| Literature References | 1. ZHU, X., JIANG, M., PEYTON, M., BOULAY, G., HURST, R., STEFANI, E. AND
BIRNBAUMER, L.
Trp, a novel mammalian gene family essential for agonist-activated
capacitative Ca2+ entry.
CELL 85 661-671 (1996).
2. BOULAY, G., ZHU, X., PEYTON, M., JIANG, M., HURST, R., STEFANI, E. AND
BIRNBAUMER, L.
Cloning and expression of a novel mammalian homolog of Drosophila transient
receptor potential (Trp) involved in calcium entry secondary to activation
of receptors coupled by the Gq class of G protein.
J.BIOL.CHEM. 272 29672-29680 (1997).
3. GUNTHORPE, M.J., BENHAM, C.D., RANDALL, A. AND DAVIS, J.B.
The diversity in the vanilloid (TRPV) receptor family of ion channels.
TRENDS PHARMACOL.SCI. 23(4) 183-191 (2002).
4. STROTMANN, R., HARTENECK, C., NUNNENMACHER, K., SCHULTZ, G. AND
PLANT, T.D.
OTRPC4, a nonselective cation channel that confers sensitivity to
extracellular osmolarity.
NAT.CELL BIOL. 2 695-702 (2000).
5. LIEDTKE, W., CHOE, Y., MARTI-RENOM, M.A., BELL, A.M., DENIS, C.S.,
SALI, A., HUDSPETH, A.J., FRIEDMAN, J.M. AND HELLER, S.
Vanilloid receptor-related osmotically activated channel (VR-OAC), a
candidate vertebrate osmoreceptor.
CELL 103 525-535 (2000).
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| Documentation | Transient receptor potential (Trp) and related proteins are thought to be
Ca2+ ion channel subunits that mediate capacitative Ca2+ entry in response
to a range of external and internal cell stimuli. Such Ca2+ entry is thought
to be an essential component of cellular responses to many hormones and
growth factors, and acts to replenish intracellular Ca2+ stores that have
been emptied through the action of inositol triphosphate (IP3) and other
agents. In non-excitable cells (i.e., those that lack voltage-gated Ca2+
channels, such as hepatocytes), this mode of Ca2+ entry is thought to be an
important step in generating the oscillations of intracellular Ca2+
concentration that characterise their response to stimulatory agents [1].
Studies on the visual transduction system in Drosophila led to the molecular
cloning of Trp and of a related protein, Trp-like, which show similarity to
voltage-gated Ca2+ channels in the regions known as S3-S6, including the S5-
S6 linker, which forms the ion-selective channel pore [2]. This provided
evidence that Trp and/or related proteins might form mammalian capacitative gd; Ca2+ entry channels. The sequences of these proteins have varying lengths gd; (usually 800-1000 amino acid residues), and hydropathy plots suggest they gd; have 6 or more transmembrane (TM) domains, flanked by cytosolic N- and C-
termini. In addition, most contain N-terminal ankyrin repeats [2,3].
Following the cloning of the vanilloid receptor (VR1), at least 4 other
related proteins have been identified. Together, these form a distinct
subgroup of the TRP family. Members of the vanilloid receptor family (TRPV)
are activated by a diverse range of stimuli, including heat, protons,
lipids, phorbols, phosphorylation, changes in extracellular osmolarity
and/or pressure, and depletion of intracellular calcium stores [3]. To date,
2 vanilloid receptor-like proteins (VRL-1 and VRL-2) and at least 2
epithelial calcium channels (ECAC) have been reported.
VRL-2 (also known as VR-OAC, OTRPC4, TRP12) is expressed at high levels in
kidney, liver, heart and central nervous system. It is an osmotically
regulated channel, which suggests that it could be activated by physical
stimuli, such as cell swelling. However, VRL-2 is not gated directly by
membrane stretch [4]; thus, as with swelling-activated anion channels, a
cytoplasmic signal transduction pathway is likely to be involved, with
cross-talk with other activation pathways. It is possible that they may play
a role in a range of conditions that result from deficits in osmoregulation.
Targeting VRL-2 might therefore be of benefit in conditions such as impaired
hearing or kidney dysfunction [5].
VRL2RECEPTOR is a 6-element fingerprint that provides a signature for the
vanilloid receptor-like 2 protein (VRL-2) family. The fingerprint was
derived from an initial alignment of 3 sequences: the motifs were drawn
from conserved regions spanning the full alignment length - motifs 1-4 lie
in the N-terminus; motif 5 encodes the third TM domain; and motif 6 resides
in the loop region between the fifth TM domain and the pore-domain. Two
iterations on SPTR40_20f were required to reach convergence, at which point
a true set comprising 11 sequences was identified.
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