Home News About DMDM Database Statistics Research Publications Contact  

 
  Domain Name: ClC_3_like
ClC-3-like chloride channel proteins. This CD includes ClC-3, ClC-4, ClC-5 and ClC-Y1. ClC-3 was initially cloned from rat kidney. Expression of ClC-3 produces outwardly-rectifying Cl currents that are inhibited by protein kinase C activation. It has been suggested that ClC-3 may be a ubiquitous swelling-activated Cl channel that has very similar characteristics to those of native volume-regulated Cl currents. The function of ClC-4 is unclear. Studies of human ClC-4 have revealed that it gives rise to Cl currents that rapidly activate at positive voltages, and are sensitive to extracellular pH, with currents decreasing when pH falls below 6.5. ClC-4 is broadly distributed, especially in brain and heart. ClC-5 is predominantly expressed in the kidney, but can be found in the brain and liver. Mutations in the ClC-5 gene cause certain hereditary diseases, including Dent's disease, an X-chromosome linked syndrome characterised by proteinuria, hypercalciuria, and kidney stones (nephrolithiasis), leading to progressive renal failure. These proteins belong to the ClC superfamily of chloride ion channels, which share the unique double-barreled architecture and voltage-dependent gating mechanism. The gating is conferred by the permeating anion itself, acting as the gating charge. This domain is found in the eukaryotic halogen ion (Cl- and I-) channel proteins, that perform a variety of functions including cell volume regulation, the membrane potential stabilization, transepithelial chloride transport and charge compensation necessary for the acidification of intracellular organelles.
No pairwise interactions are available for this conserved domain.

Total Mutations Found: 71
Total Disease Mutations Found: 36
This domain occurred 9 times on human genes (22 proteins).



  BARTTER SYNDROME, TYPE 3
  BARTTER SYNDROME, TYPE 4B
  DENT DISEASE 1
  EPILEPSY, JUVENILE MYOCLONIC, SUSCEPTIBILITY TO, 8
  HYPOPHOSPHATEMIC RICKETS, X-LINKED RECESSIVE
  INCLUDED
  MYOTONIA CONGENITA, AUTOSOMAL DOMINANT
  MYOTONIA CONGENITA, AUTOSOMAL DOMINANT, INCLUDED
  MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE
  MYOTONIA CONGENITA, AUTOSOMAL RECESSIVE, INCLUDED
  MYOTONIA LEVIOR
  NEPHROLITHIASIS, X-LINKED RECESSIVE
  OSTEOPETROSIS, AUTOSOMAL RECESSIVE 4
  PROTEINURIA, LOW MOLECULAR WEIGHT, WITH HYPERCALCIURIA AND NEPHROCALCINOSIS
  PROTEINURIA, LOW MOLECULAR WEIGHT, WITH HYPERCALCIURIA AND NEPHROCALCINOSIS,


Tips:
 If you've navigated here from a protein, hovering over a position on the weblogo will display the corresponding protein position for that domain position.

 The histograms below the weblogo indicate mutations found on the domain. Red is for disease (OMIM) and blue is for SNPs.

 Functional Features are displayed as orange boxes under the histograms. You can choose which features are displayed in the box below.



Range on the Protein:  

   Protein ID            Protein Position

Domain Position:  


Feature Name:Total Found:
putative Cl- selectivity
putative pore gating glut
putative H+/Cl- coupling

























Weblogos are Copyright (c) 2002 Regents of the University of California




Please Cite: Peterson, T.A., Adadey, A., Santana-Cruz ,I., Sun, Y., Winder A, Kann, M.G., (2010) DMDM: Domain Mapping of Disease Mutations. Bioinformatics 26 (19), 2458-2459.

   |   1000 Hilltop Circle, Baltimore, MD 21250   |   Department of Biological Sciences   |   Phone: 410-455-2258