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Protein

Protein Vpr

Gene

vpr

Organism
Human immunodeficiency virus type 1 group M subtype B (isolate NY5) (HIV-1)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

During virus entry, involved in the transport of the viral pre-integration (PIC) complex to the 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 (By similarity).By similarity
May target 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 would result in cell cycle arrest or apoptosis in infected cells. Prevents infected cells from undergoing mitosis and proliferating, by inducing arrest or delay in the G2 phase of the cell cycle. This arrest creates a favorable environment for maximizing viral expression and production by rendering the HIV-1 LTR transcriptionally more active. In this context, Vpr stimulates gene expression driven by the HIV-1 LTR by interacting with human SP1, TFIIB and TFIID. 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. Interacts with mitochondrial permeability transition pore complex (PTPC). This interaction induces a rapid dissipation of the mitochondrial transmembrane potential, and mitochondrial release of apoptogenic proteins such as cytochrome C or apoptosis inducing factors. Detected in the serum and cerebrospinal fluid of AIDS patient, Vpr may also induce cell death to bystander cells (By similarity).By similarity

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Ion channel

Keywords - Biological processi

Apoptosis, 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

Protein family/group databases

TCDBi1.A.42.1.1. the hiv viral protein r (vpr) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein Vpr
Alternative name(s):
R ORF protein
Viral protein R
Gene namesi
Name:vpr
OrganismiHuman immunodeficiency virus type 1 group M subtype B (isolate NY5) (HIV-1)
Taxonomic identifieri11698 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]

Subcellular locationi

  • 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 (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host nucleus, Virion

Pathology & Biotechi

Keywords - Diseasei

AIDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000854461 – 96Protein VprAdd BLAST96

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei79Phosphoserine; by hostBy similarity1
Modified residuei94Phosphoserine; by hostBy similarity1
Modified residuei96Phosphoserine; by hostBy similarity1

Keywords - PTMi

Phosphoprotein

Interactioni

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, mediate ubiquitination of host proteins such as TERT and ZGPAT and arrest the cell cycle in G2 phase (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CEP170Q5SW794EBI-6164519,EBI-1104799From a different organism.
DCAF8Q5TAQ92EBI-6164519,EBI-740686From a different organism.
GEMIN6Q8WXD53EBI-6164519,EBI-752301From a different organism.
GOLPH3Q9H4A63EBI-6164519,EBI-2465479From a different organism.
HAT1O149293EBI-6164519,EBI-2339359From a different organism.
TULP3O753862EBI-6164519,EBI-5357290From a different organism.
VPRBPQ9Y4B65EBI-6164519,EBI-1996353From a different organism.

Protein-protein interaction databases

IntActiP12520. 47 interactors.

Structurei

Secondary structure

196
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi35 – 37Combined sources3
Helixi38 – 50Combined sources13
Helixi52 – 78Combined sources27
Helixi81 – 83Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BDENMR-A50-82[»]
1DSJNMR-A50-75[»]
1DSKNMR-A59-86[»]
1KZSNMR-A34-51[»]
1KZTNMR-A34-51[»]
1KZVNMR-A34-51[»]
5JK7X-ray3.49F/H1-96[»]
ProteinModelPortaliP12520.
SMRiP12520.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12520.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 42HomooligomerizationBy similarityAdd BLAST42

Sequence similaritiesi

Belongs to the HIV-1 VPR protein family.Curated

Family and domain databases

InterProiIPR000012. RetroV_VpR/X.
[Graphical view]
PfamiPF00522. VPR. 1 hit.
[Graphical view]
PRINTSiPR00444. HIVVPRVPX.

Sequencei

Sequence statusi: Complete.

P12520-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEQAPEDQGP QREPYNEWTL ELLEELKSEA VRHFPRIWLH NLGQHIYETY
60 70 80 90
GDTWAGVEAI IRILQQLLFI HFRIGCRHSR IGVTRQRRAR NGASRS
Length:96
Mass (Da):11,379
Last modified:February 1, 1996 - v2
Checksum:i58BC53573479D150
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19921 Genomic RNA. Translation: AAA44990.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M19921 Genomic RNA. Translation: AAA44990.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BDENMR-A50-82[»]
1DSJNMR-A50-75[»]
1DSKNMR-A59-86[»]
1KZSNMR-A34-51[»]
1KZTNMR-A34-51[»]
1KZVNMR-A34-51[»]
5JK7X-ray3.49F/H1-96[»]
ProteinModelPortaliP12520.
SMRiP12520.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP12520. 47 interactors.

Protein family/group databases

TCDBi1.A.42.1.1. the hiv viral protein r (vpr) family.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP12520.

Family and domain databases

InterProiIPR000012. RetroV_VpR/X.
[Graphical view]
PfamiPF00522. VPR. 1 hit.
[Graphical view]
PRINTSiPR00444. HIVVPRVPX.
ProtoNetiSearch...

Entry informationi

Entry nameiVPR_HV1N5
AccessioniPrimary (citable) accession number: P12520
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: February 1, 1996
Last modified: November 30, 2016
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

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).

Keywords - Technical termi

3D-structure

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.