InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CUL3

Summary

InnateDB Protein

IDBP-292974.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CUL3

Protein Name

cullin 3

Synonyms

CUL-3; PHA2E;

Species

Homo sapiens

Ensembl Protein

ENSP00000387200

InnateDB Gene

IDBG-82331 (CUL3)

Protein Structure

UniProt Annotation

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. 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 (By similarity). 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). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4. 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. 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. The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1). 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. {ECO:0000250, ECO:0000269PubMed:10500095, ECO:0000269PubMed:11311237, ECO:0000269PubMed:15897469, ECO:0000269PubMed:15983046, ECO:0000269PubMed:16524876, ECO:0000269PubMed:17543862, ECO:0000269PubMed:18397884, ECO:0000269PubMed:19261606, ECO:0000269PubMed:19995937, ECO:0000269PubMed:20389280, ECO:0000269PubMed:21670212, ECO:0000269PubMed:21840486, ECO:0000269PubMed:22085717, ECO:0000269PubMed:22358839, ECO:0000269PubMed:22578813, ECO:0000269PubMed:22632832, ECO:0000269PubMed:23387299, ECO:0000269PubMed:23453970, ECO:0000269PubMed:23455478, ECO:0000269PubMed:23576762, ECO:0000269PubMed:24768539}.

Subcellular Localization

Nucleus. Golgi apparatus.

Disease Associations

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:0000269PubMed:22266938}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Widely expressed.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 1215 experimentally validated interaction(s) in this database.
They are also associated with 28 interaction(s) predicted by orthology.

Experimentally validated
Total	1215 [view]
Protein-Protein	1215 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	28 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0031208	POZ domain binding
GO:0031625	ubiquitin protein ligase binding

Biological Process

GO:0000082	G1/S transition of mitotic cell cycle
GO:0000090	mitotic anaphase
GO:0000209	protein polyubiquitination
GO:0000910	cytokinesis
GO:0006511	ubiquitin-dependent protein catabolic process
GO:0006513	protein monoubiquitination
GO:0006888	ER to Golgi vesicle-mediated transport
GO:0007050	cell cycle arrest
GO:0007229	integrin-mediated signaling pathway
GO:0008054	cyclin catabolic process
GO:0008284	positive regulation of cell proliferation
GO:0016477	cell migration
GO:0016567	protein ubiquitination
GO:0017145	stem cell division
GO:0032467	positive regulation of cytokinesis
GO:0035024	negative regulation of Rho protein signal transduction
GO:0040016	embryonic cleavage
GO:0043149	stress fiber assembly
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0048208	COPII vesicle coating
GO:0051322	anaphase
GO:0097193	intrinsic apoptotic signaling pathway

Cellular Component

GO:0000139	Golgi membrane
GO:0005634	nucleus
GO:0005827	polar microtubule
GO:0016020	membrane
GO:0031461	cullin-RING ubiquitin ligase complex
GO:0031463	Cul3-RING ubiquitin ligase complex
GO:0070062	extracellular vesicular exosome