| 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. The CUL4A-RBX1-DDB1-DCAF1/VPRBP complex is also involved in B-cell development: DCAF1 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. The EDVP complex also mediates ubiquitination and degradation of CCP110. 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. Involved in JNK-mediated apoptosis during cell competition process via its interaction with LLGL1 and LLGL2. By acting on TET dioxygenses, essential for oocyte maintenance at the primordial follicle stage, hence essential for female fertility. (Microbial infection) 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. (Microbial infection) 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. |
| Protein Name | Ddb1- And Cul4-Associated Factor 1Hiv-1 Vpr-Binding ProteinVprbpSerine/Threonine-Protein Kinase VprbpVpr-Interacting Protein |
| Database Links | Reactome: R-HSA-983168 |
| Cellular Localisation | CytoplasmNucleusCytoskeletonMicrotubule Organizing CenterCentrosomeAssociated 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 MitosisHomogenous Pancellular Distribution Is Observed Outside S-Phase And A Slight Cytoplasmic-To-Nuclear Translocation From Early To Late S-PhaseColocalizes With Tet1 And Pcna At Replicating Heterochromatin During Late S PhaseMore Concentrated In Nuclei Than In Cytoplasm In Germinal Vesicle (Gv) Stage OocytesZygotes And The 2-Cell StageBut Distributed In The Cytoplasm At The Mii-Stage OocytesLocalizes To Centrosomes Following Interaction With Cep78 |
| Alternative Protein Names | Ddb1- And Cul4-Associated Factor 1 proteinHiv-1 Vpr-Binding Protein proteinVprbp proteinSerine/Threonine-Protein Kinase Vprbp proteinVpr-Interacting Protein proteinDCAF1 proteinKIAA0800 proteinRIP proteinVPRBP protein |
Information sourced from Uniprot.org
