| Post Translational Modifications | Phosphorylation at Ser-433 by PKA or PKC decreases the interaction with WNK1 and WNK4, leading to inhibit their degradation by the BCR(KLHL3) complex. Phosphorylated at Ser-433 by PKC in response to angiotensin II signaling, decreasing ability to promote degradation of WNK1 and WNK4, leading to activation of Na-Cl cotransporter SLC12A3/NCC. Phosphorylation at Ser-433 is increased by insulin. Dephosphorylated at Ser-433 by calcineurin PPP3CA, promoting degradation of WNK1 and WNK4. |
| 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 and degradation of WNK1 and WNK4, two activators of Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney, thereby regulating NaCl reabsorption. The BCR(KLHL3) complex also mediates ubiquitination and degradation of WNK3. The BCR(KLHL3) complex also mediates ubiquitination of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney, leading to its degradation. |
| Protein Name | Kelch-Like Protein 3 |
| Database Links | Reactome: R-HSA-8951664Reactome: R-HSA-983168 |
| Cellular Localisation | CytoplasmCytosolCytoskeleton |
| Alternative Protein Names | Kelch-Like Protein 3 proteinKLHL3 proteinKIAA1129 protein |
Information sourced from Uniprot.org
