NameH(+)/Cl(-) exchange transporter 3
Synonyms
  • Chloride channel protein 3
  • Chloride transporter ClC-3
  • ClC-3
Gene NameCLCN3
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009053|H(+)/Cl(-) exchange transporter 3
MESEQLFHRGYYRNSYNSITSASSDEELLDGAGVIMDFQTSEDDNLLDGDTAVGTHYTMT
NGGSINSSTHLLDLLDEPIPGVGTYDDFHTIDWVREKCKDRERHRRINSKKKESAWEMTK
SLYDAWSGWLVVTLTGLASGALAGLIDIAADWMTDLKEGICLSALWYNHEQCCWGSNETT
FEERDKCPQWKTWAELIIGQAEGPGSYIMNYIMYIFWALSFAFLAVSLVKVFAPYACGSG
IPEIKTILSGFIIRGYLGKWTLMIKTITLVLAVASGLSLGKEGPLVHVACCCGNIFSYLF
PKYSTNEAKKREVLSAASAAGVSVAFGAPIGGVLFSLEEVSYYFPLKTLWRSFFAALVAA
FVLRSINPFGNSRLVLFYVEYHTPWYLFELFPFILLGVFGGLWGAFFIRANIAWCRRRKS
TKFGKYPVLEVIIVAAITAVIAFPNPYTRLNTSELIKELFTDCGPLESSSLCDYRNDMNA
SKIVDDIPDRPAGIGVYSAIWQLCLALIFKIIMTVFTFGIKVPSGLFIPSMAIGAIAGRI
VGIAVEQLAYYHHDWFIFKEWCEVGADCITPGLYAMVGAAACLGGVTRMTVSLVVIVFEL
TGGLEYIVPLMAAVMTSKWVGDAFGREGIYEAHIRLNGYPFLDAKEEFTHTTLAADVMRP
RRNDPPLAVLTQDNMTVDDIENMINETSYNGFPVIMSKESQRLVGFALRRDLTIAIESAR
KKQEGIVGSSRVCFAQHTPSLPAESPRPLKLRSILDMSPFTVTDHTPMEIVVDIFRKLGL
RQCLVTHNGRLLGIITKKDILRHMAQTANQDPASIMFN
Number of residues818
Molecular Weight90965.275
Theoretical pINot Available
GO Classification
Functions
  • ATP binding
  • chloride channel activity
  • protein heterodimerization activity
  • PDZ domain binding
  • voltage-gated chloride channel activity
  • volume-sensitive chloride channel activity
  • antiporter activity
  • protein homodimerization activity
Processes
  • transport
  • photoreceptor cell maintenance
  • ion transmembrane transport
  • regulation of anion transmembrane transport
  • synaptic transmission, GABAergic
  • positive regulation of reactive oxygen species biosynthetic process
  • phagocytosis, engulfment
  • regulation of pH
  • negative regulation of cell volume
  • endosomal lumen acidification
  • chloride transmembrane transport
  • regulation of anion transport
  • synaptic vesicle lumen acidification
  • synaptic transmission, glutamatergic
  • adult locomotory behavior
  • transmembrane transport
Components
  • secretory granule
  • membrane
  • Golgi membrane
  • axon terminus
  • plasma membrane
  • late endosome membrane
  • specific granule
  • phagocytic vesicle
  • cell surface
  • cytoplasmic vesicle
  • late endosome
  • synaptic vesicle
  • vesicle membrane
  • early endosome
  • Golgi apparatus
  • integral component of membrane
  • external side of plasma membrane
  • early endosome membrane
  • transport vesicle membrane
General FunctionVolume-sensitive chloride channel activity
Specific FunctionMediates the exchange of chloride ions against protons. Functions as antiporter and contributes to the acidification of the endosome and synaptic vesicle lumen, and may thereby affect vesicle trafficking and exocytosis. May play an important role in neuronal cell function through regulation of membrane excitability by protein kinase C. It could help neuronal cells to establish short-term memory.
Pfam Domain Function
Transmembrane Regions126-163 209-232 258-276 282-301 349-367 391-416 423-443 500-520 525-544 606-624
GenBank Protein IDNot Available
UniProtKB IDP51790
UniProtKB Entry NameCLCN3_HUMAN
Cellular LocationEarly endosome membrane
Gene sequence
>lcl|BSEQ0017676|H(+)/Cl(-) exchange transporter 3 (CLCN3)
ATGGAGTCTGAGCAGCTGTTCCATAGAGGCTACTATAGAAACAGCTACAACAGTATAACA
AGTGCAAGTAGTGATGAGGAACTTTTAGATGGAGCAGGTGTTATTATGGACTTTCAAACA
TCTGAAGATGACAATTTATTAGATGGTGACACTGCAGTTGGAACTCATTATACAATGACA
AATGGAGGCAGCATTAACAGTTCTACACATTTACTGGATCTTTTGGATGAACCAATTCCA
GGTGTTGGTACATATGATGATTTCCATACTATTGATTGGGTGCGAGAAAAATGTAAAGAC
AGAGAAAGGCATAGACGGATCAACAGCAAAAAGAAAGAATCAGCATGGGAAATGACAAAA
AGTTTGTATGATGCGTGGTCAGGATGGCTAGTAGTAACACTAACAGGATTGGCATCAGGG
GCACTGGCCGGATTAATAGACATTGCTGCCGATTGGATGACTGACCTAAAGGAGGGCATT
TGCCTTAGTGCGTTGTGGTACAACCACGAACAGTGCTGTTGGGGATCTAATGAAACAACA
TTTGAAGAGAGGGATAAATGTCCACAGTGGAAAACATGGGCAGAATTAATCATAGGTCAA
GCAGAGGGTCCTGGTTCTTATATCATGAACTACATAATGTACATCTTCTGGGCCTTGAGT
TTTGCCTTTCTTGCAGTTTCCCTGGTAAAGGTATTTGCTCCATATGCCTGTGGCTCTGGA
ATTCCAGAGATTAAAACTATTTTAAGTGGATTCATCATCAGAGGTTACTTGGGAAAATGG
ACTTTAATGATTAAAACCATCACATTAGTCCTGGCTGTGGCATCAGGTTTGAGTTTAGGA
AAAGAAGGTCCCCTGGTACATGTTGCCTGTTGCTGCGGAAATATCTTTTCCTACCTCTTT
CCAAAGTATAGCACAAACGAAGCTAAAAAAAGGGAGGTTAGCTATTATTTTCCTCTCAAA
ACTTTATGGAGATCATTTTTTGCTGCTTTAGTGGCTGCATTTGTTTTGAGGTCCATCAAT
CCATTTGGTAACAGCCGTCTGGTCCTTTTTTATGTGGAGTATCATACACCATGGTACCTT
TTTGAACTGTTTCCTTTTATTCTTCTAGGGGTATTTGGAGGGCTTTGGGGAGCCTTTTTC
ATTAGGGCAAATATTGCCTGGTGTCGTCGACGCAAGTCCACGAAATTTGGAAAGTATCCC
GTTCTGGAAGTCATTATTGTTGCAGCCATTACTGCTGTGATAGCCTTCCCTAATCCATAC
ACTAGGCTAAACACCAGTGAACTGATCAAAGAGCTTTTTACAGACTGTGGTCCCCTGGAA
TCCTCTTCTCTTTGTGACTACAGAAATGACATGAATGCCAGTAAAATTGTCGATGACATT
CCTGATCGTCCAGCAGGCATTGGAGTATATTCAGCTATATGGCAGTTATGCCTGGCACTC
ATATTTAAAATCATAATGACAGTATTCACTTTTGGCATCAAGGTTCCATCAGGCTTGTTC
ATCCCCAGCATGGCCATTGGAGCGATCGCAGGAAGGATTGTGGGGATTGCGGTGGAGCAG
CTTGCCTACTATCACCACGACTGGTTTATCTTTAAGGAGTGGTGTGAGGTCGGGGCTGAT
TGCATTACACCTGGCCTTTATGCCATGGTTGGTGCTGCTGCATGCTTAGGTGGTGTGACA
AGAATGACTGTCTCCCTGGTGGTTATTGTTTTTGAGCTTACTGGAGGCTTGGAATATATT
GTTCCCCTTATGGCTGCAGTCATGACCAGTAAATGGGTTGGAGATGCCTTTGGCAGGGAA
GGCATTTATGAAGCACACATCCGATTAAATGGATACCCTTTCTTGGATGCAAAAGAAGAA
TTCACTCATACCACCCTGGCTGCTGACGTTATGAGACCTCGAAGGAATGATCCTCCCTTA
GCTGTCCTGACACAGGACAATATGACAGTGGATGATATAGAAAACATGATTAATGAAACC
AGCTACAATGGATTTCCTGTCATAATGTCAAAAGAATCTCAGAGATTAGTGGGATTTGCC
CTCAGAAGAGACCTGACAATTGCAATAGAAAGTGCCAGGAAAAAACAAGAAGGTATCGTT
GGCAGTTCTCGGGTGTGTTTTGCACAGCACACCCCATCTCTTCCAGCAGAAAGTCCTCGG
CCATTGAAGCTTCGAAGCATTCTTGACATGAGCCCTTTTACAGTGACAGACCACACCCCA
ATGGAGATCGTGGTGGATATTTTCCGAAAGCTGGGACTGAGGCAGTGCCTTGTAACTCAC
AATGGGCGCCTCCTTGGCATTATAACAAAAAAAGATATCCTCCGGCATATGGCCCAGACG
GCAAACCAAGACCCCGCTTCAATAATGTTCAACTGA
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:2021
Chromosome Location4
LocusNot Available
References
  1. Borsani G, Rugarli EI, Taglialatela M, Wong C, Ballabio A: Characterization of a human and murine gene (CLCN3) sharing similarities to voltage-gated chloride channels and to a yeast integral membrane protein. Genomics. 1995 May 1;27(1):131-41. 7665160
  2. Shepard AR, Rae JL: Ion transporters and receptors in cDNA libraries from lens and cornea epithelia. Curr Eye Res. 1998 Jul;17(7):708-19. 9678416
  3. Huang P, Liu J, Di A, Robinson NC, Musch MW, Kaetzel MA, Nelson DJ: Regulation of human CLC-3 channels by multifunctional Ca2+/calmodulin-dependent protein kinase. J Biol Chem. 2001 Jun 8;276(23):20093-100. Epub 2001 Mar 26. 11274166
  4. Ogura T, Furukawa T, Toyozaki T, Yamada K, Zheng YJ, Katayama Y, Nakaya H, Inagaki N: ClC-3B, a novel ClC-3 splicing variant that interacts with EBP50 and facilitates expression of CFTR-regulated ORCC. FASEB J. 2002 Jun;16(8):863-5. Epub 2002 Apr 10. 11967229
  5. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. 17974005
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  7. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. 15815621
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  9. Lamb FS, Clayton GH, Liu BX, Smith RL, Barna TJ, Schutte BC: Expression of CLCN voltage-gated chloride channel genes in human blood vessels. J Mol Cell Cardiol. 1999 Mar;31(3):657-66. 10198195
  10. Gentzsch M, Cui L, Mengos A, Chang XB, Chen JH, Riordan JR: 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 Feb 21;278(8):6440-9. Epub 2002 Dec 5. 12471024