Kelch-like protein 3

KLHL3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4CH9, 4HXI
Identifiers
Aliases	KLHL3 , PHA2D, kelch like family member 3
External IDs	OMIM: 605775; MGI: 2445185; HomoloGene: 79542; GeneCards: KLHL3; OMA:KLHL3 - orthologs
Gene location (Human) Chr. Chromosome 5 (human) [1] Band 5q31.2 Start 137,617,500 bp [1] End 137,736,089 bp [1]
Gene location (Mouse) Chr. Chromosome 13 (mouse) [2] Band 13|13 B1 Start 58,148,042 bp [2] End 58,261,406 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cerebellar vermis middle temporal gyrus cerebellar hemisphere right hemisphere of cerebellum cardiac muscle tissue of right atrium Brodmann area 23 Brodmann area 46 sural nerve Region I of hippocampus proper inferior olivary nucleus Top expressed in dentate gyrus of hippocampal formation granule cell neural layer of retina hippocampus proper primary visual cortex human kidney superior frontal gyrus olfactory bulb cerebellum striatum of neuraxis cerebellar cortex More reference expression data BioGPS n/a
Gene ontology Molecular function actin binding protein binding structural molecule activity ubiquitin-protein transferase activity Cellular component cytoplasm cytoskeleton Cul3-RING ubiquitin ligase complex cytosol Biological process protein K48-linked ubiquitination distal tubule morphogenesis renal sodium ion absorption protein ubiquitination ion homeostasis post-translational protein modification ubiquitin-dependent protein catabolic process selective autophagy Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 26249 100503085 Ensembl ENSG00000146021 ENSMUSG00000014164 UniProt Q9UH77 E0CZ16 RefSeq (mRNA) NM_017415 NM_001257194 NM_001257195 NM_001195075 NM_001362415 NM_001368867 NM_001368868 RefSeq (protein) NP_001244123 NP_001244124 NP_059111 NP_001349344 NP_001355796 NP_001355797 Location (UCSC) Chr 5: 137.62 – 137.74 Mb Chr 13: 58.15 – 58.26 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Kelch-like protein 3 is a protein in humans that is encoded by the KLHL3 gene. ^[5] 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. ^[5]

Clinical significance

Pseudohypoaldosteronism Type 2D

Mutations in this gene cause pseudohypoaldosteronism type IID (PHA2D); ^{[6] [7]} a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis. ^[5]

Ischemic Stroke

A machine learning model identified the KLHL3 gene as a key gene in the occurrence and progression of ischemic stroke. ^[8]

References

1. GRCh38: Ensembl release 89: ENSG00000146021 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000014164 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: Kelch-like 3 (Drosophila)" . Retrieved 2012-04-26.
6. Louis-Dit-Picard H, Barc J, Trujillano D, Miserey-Lenkei S, Bouatia-Naji N, Pylypenko O, et al. (March 2012). "KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron". Nature Genetics. 44 (4): 609. doi: 10.1038/ng0512-609 . PMID   22406640.
7. Boyden LM, Choi M, Choate KA, Nelson-Williams CJ, Farhi A, Toka HR, et al. (January 2012). "Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities". Nature. 482 (7383): 98–102. doi:10.1038/nature10814. PMC   3278668 . PMID   22266938.
8. Huang D, Zhu Y, Shen J, Song C (May 2024). "Identification of Potential Neddylation-related Key Genes in Ischemic Stroke based on Machine Learning Methods". Molecular Neurobiology. 61 (5): 2530–2541. doi:10.1007/s12035-023-03738-5. PMID   37910287.

Further reading

• Hirosawa M, Nagase T, Ishikawa K, Kikuno R, Nomura N, Ohara O (October 1999). "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain". DNA Research. 6 (5): 329–336. doi: 10.1093/dnares/6.5.329 . PMID   10574461.
• Yeo A, Samways DS, Fowler CE, Gunn-Moore F, Henderson G (March 2001). "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): 1688–1700. doi:10.1046/j.1471-4159.2001.00185.x. PMID   11259487. S2CID   2755275.
• Mizutani A, Fukuda M, Ibata K, Shiraishi Y, Mikoshiba K (March 2000). "SYNCRIP, a cytoplasmic counterpart of heterogeneous nuclear ribonucleoprotein R, interacts with ubiquitous synaptotagmin isoforms". The Journal of Biological Chemistry. 275 (13): 9823–9831. doi: 10.1074/jbc.275.13.9823 . PMID   10734137.
• Lai F, Orelli BJ, Till BG, Godley LA, Fernald AA, Pamintuan L, et al. (May 2000). "Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene". Genomics. 66 (1): 65–75. doi:10.1006/geno.2000.6181. PMID   10843806.