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Protein

Protein Vpr

Gene

vpr

Organism
Human immunodeficiency virus type 1 group M subtype C (isolate ETH2220) (HIV-1)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Protein inferred from homologyi

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

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 C (isolate ETH2220) (HIV-1)
Taxonomic identifieri388796 [NCBI]
Taxonomic lineageiVirusesRetro-transcribing virusesRetroviridaeOrthoretrovirinaeLentivirusPrimate lentivirus group
Virus hostiHomo sapiens (Human) [TaxID: 9606]
Proteomesi
  • UP000007694 Componenti: Genome

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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 9696Protein VprPRO_0000246758Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei79 – 791Phosphoserine; by hostBy similarity
Modified residuei94 – 941Phosphoserine; by hostBy similarity
Modified residuei96 – 961Phosphoserine; by hostBy similarity

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

Structurei

3D structure databases

ProteinModelPortaliQ75004.
SMRiQ75004. Positions 1-96.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 4242HomooligomerizationBy similarityAdd
BLAST

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.

Q75004-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEQAPEDQGP QREPYNEWAL ELLEELKQEA VRHFPRPWLH NLGQYIYETY
60 70 80 90
GDTWSGVEAL IRTLQQLMFI HFRIGCQHSR IGILRQRRAR NGASRS
Length:96
Mass (Da):11,420
Last modified:November 1, 1996 - v1
Checksum:i1B2BBA347A80D04B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U46016 Genomic DNA. Translation: AAB36503.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U46016 Genomic DNA. Translation: AAB36503.1.

3D structure databases

ProteinModelPortaliQ75004.
SMRiQ75004. Positions 1-96.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

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

Entry informationi

Entry nameiVPR_HV1ET
AccessioniPrimary (citable) accession number: Q75004
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: November 1, 1996
Last modified: June 8, 2016
This is version 75 of the entry and version 1 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

Complete proteome

Documents

  1. 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.