KLHDC2
Kelch Domain Containing 2: A Substrate Adaptor in the Ubiquitin-Proteasome System
Gene Information Card
| Symbol | KLHDC2 |
|---|---|
| Full Name | Kelch Domain Containing 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q21.3 |
| NCBI Gene ID | 23588 ncbi.nlm.nih.gov/gene/23588 |
| Ensembl ID | ENSG00000100811 |
| UniProt ID | Q9Y2U9 |
| OMIM ID | 611748 |
| HGNC ID | 29195 |
| Aliases | HCLP-1, LCP1, MSTP028, dJ337O18.2 |
Description
KLHDC2 (Kelch Domain Containing 2) encodes a protein that functions as a substrate-specific adaptor for cullin-RING E3 ubiquitin ligase complexes, particularly CUL2- and CUL5-based complexes. It recognizes specific degron motifs (e.g., glycine-C-terminal degrons) in target proteins, facilitating their ubiquitination and subsequent proteasomal degradation. KLHDC2 is involved in cellular processes such as protein quality control, cell cycle regulation, and response to oxidative stress.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered expression may affect degradation of oncoproteins or tumor suppressors; potential role in tumorigenesis | Limited; expression changes observed in some cancer transcriptomes (e.g., TCGA) |
| Neurodegenerative disorders | Impaired protein degradation via ubiquitin-proteasome system may contribute to protein aggregation | Indirect; based on pathway involvement |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Lung | 8.9 | Medium |
| Liver | 7.6 | Low |
| Brain | 5.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | High expression in embryonic kidney cells |
| HeLa | 12.0 | Moderate expression in cervical cancer cells |
| K562 | 9.5 | Moderate expression in leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.100C>T (p.Arg34Trp) | Missense | <0.01% (gnomAD) | Unknown; predicted possibly damaging |
| c.457G>A (p.Gly153Ser) | Missense | <0.01% (gnomAD) | Unknown; predicted 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)
| • ubiquitin-protein transferase activity | • protein binding |
| • ubiquitin-dependent protein catabolic process | • proteasome-mediated ubiquitin-dependent protein catabolic process |
| • cytosol | • nucleus |
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• Cullin-RING ubiquitin ligase complex (Reactome: R-HSA-8951664)
Protein Summary
The KLHDC2 protein contains an N-terminal BTB/POZ domain and a C-terminal kelch repeat domain. The BTB domain mediates interaction with cullin proteins, while the kelch domain recognizes specific degrons in substrate proteins. This adaptor protein is critical for targeting proteins with C-terminal glycine or other degron motifs for ubiquitination and degradation, thereby regulating cellular homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLHDC2 Knockout HEK293T Cell Line | EDJ-KQ236 | Human | 23588 | Details Get a Quote |
| KLHDC2 Knockout HEK293 Cell Line | EDJ-KQ8080 | Human | 23588 | Details Get a Quote |
| KLHDC2 Knockout A-549 Cell Line | EDJ-KQ33914 | Human | 23588 | Details Get a Quote |
| KLHDC2 Knockout HCT 116 Cell Line | EDJ-KQ33915 | Human | 23588 | Details Get a Quote |
| KLHDC2 Knockout HeLa Cell Line | EDJ-KQ33916 | Human | 23588 | Details Get a Quote |
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