ID:CUL4B_HUMAN DESCRIPTION: RecName: Full=Cullin-4B; Short=CUL-4B; FUNCTION: Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit. CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and histone H4 in response to radiation- induced DNA damage. Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication. Required for ubiquitination of cyclin E, and consequently, normal G1 cell cycle progression. Regulates the mammalian target-of-rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism. Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Component of multiple DCX (DDB1-CUL4-X-box) E3 ubiquitin- protein ligase complexes that seem to be formed 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 DCX(DTL) complex with the putative substrate recognition component DTL. Component of the DCX(DDB2) complex with the putative substrate recognition component DDB2. Part of a complex with RBX1 and TIP120A/CAND1. Interacts with RBX1 GRWD1, MLST8, SMU1, TLE2, TLE3, VPRBP, DDA1, DCAF6, DCAF17, DDB2, DCAF8, TIP120A/CAND1 and TMEM113. Interacts with cyclin E and with importins alpha-1 (KPNA2), alpha-3 (KPNA4), alpha-5 (KPNA1) and beta-1 (KPNB1). May interact with WDR26, WDR51B, SNRNP40, WDR61, WDR76 and WDR5. INTERACTION: Q86VP6:CAND1; NbExp=3; IntAct=EBI-456067, EBI-456077; SUBCELLULAR LOCATION: Nucleus. PTM: Neddylated. Deneddylated via its interaction with the COP9 signalosome (CSN) complex. DISEASE: Defects in CUL4B are the cause of mental retardation syndromic X-linked Cabezas type (MRXC) [MIM:300354]; also known as mental retardation syndromic X-linked type 15. A syndromic form of X-linked mental retardation characterized by severe intellectual deficit associated with short stature, craniofacial dysmorphism, small testes, muscle wasting in lower legs, kyphosis, joint hyperextensibility, pes cavus, small feet, and abnormalities of the toes. Additional neurologic manifestations include speech delay and impairment, tremor, seizures, gait ataxia, hyperactivity and decreased attention span. SIMILARITY: Belongs to the cullin family. SEQUENCE CAUTION: Sequence=AAB67315.1; Type=Erroneous gene model prediction; Sequence=AAK16812.1; Type=Frameshift; Positions=115; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CUL4B";
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 Q13620
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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:0003684 damaged DNA 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: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:0007049 cell cycle GO:0010498 proteasomal protein catabolic process GO:0016567 protein ubiquitination GO:0031175 neuron projection development GO:0033683 nucleotide-excision repair, DNA incision GO:0035518 histone H2A monoubiquitination GO:0042769 DNA damage response, detection of DNA damage GO:0043687 post-translational protein modification GO:0045732 positive regulation of protein catabolic process GO:0070911 global genome nucleotide-excision repair GO:0070914 UV-damage excision repair GO:1900087 positive regulation of G1/S transition of mitotic cell cycle
BX537787 - Homo sapiens mRNA; cDNA DKFZp779P1063 (from clone DKFZp779P1063); complete cds. CR936722 - Homo sapiens mRNA; cDNA DKFZp686F1470 (from clone DKFZp686F1470). BX537641 - Homo sapiens mRNA; cDNA DKFZp686D0844 (from clone DKFZp686D0844). AB014595 - Homo sapiens mRNA for KIAA0695 protein, partial cds. BX647096 - Homo sapiens mRNA; cDNA DKFZp686H07166 (from clone DKFZp686H07166). AK299081 - Homo sapiens cDNA FLJ53167 complete cds, highly similar to Cullin-4B. BC036216 - Homo sapiens cullin 4B, mRNA (cDNA clone MGC:39677 IMAGE:5269392), complete cds. AK123688 - Homo sapiens cDNA FLJ41694 fis, clone HCHON2001217, highly similar to Cullin-4B. U58091 - Human Hs-cul-4B mRNA, partial cds. AF212995 - Homo sapiens cullin CUL4B (CUL4B) mRNA, complete cds. KJ897848 - Synthetic construct Homo sapiens clone ccsbBroadEn_07242 CUL4B gene, encodes complete protein. KR709555 - Synthetic construct Homo sapiens clone CCSBHm_00003369 CUL4B (CUL4B) mRNA, encodes complete protein. KR709556 - Synthetic construct Homo sapiens clone CCSBHm_00003371 CUL4B (CUL4B) mRNA, encodes complete protein. KR709557 - Synthetic construct Homo sapiens clone CCSBHm_00003372 CUL4B (CUL4B) mRNA, encodes complete protein. AY365125 - Homo sapiens cullin 4B (CUL4B) mRNA, complete cds. AK315037 - Homo sapiens cDNA, FLJ95982, highly similar to Homo sapiens cullin 4B (CUL4B), mRNA. DQ894750 - Synthetic construct Homo sapiens clone IMAGE:100009210; FLH178090.01L; RZPDo839H05125D cullin 4B (CUL4B) gene, encodes complete protein. JD062415 - Sequence 43439 from Patent EP1572962. JD453776 - Sequence 434800 from Patent EP1572962. CU690308 - Synthetic construct Homo sapiens gateway clone IMAGE:100017839 5' read CUL4B mRNA.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q13620 (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
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
