Protein: DDB1- and CUL4-associated factor 1 (Serine/threonine-protein kinase VPRBP) (EC 2.7.11.1) (Q80TR8)
Organism: Mus musculus (Mouse)
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. 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.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:24357321}. Nucleus {ECO:0000269|PubMed:24357321, ECO:0000269|PubMed:25557551, ECO:0000269|PubMed:36056023}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:Q9Y4B6}. 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 (PubMed:36056023). Homogenous pancellular distribution is observed outside S-phase and a slight cytoplasmic-to-nuclear translocation from early to late S-phase (PubMed:36056023). Colocalizes with TET1 and PCNA at replicating heterochromatin during late S phase (PubMed:36056023). More concentrated in nuclei than in cytoplasm in germinal vesicle (GV) stage oocytes, zygotes and the 2-cell stage, but distributed in the cytoplasm at the MII-stage oocytes (PubMed:24357321). Localizes to centrosomes following interaction with CEP78 (By similarity). {ECO:0000250|UniProtKB:Q9Y4B6, ECO:0000269|PubMed:24357321, ECO:0000269|PubMed:36056023}.
Interaction partners:
- Cullin-4A
- DNA damage-binding protein 1
- Cullin-4B
- E3 ubiquitin-protein ligase RBX1
- Deoxynucleoside triphosphate triphosphohydrolase SAMHD1
- Denticleless protein homolog
- DET1- and DDB1-associated protein 1
- Angiomotin-like protein 1
- DNA damage-binding protein 2
- Uracil-DNA glycosylase
Sequence:
MTTVVVHVDSKAELTTLLEQWEKDHGSGQDMVPILTRMSELIEKETEEYRKGDPDPFDDRHPGRADPECMLGHLLRILFKNDDFMNALVNAYVMTSREPPLNTAACRLLLDIMPGLETAVVFQEKEGIVENLFKWAREADQPLRTYSTGLLGGAMENQDIAANYRDENSQLVAIVLRRLRELQLQEVALRQDSKRPSPRKLSSEPLLPLDEEAVDMDYGDMAVDVVDGEQESSRDMEISFRLDSSHKTSSRVNSATKPEEGGLKKNKSAKHGDRENFRKAKQKLGFSSSDPDRVFVELSNSSWSEMSPWVIGTNYTLYPMTPAIEQRLILQYLTPLGEYQELLPIFMQLGSRELMMFYIDLKQTNDVLLTFEALKHLASLLLHNKFATEFVAHGGVQKLLEIPRPSMAATGVSMCLYYLSYNQDAMERVCMHPHNVLSDVVNYTLWLMECSHASGCCHATMFFSICFSFRAVLELFDRYDGLRRLVNLISTLEILNLEDQGALLSDDEIFASRQTGKHTCMALRKYFEAHLAIKLEQVKQSLQRTEGGILVHPQPPYKACSYTHEQIVEMMEFLIEYGPAQLYWEPAEVFLKLSCVQLLLQLISIACNWKTYYARNDTVRFALDVLAILTVVPKIQLQLAESVDVLDEAGSAVSTVGISIILGVAEGEFFIHDAEIQKSALQIIINCVCGPDNRISSIGKFISGTPRRKLSQTPKSSEHTLAKMWNVVQSNNGIKVLLSLLSIKMPITDADQIRALACKALVGLSRSSTVRQIISKLPLFSSCQIQQLMKEPVLQDKRSDHVKFCKYAAELIERVSGKPLLIGTDVSLARLQKADVVAQSRISFPEKELLLLIRNHLISKGLGETATVLTREADLPMTAASHSSAFTPVTAAASPVSLPRTPRIANGIASRLGSHATVGASAPSAPPAHPPPRPPQGSLPLPGPSYAGNSPLIGRISFIRERPSPCNGRKIRVLRQKSDHGAYSQSPAIKKQLDRHLPSPPTLDSIITEYLREQHARCKNPVATCPPFSLFTPHQCPEPKQRRQAPINFTSRLNRRASFPKYGGVDGGCFDRHLIFSRFRPISVFREANEDESGFTCCAFSARERFLMLGTCTGQLKLYNVFSGQEEASYNCHNSAITHLEPSRDGSLLLTSATWSQPLSALWGMKSVFDMKHSFTEDHYVEFSKHSQDRVIGTKGDIAHIYDIQTGNKLLTLFNPDLANNYKRNCATFNPTDDLVLNDGVLWDVRSAQAIHKFDKFNMNISGVFHPNGLEVIINTEIWDLRTFHLLHTVPALDQCRVVFNHTGTVMYGAMLQADDEDDLLEERMKSPFGSSFRTFNATDYKPIATIDVKRNIFDLCTDTKDCYLAVIENQGSMDALNMDTVCRLYEVGRQRLAEDEDEEEDQEEEEQEEEDDDEDDDDTDDLDELDTDQLLEAELEEDDNNENAGEDGDNDFSPSDEELANLLEEGEEGEDEDSDADEEVELILGDTDSSDNSDLEDDIILSLNE