VPR - Viral Protein R

HIV VPR is involved in targeting the nuclear localization of preintegration complexes, arrests infected cells at the G2 phase of the cell cycle, and inhibits cell division.



PDB-1M8L: HIV-1 (isolate UNKNOWN) Vpr protein - produced using SwissModel/SPDBV/POVray

Key web links:
ViralZone: HIV-1, HIV replication cycle, HIV resource
PDB: 1M8L (HIV-1 Vpr)
UniProt: P69726 (HIV-1 HXB2 Vpr)
Chime Tutorial:  not available
HIV-1/Human Protein Interaction DB: HIV-1 Vpr
Los Alamos HIV structure DB:  VPR
NCBI: K03455 [EMBL/GenBank/DDBJ]


Isoforms:

  • p10-15 (78 amino acids)

Function:

  • Plays an essential role in the entry of the viral cDNA genome into the host nucleus during infection of quiescent cells .
  • Degrades host UNG, thereby preventing its incorporation into virions.
  • During the virus replication cycle, Vpr induces host cell G2 arrest possibly through degradation of host repair proteins, stopping cell division in G2-M damage checkpoint.
  • The lymphocytes stopped in G2-M eventually go into apoptosis , which is thought to be the main cause of AIDS disease.

Localization:

  • Virion
  • Host nucleus

Additional Information:

  • Late timing of expression.
  • ~100 copies of Vpr are associated with each virion .
  • Incorporation of Vpr into virions is mediated by interactions with carboxyl-terminal region of p55 Gag.
  • Prevents activation of p34cdc2/cyclin B complex, which is a regulator of the cell cycle that is important for entry into mitosis .
  • Genetically modified p34cdc2 prevents the cell cycle inhibitory activity of Vpr.

Vpr Function & Host-Virus Protein Interactions:[TOP]




Interactions highlighted in the image:


Potential interactions (not in the image):


  • Interacts with the carboxyl-terminal (p6 & NC) region of the N-myristoylated Gag polyprotein.
  • Interactions between Vpr and cdc25c prevent p34cdc2/cyclin B activation .
  • Vpr interacts with mov34.
  • Vpr stabilises the interaction between karyopherin (mediates nuclear import) heterodimers and the nuclear localization
    signal of the HIV-1 Matrix.
  • Vpr interacts directly with nucleoporin, which make up the nuclear pore complexes and regulate the movement of molecules
    in and out of the nucleus.
  • Importin alpha 1 (KPNA2) facilitates the nuclear import of Vpr [see GUAVAh KPNA2 interaction profile].
  • Vpr interaction with RAD23A impairs its normal DNA repair function [see GUAVAh RAD23A interaction profile].


Genomic Location & Protein Sequence: [TOP]

HIV-1 (HXB2):

          10         20         30         40         50         60         70       78
| | | | | | | |
MEQAPEDQGP QREPHNEWTL ELLEELKNEA VRHFPRIWLH GLGQHIYETY GDTWAGVEAI IRILQQLLFI HFQNWVST
[download in fasta format]

Length: 78 amino acids
Molecular Weight: 9305 Da
Theoretical pI: 4.99

Protein Domains/Folds/Motifs: [TOP]

InterPro signature for Retroviral VpR/VpX protein - IPR000012

Secondary Structure prediction:

Antigenic Sites - EMBOSS:




Predicted Motifs: Printer-friendly version

N-glycosylation:
N-myristoylation:
Amidation:
Protein kinase C:
Casein kinase II:
Tyrosine kinase:
cAMP / cGMP kinase:
Cell attachment motif:
Asp Protease motif:
Asp Prot Retro motif:
Arginine-rich Region:
Cysteine-rich Region:
Tryptophan-rich Region:
Zinc-finger CCHC motif:
Leucine Zipper motif:

Primary and Secondary Database Entries: [TOP]

Identifiers:



ViralZone: HIV-1, HIV replication cycle, HIV resource
PDB/MMDB: Search for HIV-1 & VPR

UniProt: P69726 (HIV-1 HXB2 Vpr)
EMBL: K03455; AAB50261.1; [EMBL/GenBank/DDBJ]

InterPro: IPR000012
Pfam: PF00522
Prints: PR00444; HIVVPRVPX
SCOP: none
BLOCKS: P05926
Prosite: P05926
ProtoNet: P05926
Database of Interacting Proteins: P05926
ModBase: P05926
HIV-1/Human Protein Interaction DB: HIV-1 Vpr
HIV-1 Sequence Database Los Alamos HIV Sequence Database

PDB:




Reviews and References: [TOP]


Cite the resource by citing the following paper:
Doherty R et al. BioAfrica's HIV-1 Proteomics Resource: Combining protein data with bioinformatics tools. Retrovirology (2005), 9;2(1):18.

1 - HIV Sequence Compendium 2000
Kuiken CL, Foley B, Hahn B, Korber B, Marx PA, McCutchan F, Mellors JW, Mullins JI, Sodroski J, Wolinksy S.
Theoretical Biol. & Biophys. Group, Los Alamos Nat Lab, LA-UR 01-3860 [Read it online: Compendium]
2 - Retroviruses
Coffin JM, Hughes SH, Varmus HE.
CD-ROM ed. (2002) Cold Spring Harbor Laboratory Press [Read it online: NCBI Bookshelf]
3 - The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral
nucleic acids in nondividing host cells.
Heinzinger NK, Bukinsky MI, Haggerty SA.
Proc Natl Acad Sci USA 91: 7311-7315 (1994) [pubmed: 8041786]
4 - The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase
of the cell cycle.
Jowett JB, Planelles V, Poon B.
J Virol 69: 6304-6313 (1995) [pubmed: 7666531]
5 - Human immunodeficiency virus vpr product is a virion-associated regulatory protein.
Cohen EA, Dehni G, Sodroski JG.
J Virol 64: 3097-3099 (1990) [pubmed: 2139896]
6 - The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during
chronic infection.
Rogel ME, Wu LI, Emerman M.
J Virol 69: 882-888 (1995) [pubmed: 7815556]
7 - Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting
the activation of p34cdc2-cyclin B.
Braaten D, Franke EK, Luban J.
J Virol 69: 6859-6864 (1995) [pubmed: 7474100]
8 - Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of
the cell cycle by inhibiting p34cdc2 activity.
He J, Choe S, Walker R.
J Virol 69: 6705-6711 (1995) [pubmed: 7474080]
9 - Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA glycosylase
DNA repair enzyme.
Bouhamdan M, Benichou S, Rey F.
J Virol 70: 697-704 (1996) [pubmed: 8551605]
10 - HIV-1 Vpr-a still "enigmatic multitasker".
Guenzel CA, Hérate C, Benichou S.
Front Microbiol. 5:127 (2014) [pubmed: 24744753]
11 - Visualization of the intracellular behavior of HIV in living cells.
McDonald D, Vodicka MA, Lucero G, Svitkina TM, Borisy GG, Emerman M, Hope TJ.
J Cell Biol. 159(3):441-52 (2002) [pubmed: 12417576]
12 - HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT.
Andersen JL, DeHart JL, Zimmerman ES, Ardon O, Kim B, Jacquot G, Benichou S, Planelles V.
PLoS Pathog. 2(12):e127 (2006) [pubmed: 17140287]
13 - 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 ME, Wu LI, Vodicka MA, Sire J, Benarous R, Emerman M.
J Virol. 71(6):4842-6 (1997) [pubmed: 9151883]
14 - HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase.
Transy C, Margottin-Goguet F.
Cell Cycle. 8(16):2489-90 (2009) [pubmed: 19667756]
15 - Human immunodeficiency virus type 1 Vpr induces the degradation of the UNG and SMUG uracil-DNA glycosylases.
Schröfelbauer B, Yu Q, Zeitlin SG, Landau NR.
J Virol. 79(17):10978-87 (2005) [pubmed: 16103149]
16 - HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase.
Le Rouzic E, Belaïdouni N, Estrabaud E, Morel M, Rain JC, Transy C, Margottin-Goguet F.
Cell Cycle 6(2):182-8 (2007) [pubmed: 17314515]
17 - Importin-alpha promotes passage through the nuclear pore complex of human immunodeficiency virus type 1 Vpr.
Kamata M, Nitahara-Kasahara Y, Miyamoto Y, Yoneda Y, Aida Y.
J Virol. 79(6):3557-64 (2005) [pubmed: 15731250]
18 - Human immunodeficiency virus type 1 Vpr interacts with HHR23A, a cellular protein implicated in nucleotide excision DNA repair.
Withers-Ward ES, Jowett JB, Stewart SA, Xie YM, Garfinkel A, Shibagaki Y, Chow SA, Shah N, Hanaoka F, Sawitz DG, Armstrong RW, Souza LM, Chen IS.
J Virol. 71(12):9732-42 (1997) [pubmed: 9371639]



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Page last updated by Megan Druce, Paula Sommer and Tulio de Oliveira (UKZN/Africa Centre) & Philippe Le Mercier, Chantal Hulo and Patrick Masson (SIB/ViralZone).