KLHL3
entrez
26249
canonical
uniprot
Q9UH77
canonical
ensembl
ENSG00000146021
resolver
ensp
ENSP00000312397
resolver
ensp
ENSP00000422099
resolver
ensp
ENSP00000424828
resolver
genesymbol
KLHL3
resolver
genesymbol_syn
KIAA1129
resolver
hgnc
HGNC:6354
resolver
uniprot
B2RBK7
resolver
uniprot
Q9UH75
resolver
uniprot
Q9UH76
resolver
uniprot
Q9ULU0
resolver
uniprot
Q9Y6V6
resolver
uniprot_entry
KLHL3_HUMAN
resolver
uniprot_sec
B2RBK7
resolver
uniprot_sec
Q9UH75
resolver
uniprot_sec
Q9UH76
resolver
uniprot_sec
Q9ULU0
resolver
uniprot_sec
Q9Y6V6
resolver
amino_acid_sequence
MEGESVKLSSQTLIQAGDDEKNQRTITVNPAHMGKAFKVMNELRSKQLLCDVMIVAEDVEIEAHRVVLAACSPYFCAMFTGDMSESKAKKIEIKDVDGQTLSKLIDYIYTAEIEVTEENVQVLLPAASLLQLMDVRQNCCDFLQSQLHPTNCLGIRAFADVHTCTDLLQQANAYAEQHFPEVMLGEEFLSLSLDQVCSLISSDKLTVSSEEKVFEAVISWINYEKETRLEHMAKLMEHVRLPLLPRDYLVQTVEEEALIKNNNTCKDFLIEAMKYHLLPLDQRLLIKNPRTKPRTPVSLPKVMIVVGGQAPKAIRSVECYDFEEDRWDQIAELPSRRCRAGVVFMAGHVYAVGGFNGSLRVRTVDVYDGVKDQWTSIASMQERRSTLGAAVLNDLLYAVGGFDGSTGLASVEAYSYKTNEWFFVAPMNTRRSSVGVGVVEGKLYAVGGYDGASRQCLSTVEQYNPATNEWIYVADMSTRRSGAGVGVLSGQLYATGGHDGPLVRKSVEVYDPGTNTWKQVADMNMCRRNAGVCAVNGLLYVVGGDDGSCNLASVEYYNPVTDKWTLLPTNMSTGRSYAGVAVIHKSL
uniprot
proteins
disease_involvement
DISEASE: Pseudohypoaldosteronism 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. {ECO:0000269|PubMed:22266938, ECO:0000269|PubMed:22406640, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:23665031, ECO:0000269|PubMed:26435498, ECO:0000269|PubMed:27026694, ECO:0000269|PubMed:27780982, ECO:0000269|PubMed:28052936, ECO:0000269|PubMed:28511177, ECO:0000269|PubMed:34022862, ECO:0000269|PubMed:35093948}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:14528312, PubMed:22406640, PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031, PubMed:25313067, PubMed:35093948). 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:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031, PubMed:25313067, PubMed:35093948). The BCR(KLHL3) complex also mediates ubiquitination and degradation of WNK3 (PubMed:35179207). 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 (By similarity). {ECO:0000250|UniProtKB:E0CZ16, ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:22406640, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:23665031, ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:35093948}.
uniprot
proteins
mass_dalton
64970
uniprot
proteins
mutagenesis
MUTAGEN 433; /note="S->A,N: Abolished phosphorylation by PKC, promoting ubiquitination and degradation of WNK4."; /evidence="ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:30718414"; MUTAGEN 433; /note="S->E,D: Mimics phosphorylation, preventing binding and degradation of WNK4."; /evidence="ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:26435498
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:35179207}.
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 (PubMed:25313067, PubMed:26435498, PubMed:27727489, PubMed:30718414). 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 (PubMed:26435498). Dephosphorylated at Ser-433 by calcineurin PPP3CA, promoting degradation of WNK1 and WNK4 (PubMed:30718414). {ECO:0000269|PubMed:25313067, ECO:0000269|PubMed:26435498, ECO:0000269|PubMed:27727489, ECO:0000269|PubMed:30718414}.
uniprot
proteins
protein_family
KLHL3 family
uniprot
proteins
pubmed
10574461
uniprot
proteins
pubmed
10843806
uniprot
proteins
pubmed
14528312
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
22266938
uniprot
proteins
pubmed
22406640
uniprot
proteins
pubmed
23387299
uniprot
proteins
pubmed
23453970
uniprot
proteins
pubmed
23573258
uniprot
proteins
pubmed
23576762
uniprot
proteins
pubmed
23665031
uniprot
proteins
pubmed
24641320
uniprot
proteins
pubmed
25313067
uniprot
proteins
pubmed
26435498
uniprot
proteins
pubmed
27026694
uniprot
proteins
pubmed
27727489
uniprot
proteins
pubmed
27780982
uniprot
proteins
pubmed
28052936
uniprot
proteins
pubmed
28511177
uniprot
proteins
pubmed
30718414
uniprot
proteins
pubmed
34022862
uniprot
proteins
pubmed
35093948
uniprot
proteins
pubmed
35179207
uniprot
proteins
sequence_length
587
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:22406640}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:22406640}.
uniprot
proteins