Alternative titles; symbolsHOST CELL FACTOR-LIKE PROTEIN 1; HCLP1HGNC Approved Gene Symbol: KLHDC2Cytogenetic location: 14q21.3 Genomic coordinates (GRCh38):...
Alternative titles; symbols
HGNC Approved Gene Symbol: KLHDC2
Cytogenetic location: 14q21.3 Genomic coordinates (GRCh38): 14:49,767,607-49,786,384 (from NCBI)
▼ Cloning and Expression
Zhou et al. (2001) identified KLHDC2, which they originally designated host cell factor-like protein-1 (HCLP1), by mining sequence databases for putative proteins with homology to the beta-propeller domain of HCF1 (HCFC1; 300019). The deduced 406-amino acid KLHDC2 protein is composed almost entirely of 6 kelch repeats that form a beta-propeller structure. Northern blot analysis detected expression of KLHDC2 in all human tissues and cancer cell lines tested. KLHDC2 is primarily localized to the nucleus.
Chin et al. (2007) determined that the KLHDC2 shares approximately 50% amino acid sequence identity with KLHDC1 (611281). Northern blot analysis detected a 2.0-kb KLHDC2 transcript with highest expression in skeletal muscle, moderately high expression in heart, weak expression in most other tissues tested, and no expression in peripheral blood leukocytes.
By sequence analysis, Chin et al. (2007) mapped the KLHDC2 and KLHDC1 loci adjacent to each other on chromosome 14q21.3 in a head-to-tail configuration about 15 kb apart. The KDHDC1/KLHDC2 cluster is highly conserved in vertebrates as evolutionarily distant as pufferfish.
▼ Gene Function
Using a yeast 2-hybrid system, Zhou et al. (2001) found that KLHDC2 interacts with LZIP (606443) but not with herpes simplex virus VP16. The interaction with LZIP led to the repression of LZIP-dependent transcription. Zhou et al. (2001) concluded that, in contrast to HCFC1, which functions as a transcriptional coactivator, KLHDC2 serves as a transcriptional corepressor function mediated through its inhibitory interaction with LZIP.
Chin et al. (2007) determined that neither KLHDC2 nor KLHDC1 interacts with actin.
▼ Animal Model
In a study of 1,751 knockout alleles created by the International Mouse Phenotyping Consortium (IMPC), Dickinson et al. (2016) found that knockout of the mouse homolog of human KLHDC2 is homozygous-lethal (defined as absence of homozygous mice after screening of at least 28 pups before weaning). 3D imaging revealed that Klhdc2 homozygous knockout embryos at E14.5 displayed hindlimb preaxial polydactyly, edema, hypoplastic adrenal glands, displaced kidneys, short tongue, and abnormal intestines.