Tbio KLHL3 Kelch-like protein 3

Protein Summary

Description

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). The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation (PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031). The BCR(KLHL3) complex also mediates ubiquitination and degradation of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney (By similarity). 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. [provided by RefSeq, Mar 2012]

Uniprot Accession IDs

• Q9UH77
• B2RBK7
• Q9UH75
• Q9UH76
• Q9ULU0
• Q9Y6V6

Gene Name

• KLHL3

Ensembl ID

• ENST00000309755
• ENSP00000312397
• ENSG00000146021
• ENST00000506491
• ENSP00000424828
• ENST00000508657
• ENSP00000422099

Symbol

• KIAA1129
• PHA2D

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.92
cell type or tissue	0.64
cell line	0.61
microRNA	0.57
cellular component	0.55

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 39.75   (req: < 5)

Gene RIFs: 22   (req: <= 3)

Antibodies: 238   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 39.75   (req: >= 5)

Gene RIFs: 22   (req: > 3)

Antibodies: 238   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 10

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0