Kelch-like protein 3 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
in humans that is encoded by the KLHL3
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
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
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
BTB domain followed by a
BACK domain and six
kelch-like repeats in the
C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein
Proteins are large biomolecules and macromolecules that comp ...
. These kelch-like repeats promote substrate
ubiquitination
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...
of bound proteins via interaction of the BTB domain with the
CUL3
Cullin 3 is a protein that in humans is encoded by the ''CUL3'' gene.
Cullin 3 protein belongs to the family of cullins which in mammals contains eight proteins (Cullin 1, Cullin 2, Cullin 3, Cullin 4A, Cullin 4B, Cullin 5, Cullin 7 and Cullin 9 ...
(cullin 3) component of a cullin-RING E3 ubiquitin ligase (CRL) complex.
Clinical significance
Pseudohypoaldosteronism Type 2D
Mutations in this gene cause
pseudohypoaldosteronism
Pseudohypoaldosteronism (PHA) is a condition that mimics hypoaldosteronism (presenting hyperkalemia). Two major types of primary pseudohypoaldosteronism are recognized and these have major differences in etiology and presentation.
Pseudohypoaldo ...
type IID (PHA2D);
a rare Mendelian syndrome featuring
hypertension
Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
,
hyperkalaemia
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occ ...
and metabolic
acidosis
Acidosis is a biological process producing hydrogen ions and increasing their concentration in blood or body fluids. pH is the negative log of hydrogen ion concentration and so it is decreased by a process of acidosis.
Acidemia
The term ac ...
.
Ischemic Stroke
A machine learning model identified the KLHL3 gene as a key gene in the occurrence and progression of
ischemic stroke
Stroke is a medical condition in which poor blood flow to a part of the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop ...
.
References
Further reading
*
*
*
*
{{gene-5-stub
Kelch proteins