H+/Cl(-) exchange transporter 5; chloride transporter ClC-5; chloride channel protein 5; ClC-5 (CLCN5, CLCK2, NPHL2, DENTS)

Function

• proton-coupled Cl- transporter
• antiport system; exchanges Cl- against H+
• role in normal acidification of the endosome lumen
• role in renal tubular function (putative)
• ubiquitinated by NEDD4L in the presence of albumin; which promotes endocytosis & proteasomal degradation
• interacts with NEDD4 & NEDD4L

Structure

• belongs to the chloride channel (TC 2.A.49) family
• contains 2 CBS domains

Compartment

• Golgi membrane
• endosome membrane
• cell membrane
• multi-pass membrane protein

Expression

• expressed in kidney
• moderately expressed in aortic vascular smooth muscle & endothelial cells, & at a slightly higher level in coronary vascular smooth muscle

Pathology

• defects in CLCN5 are a cause of hypophosphatemic rickets X-linked recessive
• defects in CLCN5 are the cause of
  • nephrolithiasis type 1
  • nephrolithiasis type 2 (dent disease 1)
  • LMW proteinuria with hypercalciuria & nephrocalcinosis

Notes

• the CLC channel family contains both chloride channels & proton-coupled anion transporters that exchange chloride or another anion for protons
• the absence of conserved gating glutamate residues is typical for family members that function as channels

More general terms

• Cl- channel
• transmembrane 10 protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1184
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1184
• OMIM: https://mirror.omim.org/entry/300008
• OMIM: https://mirror.omim.org/entry/300009
• OMIM: https://mirror.omim.org/entry/300554
• OMIM: https://mirror.omim.org/entry/308990
• OMIM: https://mirror.omim.org/entry/310468
• UniProt: http://www.uniprot.org/uniprot/P51795.html