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10  structures 90  species 0  interactions 5858  sequences 3  architectures

Family: VPR (PF00522)

Summary: VPR/VPX protein

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This is the Wikipedia entry entitled "Vpr". More...

Vpr Edit Wikipedia article

VPR
PDB 1fi0 EBI.jpg
solution structure of hiv-1 vpr (13-33) peptide in micells
Identifiers
Symbol VPR
Pfam PF00522
InterPro IPR000012
SCOP 1dsk
SUPERFAMILY 1dsk
TCDB 1.A.42

Vpr is a Human immunodeficieny viral gene and protein product.[1][2]

Vpr stands for "Viral Protein R". Vpr, a 96 amino acid 14-kDa protein, plays an important role in regulating nuclear import of the HIV-1 pre-integration complex, and is required for virus replication in non-dividing cells such as macrophages. Vpr also induces G2 cell cycle arrest and apoptosis in proliferating cells, which can result in immune dysfunction.[3][4]

Vpr is also immunosuppressive due to its ability to sequester a proinflammatory transcriptional activator in the cytoplasm. HIV-2 contains both a Vpr protein and a related (by sequence homology) Vpx protein (Viral Protein X). Two functions of Vpr in HIV-1 are split between Vpr and Vpx in HIV-2, with the HIV-2 Vpr protein inducing cell cycle arrest and the Vpx protein required for nuclear import.

Protein[edit]

VprBP is a 1,507-amino-acid protein that contains conserved domains, including YXXY repeats, the Lis homology motif, and WD40 repeats.[5]

Function[edit]

Vpr binding protein (VprBP) regulates the p53-VprBP interaction with HIV-1 viral protein R. VprBP regulates p53-induced transcription and apoptotic pathways. p53 is an important tumor suppressor which induces either cell cycle arrest or apoptosis in response to DNA damage. This fits in with the fact that HIV attacks CD4+ cells.[5]

References[edit]

  1. ^ Vpr Gene Products, Human Immunodeficiency Virus at the US National Library of Medicine Medical Subject Headings (MeSH)
  2. ^ Genes, Vpr at the US National Library of Medicine Medical Subject Headings (MeSH)
  3. ^ Bukrinsky M, Adzhubei A (1999). "Viral protein R of HIV-1". Rev. Med. Virol. 9 (1): 39–49. doi:10.1002/(SICI)1099-1654(199901/03)9:1<39::AID-RMV235>3.0.CO;2-3. PMID 10371671. 
  4. ^ Muthumani K, Choo AY, Zong WX, et al. (February 2006). "The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1". Nat. Cell Biol. 8 (2): 170–9. doi:10.1038/ncb1352. PMID 16429131. 
  5. ^ a b Kim K, Heo K, Choi J, Jackson S, Kim H, Xiong Y et al. (2012). "Vpr-binding protein antagonizes p53-mediated transcription via direct interaction with H3 tail.". Mol Cell Biol 32 (4): 783–96. doi:10.1128/MCB.06037-11. PMC 3272969. PMID 22184063. 

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

VPR/VPX protein Provide feedback

No Pfam abstract.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000012

Human immunodeficiency virus (HIV) is the human retrovirus associated with AIDS (acquired immune deficiency syndrome), and SIV its simian counterpart. Three main groups of primate lentivirus are known, designated Human immunodeficiency virus 1 (HIV-1), Human immunodeficiency virus 2 (HIV-2)/Simian immunodeficiency virus - mac (SIVMAC)/Simian immunodeficiency virus - sm (SIVSM) and Simian immunodeficiency virus - agm (SIVAGM). Simian immunodeficiency virus - mnd (SIVMND) has been suggested to represent a fourth distinct group [PUBMED:2797181]. These groups are believed to have diverged from a common ancestor long before the spread of AIDS in humans. Genetic variation in HIV-1 and HIV-2 has been studied extensively, and the nucleotide sequences reported for several strains [PUBMED:2611042].

ORF analysis has revealed two open reading frames, yielding the so-called R- and X-ORF proteins, which show a high degree of sequence similarity.

Vpx plays a role in nuclear translocation of the viral pre-integration complex (PIC) and is thus required for the virus to infect non-dividing cells. Vpr also plays a role in nuclear translocation of the (PIC) and may target specific host proteins for degradation by the 26S proteasome. It acts by associating with the cellular CUL4A-DDB1 E3 ligase complex through direct interaction with host VPRPB/DCAF-1. This would result in cell cycle arrest or apoptosis in infected cells, creating a favourable environment for maximizing viral expression and production by rendering the HIV-1 LTR transcription more active.

Gene Ontology

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Domain organisation

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Alignments

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  Seed
(12)
Full
(5858)
Representative proteomes NCBI
(5609)
Meta
(0)
RP15
(0)
RP35
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RP55
(0)
RP75
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  Seed
(12)
Full
(5858)
Representative proteomes NCBI
(5609)
Meta
(0)
RP15
(0)
RP35
(0)
RP55
(0)
RP75
(0)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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Trees

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Curation and family details

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Curation View help on the curation process

Seed source: Pfam-B_100 (release 1.0)
Previous IDs: none
Type: Family
Author: Finn RD
Number in seed: 12
Number in full: 5858
Average length of the domain: 89.30 aa
Average identity of full alignment: 80 %
Average coverage of the sequence by the domain: 93.70 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.8 20.8
Trusted cut-off 25.6 25.4
Noise cut-off 20.2 20.2
Model length: 96
Family (HMM) version: 13
Download: download the raw HMM for this family

Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the VPR domain has been found. There are 10 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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