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PR01118

Identifier
CLCHANNEL7  [View Relations]  [View Alignment]  
Accession
PR01118
No. of Motifs
5
Creation Date
26-APR-1999
Title
CLC-7 chloride channel signature
Database References
PRINTS; PR00762 CLCHANNEL
PRODOM; PD035114; PD035115
INTERPRO; IPR002249
Literature References
1. JENTSCH, T.J. AND GUNTHER, W.
Chloride channels: an emerging molecular picture.
BIOESSAYS 19 117-126 (1997).
 
2. JENTSCH, T.J., STEINMEYER, K. AND SCHWARZ, G.
Primary structure of Torpedo marmorata chloride channel isolated by
expression cloning in Xenopus oocytes.
NATURE 348 510-514 (1990).
 
3. SCHMIDT-ROSE, T. AND JENTSCH, T.J.
Transmembrane topology of a CLC chloride channel.
PROC.NATL.ACAD.SCI.U.S.A. 94 7633-7638 (1997).
 
4. LEHMANN-HORN, F., MAILANDER, V., HEINE, R. AND GEORGE, A.L.
Myotonia levior is a chloride channel disorder.
HUM.MOL.GENET. 4 1397-1402 (1995).
 
5. LLOYD, S.E., PEARCE, S.H.S., FISHER, S.E., STEINMEYER, K.,
SCHWAPPACH, B., SCHEINMAN, S.J., HARDING, B., BOLINO, A., DEVOTO, M.,
GOODYER, P., RIGDEN, S.P.A., WRONG, O., JENTSCH, T.J., CRAIG, I.W. AND
THAKKER, R.V.
A common molecular basis for three inherited kidney stone diseases.
NATURE 379 445-449 (1996).
 
6. BRANDT, S. AND JENTSCH, T.J.
CLC-6 and CLC-7 are two broadly expressed members of the CLC chloride
channel family.
FEBS LETT. 377 15-20 (1995).

Documentation
Chloride channels (CLCs) constitute an evolutionarily well-conserved family
of voltage-gated channels that are structurally unrelated to the other known
voltage-gated channels. They are found in organisms ranging from bacteria to
yeasts and plants, and also to animals. Their functions in higher animals
likely include the regulation of cell volume, control of electrical 
excitability and trans-epithelial transport [1].
 
The first member of the family (CLC-0) was expression-cloned from the
electric organ of Torpedo marmorata [2], and subsequently nine CLC-like
proteins have been cloned from mammals. They are thought to function as
multimers of two or more identical or homologous subunits, and they have
varying tissue distributions and functional properties. To date, CLC-0, 
CLC-1, CLC-2, CLC-4 and CLC-5 have been demonstrated to form functional Cl-
channels; whether the remaining isoforms do so is either contested or 
unproven. One possible explanation for the difficulty in expressing 
activatable Cl- channels is that some of the isoforms may function as Cl- 
channels of intracellular compartments, rather than of the plasma membrane.
However, they are all thought to have a similar transmembrane (TM) topology,
initial hydropathy analysis suggesting 13 hydrophobic stretches long enough
to form putative TM domains [2]. Recently, the postulated TM topology has
been revised, and it now seems likely that the CLCs have 10 (or possibly 12)
TM domains, with both N- and C-termini residing in the cytoplasm [3].
 
A number of human disease-causing mutations have been identified in the
genes encoding CLCs. Mutations in CLCN1, the gene encoding CLC-1, the major
skeletal muscle Cl- channel, lead to both recessively and dominantly-
inherited forms of muscle stiffness or myotonia [4]. Similarly, mutations
in CLCN5, which encodes CLC-5, a renal Cl- channel, lead to several forms 
of inherited kidney stone disease [5]. These mutations have been
demonstrated to reduce or abolish CLC function.
 
CLC-7 is a CLC that, together with CLC-6, forms a distinct branch of the
CLC gene family. CLC-7 consists of 789 amino acid residues (human isoform)
and is ~45% identical to CLC-6 (at the amino acid level). CLC-7 is broadly
expressed, but, to date, functional studies have not generated measurable
Cl- currents; its identification as a functional Cl- channel therefore 
remains putative. Interestingly, CLC-7 is the only known eukaryotic CLC
protein to lack a highly conserved glycosylation site between hydrophobic
domains D8 and D9 [6].
 
CLCHANNEL7 is a 5-element fingerprint that provides a signature for the
CLC-7 voltage-gated Cl- channel. The fingerprint was derived from an
initial alignment of 2 sequences: the motifs were drawn from conserved
regions within the N-terminal quarter of the alignment focusing on those
regions that characterise the CLC-7 isoform but distinguish it from others
- motifs 1-2 reside within the putative cytoplasmic N-terminus; motif 3
encodes the C-terminal half of the first hydrophobic domain; motif 4 lies
within the second hydrophilic domain; and motif 5 resides within the second
hydrophobic domain. A single iteration on SPTR37_9f was required to reach 
convergence, no further sequences being identified beyond the starting set.
Summary Information
2 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
522222
400000
300000
200000
12345
True Positives
CLC7_RAT      O70496        
Sequence Titles
CLC7_RAT    CHLORIDE CHANNEL PROTEIN 7 (CLC-7) - RATTUS NORVEGICUS (RAT). 
O70496 PUTATIVE CHLORIDE CHANNEL PROTEIN CLC7 - MUS MUSCULUS (MOUSE).
Scan History
SPTR37_9f  2  175  NSINGLE    
Initial Motifs
Motif 1  width=9
Element Seqn Id St Int Rpt
MNNVELDDE CLC7_RAT 57 57 -
MNNVELDDE O70496 57 57 -

Motif 2 width=7
Element Seqn Id St Int Rpt
KLLSLKY CLC7_RAT 86 20 -
KLLSLKY O70496 86 20 -

Motif 3 width=11
Element Seqn Id St Int Rpt
VACFIDIVVEN CLC7_RAT 138 45 -
VACFIDIVVEN O70496 138 45 -

Motif 4 width=9
Element Seqn Id St Int Rpt
LAGLKYRVI CLC7_RAT 149 0 -
LAGLKYRVI O70496 149 0 -

Motif 5 width=12
Element Seqn Id St Int Rpt
AFVLVGSVIVAF CLC7_RAT 183 25 -
AFVLVGSVIVAF O70496 183 25 -
Final Motifs
Motif 1  width=9
Element Seqn Id St Int Rpt
MNNVELDDE CLC7_RAT 57 57 -
MNNVELDDE O70496 57 57 -

Motif 2 width=7
Element Seqn Id St Int Rpt
KLLSLKY CLC7_RAT 86 20 -
KLLSLKY O70496 86 20 -

Motif 3 width=11
Element Seqn Id St Int Rpt
VACFIDIVVEN CLC7_RAT 138 45 -
VACFIDIVVEN O70496 138 45 -

Motif 4 width=9
Element Seqn Id St Int Rpt
LAGLKYRVI CLC7_RAT 149 0 -
LAGLKYRVI O70496 149 0 -

Motif 5 width=12
Element Seqn Id St Int Rpt
AFVLVGSVIVAF CLC7_RAT 183 25 -
AFVLVGSVIVAF O70496 183 25 -