ID:CUL4A_HUMAN DESCRIPTION: RecName: Full=Cullin-4A; Short=CUL-4A; FUNCTION: Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. DCX(DET1-COP1) directs ubiquitination of JUN. DCX(DDB2) directs ubiquitination of XPC. In association with RBX1, DDB1 and DDB2 is required for histone H3 and histone H4 ubiquitination in response to ultraviolet and may be important for subsequent DNA repair. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip. Is involved in ubiquitination of HOXA9. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin- protein ligase complexes that seem to consist of DDB1, CUL4A or CUL4B, RBX1 and a variable substrate recognition component which seems to belong to a protein family described as DCAF (Ddb1- and Cul4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins. Component of the CSA complex (DCX(ERCC8) complex) containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Component of the DCX(DET1-COP1) complex with the substrate recognition component DET1 and COP1. Component of the DCX(DDB2) complex with the substrate recognition component DDB2. Component of the DCX(DTL) complex with the putative substrate recognition component DTL. Interacts with DDB1, RBX1, RNF7, CTD1, TIP120A/CAND1, SKP2, CDKN1B, MDM2, TP53 and HOXA9. Interacts with DDB2; the interactions with DDB2 and CAND1 are mutually exclusive. Interacts with VPRBP, DTL, DDA1, DCAF6, DCAF4, DCAF16, DCAF17, DET1, WDTC1, DCAF5, DCAF11, WDR24A, RFWD2, PAFAH1B1, ERCC8, GRWD1, FBXW5, RBBP7, GNB2, WSB1, WSB2, NUP43, PWP1, FBXW8, ATG16L1, KATNB1, RBBP4, RBBP5 and DCAF8. May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76, WDR5. Can self- associate. Interacts with Epstein-Barr virus BPLF1. INTERACTION: Q86VP6:CAND1; NbExp=3; IntAct=EBI-456106, EBI-456077; Q92466:DDB2; NbExp=2; IntAct=EBI-456106, EBI-1176171; Q15291:RBBP5; NbExp=3; IntAct=EBI-456106, EBI-592823; PTM: Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (By similarity). Deneddylated by Epstein-Barr virus BPLF1 leading to a S-phase-like environment that is required for efficient replication of the viral genome. SIMILARITY: Belongs to the cullin family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13619
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005515 protein binding GO:0031625 ubiquitin protein ligase binding GO:0061630 ubiquitin protein ligase activity
Biological Process: GO:0000082 G1/S transition of mitotic cell cycle GO:0000715 nucleotide-excision repair, DNA damage recognition GO:0001701 in utero embryonic development GO:0006281 DNA repair GO:0006283 transcription-coupled nucleotide-excision repair GO:0006293 nucleotide-excision repair, preincision complex stabilization GO:0006294 nucleotide-excision repair, preincision complex assembly GO:0006296 nucleotide-excision repair, DNA incision, 5'-to lesion GO:0006511 ubiquitin-dependent protein catabolic process GO:0006974 cellular response to DNA damage stimulus GO:0007050 cell cycle arrest GO:0008284 positive regulation of cell proliferation GO:0008285 negative regulation of cell proliferation GO:0016032 viral process GO:0016567 protein ubiquitination GO:0030097 hemopoiesis GO:0030853 negative regulation of granulocyte differentiation GO:0033683 nucleotide-excision repair, DNA incision GO:0035019 somatic stem cell population maintenance GO:0042769 DNA damage response, detection of DNA damage GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043687 post-translational protein modification GO:0051246 regulation of protein metabolic process GO:0070911 global genome nucleotide-excision repair GO:0097193 intrinsic apoptotic signaling pathway GO:1900087 positive regulation of G1/S transition of mitotic cell cycle GO:2000001 regulation of DNA damage checkpoint GO:2000819 regulation of nucleotide-excision repair
Protein Q13619 (Reactome details) participates in the following event(s):
R-HSA-8955245 CAND1 binds CRL4 E3 ubiquitin ligase in the nucleus R-HSA-5690988 3'-incision of DNA by ERCC5 (XPG) in GG-NER R-HSA-8955285 COMMDs displace CAND1 from CRL4 E3 ubiquitin ligase complex R-HSA-8952639 NEDD8:AcM-UBE2M binds CRL4 E3 ubiquitin ligase complex R-HSA-8956045 COP9 signalosome deneddylates nuclear CRL4 E3 ubiquitin ligase complex R-HSA-5652005 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL ubiquitin ligase complex binds PCNA:POLD,POLE:RPA:RFC associated with damaged dsDNA R-HSA-5652009 RAD18:UBE2B or RBX1:CUL4:DDB1:DTL monoubiquitinates PCNA R-HSA-6782943 UV-DDB ubiquitinates XPC R-HSA-5691006 XPC:RAD23:CETN2 and UV-DDB bind distorted dsDNA site R-HSA-5696664 PARP1 or PARP2 binds DDB2 at GG-NER site R-HSA-5690213 DNA polymerases delta, epsilon or kappa bind the GG-NER site R-HSA-5690990 5'- incision of DNA by ERCC1:ERCC4 in GG-NER R-HSA-6790487 RNF111 ubiquitinates SUMOylated XPC R-HSA-6790454 SUMOylation of XPC R-HSA-5689317 Formation of the pre-incision complex in GG-NER R-HSA-6781867 ERCC8:DDB1:CUL4:RBX1 ubiquitinates ERCC6 and RNA Pol II R-HSA-6781833 ERCC8 (CSA) binds stalled RNA Pol II R-HSA-6782004 Assembly of the pre-incision complex in TC-NER R-HSA-6782211 DNA polymerases delta, epsilon or kappa bind the TC-NER site R-HSA-6782204 5' incision of damaged DNA strand by ERCC1:ERCC4 in TC-NER R-HSA-6782224 3' incision by ERCC5 (XPG) in TC-NER R-HSA-6782227 Ligation of newly synthesized repair patch to incised DNA in TC-NER R-HSA-6782208 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER R-HSA-8952638 AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex R-HSA-5696655 PARP1 or PARP2 PARylates DDB2 and autoPARylates R-HSA-5690996 ERCC2 and ERCC3 DNA helicases form an open bubble structure in damaged DNA R-HSA-5691000 TFIIH binds GG-NER site to form a verification complex R-HSA-5690991 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in GG-NER R-HSA-6782069 UVSSA:USP7 deubiquitinates ERCC6 R-HSA-6782131 RNA Pol II backtracking in TC-NER R-HSA-6782138 ERCC5 and RPA bind TC-NER site R-HSA-5696670 CHD1L is recruited to GG-NER site R-HSA-5689861 Recruitment of XPA and release of CAK R-HSA-6782141 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in TC-NER R-HSA-8951664 Neddylation R-HSA-5696400 Dual Incision in GG-NER R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-597592 Post-translational protein modification R-HSA-110314 Recognition of DNA damage by PCNA-containing replication complex R-HSA-5696394 DNA Damage Recognition in GG-NER R-HSA-5696395 Formation of Incision Complex in GG-NER R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) R-HSA-6781823 Formation of TC-NER Pre-Incision Complex R-HSA-6782135 Dual incision in TC-NER R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-5696398 Nucleotide Excision Repair R-HSA-392499 Metabolism of proteins R-HSA-73893 DNA Damage Bypass R-HSA-73894 DNA Repair
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Common Gene Haplotype Alleles 
