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CLCN3 Membrane Protein Introduction

Introduction of CLCN3

H(+)/Cl(-) exchange transporter 3(CLCN3), also known as chloride channel protein 3, is a vital member of CLC family, which is widely existed in all cell types and localized in plasma membranes. CLCN3 is a protein with transmembrane sites which contains a ClC domain and two additional C-terminal CBS (cystathionine beta-synthase) domains. This protein takes part in both acidification process and transmitter loading of GABAergic synaptic vesicles, and in smooth muscle cell activation and neointima formation. This protein is also 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. Different isoforms have been identified encoding by multiple alternatively spliced transcript variants.

Basic Information of CLCN3
Protein Name H(+)/Cl(-) exchange transporter 3
Gene Name CLCN3
Aliases Chloride channel protein 3 Chloride transporter ClC-3
Organism Homo sapiens (Human)
UniProt ID P51790
Transmembrane Times 10
Length (aa) 818
Sequence MESEQLFHRGYYRNSYNSITSASSDEELLDGAGVIMDFQTSEDDNLLDGDTAVGTHYTMTNGGSINSSTHLLDLLDEPIPGVGTYDDFHTIDWVREKCKDRERHRRINSKKKESAWEMTKSLYDAWSGWLVVTLTGLASGALAGLIDIAADWMTDLKEGICLSALWYNHEQCCWGSNETTFEERDKCPQWKTWAELIIGQAEGPGSYIMNYIMYIFWALSFAFLAVSLVKVFAPYACGSGIPEIKTILSGFIIRGYLGKWTLMIKTITLVLAVASGLSLGKEGPLVHVACCCGNIFSYLFPKYSTNEAKKREVLSAASAAGVSVAFGAPIGGVLFSLEEVSYYFPLKTLWRSFFAALVAAFVLRSINPFGNSRLVLFYVEYHTPWYLFELFPFILLGVFGGLWGAFFIRANIAWCRRRKSTKFGKYPVLEVIIVAAITAVIAFPNPYTRLNTSELIKELFTDCGPLESSSLCDYRNDMNASKIVDDIPDRPAGIGVYSAIWQLCLALIFKIIMTVFTFGIKVPSGLFIPSMAIGAIAGRIVGIAVEQLAYYHHDWFIFKEWCEVGADCITPGLYAMVGAAACLGGVTRMTVSLVVIVFELTGGLEYIVPLMAAVMTSKWVGDAFGREGIYEAHIRLNGYPFLDAKEEFTHTTLAADVMRPRRNDPPLAVLTQDNMTVDDIENMINETSYNGFPVIMSKESQRLVGFALRRDLTIAIESARKKQEGIVGSSRVCFAQHTPSLPAESPRPLKLRSILDMSPFTVTDHTPMEIVVDIFRKLGLRQCLVTHNGRLLGIITKKDILRHMAQTANQDPASIMFN

Function of CLCN3 Membrane Protein

H(+)/Cl(-) exchange transporter 3 has an important function in mediating the exchange of chloride ions against protons, functioning as antiporter and contributing to the acidification of the endosome. It also affects synaptic vesicle lumen and may thereby affect vesicle trafficking and exocytosis. Moreover, it plays an important role in neuronal cell function by regulating membrane excitability with the help of protein kinase C. It has a positive effect on neuronal cells to establish short-term memory. Different sites have their own function. For example, the site at the position of 282 can mediate proton transfer from the outer aqueous phase to the interior of the protein and it also involves in linking H(+) and Cl(-) transport. The site of 339 can mediate proton transfer from the protein to the inner aqueous phase. Activation of the CNCL3 can participate in sensations such as pain, warmth, cold, taste pressure and vision through Stimuli-sensing channels.

Application of CLCN3 Membrane Protein in Literature

  1. Gentzsch M., et al. The PDZ-binding chloride channel ClC-3B localizes to the Golgi and associates with cystic fibrosis transmembrane conductance regulator-interacting PDZ proteins. J. Biol. Chem. 2003, 278(8):6440-9. PubMed ID: 12471024

    This article suggests that small portions of ClC-3B and CFTR may associate and co-localize, the bulk of the two populations reside in different organelles of cells where they are expressed heterologously and therefore their cellular functions are likely to be distinct and not primarily related.

  2. Huang P., et al. Regulation of human CLC-3 channels by multifunctional Ca2+/calmodulin-dependent protein kinase. J. Biol. Chem. 2001, 276(23):20093-100 PubMed ID: 11274166

    The article shows that the plasma membrane expression of a member of the ClC family of Cl(-) channels, human CLC-3 (hCLC-3), a 90-kDa protein, is regulated by CaMKII. Biotinylation experiments demonstrate that plasma membrane expression of hCLC-3 in the stably transfected cells. These results indicate that hCLC-3 encodes a Cl(-) channel that is regulated by CaMKII-dependent phosphorylation.

  3. Lamb F.S., et al. Ontogeny of CLCN3 chloride channel gene expression in human pulmonary epithelium. Am. J. Respir. Cell Mol. Biol. 2001, 24(4):376-81. PubMed ID: 11306429

    This article concludes that CLCN3 is expressed in human airway epithelia and its expression is developmentally regulated. The contribution of these channels to pulmonary epithelial liquid transport and lung development is still unclear and remains to be determined.

  4. Yeung C.H., et al. Chloride channels in physiological volume regulation of human spermatozoa. Biol. Reprod. 2005, 73(5):1057-63. PubMed ID: 16033995

    This article gives us the conclusion that clcn3 is therefore considered the most likely candidate of Cl- channel which is involved in volume regulation of human sperm by several methods, like western blotting and Immunocytochemistry. To find out molecular identities, sperm mRNA is extracted and checked for quality by the presence of protamine 2 transcripts and the absence of sperm DNA and leukocyte mRNA using reverse transcription-polymerase chain reaction.

  5. Zhou J.G., et al. Regulation of intracellular Cl- concentration through volume-regulated ClC-3 chloride channels in A10 vascular smooth muscle cells. J. Biol. Chem. 2005, 280(8):7301-8. PubMed ID: 15596438

    In this article, authors find the regulation of intracellular Cl(-) concentrations ([Cl(-)](i)) via volume-regulated ClC-3 Cl(-) channels using multiple approaches including [Cl(-)](i) measurement, whole cell patch clamp, and application of ClC-3 antisense and intracellular dialysis of an anti-ClC-3 antibody. The results conclude that the volume-regulated ClC-3 Cl(-) channels play important role in the regulation of [Cl(-)](i) and cell proliferation of vascular smooth muscle cells.

CLCN3 Preparation Options

Membrane protein studies have got great progress over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services in reconstitution forms as well as multiple active formats for worldwide customers. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CLCN3 antibody development services.


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