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Chloride channel 4

ClC-4, CLCN4
The CLCN family of voltage-dependent chloride channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional characteristics while sharing significant sequence homology. Chloride channel 4 has an evolutionary conserved CpG island and is conserved in both mouse and hamster. This gene is mapped in close proximity to APXL (Apical protein Xenopus laevis-like) and OA1 (Ocular albinism type I), which are both located on the human X chromosome at band p22.3. The physiological role of chloride channel 4 remains unknown but may contribute to the pathogenesis of neuronal disorders. Alternate splicing results in two transcript variants that encode different proteins. [provided by RefSeq, Mar 2012] (from NCBI)
Top mentioned proteins: ClC-5, ClC-3, ClC-2, HAD, ClC-7
Papers on ClC-4
X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.
Kalscheuer et al., Berlin, Germany. In Mol Psychiatry, Jan 2016
In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1).
Screen-based identification and validation of four new ion channels as regulators of renal ciliogenesis.
Giles et al., Utrecht, Netherlands. In J Cell Sci, Jan 2016
This screen revealed four candidate ion channel genes: Kcnq1, Kcnj10, Kcnf1 and Clcn4.
Prolactin stimulates sodium and chloride ion channels in A6 renal epithelial cells.
Eaton et al., Atlanta, United States. In Am J Physiol Renal Physiol, May 2015
We also identified that PRL induced activity of a 2-pS anion channel with outward rectification, electrophysiological properties consistent with ClC4 or ClC5.
Clozapine induces chloride channel-4 expression through PKA activation and modulates CDK5 expression in SH-SY5Y and U87 cells.
Kim et al., South Korea. In Prog Neuropsychopharmacol Biol Psychiatry, Feb 2015
The authors previously showed that chloride channel 4 (CLC-4) is responsible for nerve growth factor-induced neurite outgrowth in neuronal cells.
Mutations associated with Dent's disease affect gating and voltage dependence of the human anion/proton exchanger ClC-5.
Alekov, Hannover, Germany. In Front Physiol, 2014
Remarkably, two other mammalian isoforms, ClC-3 and ClC-4, also differ from ClC-5 in gating characteristics affected by the here investigated disease-causing mutations.
Cell biology and physiology of CLC chloride channels and transporters.
Jentsch et al., Berlin, Germany. In Compr Physiol, 2012
ClC-3 is also present on synaptic vesicles, whereas ClC-4 and -5 can reach the plasma membrane to some extent.
Anion- and proton-dependent gating of ClC-4 anion/proton transporter under uncoupling conditions.
Alekov et al., Hannover, Germany. In Biophys J, 2011
the voltage dependence of uncoupled ClC-4 by protons and anions
Clcn4-2 genomic structure differs between the X locus in Mus spretus and the autosomal locus in Mus musculus: AT motif enrichment on the X.
Disteche et al., Seattle, United States. In Genome Res, 2011
In Mus spretus, the chloride channel 4 gene Clcn4-2 is X-linked and dosage compensated by X up-regulation and X inactivation, while in the closely related mouse species Mus musculus, Clcn4-2 has been translocated to chromosome 7.
Gene trapping identifies chloride channel 4 as a novel inducer of colon cancer cell migration, invasion and metastases.
Boyd et al., Houston, United States. In Br J Cancer, 2010
CLCN4 is a novel driver of colon cancer progression.
Channel-like slippage modes in the human anion/proton exchanger ClC-4.
Fahlke et al., Hannover, Germany. In J Gen Physiol, 2009
The proposed mechanism results in anion-dependent conversion of ClC-type exchanger into an anion channel with typical attributes of ClC anion channels.
Physiological roles of CLC Cl(-)/H (+) exchangers in renal proximal tubules.
Jentsch et al., Berlin, Germany. In Pflugers Arch, 2009
No renal functions could be assigned so far to ClC-3 and ClC-4, which are also expressed in PTs.
Mutational analysis of CLC-5, cofilin and CLC-4 in patients with Dent's disease.
Thakker et al., Oxford, United Kingdom. In Nephron Physiol, 2008
Studies showed that three novel CLC-5 mutations were identified, and mutations in OCRL1, CLC-4 and cofilin excluded in causing Dent's disease.
The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes.
Mindell et al., Bethesda, United States. In Nature, 2008
Several mammalian members of the CLC family have been characterized in detail; some (including ClC-0, ClC-1 and ClC-2) function as Cl--conducting ion channels, whereas others act as Cl-/H+antiporters (ClC-4 and ClC-5).
CLC chloride channels and transporters: from genes to protein structure, pathology and physiology.
Jentsch, Berlin, Germany. In Crit Rev Biochem Mol Biol, 2008
All vesicular CLCs may be Cl(-)/H(+)-exchangers, as shown for the endosomal ClC-4 and -5 proteins.
CLC chloride channels and transporters: a biophysical and physiological perspective.
Pusch et al., Genova, Italy. In Rev Physiol Biochem Pharmacol, 2006
Surprisingly, ClC-4, ClC-5, and probably also ClC-3, are not Cl- ion channels but exhibit significant Cl-/H+ antiporter activity, as does the bacterial homolog ClC-ec1 and the plant homolog AtCLCa.
Molecular physiology of renal ClC chloride channels/transporters.
George et al., Nashville, United States. In Curr Opin Nephrol Hypertens, 2006
X-ray crystallographic and electrophysiological studies have identified two glutamate residues required for gated Cl movement and proton permeation in bacterial and two mammalian (ClC-4, ClC-5) ClC transporters.
The nitrate/proton antiporter AtCLCa mediates nitrate accumulation in plant vacuoles.
Barbier-Brygoo et al., Gif-sur-Yvette, France. In Nature, 2006
Some members of the chloride channel (CLC) protein family, such as the torpedo-fish ClC-0 and mammalian ClC-1, are anion channels, whereas the bacterial ClC-ec1 and mammalian ClC-4 and ClC-5 have recently been characterized as Cl-/H+ exchangers with unknown cellular functions.
Voltage-dependent electrogenic chloride/proton exchange by endosomal CLC proteins.
Jentsch et al., Hamburg, Germany. In Nature, 2005
Vesicular CLCs have been thought to be Cl- channels, in particular because ClC-4 and ClC-5 mediate plasma membrane Cl- currents upon heterologous expression.
Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5.
Pusch et al., Genova, Italy. In Nature, 2005
coupled Cl-/H+ transport of ClC-4 and ClC-5 is of significant magnitude in vivo
A contravention of Ohno's law in mice.
Ashworth et al., London, United Kingdom. In Nat Genet, 1995
The chloride channel gene, CLCN4, has been previously mapped to the X chromosome in humans.
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