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HAMAP rule MF_04080

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General rule information [?]

Accession MF_04080
Dates 30-MAY-2017 (Created)
7-FEB-2023 (Last updated, Version 11)
Viruses; Lentivirus
Template P69726 (VPR_HV1H2)

Propagated annotation [?]

Identifier, protein and gene names [?]

Protein name
RecName: Full=Protein Vpr;
AltName: Full=R ORF protein;
AltName: Full=Viral protein R;
Gene name

Comments [?]

Function 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.
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.
Subunit 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.
Subcellular location Virion. Host nucleus. Host extracellular space. 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.
Ptm Phosphorylated on several residues by host. These phosphorylations regulate VPR activity for the nuclear import of the HIV-1 pre-integration complex.
Miscellaneous 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).
Similarity Belongs to the HIV-1 VPR protein family.

Keywords [?]

Gene Ontology [?]

GO:0043655; Cellular component: host extracellular space.
GO:0042025; Cellular component: host cell nucleus.
GO:0044423; Cellular component: virion component.
GO:0000278; Biological process: mitotic cell cycle.
GO:0019051; Biological process: induction by virus of host apoptotic process.
GO:0051701; Biological process: biological process involved in interaction with host.
GO:0006811; Biological process: monoatomic ion transport.
GO:0051260; Biological process: protein homooligomerization.
GO:0006355; Biological process: regulation of DNA-templated transcription.
GO:0039592; Biological process: suppression by virus of G2/M transition of host mitotic cell cycle.
GO:0006351; Biological process: DNA-templated transcription.
GO:0075732; Biological process: viral penetration into host nucleus.

Cross-references [?]

Pfam PF00522; VPR; 1;

Features [?]

From: VPR_HV1H2 (P69726)
Key     From     To       Description   Tag   Condition   FTGroup
REGION     1     42       Homooligomerization        
MOD_RES     79     79       Phosphoserine; by host     S  
MOD_RES     94     94       Phosphoserine; by host     S  
MOD_RES     96     96       Phosphoserine; by host     S  

Additional information [?]

Size range 78-100 amino acids
Related rules None
Fusion None