Homo sapiens Protein: VPRBP
InnateDB Protein IDBP-37407.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol VPRBP
Protein Name Vpr (HIV-1) binding protein
Synonyms DCAF1;
Species Homo sapiens
Ensembl Protein ENSP00000338857
InnateDB Gene IDBG-37403 (VPRBP)
Protein Structure
UniProt Annotation
Function Acts both as a substrate recognition component of E3 ubiquitin-protein ligase complexes and as an atypical serine/threonine-protein kinase, playing key roles in various processes such as cell cycle, telomerase regulation and histone modification. Probable substrate-specific adapter of a DCX (DDB1- CUL4-X-box) E3 ubiquitin-protein ligase complex, named CUL4A-RBX1- DDB1-DCAF1/VPRBP complex, which mediates ubiquitination and proteasome-dependent degradation of proteins such as NF2. Involved in the turnover of methylated proteins: recognizes and binds methylated proteins via its chromo domain, leading to ubiquitination of target proteins by the RBX1-DDB1-DCAF1/VPRBP complex (PubMed:23063525). The CUL4A-RBX1-DDB1-DCAF1/VPRBP complex is also involved in B-cell development: VPRBP is recruited by RAG1 to ubiquitinate proteins, leading to limit error-prone repair during V(D)J recombination. Also part of the EDVP complex, an E3 ligase complex that mediates ubiquitination of proteins such as TERT, leading to TERT degradation and telomerase inhibition (PubMed:23362280). Also acts as an atypical serine/threonine- protein kinase that specifically mediates phosphorylation of 'Thr- 120' of histone H2A (H2AT120ph) in a nucleosomal context, thereby repressing transcription. H2AT120ph is present in the regulatory region of many tumor suppresor genes, down-regulates their transcription and is present at high level in a number of tumors (PubMed:24140421). Involved in JNK-mediated apoptosis during cell competition process via its interaction with LLGL1 and LLGL2 (PubMed:20644714). In case of infection by HIV-1 virus, it is recruited by HIV-1 Vpr in order to hijack the CUL4A-RBX1-DDB1- DCAF1/VPRBP function leading to arrest the cell cycle in G2 phase, and also to protect the viral protein from proteasomal degradation by another E3 ubiquitin ligase. The HIV-1 Vpr protein hijacks the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to promote ubiquitination and degradation of proteins such as TERT and ZIP/ZGPAT. In case of infection by HIV-2 virus, it is recruited by HIV-2 Vpx in order to hijack the CUL4A-RBX1-DDB1-DCAF1/VPRBP function leading to enhanced efficiency of macrophage infection and promotion of the replication of cognate primate lentiviruses in cells of monocyte/macrophage lineage. {ECO:0000269PubMed:16964240, ECO:0000269PubMed:17314515, ECO:0000269PubMed:17559673, ECO:0000269PubMed:17609381, ECO:0000269PubMed:17620334, ECO:0000269PubMed:17626091, ECO:0000269PubMed:17630831, ECO:0000269PubMed:18332868, ECO:0000269PubMed:18464893, ECO:0000269PubMed:18524771, ECO:0000269PubMed:18606781, ECO:0000269PubMed:19264781, ECO:0000269PubMed:19287380, ECO:0000269PubMed:19923175, ECO:0000269PubMed:20644714, ECO:0000269PubMed:22184063, ECO:0000269PubMed:23063525, ECO:0000269PubMed:23362280, ECO:0000269PubMed:24116224, ECO:0000269PubMed:24140421, ECO:0000269PubMed:24336198}.
Subcellular Localization Cytoplasm. Nucleus. Note=Associated with chromatin in a DDB1-independent and cell cycle-dependent manner: recruited to chromatin as DNA is being replicated and is released from chromatin before mitosis.
Disease Associations
Tissue Specificity Ubiquitously expressed. {ECO:0000269PubMed:11223251}.
Number of Interactions This gene and/or its encoded proteins are associated with 83 experimentally validated interaction(s) in this database.
Experimentally validated
Total 83 [view]
Protein-Protein 83 [view]
Protein-DNA 0
Protein-RNA 0
Gene Ontology

Molecular Function
Accession GO Term
GO:0005488 binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:1990244 histone kinase activity (H2A-T120 specific)
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006351 transcription, DNA-templated
GO:0016032 viral process
GO:0016567 protein ubiquitination
GO:0030183 B cell differentiation
GO:0033151 V(D)J recombination
GO:0035212 cell competition in a multicellular organism
GO:1990245 histone H2A-T120 phosphorylation
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0008180 COP9 signalosome
Protein Structure and Domains
InterPro IPR006594 LisH dimerisation motif
IPR016024 Armadillo-type fold
IPR017986 WD40-repeat-containing domain
Post-translational Modifications
SwissProt Q9Y4B6
PhosphoSite PhosphoSite-Q9Y4B6
UniProt Splice Variant
Entrez Gene 9730
UniGene Hs.716623
HPRD 11674
EMBL AB018343 AC092037 AF061935 AL080145 BC022792 BC110371
GenPept AAG27134 AAH22792 AAI10372 BAA34520 CAB45738