VPR - Viral Protein R

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


PDB-1M8L: HIV-1 (isolate UNKNOWN) Vpr protein - produced using SwissModel/SPDBV/POVray
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ViralZone:HIV-1
PDB: 1M8L (HIV-1 Vpr)
SwissProt: P69726 (HIV-1 HXB2 Vpr)
Chime Tutorial:  not available
Los Alamos HIV structure DB:  VPR
NCBI: K03455 [EMBL/GenBank/DDBJ]
BioAfrica: Vpr Protein Data Mining Tool

Isoforms:

  • p10-15 (78 amino acids)

Localization:

  • Virion
  • Cell internal membranes
  • Cell nucleus

Function:

  • blocks cell division (Ref. #6)
  • promotes nuclear localization of preintegration complex (Ref. #3)
  • arrests cell in G2 phase of cell cycle (Ref. #4)

Additional Information:

  • ~100 copies of Vpr are associated with each virion (Ref. #5)
  • prevents activation of p34cdc2/cyclin B complex, which is a regulator of the cell cycle that important for entry into mitosis (Ref. #7 & #8)
  • genetically modified p34cdc2 prevents the cell cycle inhibitory activity of Vpr
  • incorporation of Vpr into virions is mediated by interactions with carboxyl-terminal region of p55 Gag
  • reduces mutation rate of HIV during replication

Genomic Location: [TOP]

Reference Sequences:

HIV-1 (HXB2): 

          10         20         30         40         50         60         70
           |          |          |          |          |          |          |
  MEQAPEDQGP QREPHNEWTL ELLEELKNEA VRHFPRIWLH GLGQHIYETY GDTWAGVEAI IRILQQLLFI
        78
         |
  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:

Protein-Protein Interactions: [TOP]

  • interacts with carboxyl-terminal (p6 & NCp7) region of the N-myristoylated Gag polyprotein
  • cdc25c is a phosphatase that regulates the cell cycle by activating the p34cdc2/cyclin B complex through the removal of phosphates from p34cdc2
  • Vpr induces cell cycle arrest by interacting with cdc25c.
  • Interactions between Vpr and cdc25c prevent p34cdc2/cyclin B activation (Ref. #7 & #8)
  • Vpr interacts with HHR23A and mov34
  • interacts with Human cellular protein uracil-DNA glycosylase (UNG) (Ref. #9)
  • stabilizes the interaction between karyopherin heterodimers and the nuclear localization signal of HIV-1 Matrix
  • karyopherin mediates nuclear import
  • Vpr interacts directly with nucleoporin, which make up the nuclear pore complexes and regulate the movement of molecules in and out of the nucleus
Primary and Secondary Database Entries: [TOP]

Identifiers:

ViralZone: HIV-1
PDB/MMDB: Search for HIV-1 & VPR

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

PIR: UNKNOWN
HIV: K03455; VPR$HXB2
InterPro: IPR000012
Pfam: PF00522
Prints: PR00444; HIVVPRVPX
ProDom: PD000233 (residues 1 - 36) / PD000213 (residues 38 - 71)
SCOP: none
BLOCKS: P05926
Prosite: P05926
ProtoNet: P05926
ProtoMap: P05926
PRESAGE: P05926
Database of Interacting Proteins: P05926
ModBase: P05926
Swiss-2DPAGE: 2D gel

BioAfrica Tools:
- Vpr Protein Data Mining Tool provides real-time analysis of HIV-1 Vpr isolates
- HIV Structure BLAST searches for similar HIV sequences that have known structures
- HIV Proteomics Resource contains protein sequence and structure analysis tools
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]



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