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Protein

Protein Vpr

Gene

vpr

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

Functioni

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

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).UniRule annotation

GO - Biological processi

Keywordsi

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]
Proteomesi
  • 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

  • extracellular space of host Source: UniProtKB-SubCell
  • host cell nucleus Source: UniProtKB
  • virion Source: UniProtKB

Keywords - Cellular componenti

Host nucleus, Virion

Pathology & Biotechi

Keywords - Diseasei

AIDS

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

Phosphoprotein

PTM databases

iPTMnetiP69726

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, 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.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4U1SX-ray1.76C34-42[»]
SMRiP69726
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

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

Sequence similaritiesi

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

Phylogenomic databases

OrthoDBiVOG090001DK

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
PRINTSiPR00444 HIVVPRVPX

Sequencei

Sequence statusi: Complete.

P69726-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEQAPEDQGP QREPHNEWTL ELLEELKNEA VRHFPRIWLH GLGQHIYETY
60 70 80 90
GDTWAGVEAI IRILQQLLFI HFRIGCRHSR IGVTRQRRAR NGASRS
Length:96
Mass (Da):11,323
Last modified:February 4, 2015 - v2
Checksum:i42892A4249E83D3E
GO

Sequence cautioni

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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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: April 25, 2018
This is version 87 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome