ID:CUL3_HUMAN DESCRIPTION: RecName: Full=Cullin-3; Short=CUL-3; FUNCTION: Core component of multiple cullin-RING-based BCR (BTB- CUL3-RBX1) 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 (By similarity). The functional specificity of the BCR complex depends on the BTB domain-containing protein as the susbstrate recognition component. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, H2AFY and DAXX, and probably GLI2 or GLI3. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; possibly by mediating ubiquitination of SLC12A3/NCC. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Forms neddylation-dependent homodimers. Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein acting as both, adapter to cullin and substrate recognition subunit. The BCR complex may be active as a heterodimeric complex, in which NEDD8, covalently attached to one CUL3 molecule, binds to the C-terminus of a second CUL3 molecule. Interacts with RBX1, RNF7, CYCE and TIP120A/CAND1. Part of the BCR(SPOP) containing SPOP. Part of the probable BCR(KLHL9-KLHL13) complex with BTB domain proteins KLHL9 and KLHL13. Part of the BCR(KBTBD10) complex containing KBTBD10. Component of the BCR(KLHL12) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL12 and RBX1. Component of the BCR(KLHL3) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL3 and RBX1 (Probable). Part of the BCR(ENC1) complex containing ENC1. Part of a complex consisting of BMI1/PCGF4, CUL3 and SPOP. Part of a complex consisting of H2AFY, CUL3 and SPOP. Interacts with KCTD5, KLHL9, KLHL13, GAN, ZBTB16, KLHL21, KLHL3, KLHL15, KLHL20, C16orf44, GMCL1P1, BTBD1. Part of a complex that contains CUL3, RBX1 and GAN. Interacts (via BTB domain) with KLHL17; the interaction regulates surface GRIK2 expression. Interacts with KCTD7. INTERACTION: Q86VP6:CAND1; NbExp=2; IntAct=EBI-456129, EBI-456077; Q14790:CASP8; NbExp=6; IntAct=EBI-456129, EBI-78060; O43791:SPOP; NbExp=2; IntAct=EBI-456129, EBI-743549; P50591:TNFSF10; NbExp=2; IntAct=EBI-456129, EBI-495373; SUBCELLULAR LOCATION: Nucleus. Golgi apparatus. TISSUE SPECIFICITY: Widely expressed. PTM: Neddylated. Attachment of NEDD8 is required for the E3 ubiquitin-protein ligase activity of the BCR complex. Deneddylated via its interaction with the COP9 signalosome (CSN) complex. DISEASE: Defects in CUL3 are the cause of Pseudohypoaldosteronism type 2E (PHA2E) [MIM:614496]. An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics. SIMILARITY: Belongs to the cullin family. SEQUENCE CAUTION: Sequence=AAC28621.1; Type=Frameshift; Positions=452; Sequence=AAC36682.1; Type=Frameshift; Positions=159, 179; Sequence=BAA31592.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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 Q13618
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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.
AB014517 - Homo sapiens KIAA0617 mRNA for KIAA0617 protein. AK291151 - Homo sapiens cDNA FLJ76286 complete cds, highly similar to Homo sapiens cullin 3 (CUL3), mRNA. AF064087 - Homo sapiens cullin 3 mRNA, complete cds. AF062537 - Homo sapiens cullin 3 mRNA, complete cds. BC092409 - Homo sapiens cullin 3, mRNA (cDNA clone MGC:102838 IMAGE:6168545), complete cds. BC039598 - Homo sapiens cullin 3, mRNA (cDNA clone MGC:48882 IMAGE:5784147), complete cds. AK299644 - Homo sapiens cDNA FLJ53180 complete cds, highly similar to Cullin-3. KJ897849 - Synthetic construct Homo sapiens clone ccsbBroadEn_07243 CUL3 gene, encodes complete protein. AB383923 - Synthetic construct DNA, clone: pF1KSDA0617, Homo sapiens CUL3 gene for cullin-3, complete cds, without stop codon, in Flexi system. JD557103 - Sequence 538127 from Patent EP1572962. JD197550 - Sequence 178574 from Patent EP1572962. JD305468 - Sequence 286492 from Patent EP1572962. JD168363 - Sequence 149387 from Patent EP1572962. JD251102 - Sequence 232126 from Patent EP1572962. JD350882 - Sequence 331906 from Patent EP1572962. JD145305 - Sequence 126329 from Patent EP1572962. JD502677 - Sequence 483701 from Patent EP1572962. JD280065 - Sequence 261089 from Patent EP1572962. JD155225 - Sequence 136249 from Patent EP1572962. JD510046 - Sequence 491070 from Patent EP1572962. JD357320 - Sequence 338344 from Patent EP1572962. JD093602 - Sequence 74626 from Patent EP1572962. JD315628 - Sequence 296652 from Patent EP1572962. JD109605 - Sequence 90629 from Patent EP1572962. JD507300 - Sequence 488324 from Patent EP1572962. JD091400 - Sequence 72424 from Patent EP1572962. AY007151 - Homo sapiens clone CDABP0090 mRNA sequence. JD250729 - Sequence 231753 from Patent EP1572962. JD285092 - Sequence 266116 from Patent EP1572962. JD234590 - Sequence 215614 from Patent EP1572962. JD490484 - Sequence 471508 from Patent EP1572962. JD429268 - Sequence 410292 from Patent EP1572962. JD177342 - Sequence 158366 from Patent EP1572962. JD305461 - Sequence 286485 from Patent EP1572962. JD551338 - Sequence 532362 from Patent EP1572962. JD297331 - Sequence 278355 from Patent EP1572962. JD274374 - Sequence 255398 from Patent EP1572962. AK098531 - Homo sapiens cDNA FLJ25665 fis, clone TST02955. U58089 - Human Hs-cul-3 mRNA, partial cds. BC031844 - Homo sapiens cullin 3, mRNA (cDNA clone IMAGE:3861760), partial cds. AK308496 - Homo sapiens cDNA, FLJ98537. AF052147 - Homo sapiens clone 24454 cul-3 mRNA, complete cds. AY337761 - Homo sapiens cullin 3 isoform (CUL3) mRNA, complete cds. JD136041 - Sequence 117065 from Patent EP1572962. JD406067 - Sequence 387091 from Patent EP1572962. JD371494 - Sequence 352518 from Patent EP1572962. JD458485 - Sequence 439509 from Patent EP1572962. JD458509 - Sequence 439533 from Patent EP1572962. JD056229 - Sequence 37253 from Patent EP1572962. JD271291 - Sequence 252315 from Patent EP1572962. JD458510 - Sequence 439534 from Patent EP1572962. JD406055 - Sequence 387079 from Patent EP1572962. JD271292 - Sequence 252316 from Patent EP1572962. JD458514 - Sequence 439538 from Patent EP1572962. JD057274 - Sequence 38298 from Patent EP1572962. JD406801 - Sequence 387825 from Patent EP1572962. JD461601 - Sequence 442625 from Patent EP1572962. JD056228 - Sequence 37252 from Patent EP1572962. JD458513 - Sequence 439537 from Patent EP1572962. JD458511 - Sequence 439535 from Patent EP1572962. JD458512 - Sequence 439536 from Patent EP1572962. JD389924 - Sequence 370948 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q13618 (Reactome details) participates in the following event(s):
R-HSA-1504213 DVL is bound by the CUL3:KLHL12:RBX1 ubiquitin ligase complex R-HSA-5635855 phosphorylated GLI proteins bind SPOP:CUL3:RBX1 R-HSA-8955241 CAND1 binds cytosolic CRL E3 ubiquitin ligases R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex R-HSA-983147 Release of E3 from polyubiquitinated substrate R-HSA-1504190 DVL is ubiquitinated by CUL3:KLHL12:RBX1 R-HSA-5658424 KBTBD7:CUL3:RBX1 ubiquitinates NF1 R-HSA-5635856 SPOP:CUL3:RBX1 ubiquitinates GLI2,3 R-HSA-8955289 COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes R-HSA-8956040 COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2 R-HSA-4641258 Degradation of DVL R-HSA-5632684 Hedgehog 'on' state R-HSA-8951664 Neddylation R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation R-HSA-201681 TCF dependent signaling in response to WNT R-HSA-5658442 Regulation of RAS by GAPs R-HSA-5358351 Signaling by Hedgehog R-HSA-597592 Post-translational protein modification R-HSA-983169 Class I MHC mediated antigen processing & presentation R-HSA-195721 Signaling by WNT R-HSA-5673001 RAF/MAP kinase cascade R-HSA-162582 Signal Transduction R-HSA-392499 Metabolism of proteins R-HSA-1280218 Adaptive Immune System R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-168256 Immune System R-HSA-5683057 MAPK family signaling cascades
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
