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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: 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 (PubMed:12417576). This function is crucial for viral infection of non-dividing macrophages (PubMed:12417576). May act directly at the nuclear pore complex, by binding nucleoporins phenylalanine-glycine (FG)-repeat regions.3 Publications
During virus replication, may deplete host UNG protein, and incude G2-M cell cycle arrest(PubMed:7666531, PubMed:7474100). 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 (PubMed:11000244).8 Publications

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

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 Vpr
Alternative name(s):
R ORF protein
Viral protein R
Gene namesi
Name:vpr
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 2 Publications
  • Host nucleus 1 Publication
  • Host extracellular space

  • Note: Incorporation into virion is dependent on p6 GAG sequences (PubMed:8411357). 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.1 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
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_0000085451Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei79 – 791Phosphoserine; by host2 Publications
Modified residuei94 – 941Phosphoserine; by host1 Publication
Modified residuei96 – 961Phosphoserine; by host1 Publication

Post-translational modificationi

Phosphorylated on several residues by host. These phosphorylations regulates VPR activity for the nuclear import of the HIV-1 pre-integration complex.2 Publications

Keywords - PTMi

Phosphoprotein

PTM databases

iPTMnetiP69726.

Interactioni

Subunit structurei

Homooligomer, may form homodimer (PubMed:7798208). 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 (PubMed:7474102). Interacts with host UNG (PubMed:9151883). May interact with host RAD23A/HHR23A (PubMed:9371639). 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 (PubMed:17314515, PubMed:17630831, PubMed:17314515).7 Publications

Protein-protein interaction databases

IntActiP69726. 4 interactions.

Structurei

3D structure databases

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

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 4242Homooligomerization1 PublicationAdd
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.

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 AAB50261.1 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.

Cross-referencesi

Web resourcesi

BioAfrica HIV proteomics resource

Vpr entry

Sequence databases

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

3D structure databases

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

Protein-protein interaction databases

IntActiP69726. 4 interactions.

PTM databases

iPTMnetiP69726.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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.

Family and domain databases

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

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. "Identification of HIV-1 vpr product and function."
    Cohen E.A., Terwilliger E.F., Jalinoos Y., Proulx J., Sodroski J.G., Haseltine W.A.
    J. Acquir. Immune Defic. Syndr. 3:11-18(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
    Strain: isolate BRU/LAI.
  3. "Human immunodeficiency virus vpr product is a virion-associated regulatory protein."
    Cohen E.A., Dehni G., Sodroski J.G., Haseltine W.A.
    J. Virol. 64:3097-3099(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
    Strain: isolate BRU/LAI.
  4. "Human immunodeficiency virus type 1 viral protein R localization in infected cells and virions."
    Lu Y.L., Spearman P., Ratner L.
    J. Virol. 67:6542-6550(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
    Strain: isolate BRU/LAI.
  5. "Biochemical mechanism of HIV-1 Vpr function. Oligomerization mediated by the N-terminal domain."
    Zhao L.J., Wang L., Mukherjee S., Narayan O.
    J. Biol. Chem. 269:32131-32137(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: HOMOOLIGOMERIZATION.
  6. "A leucine triplet repeat sequence (LXX)4 in p6gag is important for Vpr incorporation into human immunodeficiency virus type 1 particles."
    Lu Y.L., Bennett R.P., Wills J.W., Gorelick R., Ratner L.
    J. Virol. 69:6873-6879(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH P6-GAG.
    Strain: isolate BRU/LAI.
  7. "Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B."
    Re F., Braaten D., Franke E.K., Luban J.
    J. Virol. 69:6859-6864(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
    Strain: isolate BRU/LAI.
  8. "The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle."
    Jowett J.B., Planelles V., Poon B., Shah N.P., Chen M.L., Chen I.S.
    J. Virol. 69:6304-6313(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
    Strain: isolate BRU/LAI.
  9. "Uracil DNA glycosylase specifically interacts with Vpr of both human immunodeficiency virus type 1 and simian immunodeficiency virus of sooty mangabeys, but binding does not correlate with cell cycle arrest."
    Selig L., Benichou S., Rogel M.E., Wu L.I., Vodicka M.A., Sire J., Benarous R., Emerman M.
    J. Virol. 71:4842-4846(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN UNG.
    Strain: isolate BRU/LAI.
  10. "Human immunodeficiency virus type 1 Vpr interacts with HHR23A, a cellular protein implicated in nucleotide excision DNA repair."
    Withers-Ward E.S., Jowett J.B., Stewart S.A., Xie Y.M., Garfinkel A., Shibagaki Y., Chow S.A., Shah N., Hanaoka F., Sawitz D.G., Armstrong R.W., Souza L.M., Chen I.S.
    J. Virol. 71:9732-9742(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN RAD23A.
    Strain: isolate BRU/LAI.
  11. "Lentiviral delivery of HIV-1 Vpr protein induces apoptosis in transformed cells."
    Stewart S.A., Poon B., Jowett J.B., Xie Y., Chen I.S.
    Proc. Natl. Acad. Sci. U.S.A. 96:12039-12043(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  12. "Human immunodeficiency virus type 1 Vpr induces apoptosis in human neuronal cells."
    Patel C.A., Mukhtar M., Pomerantz R.J.
    J. Virol. 74:9717-9726(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. "Phosphorylation of human immunodeficiency virus type 1 Vpr regulates cell cycle arrest."
    Zhou Y., Ratner L.
    J. Virol. 74:6520-6527(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-79; SER-94 AND SER-96.
    Strain: Clone pNL4-3.
  14. "Visualization of the intracellular behavior of HIV in living cells."
    McDonald D., Vodicka M.A., Lucero G., Svitkina T.M., Borisy G.G., Emerman M., Hope T.J.
    J. Cell Biol. 159:441-452(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
    Strain: isolate BRU/LAI.
  15. "Phosphorylation of Vpr regulates HIV type 1 nuclear import and macrophage infection."
    Agostini I., Popov S., Hao T., Li J.H., Dubrovsky L., Chaika O., Chaika N., Lewis R., Bukrinsky M.
    AIDS Res. Hum. Retroviruses 18:283-288(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-79.
    Strain: isolate BRU/LAI.
  16. "Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells."
    Moon H.S., Yang J.S.
    Mol. Cells 21:7-20(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  17. "HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase."
    Le Rouzic E., Belaiedouni N., Estrabaud E., Morel M., Rain J.-C., Transy C., Margottin-Goguet F.
    Cell Cycle 6:182-188(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT.
    Strain: isolate BRU/LAI.
  18. "HIV-1 Vpr-mediated G2 arrest involves the DDB1-CUL4A[VPRBP] E3 ubiquitin ligase."
    Belzile J.P., Duisit G., Rougeau N., Mercier J., Finzi A., Cohen E.A.
    PLoS Pathog. 3:E85-E85(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT.
    Strain: isolate BRU/LAI.
  19. "HIV-1 Vpr protein inhibits telomerase activity via the EDD-DDB1-VPRBP E3 ligase complex."
    Wang X., Singh S., Jung H.Y., Yang G., Jun S., Sastry K.J., Park J.I.
    J. Biol. Chem. 288:15474-15480(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HOST VPRBP.
    Strain: isolate BRU/LAI.
  20. "HIV-1 Vpr Induces the Degradation of ZIP and sZIP, Adaptors of the NuRD Chromatin Remodeling Complex, by Hijacking DCAF1/VprBP."
    Maudet C., Sourisce A., Dragin L., Lahouassa H., Rain J.C., Bouaziz S., Ramirez B.C., Margottin-Goguet F.
    PLoS ONE 8:E77320-E77320(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH HOST VPRBP.
    Strain: isolate BRU/LAI.
  21. Cited for: REVIEW.

Entry informationi

Entry nameiVPR_HV1H2
AccessioniPrimary (citable) accession number: P69726
Secondary accession number(s): P05926, Q85577
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: February 4, 2015
Last modified: June 8, 2016
This is version 79 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, Complete proteome, Reference proteome

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.