background:
KLHL3 protein contains a poxvirus and zinc finger domain at the N-terminus and six tandem repeats (kelch repeats) at the SLCterminus. At the amino acid level, KLHL3 shares 77% similarity with Drosophila kelch and 89% similarity with Mayven (KLHL2), another human kelch homolog. At least three isoforms are produced and may be the result of alternative promoter usage. The KLHL3 maps within the smallest commonly deleted segment in myeloid leukemias characterized by a deletion of 5q; however, no inactivating mutations of KLHL3 could be detected in malignant myeloid disorders with loss of 5q.
Function:
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron. The BCR(KLHL3) complex may act by mediating ubiquitination of SLC12A3/NCC, thereby regulating SLC12A3/NCC subcellular location at the cell membrane.
Subunit:
Component of the BCR(KLHL3) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL3 and RBX1 (Probable). Interacts with SLC12A3.
Subcellular Location:
Cytoplasm, cytoskeleton. Cytoplasm, cytosol.
Tissue Specificity:
Widely expressed.
DISEASE:
Defects in KLHL3 are the cause of Pseudohypoaldosteronism type 2D (PHA2D) [MIM:614495]. A disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics. PHA2D inheritance is autosomal dominant or recessive.
Similarity:
Contains 1 BACK (BTB/Kelch associated) domain.
Contains 1 BTB (POZ) domain.
Contains 6 Kelch repeats.
Database links:
UniProtKB/Swiss-Prot: Q9UH77.2
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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