Transient Receptor Potential channel, Vanilloid subfamily (TRPV); The vanilloid TRP subfamily (TRPV), named after the vanilloid receptor 1 (TRPV1), consists of six members: four thermo-sensing channels (TRPV1, TRPV2, TRPV3, and TRPV4) and two Ca2+ selective channels (TRPV5 and TRPV6). The calcium-selective channels TRPV5 and TRPV6 can be heterotetramers and are important for general Ca2+ homeostasis. All four channels within the TRPV1-4 group show temperature-invoked currents when expressed in heterologous cell systems, ranging from activation at ~25C for TRPV4 to ~52C for TRPV2. The structure of TRPV shows the typical topology features of all Transient Receptor Potential (TRP) ion channel family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6 and large intracellular N- and C-terminal domains. The TRP family consists of membrane proteins that function as ion channels that communicate between the cell and its environment, by a vast array of physical or chemical stimuli, including radiation (in the form of temperature, infrared ,or light) and pressure (osmotic or mechanical). TRP channels are formed by a tetrameric complex of channel subunits. Based on sequence identity, the mammalian TRP channel family is classified into six subfamilies, with significant sequence similarity within the transmembrane domains, but very low similarity in their N- and C-terminal cytoplasmic regions. The six subfamilies are named based on their first member: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPML (mucolipin), and TRPP (polycystic).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2154713004  41 LRLIHIFTVSRNLGPKIIMLQRMLI-DVFFFLFLFAVWMVAFGVARQGILRQneqrwrwifrsviYEP--YLAMFGQVPS 117
Cdd:TIGR00870 481 LNLLYIFRGNQHLGPLQIMIGRMILgDILRFLFIYAVVLFGFACGLNQLYQY-------------YDElkLNECSNPHAR 547

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2154713004 118 DVDGTTYDFAHCTFTgneskplCVEL-----DEHNLPRFP----EWITIPLVCIYMLSTNILLVNLLVAMFGYTVGTVQE 188
Cdd:TIGR00870 548 SCEKQGNAYSTLFET-------SQELfwaiiGLGDLLANEhkftEFVGLLLFGAYNVIMYILLLNMLIAMMGNTYQLIAD 620

                         170
                  ....*....|....*..
gi 2154713004 189 NNDQVWKFQRYFLVQEY 205
Cdd:TIGR00870 621 DADEEWKFQRAKLWMSY 637

transient-receptor-potential calcium channel protein; The Transient Receptor Potential Ca2+ Channel (TRP-CC) Family (TC. 1.A.4)The TRP-CC family has also been called the store-operated calcium channel (SOC) family. The prototypical members include the Drosophila retinal proteinsTRP and TRPL (Montell and Rubin, 1989; Hardie and Minke, 1993). SOC members of the family mediate the entry of extracellular Ca2+ into cells in responseto depletion of intracellular Ca2+ stores (Clapham, 1996) and agonist stimulated production of inositol-1,4,5 trisphosphate (IP3). One member of the TRP-CCfamily, mammalian Htrp3, has been shown to form a tight complex with the IP3 receptor (TC #1.A.3.2.1). This interaction is apparently required for IP3 tostimulate Ca2+ release via Htrp3. The vanilloid receptor subtype 1 (VR1), which is the receptor for capsaicin (the ?hot? ingredient in chili peppers) and servesas a heat-activated ion channel in the pain pathway (Caterina et al., 1997), is also a member of this family. The stretch-inhibitable non-selective cation channel(SIC) is identical to the vanilloid receptor throughout all of its first 700 residues, but it exhibits a different sequence in its last 100 residues. VR1 and SICtransport monovalent cations as well as Ca2+. VR1 is about 10x more permeable to Ca2+ than to monovalent ions. Ca2+ overload probably causes cell deathafter chronic exposure to capsaicin. (McCleskey and Gold, 1999). [Transport and binding proteins, Cations and iron carrying compounds]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2154713004  41 LRLIHIFTVSRNLGPKIIMLQRMLI-DVFFFLFLFAVWMVAFGVARQGILRQneqrwrwifrsviYEP--YLAMFGQVPS 117
Cdd:TIGR00870 481 LNLLYIFRGNQHLGPLQIMIGRMILgDILRFLFIYAVVLFGFACGLNQLYQY-------------YDElkLNECSNPHAR 547

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2154713004 118 DVDGTTYDFAHCTFTgneskplCVEL-----DEHNLPRFP----EWITIPLVCIYMLSTNILLVNLLVAMFGYTVGTVQE 188
Cdd:TIGR00870 548 SCEKQGNAYSTLFET-------SQELfwaiiGLGDLLANEhkftEFVGLLLFGAYNVIMYILLLNMLIAMMGNTYQLIAD 620

                         170
                  ....*....|....*..
gi 2154713004 189 NNDQVWKFQRYFLVQEY 205
Cdd:TIGR00870 621 DADEEWKFQRAKLWMSY 637

transient-receptor-potential calcium channel protein; The Transient Receptor Potential Ca2+ Channel (TRP-CC) Family (TC. 1.A.4)The TRP-CC family has also been called the store-operated calcium channel (SOC) family. The prototypical members include the Drosophila retinal proteinsTRP and TRPL (Montell and Rubin, 1989; Hardie and Minke, 1993). SOC members of the family mediate the entry of extracellular Ca2+ into cells in responseto depletion of intracellular Ca2+ stores (Clapham, 1996) and agonist stimulated production of inositol-1,4,5 trisphosphate (IP3). One member of the TRP-CCfamily, mammalian Htrp3, has been shown to form a tight complex with the IP3 receptor (TC #1.A.3.2.1). This interaction is apparently required for IP3 tostimulate Ca2+ release via Htrp3. The vanilloid receptor subtype 1 (VR1), which is the receptor for capsaicin (the ?hot? ingredient in chili peppers) and servesas a heat-activated ion channel in the pain pathway (Caterina et al., 1997), is also a member of this family. The stretch-inhibitable non-selective cation channel(SIC) is identical to the vanilloid receptor throughout all of its first 700 residues, but it exhibits a different sequence in its last 100 residues. VR1 and SICtransport monovalent cations as well as Ca2+. VR1 is about 10x more permeable to Ca2+ than to monovalent ions. Ca2+ overload probably causes cell deathafter chronic exposure to capsaicin. (McCleskey and Gold, 1999). [Transport and binding proteins, Cations and iron carrying compounds]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2154713004  41 LRLIHIFTVSRNLGPKIIMLQRMLI-DVFFFLFLFAVWMVAFGVARQGILRQneqrwrwifrsviYEP--YLAMFGQVPS 117
Cdd:TIGR00870 481 LNLLYIFRGNQHLGPLQIMIGRMILgDILRFLFIYAVVLFGFACGLNQLYQY-------------YDElkLNECSNPHAR 547

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2154713004 118 DVDGTTYDFAHCTFTgneskplCVEL-----DEHNLPRFP----EWITIPLVCIYMLSTNILLVNLLVAMFGYTVGTVQE 188
Cdd:TIGR00870 548 SCEKQGNAYSTLFET-------SQELfwaiiGLGDLLANEhkftEFVGLLLFGAYNVIMYILLLNMLIAMMGNTYQLIAD 620

                         170
                  ....*....|....*..
gi 2154713004 189 NNDQVWKFQRYFLVQEY 205
Cdd:TIGR00870 621 DADEEWKFQRAKLWMSY 637

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 1-4; TRPV1-4 are thermo-sensing channels that function directly in temperature-sensing and nociception; they share substantial structural and functional properties. Transient Receptor Potential (TRP) ion channels activated by temperature (thermo TRPs) are important molecular players in acute, inflammatory, and chronic pain states. So far, 11 TRP channels in mammalian cells have been identified as thermosensitive TRP (thermo-TRP) channels. TRPV1-4 channels are activated by different heat temperatures, for example, TRPV1 and TRPV2 are activated by high temperatures (>43C and >55C, respectively). TRPV1-4 belong to the vanilloid TRP subfamily (TRPV), named after the founding member vanilloid receptor 1 (TRPV1). The structure of TRPV shows the typical topology features of all TRP ion channel family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6 and large intracellular N- and C-terminal domains.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2154713004 142 ELDEHNLPRFPEWITIPLVCiYMLSTNILLVNLLVAMFGYTVGTVQENNDQVWKFQR 198
Cdd:cd22193   506 DLEFQENSTYPAVFLILLLT-YVILTFVLLLNMLIALMGETVNNVSKESKRIWKLQR 561

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), type 1; Vanilloid receptor 1 (TRPV1), a capsaicin (vanilloid) receptor, is the founding member of the vanilloid TRP subfamily (TRPV). In humans, it is expressed in the brain, kidney, pancreas, testis, uterus, spleen, stomach, small intestine, lung and liver. TRPV1 has been implicated to have function in thermo-sensation (heat), autonomic thermoregulation, nociception, food intake regulation, and multiple functions in the gastrointestinal (GI) tract. The receptor has also been involved in growth cone guidance, long-term depression, endocannabinoid signaling and osmosensing in the central nervous system. TRPV1 is up regulated in several human pathological conditions including vulvodynia, GI inflammation, Crohn's disease and ulcerative colitis. TRPV1 knock-out mice exhibit impaired sensation to thermal-mechanical acute pain. The structure of TRPV shows the typical topology features of all Transient Receptor Potential (TRP) ion channel family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6 and large intracellular N- and C-terminal domains.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 2154713004 150 RFPEWITIPLVCiYMLSTNILLVNLLVAMFGYTVGTVQENNDQVWKFQR 198
Cdd:cd22196   543 KFKEVFIFLLIS-YVILTYILLLNMLIALMGETVSKIAQESKNIWKLQR 590

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and TRPV6 (TRPV5/6) are two homologous members within the vanilloid subfamily of the transient receptor potential (TRP) family. TRPV5 and TRPV6 show only 30-40% homology with other members of the TRP family and have unique properties that differentiates them from other TRP channels. They mediate calcium uptake in epithelia and their expression is dramatically increased in numerous types of cancer. The structure of TRPV5/6 shows the typical topology features of all TRP family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6, which is predicted to form the Ca2+ pore, and large intracellular N- and C-terminal domains. The N-terminal domain of TRPV5/6 contains three ankyrin repeats. This structural element is present in several proteins and plays a role in protein-protein interactions. The N- and C-terminal tails of TRPV5/6 each contain an internal PDZ motif which can function as part of a molecular scaffold via interaction with PDZ-domain containing proteins. A major difference between the properties of TRPV5 and TRPV6 is in their tissue distribution: TRPV5 is predominantly expressed in the distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, with limited expression in extrarenal tissues. In contrast, TRPV6 has a broader expression pattern such as expression in the intestine, kidney, placenta, epididymis, exocrine tissues, and a few other tissues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2154713004  53 LGPKIIMLQRMLI-DVFFFLFLFAVWMVAFGVArqgilrqneqrwrwifrsvIYepylAMFGQVPSDVDGTTYDFAHCTF 131
Cdd:cd22192   447 LGPFTIMIQKIIFgDLMKFCWLMFVVILGFSSA-------------------FY----MIFQTEDPDSLGHFYDFPMTLF 503

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2154713004 132 TGNEskpLCVELdeHNLPRFPEWITIPLVCI----YMLSTNILLVNLLVAMFGYTVGTVQENNDQVWKFQ 197
Cdd:cd22192   504 STFE---LFLGL--IDGPANYTVDLPFMYKVlytaFAVIAYLLMLNLLIAMMGDTHWRVAHERDELWRAQ 568