CLCN3

Chloride channel, voltage-sensitive 3

Identifiers

CLCN3 ; CLC3; ClC-3

External IDs

OMIM: 600580 MGI: 103555 HomoloGene: 20435 IUPHAR: 702 GeneCards: CLCN3 Gene

Gene ontology
Molecular function	• voltage-gated chloride channel activity • chloride channel activity • protein binding • ATP binding • antiporter activity • PDZ domain binding • protein homodimerization activity • protein heterodimerization activity • volume-sensitive chloride channel activity
Cellular component	• Golgi membrane • early endosome • late endosome • Golgi apparatus • plasma membrane • synaptic vesicle • external side of plasma membrane • cell surface • vesicle membrane • membrane • integral component of membrane • secretory granule • transport vesicle membrane • cytoplasmic vesicle • early endosome membrane • late endosome membrane • specific granule • axon terminus • phagocytic vesicle
Biological process	• transport • regulation of pH • phagocytosis, engulfment • adult locomotory behavior • ion transmembrane transport • synaptic transmission, glutamatergic • regulation of anion transport • photoreceptor cell maintenance • negative regulation of cell volume • endosomal lumen acidification • synaptic transmission, GABAergic • transmembrane transport • synaptic vesicle lumen acidification • chloride transmembrane transport • positive regulation of reactive oxygen species biosynthetic process • regulation of anion transmembrane transport
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 4:
169.61 – 169.72 Mb

Chr 8:
60.91 – 60.98 Mb

PubMed search

H⁺/Cl⁻ exchange transporter 3 is a protein that in humans is encoded by the CLCN3 gene.^[1]

Interactions

CLCN3 has been shown to interact with PDZK1.^[2]

References

↑ "Entrez Gene: CLCN3 chloride channel 3".
↑ Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR (Feb 2003). "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. 278 (8): 6440–9. doi:10.1074/jbc.M211050200. PMID 12471024.

Borsani G, Rugarli EI, Taglialatela M, Wong C, Ballabio A (1995). "Characterization of a human and murine gene (CLCN3) sharing similarities to voltage-gated chloride channels and to a yeast integral membrane protein". Genomics 27 (1): 131–41. doi:10.1006/geno.1995.1015. PMID 7665160.
Taine L, Coupry I, Boisseau P, Saura R, Lacombe D, Arveiler B (1998). "Refined localisation of the voltage-gated chloride channel, CLCN3, to 4q33". Hum. Genet. 102 (2): 178–81. doi:10.1007/s004390050673. PMID 9521585.
Shepard AR, Rae JL (1998). "Ion transporters and receptors in cDNA libraries from lens and cornea epithelia". Curr. Eye Res. 17 (7): 708–19. doi:10.1080/02713689808951247. PMID 9678416.
Loo MA, Jensen TJ, Cui L, Hou Y, Chang XB, Riordan JR (1998). "Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome". EMBO J. 17 (23): 6879–87. doi:10.1093/emboj/17.23.6879. PMC 1171036. PMID 9843494.
Lamb FS, Clayton GH, Liu BX, Smith RL, Barna TJ, Schutte BC (1999). "Expression of CLCN voltage-gated chloride channel genes in human blood vessels". J. Mol. Cell. Cardiol. 31 (3): 657–66. doi:10.1006/jmcc.1998.0901. PMID 10198195.
Hartley JL, Temple GF, Brasch MA (2000). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
Huang P, Liu J, Di A, Robinson NC, Musch MW, Kaetzel MA, Nelson DJ (2001). "Regulation of human CLC-3 channels by multifunctional Ca2+/calmodulin-dependent protein kinase". J. Biol. Chem. 276 (23): 20093–100. doi:10.1074/jbc.M009376200. PMID 11274166.
Lamb FS, Graeff RW, Clayton GH, Smith RL, Schutte BC, McCray PB (2001). "Ontogeny of CLCN3 chloride channel gene expression in human pulmonary epithelium". Am. J. Respir. Cell Mol. Biol. 24 (4): 376–81. doi:10.1165/ajrcmb.24.4.4114. PMID 11306429.
Ogura T, Furukawa T, Toyozaki T, Yamada K, Zheng YJ, Katayama Y, Nakaya H, Inagaki N (2002). "ClC-3B, a novel ClC-3 splicing variant that interacts with EBP50 and facilitates expression of CFTR-regulated ORCC". FASEB J. 16 (8): 863–5. doi:10.1096/fj.01-0845fje. PMID 11967229.
Hermoso M, Satterwhite CM, Andrade YN, Hidalgo J, Wilson SM, Horowitz B, Hume JR (2002). "ClC-3 is a fundamental molecular component of volume-sensitive outwardly rectifying Cl- channels and volume regulation in HeLa cells and Xenopus laevis oocytes". J. Biol. Chem. 277 (42): 40066–74. doi:10.1074/jbc.M205132200. PMID 12183454.
Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR (2003). "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. 278 (8): 6440–9. doi:10.1074/jbc.M211050200. PMID 12471024.
Jin NG, Kim JK, Yang DK, Cho SJ, Kim JM, Koh EJ, Jung HC, So I, Kim KW (2003). "Fundamental role of ClC-3 in volume-sensitive Cl- channel function and cell volume regulation in AGS cells". Am. J. Physiol. Gastrointest. Liver Physiol. 285 (5): G938–48. doi:10.1152/ajpgi.00470.2002. PMID 12842831.
Olsen ML, Schade S, Lyons SA, Amaral MD, Sontheimer H (2003). "Expression of voltage-gated chloride channels in human glioma cells". J. Neurosci. 23 (13): 5572–82. PMID 12843258.
Salazar G, Love R, Styers ML, Werner E, Peden A, Rodriguez S, Gearing M, Wainer BH, Faundez V (2004). "AP-3-dependent mechanisms control the targeting of a chloride channel (ClC-3) in neuronal and non-neuronal cells". J. Biol. Chem. 279 (24): 25430–9. doi:10.1074/jbc.M402331200. PMID 15073168.
Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
Zhou JG, Ren JL, Qiu QY, He H, Guan YY (2005). "Regulation of intracellular Cl- concentration through volume-regulated ClC-3 chloride channels in A10 vascular smooth muscle cells". J. Biol. Chem. 280 (8): 7301–8. doi:10.1074/jbc.M412813200. PMID 15596438.
Yeung CH, Barfield JP, Cooper TG (2005). "Chloride channels in physiological volume regulation of human spermatozoa". Biol. Reprod. 73 (5): 1057–63. doi:10.1095/biolreprod.105.044123. PMID 16033995.
Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.

External links

CLCN3 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3

Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ

Proton-gated	Amiloride-sensitive cation channel 1 2 3 4

Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1

Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1

Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18

Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker gene

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4

M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6

H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family

Cytoplasm: Gap junction	Connexin: A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4) Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

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CLCN3

Interactions

See also

References

Further reading

External links