CUL3
entrez
8452
canonical
uniprot
Q13618
canonical
ensembl
ENSG00000036257
resolver
ensp
ENSP00000264414
resolver
ensp
ENSP00000343601
resolver
ensp
ENSP00000386525
resolver
ensp
ENSP00000387200
resolver
genesymbol
CUL3
resolver
genesymbol_syn
KIAA0617
resolver
hgnc
HGNC:2553
resolver
uniprot
A8K536
resolver
uniprot
B7Z600
resolver
uniprot
B8ZZC3
resolver
uniprot
O75415
resolver
uniprot
Q569L3
resolver
uniprot
Q9UBI8
resolver
uniprot
Q9UET7
resolver
uniprot_entry
B7Z600_HUMAN
resolver
uniprot_entry
CUL3_HUMAN
resolver
uniprot_sec
A8K536
resolver
uniprot_sec
B8ZZC3
resolver
uniprot_sec
O75415
resolver
uniprot_sec
Q569L3
resolver
uniprot_sec
Q9UBI8
resolver
uniprot_sec
Q9UET7
resolver
amino_acid_sequence
MSNLSKGTGSRKDTKMRIRAFPMTMDEKYVNSIWDLLKNAIQEIQRKNNSGLSFEELYRNAYTMVLHKHGEKLYTGLREVVTEHLINKVREDVLNSLNNNFLQTLNQAWNDHQTAMVMIRDILMYMDRVYVQQNNVENVYNLGLIIFRDQVVRYGCIRDHLRQTLLDMIARERKGEVVDRGAIRNACQMLMILGLEGRSVYEEDFEAPFLEMSAEFFQMESQKFLAENSASVYIKKVEARINEEIERVMHCLDKSTEEPIVKVVERELISKHMKTIVEMENSGLVHMLKNGKTEDLGCMYKLFSRVPNGLKTMCECMSSYLREQGKALVSEEGEGKNPVDYIQGLLDLKSRFDRFLLESFNNDRLFKQTIAGDFEYFLNLNSRSPEYLSLFIDDKLKKGVKGLTEQEVETILDKAMVLFRFMQEKDVFERYYKQHLARRLLTNKSVSDDSEKNMISKLKTECGCQFTSKLEGMFRDMSISNTTMDEFRQHLQATGVSLGGVDLTVRVLTTGYWPTQSATPKCNIPPAPRHAFEIFRRFYLAKHSGRQLTLQHHMGSADLNATFYGPVKKEDGSEVGVGGAQVTGSNTRKHILQVSTFQMTILMLFNNREKYTFEEIQQETDIPERELVRALQSLACGKPTQRVLTKEPKSKEIENGHIFTVNDQFTSKLHRVKIQTVAAKQGESDPERKETRQKVDDDRKHEIEAAIVRIMKSRKKMQHNVLVAEVTQQLKARFLPSPVVIKKRIEGLIEREYLARTPEDRKVYTYVA
uniprot
proteins
disease_involvement
DISEASE: Pseudohypoaldosteronism 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. {ECO:0000269|PubMed:22266938}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Neurodevelopmental disorder with or without autism or seizures (NEDAUS) [MIM:619239]: An autosomal dominant disorder manifesting in infancy and characterized by global developmental delay, variably impaired intellectual development, and speech delay. Some patients have seizures, others have autistic features or behavioral abnormalities. Additional variable features include cardiac defects, failure to thrive, or brain imaging anomalies. {ECO:0000269|PubMed:32341456, ECO:0000269|PubMed:33097317}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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 (PubMed:29695787). 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:21670212, PubMed:21840486, 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(KLHL25) ubiquitin ligase complex is also involved in lipid synthesis by mediating ubiquitination and degradation of ACLY (PubMed:27664236). 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). The BCR(KBTBD4) E3 ubiquitin ligase complex targets CoREST corepressor complex components RCOR1, KDM1A/LSD1 and HDAC2 for proteasomal degradation with RCOR1 likely to be the primary target while degradation of KDM1A and HDAC2 is likely due to their association with RCOR1 (PubMed:33417871). It also targets RCOR3, MIER2 and MIER3 for proteasomal degradation as well as associated proteins ZNF217 and RREB1 with degradation being dependent on the presence of an ELM2 domain in the target proteins (PubMed:36997086). The BCR(ARMC5) complex mediates premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation by mediating ubiquitination of Pol II subunit POLR2A (PubMed:35687106, PubMed:38225631, PubMed:39504960, PubMed:39667934). Required for 'Lys-63'-linked ubiquitination of large ribosomal subunit protein MRPL12 (PubMed:37526061). Protects against human enterovirus D68 infection by mediating the ubiquitination and subsequent degradation of viral protein VP1 (PubMed:40396757). {ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:11311237, ECO:0000269|PubMed:15601839, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16006525, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:19261606, ECO:0000269|PubMed:19995937, ECO:0000269|PubMed:20389280, ECO:0000269|PubMed:21670212, ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22358839, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:23213400, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:24768539, ECO:0000269|PubMed:25270598, ECO:0000269|PubMed:25684205, ECO:0000269|PubMed:26399832, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:27664236, ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27798626, ECO:0000269|PubMed:29695787, ECO:0000269|PubMed:29769719, ECO:0000269|PubMed:33417871, ECO:0000269|PubMed:35687106, ECO:0000269|PubMed:36997086, ECO:0000269|PubMed:37526061, ECO:0000269|PubMed:38225631, ECO:0000269|PubMed:39504960, ECO:0000269|PubMed:39667934, ECO:0000269|PubMed:40396757}.
uniprot
proteins
mass_dalton
88930
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:27664236, ECO:0000269|PubMed:35687106, ECO:0000269|PubMed:38225631, ECO:0000269|PubMed:39504960, ECO:0000269|PubMed:39667934}.
uniprot
proteins
post_translational_modification
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. {ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:10597293, ECO:0000269|PubMed:24076655, ECO:0000269|PubMed:27565346}.; PTM: (Microbial infection) Cleaved at Gln-681 by human enterovirus D68 protease 3C; leading to inhibition of CUL3-dependent ubiquitination activity. {ECO:0000269|PubMed:40396757}.
uniprot
proteins
protein_family
Cullin family
uniprot
proteins
pubmed
10230407
uniprot
proteins
pubmed
10500095
uniprot
proteins
pubmed
10597293
uniprot
proteins
pubmed
11311237
uniprot
proteins
pubmed
12609982
uniprot
proteins
pubmed
14528312
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15107402
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15601839
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
15897469
uniprot
proteins
pubmed
15983046
uniprot
proteins
pubmed
16006525
uniprot
proteins
pubmed
16524876
uniprot
proteins
pubmed
17192413
uniprot
proteins
pubmed
17254749
uniprot
proteins
pubmed
17543862
uniprot
proteins
pubmed
18397884
uniprot
proteins
pubmed
18573101
uniprot
proteins
pubmed
19261606
uniprot
proteins
pubmed
19995937
uniprot
proteins
pubmed
20389280
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21670212
uniprot
proteins
pubmed
21840486
uniprot
proteins
pubmed
22085717
uniprot
proteins
pubmed
22266938
uniprot
proteins
pubmed
22358839
uniprot
proteins
pubmed
22578813
uniprot
proteins
pubmed
22632832
uniprot
proteins
pubmed
22748208
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23135275
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23201271
uniprot
proteins
pubmed
23213400
uniprot
proteins
pubmed
23349464
uniprot
proteins
pubmed
23387299
uniprot
proteins
pubmed
23453970
uniprot
proteins
pubmed
23455478
uniprot
proteins
pubmed
23573258
uniprot
proteins
pubmed
23576762
uniprot
proteins
pubmed
23776465
uniprot
proteins
pubmed
24076655
uniprot
proteins
pubmed
24192928
uniprot
proteins
pubmed
24768539
uniprot
proteins
pubmed
25270598
uniprot
proteins
pubmed
25349211
uniprot
proteins
pubmed
25684205
uniprot
proteins
pubmed
25969726
uniprot
proteins
pubmed
26399832
uniprot
proteins
pubmed
26906416
uniprot
proteins
pubmed
27561354
uniprot
proteins
pubmed
27565346
uniprot
proteins
pubmed
27664236
uniprot
proteins
pubmed
27708159
uniprot
proteins
pubmed
27716508
uniprot
proteins
pubmed
27798626
uniprot
proteins
pubmed
28395323
uniprot
proteins
pubmed
29276004
uniprot
proteins
pubmed
29695787
uniprot
proteins
pubmed
29769719
uniprot
proteins
pubmed
30819806
uniprot
proteins
pubmed
32341456
uniprot
proteins
pubmed
33097317
uniprot
proteins
pubmed
33417871
uniprot
proteins
pubmed
35687106
uniprot
proteins
pubmed
35862218
uniprot
proteins
pubmed
36997086
uniprot
proteins
pubmed
37526061
uniprot
proteins
pubmed
38225631
uniprot
proteins
pubmed
39504960
uniprot
proteins
pubmed
39667934
uniprot
proteins
pubmed
40396757
uniprot
proteins
pubmed
8681378
uniprot
proteins
pubmed
9663463
uniprot
proteins
pubmed
9733711
uniprot
proteins
pubmed
9734811
uniprot
proteins
sequence_length
768
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:23213400}. Golgi apparatus {ECO:0000269|PubMed:10500095}. Cell projection, cilium, flagellum {ECO:0000269|PubMed:28395323}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:23213400}. Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:23213400}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:23213400}. Note=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). {ECO:0000269|PubMed:23213400, ECO:0000269|PubMed:28395323}.
uniprot
proteins