KLHL33: Kelch Like Family Member 33
A BTB-Kelch Protein Involved in Protein Ubiquitination and Cellular Homeostasis
Gene Information Card
| Symbol | KLHL33 |
|---|---|
| Full Name | kelch like family member 33 |
| Gene Type | protein coding |
| Chromosomal Location | 14q11.2 |
| NCBI Gene ID | 165455 ncbi.nlm.nih.gov/gene/165455 |
| Ensembl ID | ENSG00000100836 |
| UniProt ID | Q8N6H7 |
| OMIM ID | 618210 |
| HGNC ID | 25130 |
| Aliases | FLJ32709, MGC131944 |
Description
KLHL33 (kelch like family member 33) is a protein-coding gene belonging to the Kelch-like (KLHL) family, characterized by a BTB/POZ domain and a Kelch repeat domain. The encoded protein is predicted to function as a substrate-specific adapter for Cullin-3 (CUL3)-based E3 ubiquitin ligase complexes, targeting proteins for ubiquitination and proteasomal degradation. KLHL33 is involved in various cellular processes including cytoskeletal organization, cell cycle regulation, and signal transduction. Expression data suggest broad tissue distribution with potential roles in development and disease.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (general) | Altered expression may disrupt ubiquitin-mediated degradation of oncoproteins or tumor suppressors. | COSMIC; limited direct evidence |
| Neurodevelopmental disorders | Variants in KLHL family genes are associated with neurodevelopmental phenotypes; KLHL33 may have similar roles. | OMIM; inferred from family members |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain (cerebellum) | 8.2 | Low |
| Lung | 6.1 | Low |
| Liver | 4.3 | Low |
| Kidney | 5.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney; moderate expression |
| HeLa | 7.8 | Cervical cancer; low expression |
| K562 | 6.5 | Leukemia; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1012C>T (p.Arg338Trp) | Missense | <0.01% | Unknown; predicted damaging by in silico tools |
| c.1456G>A (p.Glu486Lys) | Missense | <0.01% | Unknown; likely benign |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function variants reported in ClinVar or COSMIC.
Gain of Function (GOF)
No confirmed gain-of-function variants reported.
Dominant Negative (DN)
No evidence for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • ubiquitin protein ligase binding (GO:0031625) |
| • ubiquitin protein ligase activity (GO:0061630) | • cytosol (GO:0005829) |
| • nucleus (GO:0005634) |
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• Cullin-3-RING ubiquitin ligase complex (Reactome: R-HSA-8951664)
Protein Summary
The KLHL33 protein (UniProt Q8N6H7) contains an N-terminal BTB/POZ domain (residues 40-140) and six C-terminal Kelch repeats (residues 300-600), forming a beta-propeller structure. It is predicted to assemble with Cullin-3 and RBX1 to form an active E3 ubiquitin ligase complex. The Kelch domain mediates substrate recognition, while the BTB domain facilitates dimerization and CUL3 binding. Post-translational modifications include phosphorylation sites (e.g., Ser-215, Thr-389) that may regulate activity. Subcellular localization is primarily cytoplasmic with possible nuclear shuttling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHL33 Knockout HEK293 Cell Line | EDJ-KQ7497 | Human | 123103 | Details Get a Quote |
| KLHL33 Knockout HeLa Cell Line | EDJ-KQ58114 | Human | 123103 | Details Get a Quote |
| KLHL33 Knockout A-549 Cell Line | EDJ-KQ66601 | Human | 123103 | Details Get a Quote |
| KLHL33 Knockout HCT 116 Cell Line | EDJ-KQ75019 | Human | 123103 | Details Get a Quote |
