Tbio CUL3 Cullin-3

Protein Summary

Description

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, H2AFY 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. 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). This gene encodes a member of the cullin protein family. The encoded protein plays a critical role in the polyubiquitination and subsequent degradation of specific protein substrates as the core component and scaffold protein of an E3 ubiquitin ligase complex. Complexes including the encoded protein may also play a role in late endosome maturation. Mutations in this gene are a cause of type 2E pseudohypoaldosteronism. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]

Uniprot Accession IDs

• Q13618
• A8K536
• B8ZZC3
• O75415
• Q569L3
• Q9UBI8
• Q9UET7
• CUL-3

Gene Name

• CUL3

Ensembl ID

• ENST00000264414
• ENSP00000264414
• ENSG00000036257
• ENST00000344951
• ENSP00000343601
• ENST00000409096
• ENSP00000387200
• ENST00000409777
• ENSP00000386525

Symbol

• KIAA0617
• CUL-3
• PHA2E

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
interacting protein	1
biological process	0.98
kinase perturbation	0.88
drug perturbation	0.87
hub protein	0.85

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 322.87   (req: < 5)

Gene RIFs: 73   (req: <= 3)

Antibodies: 362   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 322.87   (req: >= 5)

Gene RIFs: 73   (req: > 3)

Antibodies: 362   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 40

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

Find Targets by Sequence

Show Full Sequence

ProtVista Viewer

Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

Go To Tool

GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

Go To Tool

GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

Go To Tool

ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

Go To Tool

Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (569)

Explore Interacting Targets

1 – 10 of 569

• See Interactions on String-DB

LRRC42

Tdark

Novelty:  1.83168269

p_int:  0.999999825

p_ni:  1.75e-7

Score:  0.186

Data Source:  BioPlex,STRINGDB

KLHL8

Tdark

Novelty:  0.4838314

p_int:  0.999999523

p_ni:  4.76e-7

p_wrong:  1e-9

Score:  0.79

Data Source:  BioPlex,STRINGDB

KLHL21

Tbio

Novelty:  0.20694121

p_int:  0.999999488

p_ni:  5.1e-7

p_wrong:  1e-9

Score:  0.984

Data Source:  BioPlex,STRINGDB

KLHL25

Tbio

Novelty:  0.14475787

p_int:  0.99999919

p_ni:  8.1e-7

Score:  0.976

Data Source:  BioPlex,STRINGDB

KCTD20

Tdark

Novelty:  0.47655751

p_int:  0.999999103

p_ni:  8.96e-7

p_wrong:  1e-9

Score:  0.256

Data Source:  BioPlex,STRINGDB

KLHL18

Tdark

Novelty:  0.52915213

p_int:  0.999998933

p_ni:  0.000001067

Score:  0.718

Data Source:  BioPlex,STRINGDB

ANKRD39

Tdark

Novelty:  8.68843298

p_int:  0.99999872

p_ni:  5e-9

p_wrong:  0.000001276

Score:  0.361

Data Source:  BioPlex,STRINGDB

KLHL7

Tbio

Novelty:  0.0522116

p_int:  0.9999986

p_ni:  0.0000014

Score:  0.702

Data Source:  BioPlex,STRINGDB

BTBD10

Tbio

Novelty:  0.23077172

p_int:  0.999998488

p_ni:  0.00000151

p_wrong:  1e-9

Score:  0.235

Data Source:  BioPlex,STRINGDB

KLHL42

Tdark

Novelty:  0.25822395

p_int:  0.999997975

p_ni:  0.000002025

Score:  0.977

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (30)

Reactome (21)

KEGG (2)

PathwayCommons (3)

UniProt (1)

WikiPathways (3)

Adaptive Immune System (R-HSA-1280218)

Click on a row in the table to change the structure displayed.

Find Similar Targets

Items per page:

5

1 – 5 of 21

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
Reactome	Class I MHC mediated antigen processing & presentation	437 targets	R-HSA-983169
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	Degradation of DVL	58 targets	R-HSA-4641258

Name	Explore in Pharos	Explore in Source
Adaptive Immune System	894 targets	R-HSA-1280218
Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
Class I MHC mediated antigen processing & presentation	437 targets	R-HSA-983169
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Degradation of DVL	58 targets	R-HSA-4641258

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (50)

Functions (6)

Components (10)

Processes (34)

Find Similar Targets

Items per page:

10

1 – 6 of 6

GO Term	Evidence	Assigned by
POZ domain binding	Inferred from Direct Assay (IDA)	UniProtKB
Notch binding	Inferred from Physical Interaction (IPI)	MGI
ubiquitin protein ligase binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
cyclin binding	Inferred from Electronic Annotation (IEA)	Ensembl
protein heterodimerization activity	Inferred from Electronic Annotation (IEA)	Ensembl
protein homodimerization activity	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations (null)

No disease associations found

GWAS Traits (12)

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 12

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mathematical ability	EFO_0004875	4	3	5		83.2
smoking initiation	EFO_0005670	2	2	2		75
smoking status measurement	EFO_0006527	2	1	2		68.8
risk-taking behaviour	EFO_0008579	1	1	1		66.3
alcohol consumption measurement	EFO_0007878	3	2	3		61.9

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 12

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mathematical ability	EFO_0004875	5		83.2
smoking initiation	EFO_0005670	2		75
smoking status measurement	EFO_0006527	2		68.8
risk-taking behaviour	EFO_0008579	1		66.3
alcohol consumption measurement	EFO_0007878	3		61.9

Reset Zoom  Beta Count   Odds Ratio

Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Cell projection
Cilium
Cilium biogenesis/degradation
Complete proteome
Cytoplasm
Disease mutation
ER-Golgi transport

GWAS Trait Find Similar Targets

No Header	No Header
age at first sexual intercourse measurement
alcohol consumption measurement
anorexia nervosa
autism spectrum disorder
cognitive function measurement
mathematical ability
risk-taking behaviour
schizophrenia
self reported educational attainment
smoking cessation

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
embryo phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
liver/biliary system phenotype
mortality/aging
muscle phenotype

IDG Resources

No IDG generated resources found

Orthologs (15)

1 – 5 of 15

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cullin 3	VGNC:152	744812
Macaque	cullin 3		707550
Mouse	cullin 3	MGI:1347360	26554
Rat	cullin 3	RGD:1308190	301555
Dog	cullin 3	VGNC:39730	477392

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cullin 3
Macaque	cullin 3
Mouse	cullin 3
Rat	cullin 3
Dog	cullin 3

Publication Statistics

PubMed Score 322.87

PubMed score by year

Reset Zoom

PubTator Score 165.88

PubTator score by year

Reset Zoom

Related Publications

Text Mined References (130)

GeneRif Annotations (73)

Items per page:

10

0 of 0

PMID	Year	Title