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HMDB Protein ID HMDBP12790
Secondary Accession Numbers None
Name Cullin-3
  1. CUL-3
Gene Name CUL3
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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. 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).
  • Hedgehog signaling pathway
  • protein ubiquitination
  • Ubiquitin mediated proteolysis
Reactions Not Available
GO Classification
Biological Process
protein polyubiquitination
positive regulation of cell proliferation
COPII vesicle coating
fibroblast apoptotic process
mitotic metaphase plate congression
negative regulation of Rho protein signal transduction
nuclear protein quality control by the ubiquitin-proteasome system
positive regulation of cytokinesis
positive regulation of mitotic cell cycle phase transition
positive regulation of mitotic metaphase/anaphase transition
stem cell division
stress fiber assembly
trophectodermal cellular morphogenesis
ER to Golgi vesicle-mediated transport
cell migration
integrin-mediated signaling pathway
G1/S transition of mitotic cell cycle
positive regulation of protein ubiquitination
anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
ubiquitin-dependent protein catabolic process
protein monoubiquitination
post-translational protein modification
intrinsic apoptotic signaling pathway
protein autoubiquitination
embryonic cleavage
Wnt receptor signaling pathway
liver morphogenesis
negative regulation of transcription from RNA polymerase II promoter
MAPK cascade
negative regulation of canonical Wnt receptor signaling pathway
cell projection organization
proteasomal ubiquitin-dependent protein catabolic process
protein destabilization
protein ubiquitination
Cellular Component
Cul3-RING ubiquitin ligase complex
cullin-RING ubiquitin ligase complex
mitotic spindle
polar microtubule
extracellular vesicular exosome
plasma membrane
Golgi apparatus
sperm flagellum
spindle pole
Molecular Function
cyclin binding
Notch binding
POZ domain binding
ubiquitin protein ligase activity
ubiquitin protein ligase binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 768
Molecular Weight 88929.645
Theoretical pI 8.487
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q13618
UniProtKB/Swiss-Prot Entry Name CUL3_HUMAN
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
General References
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