TRPV5
Description
The TRPV5 (transient receptor potential cation channel subfamily V member 5) is a protein-coding gene located on chromosome 7.
TRPV5, a member of the transient receptor potential family and the TRPV subfamily, is a calcium channel protein encoded by the TRPV5 gene. It has six transmembrane-spanning domains, multiple potential phosphorylation sites, an N-linked glycosylation site, and five ANK repeats. TRPV5 forms homotetramers or heterotetramers and is activated by low internal calcium levels. Both TRPV5 and TRPV6 are expressed in kidney and intestinal epithelial cells. TRPV5 is primarily expressed in kidney epithelial cells, where it plays a vital role in calcium reabsorption, while TRPV6 is primarily expressed in the intestine. The enzyme α-klotho enhances kidney calcium reabsorption by stabilizing TRPV5. Klotho, a beta-glucuronidase-like enzyme, activates TRPV5 by removing sialic acid. In normal conditions, the kidney reabsorbs approximately 95% to 98% of the calcium filtered from the blood through the renal tubule, mediated by TRPV5. Genetic deletion of TRPV5 in mice leads to calcium loss in the urine, hyperparathyroidism, and bone loss.
TRPV5 is a constitutively active calcium-selective cation channel that plays a crucial role in calcium reabsorption in the kidney and intestine. It is essential for normal calcium reabsorption in the kidney's distal convoluted tubules. Activation occurs when internal calcium levels are low, and the channel exhibits inward rectification. A calcium-dependent feedback mechanism regulates the channel, involving fast inactivation and slow current decay. The channel's properties can be modified by heteromeric assembly with TRPV6, and TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating.
TRPV5 is also known as CAT2, ECAC1, OTRPC3.
Associated Diseases
- type 2 diabetes mellitus
- Dent disease
- nephronophthisis
- hypophosphatemic nephrolithiasis/osteoporosis 1
- hypercalcemia, infantile, 2
- familial idiopathic steroid-resistant nephrotic syndrome
- Dent disease type 1
- familial juvenile hyperuricemic nephropathy type 1
- nephronophthisis 1
- primary Fanconi syndrome
- nephronophthisis 3
- hypophosphatemic rickets, X-linked recessive
- Fanconi renotubular syndrome 1
- congenital sucrase-isomaltase deficiency
