TRPV6
Function
Calcium selective cation channel that mediates Ca(2+) uptake in various tissues, including the intestine (PubMed:11097838, PubMed:11248124, PubMed:11278579, PubMed:15184369, PubMed:23612980, PubMed:29258289). Important for normal Ca(2+) ion homeostasis in the body, including bone and skin (By similarity). The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification (PubMed:15184369). Inactivation includes both a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism; the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating.
Involvement in disease
Hyperparathyroidism, transient neonatal
HRPTTN
An autosomal recessive disease characterized by impaired transplacental maternal-fetal transport of calcium, high serum PTH levels and signs of metabolic bone disease in the neonatal period. Skeletal anomalies include generalized osteopenia, narrow chest, short ribs with multiple healing fractures, and bowing or fractures of long bones. Affected individuals experience postnatal respiratory and feeding difficulties. The condition improves within a short time after birth once calcium is provided orally.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Glycosylated.
Phosphorylation at Tyr-201 by SRC leads to an increased calcium influx through the channel. Probably dephosphorylated at this site by PTPN1 (By similarity). Phosphorylation by PRKCA at the calmodulin binding site delays channel inactivation (PubMed:11248124).
Sequence Similarities
Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV6 sub-subfamily.
Tissue Specificity
Expressed at high levels in the gastrointestinal tract, including esophagus, stomach, duodenum, jejunum, ileum and colon, and in pancreas, placenta, prostate and salivary gland. Expressed at moderate levels in liver, kidney and testis. Expressed in trophoblasts of placenta villus trees (at protein level) (PubMed:23612980). Expressed in locally advanced prostate cancer, metastatic and androgen-insensitive prostatic lesions but not detected in healthy prostate tissue and benign prostatic hyperplasia.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
ECAC2, TRPV6, Transient receptor potential cation channel subfamily V member 6, TrpV6, CaT-like, Calcium transport protein 1, Epithelial calcium channel 2, CaT-L, CaT1, ECaC2