TRPV2 gene consists of 15 exons and 14 introns spanning 1 to 21462 bp of DNA from 17p11.2 and includes a 5-/3- non-coding regions. The position of exons is: 1-292, 2021-2327, 4574-4707, 7058-7348, 7928-8226, 10558-10728, 11181-11336, 11908-12006, 12776-12846, 13276-13441, 16243-16309, 16425-16759, 18033-18157, 19349-19428, 21248-21462.

mRNA product length 2829 bp. No alternative splice variants have been found so far.

A transmembrane protein of vanilloid family, member 2, TRPV2 channel.

It is a glycosylated membrane protein (764 aa, MW ~86 kDa) with 6 transmembrane regions and a pore-forming loop. N- and C-terminal tails are in cytoplasmic side. TRPV2 contains 6 ankyrin repeats may play a role in the interaction between subunits and is probably homotetramer. Interacts with a cAMP-dependent protein kinase type II regulatory subunit (PRKAR2A or PRKAR2B) and ACBD3. Interacts with SLC50A1; the interaction probably occurs intracellularly and depends on TRPV2 N-glycosylation. This protein forms a non-selective cationic channel in the plasma membrane and is activated by temperatures higher than 52 degrees Celsius; and is not activated by vanilloids and acidic pH.

TRPV2 channel is expressed in the advanced stages of prostate cancer. TRPV2 transcript levels are higher in patients with metastatic cancer (stage M1) compared with primary solid tumors (stages T2a and T2b). TRPV2 channel is expressed in PC3 and DU-145 cell lines derived from bone and brain metastasis, respectively (Monet et al., 2009; Monet et al., 2010). TRPV2 protein is expressed in human hepatoblastoma (HepG2) cells (Vriens et al., 2004). TRPV2 was found to be more expressed at both the mRNA and protein levels in cirrhotic livers compared with chronic hepatitis, whereas it also occurred in moderately and well-differentiated tumors compared with that of poorly differentiated tumors (Liu et al., 2010). In hepatocellular carcinoma the increased expression of TRPV2 was identified in 16/55 (29%) cases. The enhanced TRPV2 mRNA and protein expression was also found in high-grade and -stage urothelial carcinoma specimens and urothelial carcinoma cell lines. Both the full-length TRPV2 (hTRPV2) and a short splice-variant (s-TRPV2) were detected in normal human urothelial cells and normal bladder specimens, whereas a progressive decline of s-TRPV2 in pTa, pT1, and pT2 stages was observed, up to a complete loss in pT3 and pT4 urothelial carcinoma specimens (Caprodossi et al., 2008). TRPV2 mRNA was abundantly expressed in T24 cells as well (a poorly differentiated urothelial carcinoma cell line). TRPV2 is also expressed in the rat dorsal root ganglia and in F-11 cells, a hybridoma derived from rat dorsal root ganglia and mouse neuroblastoma (Yamada et al., 2010). TRPV2 is expressed in the human larynx, which may act as laryngeal nociceptors perceiving luminal noxious stimuli. TRPV2 mRNA and protein are expressed in benign astrocyte tissues, and its expression progressively declined in high-grade glioma tissues as histological grade increased (n = 49 cases), and in U87MG cells and in MZC, FCL and FSL primary glioma cells (Nabissi et al., 2010).

The biotinylation studies as well as calcium imaging experiments in some works suggest its expression on the plasma membrane (Monet et al., 2009; Monet et al., 2010). It translocates from the cytoplasm to the plasma membrane upon ligand stimulation.

TRPV2 is a calcium-permeable, non-selective cation channel with an outward rectification. Seems to be regulated, at least in part, by IGF-I, PDGF and neuropeptide head activator. May transduce physical stimuli in mast cells. Activated by temperatures higher than 52 degrees Celsius; is not activated by vanilloids and acidic pH.

TRPV2 channel shares around 50% homology with TRPV1.

An experimental mutation published in the C-Terminus. In this study the authors identified a calmodulin binding site on the C-termini of TRPV2 (654-683). The R679 and K681 single mutants of TRPV2 caused a 50% decrease in binding affinity and a double mutation of K661/K664 of the same peptide lowered the binding affinity by up to 75% (Holakovska et al., 2011).