TRPV3 is a tetramer, and each subunit is composed of six transmembrane (TM) domains and two relatively large cytoplasmic amino- (N-) and carboxy- (C-) termini on which additional structural motifs are present, notably the ankyrin repeats on the N terminus. The putative pore loop is located between TM5 and TM6, which forms the pore for ion flux. Although the central TM domains are highly conserved, the amino acid sequences of the N- and C-termini of the TRPV3 channels are highly diversified among different species. TRPV3 is predominantly expressed in skin, where it is activated by warm temperatures and chemical activators. Activation of epidermal TRPV3 has been shown to increase the release of diffusible molecules that are capable of activating or sensitizing primary sensory neurons, leading to sensory hypersensitivity. Besides keratinocytes, TRPV3 is also expressed in many neuronal and non-neuronal tissues, indicating that TRPV3 might play important roles in many unknown cellular and physiological functions.
Basic Information of TRPV3 | |
Protein Name | Transient receptor potential cation channel subfamily V member 3 |
Gene Name | TRPV3 |
Aliases | Vanilloid receptor-like 3 (VRL-3) |
Organism | Homo sapiens (Human) |
UniProt ID | Q8NET8 |
Transmembrane Times | 6 |
Length (aa) | 790 |
Sequence | MKAHPKEMVPLMGKRVAAPSGNPAILPEKRPAEITPTKKSAHFFLEIEGFEPNPTVAKTSPPVFSKPMDSNIRQCISGNCDDMDSPQSPQDDVTETPSNPNSPSAQLAKEEQRRKKRRLKKRIFAAVSEGCVEELVELLVELQELCRRRHDEDVPDFLMHKLTASDTGKTCLMKALLNINPNTKEIVRILLAFAEENDILGRFINAEYTEEAYEGQTALNIAIERRQGDIAALLIAAGADVNAHAKGAFFNPKYQHEGFYFGETPLALAACTNQPEIVQLLMEHEQTDITSRDSRGNNILHALVTVAEDFKTQNDFVKRMYDMILLRSGNWELETTRNNDGLTPLQLAAKMGKAEILKYILSREIKEKRLRSLSRKFTDWAYGPVSSSLYDLTNVDTTTDNSVLEITVYNTNIDNRHEMLTLEPLHTLLHMKWKKFAKHMFFLSFCFYFFYNITLTLVSYYRPREEEAIPHPLALTHKMGWLQLLGRMFVLIWAMCISVKEGIAIFLLRPSDLQSILSDAWFHFVFFIQAVLVILSVFLYLFAYKEYLACLVLAMALGWANMLYYTRGFQSMGMYSVMIQKVILHDVLKFLFVYIVFLLGFGVALASLIEKCPKDNKDCSSYGSFSDAVLELFKLTIGLGDLNIQQNSKYPILFLFLLITYVILTFVLLLNMLIALMGETVENVSKESERIWRLQRARTILEFEKMLPEWLRSRFRMGELCKVAEDDFRLCLRINEVKWTEWKTHVSFLNEDPGPVRRTDFNKIQDSSRNNSKTTLNAFEEVEEFPETSV |
TRPV3 is a versatile receptor integrating diversified sensory signals, though it is unlikely to play a major role in sensing warm temperatures in rodents in vivo. TRPV3 is also involved in many cellular functions in addition to its role as a polymodal sensory transducer. Recent findings that both gain-of-function and loss-of-function mutations of TRPV3 produce severe skin disorders and disruption of hair morphogenesis provide compelling evidence that TRPV3 activity is critical to maintaining epidermal homeostasis. Future research on investigations into the cellular and systemic functions of TRPV3 may greatly benefit from the advent of selective agonists and antagonists as well as specific antibodies. The prominent role of TRPV3 in skin disorders and chronic itch makes it a promising drug target.
Fig.1 Proposed role of TRPV3 in itch signaling and hair growth. (Wang, 2014)
This article finds that TRPV3 sparklets cause dilation of cerebral parenchymal arterioles by activating IK and SK channels in the endothelium.
This article suggests that TRPV3 plays an important role in regulating oral epithelial proliferation and wound closure. Systemic and/or local up-regulation of TRPV3 channel activity may represent a novel therapeutic strategy for wound treatment.
This article suggests that gain-of-function genetic mutations of TRPV3 in rodents and humans have been instrumental in unveiling the critical role of this channel in skin health and disease.
This article reveals the prominent role of TRPV3 in skin disorders and chronic itch, making it a promising drug target.
This article suggests that the cold sensitivity of TRP channels established using Xenopus oocytes as a functional expression system may need to be revisited.
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