chloride channel protein 3; H+/Cl(-) exchange transporter 3; chloride transporter ClC-3; ClC-3 (CLCN3)

Function

• mediates the exchange of Cl- against H+
• functions as antiporter & contributes to the acidification of the endosome & synaptic vesicle lumen, & thus may affect vesicle trafficking & exocytosis
• may play role in neuronal cell function through regulation of membrane excitability by protein kinase C
• may help neuronal cells to establish short-term memory
• homo- or heterodimer
• isoform 2 interacts with GOPC, PDZK1 & SLC9A3R1/EBP50

Structure

• N-glycosylated
• isoform 2 contains a C-terminal PDZ-binding motif mediating the interaction with GOPC
• belongs to the chloride channel (TC 2.A.49) family
• contains 2 CBS domains

Compartment

• isoform 1:
  • membrane; multi-pass membrane protein
  • early endosome membrane, late endosome membrane
  • cytoplasmic vesicle, secretory vesicle membrane
  • localized mainly in early & late endosomes
• isoform 2:
  • membrane; multi-pass membrane protein
  • early endosome membrane, late endosome membran
  • Golgi membrane
  • partially colocalized with isoform 1 but is mainly enriched in the Golgi

Alternative splicing

named isoforms=2

Expression

• expressed primarily in tissues derived from neuroectoderm
• within the brain, expression is particularly evident in the hippocampus, olfactory cortex, & olfactory bulb
• highly expressed in aortic & coronary vascular smooth muscle cells, & aortic endothelial cells
• also expressed in tracheal & alveolar epithelial cells, & intima & media of the pulmonary vessels
• expressed in bronchus & colon (at protein level)

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=1182
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1182
• OMIM: https://mirror.omim.org/entry/600580
• UniProt: http://www.uniprot.org/uniprot/P51790.html