Kelch-like protein 3

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.

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

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]