSA-177539. Autointegration results in viral DNA circles.
R-HSA-180689. APOBEC3G mediated resistance to HIV-1 infection.
R-HSA-180897. Vpr-mediated induction of apoptosis by mitochondrial outer membrane permeabilization.
R-HSA-180910. Vpr-mediated nuclear import of PICs.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein VprUniRule annotation
Alternative name(s):
R ORF proteinUniRule annotation
Viral protein RUniRule annotation
Gene namesi
Name:vprUniRule annotation
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate HXB2) (HIV-1)
Taxonomic identifieri11706 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
  • UP000002241 Componenti: Genome

Subcellular locationi

  • Virion UniRule annotation2 Publications
  • Host nucleus UniRule annotation1 Publication
  • Host extracellular space UniRule annotation

  • Note: Incorporation into virion is dependent on p6 GAG sequences. Lacks a canonical nuclear localization signal, thus import into nucleus may function independently of the human importin pathway. Detected in high quantity in the serum and cerebrospinal fluid of AIDS patient.UniRule annotation1 Publication

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular region Source: Reactome
  • extracellular space of host Source: UniProtKB-SubCell
  • host cell nucleus Source: UniProtKB
  • mitochondrial intermembrane space Source: Reactome
  • nucleoplasm Source: Reactome
  • virion Source: UniProtKB

Keywords - Cellular componenti

Host nucleus, Virion

Pathology & Biotechi

Keywords - Diseasei


PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000854511 – 96Protein VprAdd BLAST96

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei79Phosphoserine; by hostUniRule annotation2 Publications1
Modified residuei94Phosphoserine; by hostUniRule annotation1 Publication1
Modified residuei96Phosphoserine; by hostUniRule annotation1 Publication1

Post-translational modificationi

Phosphorylated on several residues by host. These phosphorylations regulate VPR activity for the nuclear import of the HIV-1 pre-integration complex.UniRule annotation2 Publications

Keywords - PTMi


PTM databases



Subunit structurei

Homooligomer, may form homodimer. Interacts with p6-gag region of the Pr55 Gag precursor protein through a (Leu-X-X)4 motif near the C-terminus of the P6gag protein. Interacts with host UNG. May interact with host RAD23A/HHR23A. Interacts with host VPRBP/DCAF1, leading to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex, mediating ubiquitination of host proteins such as TERT and ZGPAT and arrest of the cell cycle in G2 phase.UniRule annotation7 Publications

Protein-protein interaction databases

IntActiP69726. 4 interactors.


3D structure databases

Select the link destinations:
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum

Family & Domainsi


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 42HomooligomerizationUniRule annotation1 PublicationAdd BLAST42

Sequence similaritiesi

Belongs to the HIV-1 VPR protein family.UniRule annotation

Phylogenomic databases


Family and domain databases

HAMAPiMF_04080. HIV_VPR. 1 hit.
InterProiView protein in InterPro
IPR000012. RetroV_VpR/X.
PfamiView protein in Pfam
PF00522. VPR. 1 hit.


Sequence statusi: Complete.

P69726-1 [UniParc]FASTAAdd to basket

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Mass (Da):11,323
Last modified:February 4, 2015 - v2

Sequence cautioni

The sequence AAB50261 differs from that shown. Reason: Frameshift at position 72.Curated

Sequence databases

Select the link destinations:
Links Updated
K03455 Genomic RNA. Translation: AAB50261.1. Frameshift.

Similar proteinsi

Entry informationi

Entry nameiVPR_HV1H2
AccessioniPrimary (citable) accession number: P69726
Secondary accession number(s): P05926, Q85577
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: February 4, 2015
Last modified: August 30, 2017
This is version 84 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program


Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome


  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families