TRPV1 gene consists of 17 exons and 17 introns including a coding region and a 5 and a 3 non-coding region.

There are four transcript variants encoding the same protein, but with different segments in the 5 UTR (var.1, var.2, var.3, var.4) and one alternative splice variant lacking exon 7 (TRPV1b). TRPV1 gene transcription was demonstrated in different cells and tissues, but no data are available on TRPV1 variant expression profiles.

The canonical form comprises 839 aa (MW~96 kDa) and is composed of six transmembrane spanning domains and a pore forming region between transmembrane domains 5 and 6. The N-terminal and C-terminal tails are in cytoplasmatic side. Three N terminal ankyrin (ANK) repeats are present in N-terminal tail. The variant form TRPV1b is identical to TRPV1 except for the partial deletion of the third ankyrin repeat domain and adjoining polypeptide sequence. Aminoacid modifications has been found (according to Swiss-Prot) in different residues (Table 1). The N-terminal intracellular domain appears to play a pivotal role in intracellular activation of TRPV1, in fact, by mutagenesis analysis a loss of sensitivity to capsaicin has been found related to residue Tyr-511 (Gavva et al., 2004). Modification of a single N-terminal cysteine altered activation of TRPV1 by pungent compounds ranging from onions to garlic (Salazar et al., 2008). The N-terminal intracellular domain also interacts with adjacent modulatory proteins and with the C-terminal intracellular domain. In the closed state, the N-terminal domain is likely exposed to the binding of ATP and a C-terminal region residues interact with PIP-2, facilitating channel activation. In contrast, a desensitized state may be promoted through the interaction of the N- and C-terminal domains through modulatory action involving calcium-calmodulin interacting regions. Moreover, the ankyrin repeat domains residing within the N-terminal intracellular domain forming a region of three repeats spanning amino acids participating in protein-protein (subunit) interactions (Bork, 1993). The presence of concave binding surfaces for ATP within the ANK regions suggest a role of ANKs in modulating channel activation and function (Lishko et al., 2007).

Aminoacid	Residue modification
117	Phosphoserine
145	Phosphoserine
371	Phosphoserine
502	Phosphoserine
604	Glycosylation
705	Phosphoserine
775	Phosphoserine
801	Phosphoserine
821	Phosphoserine

Table 1. Aminoacid number and type of putative modification in TRPV1 protein.

TRPV1 has also been found in different brain region, such as in dopaminergic neurones of the substantia nigra, hippocampal pyramidal neurones, hypothalamic neurones, neurones in the locus coeruleus, and in various layers of the cortex as in small to medium diameter primary afferent fibres, In non-neuronal cells TRPV1 has been found in keratinocytes, bladder urothelium, smooth muscle, liver, polymorphonuclear granulocytes, pancreatic beta-cells, endothelial cells, lymphocytes, thymocytes and macrophages. Moreover by expression profile studies more cells and tissues has been analyzed for TRPV1 expression.

TRPV1 is expressed in discrete spots in the plasma membrane and cytosol of different cell types (e.g. urothelial cells). Moreover, dorsal root ganglion (DRG) neurons express ectopic but functional TRPV1 channels in the endoplasmic reticulum (ER) (TRPV1(ER)).

TRPV1 agonists. TRPV1 is a non-selective cation channel, belonging to the superfamily of TRP channels. TRPV1 agonists are of exogenous and endogenous origins. Exogenous agonist are of natural, semi-synthetic and synthetic origin. The natural compounds include dietary derived compounds as: capsaicinoids, capsinoids, piperine, allicin, alliin, eugenol and gingerol or non dietary plant compounds as resiniferatoxin, Δ9-tetrahydrocannabinol, cannabidiol and venom from animal origins (Pertwee, 2005; Vriens et al., 2009). Moreover, other environmental irritants as well as noxious heat (> 43-45 °C) has been found to act as TRPV1 agonist. The existence of endogenous vanilloid agonists, a class of compounds referred to as endovanilloids, as TRPV1 channels modulators as been also investigated. TRPV1 has been found to be activated by biogenic amines like N-arachidonylethanolamine (AEA, anandamide), N-arachidonoyldopamine (NADA), N-oleoylethanolamine (OLEA), N-arachidonolylserine, and various N-acyltaurines and N-acylsalsolinols. Various lipids from the fatty acid pool have also been identified as TRPV1 activators, as inflammatory compounds such as bradykinin, products of the lipoxygenases (12-HPETE and leukotriene B4, 5(S)-HPETE (hydroperoxyeicosatetranoic acid) and/or leukotriene B4) (Van Der Stelt and Di Marzo, 2004). Also nerve growth factor (NGF), an inflammatory mediator is known to activate/sensitize TRPV1 through the TrkA receptor, act primarily through phosphoinositide-3- kinase (PI3K) and mitogen activated protein kinase (MAPK) signaling pathways (Chuang et al., 2001).
TRPV1 antagonists. Natural TRPV1 antagonists are actually restricted to two plant derived compounds, the thapsigargin that is the irritant principle of Thapsia garganica L. and yohimbine, an indole alkaloid from the tree Corynanthe yohimbe K. The endogenous TRPV1 antagonists discovery up to now are dynorphins, adenosine, various dietary omega-3 fatty acids like eicosapentaenoic and linolenic acids, the endogenous fatty acid amide hydrolase (FAAH) and different polyamines as putrescine, spermidine, and spermine permeate. The most active non-natural compound that act as TRPV1 antagonist are capsazepine and 5-iodoRTX.
Ligand-binding site. By comparative analysis of the primary structure of theTRPV1 and by mutagenesis studies has been revealed a critical role for Tyr511 and Ser512 (between the second intracellular loop and TM3), confirming that the vanilloid binding site is located intracellulary, moreover a third critical residue in the putative TM4 segment (Leu547) was indicated as relevant in ligand-binding.
The effect of extracellular protons (as Ca²⁺), acts primarily by increasing channel opening, rather than interacting directly with the vanilloid binding site.

Related TRPV1 intracellular signaling pathways
EGFR (epidermal growth factor receptor). TRPV1 has been found to down-regulate epidermal growth factor receptor (EGFR) expression. Interaction of TRPV1 terminal cytosolic domain with EGFR induces EGFR ubiquitination and degradation. Moreover, by transfection of TRPV1 in HEK293 cells a decreased EGFR protein expression was observed (Bode et al., 2009).
Fas/CD95. Activation of TRPV1 with capsaicin, in low-grade urothelial cancer cells, induced a TRPV1-dependent G0/G1 cell cycle arrest and apoptosis by inducing transcription of pro-apoptotic genes Fas/CD95, Bcl-2 and caspases, and by activation of the DNA damage response pathway. Moreover, CPS stimulation induced a TRPV1-dependent redistribution and its clustering with Fas/CD95. In addition, an involvement of capsaicin in activation of the ATM kinase/p53 pathways was found (Amantini et al., 2009).
PKA (protein kinase A). TRPV1 are found phosphorylated by PKA in the amino terminus Ser116 and Thr370 and involved in desensitisation while phosphorylation of Ser116 by PKA inhibits dephosphorylation of TRPV1 caused by capsaicin exposure (Mohapatra and Nau, 2003).
PKC (protein kinase C). Several inflammatory mediators, like ATP, bradykinin, prostaglandins and trypsin or tryptase activated Gq coupled receptors and induced PKC-dependent phosphorylation of TRPV1 (Moriyama et al., 2003). PKC dependent phosphorylation of TRPV1 potentiates capsaicin- or proton-evoked responses and reduces temperature threshold for TRPV1 activation. Direct phosphorylation of TRPV1 by PKC has been located at Ser502 and Ser800 (Bhave et al., 2003).
IGF-I (insulin growth factor I). Insulin and IGF-I increase translocation of TRPV1 to the plasma membrane via activation of IGF receptors, which, in turn, induced PI(3) kinase and PKC activation (Van Buren et al., 2005).
CdK5 (cyclin-dependent kinase 5). CdK5 can directly phosphorylate Thr407 in TRPV1, while inhibition of CdK5 activity decreases TRPV1 function and Ca²⁺ influx (Pareek et al., 2007).

86% identity with Mus musculus TRPV1, 85% with Rattus norvegicus TRPV1, 65% with human TRPV3.