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CUL3 a 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 CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the susbstrate recognition component. SPOP is involved in ubiquitination of BMI1, 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 SEC31A or -B. 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. 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 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, 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. Widely expressed. Belongs to the cullin family. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Cell cycle regulation; Ubiquitin conjugating system; Ubiquitin ligase
Chromosomal Location of Human Ortholog: 2q36.2
Cellular Component: cytosol; membrane; nucleoplasm; polar microtubule
Molecular Function: Notch binding; POZ domain binding; protein binding; ubiquitin protein ligase binding; ubiquitin-protein ligase activity
Biological Process: anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; cell cycle arrest; cell migration; COPII coating of Golgi vesicle; embryonic cleavage; ER to Golgi vesicle-mediated transport; G1/S transition of mitotic cell cycle; integrin-mediated signaling pathway; MAPKKK cascade; mitotic metaphase plate congression; negative regulation of Rho protein signal transduction; positive regulation of cell proliferation; positive regulation of cytokinesis; positive regulation of mitotic metaphase/anaphase transition; post-translational protein modification; proteasomal ubiquitin-dependent protein catabolic process; protein monoubiquitination; protein polyubiquitination; protein ubiquitination; protein ubiquitination during ubiquitin-dependent protein catabolic process; stem cell division; stress fiber formation; ubiquitin-dependent protein catabolic process
Disease: Pseudohypoaldosteronism, Type Iie
Reference #:  Q13618 (UniProtKB)
Alt. Names/Synonyms: CUL-3; CUL3; cullin 3; Cullin-3; KIAA0617
Gene Symbols: CUL3
Molecular weight: 88,930 Da
Basal Isoelectric point: 8.68  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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