Kelch-like protein 3 explained
Kelch-like protein 3 is a protein in humans that is encoded by the KLHL3 gene.[1] Alternative splicing results in multiple transcript variants encoding distinct isoforms.
Function
This gene is ubiquitously expressed and encodes a full-length protein which has an N-terminal BTB domain followed by a BACK domain and six kelch-like repeats in the C-terminus. These kelch-like repeats promote substrate ubiquitination of bound proteins via interaction of the BTB domain with the CUL3 (cullin 3) component of a cullin-RING E3 ubiquitin ligase (CRL) complex.[1]
Clinical significance
Pseudohypoaldosteronism Type 2D
Mutations in this gene cause pseudohypoaldosteronism type IID (PHA2D); a rare Mendelian syndrome featuring hypertension, hyperkalaemia[2] and metabolic acidosis.[1]
Ischemic Stroke
A machine learning model identified the KLHL3 gene as a key gene in the occurrence and progression of ischemic stroke.[3]
Further reading
- Hirosawa M, Nagase T, Ishikawa K, Kikuno R, Nomura N, Ohara O . Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain . DNA Research . 6 . 5 . 329–36 . Oct 1999 . 10574461 . 10.1093/dnares/6.5.329 . free .
- Yeo A, Samways DS, Fowler CE, Gunn-Moore F, Henderson G . Coincident signalling between the Gi/Go-coupled delta-opioid receptor and the Gq-coupled m3 muscarinic receptor at the level of intracellular free calcium in SH-SY5Y cells . Journal of Neurochemistry . 76 . 6 . 1688–700 . Mar 2001 . 11259487 . 10.1046/j.1471-4159.2001.00185.x . 2755275 .
- Mizutani A, Fukuda M, Ibata K, Shiraishi Y, Mikoshiba K . SYNCRIP, a cytoplasmic counterpart of heterogeneous nuclear ribonucleoprotein R, interacts with ubiquitous synaptotagmin isoforms . The Journal of Biological Chemistry . 275 . 13 . 9823–31 . Mar 2000 . 10734137 . 10.1074/jbc.275.13.9823 . free .
- Lai F, Orelli BJ, Till BG, Godley LA, Fernald AA, Pamintuan L, Le Beau MM . Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene . Genomics . 66 . 1 . 65–75 . May 2000 . 10843806 . 10.1006/geno.2000.6181 .
Notes and References
- Web site: Entrez Gene: Kelch-like 3 (Drosophila) . 2012-04-26 .
- KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. . Nature Genetics . 44 . 5 . 609 . Apr 26, 2012 . . 10.1038/ng0512-609 . free .
- Huang . Dian . Identification of Potential Neddylation-related Key Genes in Ischemic Stroke based on Machine Learning Methods . Molecular Neurobiology . 1 November 2023 . 61 . 5 . 2530–2541 . 10.1007/s12035-023-03738-5 . 37910287 .