The mammalian TRP channels encode a family of about 30 ion channel proteins. This superfamily consists of seven diverse groups structurally similar to the originally found Drosophila TRP and they differ in ion selectivities, modes of activation and physiological functions. TRP proteins are expressed predominantly in the nervous system and are of particular importance in sensory physiology. (1)Montell C.
The TRP superfamily of cation channels.
Sci STKE. 2005 Feb 22;2005(272):re3.

The reason to identify mammalian TRPs is to characterize those channels that might account for highly Ca2+ selective Ca2+ entry mechanism in nonexcitable cells, referred to as store-operated Ca2+ entry (SOCE). SOCE is interesting, due to association of these modes of Ca2+ entry with processes ranging from T cell activation to apoptosis, cell proliferation, fluid secretion and cell migration.(1)Montell C.
The TRP superfamily of cation channels.
Sci STKE. 2005 Feb 22;2005(272):re3.

The TRP superfamily can be divided into two structurally different groups(1Montell C.
The TRP superfamily of cation channels.
Sci STKE. 2005 Feb 22;2005(272):re3. ,3Clapham DE, Montell C, Schultz G, Julius D;
International Union of Pharmacology.
XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels.
Pharmacol Rev. 2003 Dec;55(4):591-6. Review.):

1. Group 1: TRPC, TRPV, TRPM, TRPN, TRPA
   They share substantial sequence identity in the transmembrane domains.
2. Group 2: TRPP and TRPML
   They have low sequence similarity and a large extracellular loop between the first and the second transmembrane domains.

TRP proteins are supposed to form 6 membrane-spanning segments whereas the pore region is formed by a hydrophilic region between S5 and S6 forms. The N- and C-termini are located intracellularly. The N-terminus often contains ankyrin repeats as well as a coiled-coil domain, which are suspected to bind with other proteins or the cytoskeleton. Especially they are thought to be needed for TRP protein interaction because a functional channel contains 4 TRP subunits, either similar or different ones, to form homo- or heteromers (4Goel M, Sinkins WG, Schilling WP.
Selective association of TRPC channel subunits in rat brain synaptosomes.
J Biol Chem. 2002 Dec 13;277(50):48303-10. Epub 2002 Oct 10.,5Hoenderop JG, Voets T, Hoefs S, Weidema F, Prenen J, Nilius B, Bindels RJ.
Homo- and heterotetrameric architecture of the epithelial Ca2+ channels TRPV5 and TRPV6.
EMBO J. 2003 Feb 17;22(4):776-85).

TRPC (canonical) family consists of seven members, which are subdivided into four groups (TRPC1; TRPC4,5; TRPC3,6,7; TRPC2) by sequence homology as well as functional similarities. The TRPC2 protein only appears in mice and rats but humans only express six TRPC; there TRPC2 is a pseudogen. The TRPC proteins include three to four ankyrin repeats, six putative transmembrane domains and have a sequence homology bigger than 30%. Most of these ion channels appear to form heteromultimers. (3)Clapham DE, Montell C, Schultz G, Julius D;
International Union of Pharmacology.
XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels.
Pharmacol Rev. 2003 Dec;55(4):591-6. Review.

TRPV (vanilloid) family has six mammalian members grouped into three subfamilies. These proteins contain three to five ankyrin repeats and share ~25% amino acid identity to TRPC proteins (1)Montell C.
The TRP superfamily of cation channels.
Sci STKE. 2005 Feb 22;2005(272):re3. . TRPV1-TRPV4 form poor selective cation channels and are sensitive to heat (6Hellwig N, Albrecht N, Harteneck C, Schultz G, Schaefer M.
Homo- and heteromeric assembly of TRPV channel subunits.
J Cell Sci. 2005 Mar 1;118(Pt 5):917-28. Epub 2005 Feb 15. ,7Wang H, Woolf CJ.
Pain TRPs.
Neuron. 2005 Apr 7;46(1):9-12. Review. ). TRPV5 and TRPV6 are phylogenetically closely related Ca2+ selective channels (PCa:PNa > 100) expressed in epithelia of kidney and intestine and exhibit a constitutive activity. (3)Clapham DE, Montell C, Schultz G, Julius D;
International Union of Pharmacology.
XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels.
Pharmacol Rev. 2003 Dec;55(4):591-6. Review. Both proteins become permeable to monovalent cations in the absence of divalent cations. It was proposed that TRPV6 may be the highly Ca2+-selective, store-operated channels, referred to CRAC but several biophysical properties of TRPV6 are distinct from those of ICRAC (8)Kahr H, Schindl R, Fritsch R, Heinze B, Hofbauer M, Hack ME, Mortelmaier MA, Groschner K, Peng JB, Takanaga H, Hediger MA, Romanin C.
CaT1 knock-down strategies fail to affect CRAC channels in mucosal-type mast cells.
J Physiol. 2004 May 15;557(Pt 1):121-32. Epub 2004 Mar 12. . Nevertheless there remains still the option that TRPV5/ TRPV6 may be subunits of CRAC channels.(1)Montell C.
The TRP superfamily of cation channels.
Sci STKE. 2005 Feb 22;2005(272):re3.

TRPM (long TRPC, melastatin) family is composed of eight members. They share ~20% identity , have a TRP domain and contain ankyrin repeats at the N-terminus which is longer than that of TRPCs and TRPVs. (9)Fleig A, Penner R.
Emerging roles of TRPM channels.
Novartis Found Symp. 2004;258:248-58; discussion 258-66. Review.

1. Montell, C. (2005) Sci STKE 2005, re3
2. Hoenderop, J. G., Nilius, B., and Bindels, R. J. (2005) Physiol Rev 85, 373-422
3. Clapham, D. E., Montell, C., Schultz, G., and Julius, D. (2003) Pharmacol Rev 55, 591-596
4. Goel, M., Sinkins, W. G., and Schilling, W. P. (2002) J Biol Chem 277, 48303-48310
5. Hoenderop, J. G., Voets, T., Hoefs, S., Weidema, F., Prenen, J., Nilius, B., and Bindels, R. J. (2003) Embo J 22, 776-785
6. Hellwig, N., Albrecht, N., Harteneck, C., Schultz, G., and Schaefer, M. (2005) J Cell Sci 118, 917-928
7. Wang, H., and Woolf, C. J. (2005) Neuron 46, 9-12
8. Kahr, H., Schindl, R., Fritsch, R., Heinze, B., Hofbauer, M., Hack, M. E., Mortelmaier, M. A., Groschner, K., Peng, J. B., Takanaga, H., Hediger, M. A., and Romanin, C. (2004) J Physiol 557, 121-132
9. Fleig, A., and Penner, R. (2004) Novartis Found Symp 258, 248-258; discussion 258-266