Recombinant Human Kelch-like protein 3 (KLHL3)

Uniprot Id

Q9UH77

Target Species

Human

Target Name

KLHL3

Target Full Name

Kelch-like protein 3

Target 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 acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation. The BCR(KLHL3) complex also mediates ubiquitination and degradation of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney.

Target Involvement

Pseudohypoaldosteronism 2D (PHA2D)

Target Subcellular Location

Cytoplasm, cytoskeleton. Cytoplasm, cytosol.

Target Tissue Specificity

Widely expressed.

Target Synonyms

KLHL3; KIAA1129; Kelch-like protein 3

Target Background

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. Muatations in this gene cause pseudohypoaldosteronism type IID (PHA2D); a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms.