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1.A.4.2.9
The temperature (heat; >39°C)-sensitive, capsaicin-insensitive receptor cation-selective channel, TRPV3 or TRL3 (may form heterooligomers with VR1 (TRPV1; TC #1.A.4.2.1)). Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain (Moussaieff et al., 2008).  TRPV3 is activated by synthetic small-molecule chemicals and natural compounds from plants as well as warm temperatures. Its function is regulated by a variety of physiological factors including extracellular divalent cations and acidic pH, intracellular ATP, membrane voltage, and arachidonic acid. It shows a broad expression pattern in both neuronal and non-neuronal tissues including epidermal keratinocytes, epithelial cells in the gut, endothelial cells in blood vessels, and neurons in dorsal root ganglia and the CNS. TRPV3 null mice exhibit abnormal hair morphogenesis and compromised skin barrier function, and it may play critical roles in inflammatory skin disorders, itch, and pain sensation (Luo and Hu 2014). TRPV3 gating involves large rearrangements at the cytoplasmic inter-protomer interface, and this motion triggers coupling between cytoplasmic and transmembrane domains, priming the channel for opening (Zubcevic et al. 2019). Mutations in TRPV3 cause painful focal plantar keratoderma (Peters et al. 2020). TRPV3 is a temperature-sensitive, nonselective cation channel expressed prominently in skin keratinocytes that plays important roles in hair morphogenesis and maintenance of epidermal barrier function. Mechanisms of proton inhibition and sensitization have been discussed (Wang et al. 2021). Mechanisms of proton inhibition and sensitization of TRPV3 have been considered (Wang et al. 2021). TRPV3 is predominantly expressed in skin keratinocytes and has been implicated in cutaneous sensation and associated with numerous skin pathologies and cancers. TRPV3 is inhibited by the natural coumarin derivative osthole, an active ingredient of Cnidium monnieri, which has been used in traditional Chinese medicine for the treatment of various human diseases. Neuberger et al. 2021 presented cryo-EM structures of TRPV3 in complex with osthole, revealing two types of osthole binding sites in the transmembrane region of TRPV3 that coincide with the binding sites of agonist 2-APB. Osthole binding converts the channel pore into a previously unidentified conformation with a widely open selectivity filter and closed intracellular gate. The structures provide insight into competitive inhibition of TRPV3 by osthole (Neuberger et al. 2021).

Accession Number:Q8NET8
Protein Name:Transient receptor potential cation channel subfamily V member 3
Length:790
Molecular Weight:90636.00
Species: [9606]
Number of TMSs:7
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate Ca2+

Cross database links:

RefSeq: NP_659505.1   
Entrez Gene ID: 162514   
Pfam: PF00023   
OMIM: 607066  gene
KEGG: hsa:162514   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005262 F:calcium channel activity
GO:0006816 P:calcium ion transport

References (3)

[1] “TRPV3 is a temperature-sensitive vanilloid receptor-like protein.”  Smith G.D.et.al.   12077606
[2] “TRPV3 is a calcium-permeable temperature-sensitive cation channel.”  Xu H.et.al.   12077604
[3] “Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column.”  Imami K.et.al.   18187866
Structure:
6H9J   6HA6   6MHO   6MHS   6MHV   6MHW   6MHX   6OT2   6OT5   6UW4   [...more]

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MKAHPKEMVP LMGKRVAAPS GNPAILPEKR PAEITPTKKS AHFFLEIEGF EPNPTVAKTS 
61:	PPVFSKPMDS NIRQCISGNC DDMDSPQSPQ DDVTETPSNP NSPSAQLAKE EQRRKKRRLK 
121:	KRIFAAVSEG CVEELVELLV ELQELCRRRH DEDVPDFLMH KLTASDTGKT CLMKALLNIN 
181:	PNTKEIVRIL LAFAEENDIL GRFINAEYTE EAYEGQTALN IAIERRQGDI AALLIAAGAD 
241:	VNAHAKGAFF NPKYQHEGFY FGETPLALAA CTNQPEIVQL LMEHEQTDIT SRDSRGNNIL 
301:	HALVTVAEDF KTQNDFVKRM YDMILLRSGN WELETTRNND GLTPLQLAAK MGKAEILKYI 
361:	LSREIKEKRL RSLSRKFTDW AYGPVSSSLY DLTNVDTTTD NSVLEITVYN TNIDNRHEML 
421:	TLEPLHTLLH MKWKKFAKHM FFLSFCFYFF YNITLTLVSY YRPREEEAIP HPLALTHKMG 
481:	WLQLLGRMFV LIWAMCISVK EGIAIFLLRP SDLQSILSDA WFHFVFFIQA VLVILSVFLY 
541:	LFAYKEYLAC LVLAMALGWA NMLYYTRGFQ SMGMYSVMIQ KVILHDVLKF LFVYIVFLLG 
601:	FGVALASLIE KCPKDNKDCS SYGSFSDAVL ELFKLTIGLG DLNIQQNSKY PILFLFLLIT 
661:	YVILTFVLLL NMLIALMGET VENVSKESER IWRLQRARTI LEFEKMLPEW LRSRFRMGEL 
721:	CKVAEDDFRL CLRINEVKWT EWKTHVSFLN EDPGPVRRTD FNKIQDSSRN NSKTTLNAFE 
781:	EVEEFPETSV