- https://www.ncbi.nlm.nih.gov/gene/55175
- Expression
- Broad expression in testis (RPKM 5.8), brain (RPKM 4.6) and 25 other tissues See more
-
Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases.
Canning P, et al. J Biol Chem, 2013 Mar 15. PMID 23349464, Free PMC Article Cullin-RING ligases are multisubunit E3 ubiquitin ligases that recruit substrate-specific adaptors to catalyze protein ubiquitylation. Cul3-based Cullin-RING ligases are uniquely associated with BTB adaptors that incorporate homodimerization, Cul3 assembly, and substrate recognition into a single multidomain protein, of which the best known are BTB-BACK-Kelch domain proteins, including KEAP1.
Cul3 assembly requires a BTB protein "3-box" motif, analogous to the F-box and SOCS box motifs of other Cullin-based E3s. To define the molecular basis for this assembly and the overall architecture of the E3, we determined the crystal structures of the BTB-BACK domains of KLHL11 both alone and in complex with Cul3, along with the Kelch domain structures of KLHL2 (Mayven), KLHL7, KLHL12, and KBTBD5. We show that Cul3 interaction is dependent on a unique N-terminal extension sequence that packs against the 3-box in a hydrophobic groove centrally located between the BTB and BACK domains. Deletion of this N-terminal region results in a 30-fold loss in affinity. The presented data offer a model for the quaternary assembly of this E3 class that supports the bivalent capture of Nrf2 and reveals potential new sites for E3 inhibitor design.- PMID:
- 23349464
- PMCID:
- PMC3597819
- DOI:
- 10.1074/jbc.M112.437996
- Update on the Kelch-like (KLHL) gene family. Dhanoa BS, et al. Hum Genomics, 2013 May 15. PMID 23676014, Free PMC Article
- Proteomic analysis reveals novel ligands and substrates for LNX1 E3 ubiquitin ligase. Lenihan JA, et al. PLoS One, 2017. PMID 29121065, Free PMC Article
- Mapping the interactome of HPV E6 and E7 oncoproteins with the ubiquitin-proteasome system. Poirson J, et al. FEBS J, 2017 Oct. PMID 28786561
- Why do cellular proteins linked to K63-polyubiquitin chains not associate with proteasomes? Nathan JA, et al. EMBO J, 2013 Feb 20. PMID 23314748, Free PMC Article
GeneRIFs: Gene References Into Functions
- Related
- Conserved Domains (3) summary
-
- smart00612
Location:611 → 657 - Kelch; Kelch domain
- sd00038
Location:399 → 439 - Kelch; KELCH repeat [structural motif]
- cl28614
Location:90 → 553 - BTB; Broad-Complex, Tramtrack and Bric a brac
- smart00612
-
Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases.
Canning P, et al. J Biol Chem, 2013 Mar 15. PMID 23349464, Free PMC Article
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onsdag 23 oktober 2019
KLHL11 (17q21.2)
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