ID:CUL3_MOUSE 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(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 (By similarity). 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). 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. 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. 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 (By similarity). Interacts with KCTD7 (By similarity). SUBCELLULAR LOCATION: Nucleus. Golgi apparatus. TISSUE SPECIFICITY: Widely expressed, with highest expression in brain, spleen and testis. PTM: Neddylated. Attachment of NEDD8 is required for the E3 ubiquitin-protein ligase activity of the BCR E3 ligase complex. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (By similarity). DISRUPTION PHENOTYPE: Null deficient mice are not viable. Extraembryonic ectoderm shows a greatly increased number of cells in S phase. In the trophectoderm cells are blocked to entry into S phase. Embryonic stem (ES) cells form tightly packed cell clusters with prominent actin cables and aberrant adhesions. ES cells are retained in proliferation, yet retain their pluripotency. 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 Q9JLV5
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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.
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0000209 protein polyubiquitination GO:0000278 mitotic cell cycle GO:0000902 cell morphogenesis GO:0001701 in utero embryonic development GO:0001831 trophectodermal cellular morphogenesis GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006511 ubiquitin-dependent protein catabolic process GO:0006513 protein monoubiquitination GO:0006888 ER to Golgi vesicle-mediated transport GO:0007080 mitotic metaphase plate congression GO:0007229 integrin-mediated signaling pathway GO:0007369 gastrulation GO:0016055 Wnt signaling pathway GO:0016192 vesicle-mediated transport GO:0016477 cell migration GO:0016567 protein ubiquitination GO:0017145 stem cell division GO:0030030 cell projection organization GO:0031145 anaphase-promoting complex-dependent catabolic process GO:0031398 positive regulation of protein ubiquitination GO:0031648 protein destabilization GO:0032467 positive regulation of cytokinesis GO:0035024 negative regulation of Rho protein signal transduction GO:0040016 embryonic cleavage GO:0043149 stress fiber assembly GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0044346 fibroblast apoptotic process GO:0045842 positive regulation of mitotic metaphase/anaphase transition GO:0048208 COPII vesicle coating GO:0071630 nucleus-associated proteasomal ubiquitin-dependent protein catabolic process GO:0072576 liver morphogenesis
AK034695 - Mus musculus 12 days embryo embryonic body between diaphragm region and neck cDNA, RIKEN full-length enriched library, clone:9430025L12 product:inferred: cullin 3, full insert sequence. AK129174 - Mus musculus premature mRNA for mKIAA0617 protein. AK003885 - Mus musculus 18-day embryo whole body cDNA, RIKEN full-length enriched library, clone:1110021B17 product:cullin 3, full insert sequence. AF129738 - Mus musculus cullin 3 (Cul3) mRNA, complete cds. BC027304 - Mus musculus cullin 3, mRNA (cDNA clone MGC:28933 IMAGE:3981170), complete cds.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes mmu04120 - Ubiquitin mediated proteolysis
Reactome (by CSHL, EBI, and GO)
Protein Q9JLV5 (Reactome details) participates in the following event(s):
R-MMU-1504213 DVL is bound by the CUL3:KLHL12:RBX1 ubiquitin ligase complex R-MMU-5635855 phosphorylated GLI proteins bind SPOP:CUL3:RBX1 R-MMU-8955241 CAND1 binds cytosolic CRL E3 ubiquitin ligases R-MMU-983157 Interaction of E3 with substrate and E2-Ub complex R-MMU-983147 Release of E3 from polyubiquitinated substrate R-MMU-1504190 DVL is ubiquitinated by CUL3:KLHL12:RBX1 R-MMU-5635856 SPOP:CUL3:RBX1 ubiquitinates GLI2,3 R-MMU-8955289 COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes R-MMU-8956040 COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes R-MMU-983140 Transfer of Ub from E2 to substrate and release of E2 R-MMU-4641258 Degradation of DVL R-MMU-5632684 Hedgehog 'on' state R-MMU-8951664 Neddylation R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation R-MMU-201681 TCF dependent signaling in response to WNT R-MMU-5358351 Signaling by Hedgehog R-MMU-597592 Post-translational protein modification R-MMU-983169 Class I MHC mediated antigen processing & presentation R-MMU-195721 Signaling by WNT R-MMU-162582 Signal Transduction R-MMU-392499 Metabolism of proteins R-MMU-1280218 Adaptive Immune System R-MMU-168256 Immune System
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