CUL3

CUL3 is a component of a ubiquitin E3 ligase that is essential for mitotic division (Sumara et al., 2007 [PubMed 17543862]).[supplied by OMIM

cullin 3

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. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346).

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 BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, MACROH2A1 and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. 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) (PubMed:22358839, PubMed:27716508).

BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23576762).

The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination (PubMed:20389280, PubMed:21840486, PubMed:21670212, PubMed:24768539).

The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB (PubMed:19995937).

The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (PubMed:23455478).

The BCR(KLHL22) ubiquitin ligase complex is also responsible for the amino acid-stimulated 'Lys-48' polyubiquitination and proteasomal degradation of DEPDC5. Through the degradation of DEPDC5, releases the GATOR1 complex-mediated inhibition of the TORC1 pathway (PubMed:29769719).

The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) (PubMed:22578813).

The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832).

Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41 (PubMed:15983046).

In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis (PubMed:25270598).

The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity (PubMed:27798626).

The BCR(KLHL18) E3 ubiquitin ligase complex mediates the ubiquitination of AURKA leading to its activation at the centrosome which is required for initiating mitotic entry (PubMed:23213400).

The BCR(KEAP1) E3 ubiquitin ligase complex acts as a key sensor of oxidative and electrophilic stress by mediating ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525).

As part of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex functions mediates 'Lys-48' ubiquitination and proteasomal degradation of TIAM1 (PubMed:25684205).

By controlling the ubiquitination of that RAC1 guanine exchange factors (GEF), regulates RAC1 signal transduction and downstream biological processes including the organization of the cytoskeleton, cell migration and cell proliferation (PubMed:25684205).

Anaphase-promoting complex-dependent catabolic process Source: MGI
Cell migration Source: UniProtKB
Cell projection organization Source: UniProtKB-KW
COPII vesicle coating Source: UniProtKB
Embryonic cleavage Source: UniProtKB
Endoplasmic reticulum to Golgi vesicle-mediated transport Source: UniProtKB
Fibroblast apoptotic process Source: Ensembl
G1/S transition of mitotic cell cycle Source: ProtInc
Gastrulation Source: Ensembl
Integrin-mediated signaling pathway Source: UniProtKB
Intrinsic apoptotic signaling pathway Source: ProtInc
Liver morphogenesis Source: Ensembl
MAPK cascade Source: Reactome
Mitotic metaphase plate congression Source: UniProtKB
Negative regulation of canonical Wnt signaling pathway Source: Reactome
Negative regulation of Rho protein signal transduction Source: UniProtKB
Negative regulation of transcription by RNA polymerase II Source: Ensembl
Nuclear protein quality control by the ubiquitin-proteasome system Source: UniProtKB
Positive regulation of cell population proliferation Source: ProtInc
Positive regulation of cytokinesis Source: UniProtKB
Positive regulation of mitotic cell cycle phase transition Source: UniProtKB
Positive regulation of mitotic metaphase/anaphase transition Source: UniProtKB
Positive regulation of protein ubiquitination Source: BHF-UCL
Post-translational protein modification Source: Reactome
Proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
Protein autoubiquitination Source: UniProtKB
Protein destabilization Source: BHF-UCL
Protein monoubiquitination Source: UniProtKB
Protein polyubiquitination Source: UniProtKB
Protein ubiquitination Source: UniProtKB
Stem cell division Source: UniProtKB
Stress fiber assembly Source: UniProtKB
Trophectodermal cellular morphogenesis Source: Ensembl
Ubiquitin-dependent protein catabolic process Source: UniProtKB
Wnt signaling pathway Source: Ensembl

Spindle; Centrosome; Spindle pole; Golgi apparatus; Cytoplasm; Nucleus; Flagellum. Detected along the length of the sperm flagellum and in the cytoplasm of the germ cells (PubMed:28395323). Predominantly found in the nucleus in interphase cells, found at the centrosome at late G2 or prophase, starts accumulating at the spindle poles in prometaphase and stays on the spindle poles and the mitotic spindle at metaphase (PubMed:23213400).

Pseudohypoaldosteronism 2E (PHA2E):
An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.

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.