CLCN3

This gene encodes a member of the voltage-gated chloride channel (ClC) family. The encoded protein is present in all cell types and localized in plasma membranes and in intracellular vesicles. It is a multi-pass membrane protein which contains a ClC domain and two additional C-terminal CBS (cystathionine beta-synthase) domains. The ClC domain catalyzes the selective flow of Cl- ions across cell membranes, and the CBS domain may have a regulatory function. This protein plays a role in both acidification and transmitter loading of GABAergic synaptic vesicles, and in smooth muscle cell activation and neointima formation. This protein is required for lysophosphatidic acid (LPA)-activated Cl- current activity and fibroblast-to-myofibroblast differentiation. The protein activity is regulated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in glioma cells. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

Full Name

Chloride Voltage-Gated Channel 3

Function

Isoform 1:
Strongly outwardly rectifying, electrogenic H+/Cl-exchanger which mediates the exchange of chloride ions against protons (By similarity).

The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (PubMed:29845874).

The presence of conserved gating glutamate residues is typical for family members that function as antiporters (PubMed:29845874).

Isoform 2:
Strongly outwardly rectifying, electrogenic H+/Cl-exchanger which mediates the exchange of chloride ions against protons.

Biological Process

Adult locomotory behavior Source: Ensembl
Chloride transmembrane transport Source: GO_Central
Endosomal lumen acidification Source: UniProtKB
Negative regulation of cell volume Source: GO_Central
Phagocytosis, engulfment Source: Ensembl
Photoreceptor cell maintenance Source: Ensembl
Positive regulation of reactive oxygen species biosynthetic process Source: Ensembl
Regulation of pH Source: UniProtKB
Synaptic transmission, GABAergic Source: Ensembl
Synaptic transmission, glutamatergic Source: Ensembl
Synaptic vesicle lumen acidification Source: Ensembl

Cellular Location

Isoform 1: Early endosome membrane; Late endosome membrane; Cell membrane; Lysosome membrane. Isoform 1 is localized mainly in late endosomes.
Isoform 2: Ruffle membrane; Golgi apparatus membrane. Isoform 2 is mainly enriched in the Golgi (PubMed:12471024). Colocalizes with SLC9A3R1/EBP50 in membrane ruffles (PubMed:11967229).

Topology

Cytoplasmic: 1-125
Helical: 126-163
Helical: 209-232
Helical: 241-248
Helical: 258-276
Helical: 282-301
Helical: 313-325
Helical: 329-337
Helical: 349-367
Helical: 391-416
Helical: 423-443
Helical: 500-520
Helical: 525-544
Helical: 572-586
Helical: 590-601
Loop between two helices: 602-605
Helical: 606-624
Cytoplasmic: 625-818

PTM

N-glycosylated.