Klhl3
entrez
100503085
canonical
uniprot
E0CZ16
canonical
ensembl
ENSMUSG00000014164
resolver
ensp
ENSMUSP00000123701
resolver
ensp
ENSMUSP00000307055
resolver
genesymbol
Klhl3
resolver
uniprot
F7A5U9
resolver
uniprot
I6L891
resolver
uniprot_entry
KLHL3_MOUSE
resolver
uniprot_sec
F7A5U9
resolver
uniprot_sec
I6L891
resolver
amino_acid_sequence
MEGESVKPSPQPTAQAEDEEKNRRTVTVNAAHMGKAFKVMNELRSKRLLCDVMIVAEDVEVEAHRVVLAACSPYFCAMFTGDMSESKAKKIEIKDVDGQTLSKLIDYIYTAEIEVTEENVQVLLPAASLLQLMDVRQNCCDFLQSQLHPTNCLGIRAFADVHTCTDLLQQANAYAEQHFPEVMLGEEFLSLSLDQVCSLISSDKLTVSSEEKVFEAVISWINYEKETRLDHMAKLMEHVRLPLLPRDYLVQTVEEEALIKNNNTCKDFLIEAMKYHLLPLDQRLLIKNPRTKPRTPVSLPKVMIVVGGQAPKAIRSVECYDFEEGRWDQIAELPSRRCRAGVVFMAGHVYAVGGFNGSLRVRTVDVYDGVKDQWTSIASMQERRSTLGAAVLNDLLYAVGGFDGSTGLASVEAYSYKTNEWFFVAPMNTRRSSVGVGVVEGKLYAVGGYDGASRQCLSTVEQYNPATNEWIYVADMSTRRSGAGVGVLSGQLYATGGHDGPLVRKSVEVYDPGTNTWKQVADMNMCRRNAGVCAVNGLLYVVGGDDGSCNLASVEYYNPVTDKWTLLPTNMSTGRSYAGVAVIHKSL
uniprot
proteins
function
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 (PubMed:24821705, PubMed:25831548, PubMed:28052936, PubMed:35621709). 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 (PubMed:24821705, PubMed:28052936, PubMed:35621709). 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 (PubMed:25831548). {ECO:0000269|PubMed:24821705, ECO:0000269|PubMed:25831548, ECO:0000269|PubMed:28052936, ECO:0000269|PubMed:35621709}.
uniprot
proteins
mass_dalton
64922
uniprot
proteins
mutagenesis
MUTAGEN 470..587; /note="Missing: Knockin mice display a pseudohypoaldosteronism type II (PHA2)-like phenotype, characterized by low-renin hypertension, hyperkalemia with reduced renal potassium excretion and hyperchloremic metabolic acidosis. Cells show increased levels of WNK1 and WNK4."; /evidence="ECO:0000269|PubMed:35621709"; MUTAGEN 528; /note="R->H: Knockin mice display a pseudohypoaldosteronism type II (PHA2)-like phenotype, characterized by low-renin hypertension, hyperkalemia with reduced renal potassium excretion and hyperchloremic metabolic acidosis. Cells show increased levels of WNK1 and WNK4."; /evidence="ECO:0000269|PubMed:24821705
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000250|UniProtKB:Q9UH77}.
uniprot
proteins
post_translational_modification
PTM: 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 (By similarity). 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 (PubMed:25313067). Phosphorylation at Ser-433 is increased by insulin (By similarity). Dephosphorylated at Ser-433 by calcineurin PPP3CA, promoting degradation of WNK1 and WNK4 (By similarity). {ECO:0000250|UniProtKB:Q9UH77, ECO:0000269|PubMed:25313067}.
uniprot
proteins
protein_family
KLHL3 family
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
22266938
uniprot
proteins
pubmed
22406640
uniprot
proteins
pubmed
24821705
uniprot
proteins
pubmed
25313067
uniprot
proteins
pubmed
25831548
uniprot
proteins
pubmed
28052936
uniprot
proteins
pubmed
35621709
uniprot
proteins
sequence_length
587
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9UH77}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q9UH77}.
uniprot
proteins