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PR01766

Identifier
ECACCHANNEL1  [View Relations]  [View Alignment]  
Accession
PR01766
No. of Motifs
5
Creation Date
26-SEP-2002
Title
Epithelial calcium channel 1 (ECAC1) family signature
Database References
PRINTS; PR01765 ECACCHANNEL
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. HOENDEROP, J.G.J., VAN DER KEMP, A.W.C.M., HARTOG, A., VAN OS, C.H.,
WILLEMS, P.H.G.M. AND BINDELS R.J.M.
The epithelial calcium channel, ECaC, is activated by hyperpolarisation and
regulated by cytosolic calcium.
BIOCHEM.BIOPHYS.RES.COMMUM. 261 488-492 (1999).
 
5. BARLEY, N.F., HOWARD, A., O'CALLAGHAN, D., LEGON, S. AND WALTERS, J.R.F.
Epithelial calcium transporter expression in human duodenum.
AM.J.PHYSIOL.GASTROINTEST.LIVER PHYSIOL. 280(2) G285-290 (2001).
 
6. PENG, J.B., CHEN, X.Z., BERGER, U.V., VASSILEV, P.M., BROWN, E.M. AND
HEDIGER, M.A.
A rat kidney-specific calcium transporter in the distal nephron.
J.BIOL.CHEM. 275 28186-28194 (1999).
 
7. MULLER, D., HOENDEROP, J.G., MEIJ, I.C., VAN DEN HEUVEL, L.P., KNOERS,
N.V., DEN HOLLANDER, A.I., GARCIA-NIETO, V., CLAVERIE-MARTIN, F. AND
BINDELS, R.J.
Molecular cloning, tissue distribution, and chromosomal mapping of the human
epithelial calcium channel (ECAC1).
GENOMICS 67 48-53 (2000).

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 
Ca2+ entry channels. The sequences of these proteins have varying lengths 
(usually 800-1000 amino acid residues), and hydropathy plots suggest they 
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.
 
The cloning of ECAC1 (also known as ECAC or CaT2) [4] and ECAC2 (CaT1) [5]
revealed proteins distantly related to VRL. They are highly selective for
calcium and are constitutively active, which gives them an appearance of
calcium-transporter proteins under experimental conditions. They are
important in cellular calcium homeostasis and are tightly regulated by
intracellular and extracellular calcium, which cause channel inactivation
and block respectively [3].
 
ECAC1 was originally cloned from rabbit kidney cells [6], but has also been
found in human [7]. It is responsible for epithelial calcium reabsorption in
response to vitamin D3, parathyroid hormone and calcitonin. Consequently,
ECAC1 might be involved in diseases that are associated with calcium
malabsorption, such as osteoporosis, hypercalciuric stone disease and
chronic renal failure [3,6].
 
ECACCHANNEL1 is a 5-element fingerprint that provides a signature for the
epithelial calcium channel 1 (ECAC1) family. The fingerprint was derived
from an initial alignment of 6 sequences: the motifs were drawn from 
conserved regions spanning the full alignment length - motif 1 resides in 
the N-terminus; and motifs 2-4 are found at the C-terminus. Two iterations
on SPTR40_20f were required to reach convergence, at which point a true set
comprising 7 sequences was identified.
Summary Information
7 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
577777
400000
300000
200000
12345
True Positives
Q8WXR8        Q91WD2        Q9H1D0        Q9H1D1        
Q9H296 Q9JJJ0 Q9R186
Sequence Titles
Q8WXR8      CALCIUM TRANSPORT PROTEIN CAT1 - Homo sapiens (Human). 
Q91WD2 SIMILAR TO EPITHELIAL APICAL MEMBRANE CALCIUM TRANSPORTER/CHANNEL CAT1 - Mus musculus (Mouse).
Q9H1D0 CAT-LIKE B PROTEIN - Homo sapiens (Human).
Q9H1D1 CAT-LIKE A PROTEIN - Homo sapiens (Human).
Q9H296 CALCIUM TRANSPORT PROTEIN CAT1 - Homo sapiens (Human).
Q9JJJ0 CALCIUM TRANSPORTING PROTEIN HOMOLOG - Mus musculus (Mouse).
Q9R186 CALCIUM TRANSPORTER CAT1 - Rattus norvegicus (Rat).
Scan History
SPTR40_20f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
GLSLPKEKGLILCLWSKFCRWFQ Q9H296 2 2 -
GLSLPKEKGLILCLWSKFCRWFQ Q9H1D0 2 2 -
GLSLPKEKGLILCLWSKFCRWFQ Q9H1D1 2 2 -
GWSLPKEKGLILCLWNKFCRWFH Q91WD2 2 2 -
GWSLPKEKGLILCLWNKFCRWFH Q9JJJ0 2 2 -
GWSLPKEKGLILCLWNKFCRWFH Q9R186 2 2 -

Motif 2 width=18
Element Seqn Id St Int Rpt
FHTRGSEDLDKDSVEKLE Q9H296 651 626 -
FHTRGSEDLDKDSVEKLE Q9H1D0 651 626 -
FHTRGSEDLDKDSVEKLE Q9H1D1 651 626 -
QDGLYSEDLEKDSGEKLE Q91WD2 653 628 -
QDGLYSEDLEKDSGEKLE Q9JJJ0 655 630 -
QDDLYSEDLEKDSGEKLE Q9R186 653 628 -

Motif 3 width=13
Element Seqn Id St Int Rpt
PFSPHLSLPMPSV Q9H296 672 3 -
PFSPHLSLPMPSV Q9H1D0 672 3 -
PFSPHLSLPTPSV Q9H1D1 672 3 -
PFGAYLSFPTPSV Q91WD2 674 3 -
PFGAYLSFPTPSV Q9JJJ0 676 3 -
PFGAYLSFPTPSV Q9R186 674 3 -

Motif 4 width=17
Element Seqn Id St Int Rpt
RSSANWERLRQGTLRRD Q9H296 690 5 -
RSSANWERLRQGTLRRD Q9H1D0 690 5 -
RSSANWERLRQGTLRRD Q9H1D1 690 5 -
RSSTNWERLRQGALRKD Q91WD2 692 5 -
RSSTNWERLRQGALRKD Q9JJJ0 694 5 -
RSSTNWDRLRQGALRKD Q9R186 692 5 -

Motif 5 width=20
Element Seqn Id St Int Rpt
DLRGIINRGLEDGESWEYQI Q9H296 706 -1 -
DLRGIINRGLEDGESWEYQI Q9H1D0 706 -1 -
DLRGIINRGLEDGESWEYQI Q9H1D1 706 -1 -
DLRGIINRGLEDGEGWEYQI Q91WD2 708 -1 -
DLRGIINRGLEDGEGWEYQI Q9JJJ0 710 -1 -
DLQGIINRGLEDGEGWEYQI Q9R186 708 -1 -
Final Motifs
Motif 1  width=23
Element Seqn Id St Int Rpt
GLSLPKEKGLILCLWSKFCRWFQ Q8WXR8 2 2 -
GLSLPKEKGLILCLWSKFCRWFQ Q9H296 2 2 -
GLSLPKEKGLILCLWSKFCRWFQ Q9H1D0 2 2 -
GLSLPKEKGLILCLWSKFCRWFQ Q9H1D1 2 2 -
GWSLPKEKGLILCLWNKFCRWFH Q91WD2 2 2 -
GWSLPKEKGLILCLWNKFCRWFH Q9JJJ0 2 2 -
GWSLPKEKGLILCLWNKFCRWFH Q9R186 2 2 -

Motif 2 width=18
Element Seqn Id St Int Rpt
FHTRGSEDLDKDSVEKLE Q8WXR8 651 626 -
FHTRGSEDLDKDSVEKLE Q9H296 651 626 -
FHTRGSEDLDKDSVEKLE Q9H1D0 651 626 -
FHTRGSEDLDKDSVEKLE Q9H1D1 651 626 -
QDGLYSEDLEKDSGEKLE Q91WD2 653 628 -
QDGLYSEDLEKDSGEKLE Q9JJJ0 655 630 -
QDDLYSEDLEKDSGEKLE Q9R186 653 628 -

Motif 3 width=13
Element Seqn Id St Int Rpt
PFSPHLSLPMPSV Q8WXR8 672 3 -
PFSPHLSLPMPSV Q9H296 672 3 -
PFSPHLSLPMPSV Q9H1D0 672 3 -
PFSPHLSLPTPSV Q9H1D1 672 3 -
PFGAYLSFPTPSV Q91WD2 674 3 -
PFGAYLSFPTPSV Q9JJJ0 676 3 -
PFGAYLSFPTPSV Q9R186 674 3 -

Motif 4 width=17
Element Seqn Id St Int Rpt
RSSANWERLRQGTLRRD Q8WXR8 690 5 -
RSSANWERLRQGTLRRD Q9H296 690 5 -
RSSANWERLRQGTLRRD Q9H1D0 690 5 -
RSSANWERLRQGTLRRD Q9H1D1 690 5 -
RSSTNWERLRQGALRKD Q91WD2 692 5 -
RSSTNWERLRQGALRKD Q9JJJ0 694 5 -
RSSTNWDRLRQGALRKD Q9R186 692 5 -

Motif 5 width=20
Element Seqn Id St Int Rpt
DLRGIINRGLEDGESWEYQI Q8WXR8 706 -1 -
DLRGIINRGLEDGESWEYQI Q9H296 706 -1 -
DLRGIINRGLEDGESWEYQI Q9H1D0 706 -1 -
DLRGIINRGLEDGESWEYQI Q9H1D1 706 -1 -
DLRGIINRGLEDGEGWEYQI Q91WD2 708 -1 -
DLRGIINRGLEDGEGWEYQI Q9JJJ0 710 -1 -
DLQGIINRGLEDGEGWEYQI Q9R186 708 -1 -