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Identification
HMDB Protein ID HMDBP08185
Secondary Accession Numbers
  • 13896
Name H(+)/Cl(-) exchange transporter 3
Synonyms
  1. Chloride channel protein 3
  2. Chloride transporter ClC-3
  3. ClC-3
Gene Name CLCN3
Protein Type Unknown
Biological Properties
General Function Involved in ion channel activity
Specific Function Mediates 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.
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
endosomal lumen acidification
Cellular Component
cell surface
Golgi apparatus
early endosome
early endosome membrane
vesicle membrane
late endosome
apical plasma membrane
transport vesicle membrane
late endosome membrane
integral to membrane
Golgi membrane
Component
membrane
cell part
Function
voltage-gated chloride channel activity
anion channel activity
chloride channel activity
transmembrane transporter activity
substrate-specific transmembrane transporter activity
ion transmembrane transporter activity
transporter activity
ion channel activity
Molecular Function
ATP binding
PDZ domain binding
protein homodimerization activity
antiporter activity
voltage-gated chloride channel activity
protein heterodimerization activity
Process
establishment of localization
transport
chloride transport
transmembrane transport
anion transport
inorganic anion transport
ion transport
Cellular Location
  1. Golgi apparatus membrane
  2. Late endosome membrane
  3. Multi-pass membrane protein
  4. Multi-pass membrane protein
  5. Multi-pass membrane protein
  6. Multi-pass membrane protein
  7. Early endosome membrane
  8. Isoform 2:Membrane
Gene Properties
Chromosome Location 4
Locus 4q33
SNPs CLCN3
Gene Sequence
>2457 bp
ATGGAGTCTGAGCAGCTGTTCCATAGAGGCTACTATAGAAACAGCTACAACAGTATAACA
AGTGCAAGTAGTGATGAGGAACTTTTAGATGGAGCAGGTGTTATTATGGACTTTCAAACA
TCTGAAGATGACAATTTATTAGATGGTGACACTGCAGTTGGAACTCATTATACAATGACA
AATGGAGGCAGCATTAACAGTTCTACACATTTACTGGATCTTTTGGATGAACCAATTCCA
GGTGTTGGTACATATGATGATTTCCATACTATTGATTGGGTGCGAGAAAAATGTAAAGAC
AGAGAAAGGCATAGACGGATCAACAGCAAAAAGAAAGAATCAGCATGGGAAATGACAAAA
AGTTTGTATGATGCGTGGTCAGGATGGCTAGTAGTAACACTAACAGGATTGGCATCAGGG
GCACTGGCCGGATTAATAGACATTGCTGCCGATTGGATGACTGACCTAAAGGAGGGCATT
TGCCTTAGTGCGTTGTGGTACAACCACGAACAGTGCTGTTGGGGATCTAATGAAACAACA
TTTGAAGAGAGGGATAAATGTCCACAGTGGAAAACATGGGCAGAATTAATCATAGGTCAA
GCAGAGGGTCCTGGTTCTTATATCATGAACTACATAATGTACATCTTCTGGGCCTTGAGT
TTTGCCTTTCTTGCAGTTTCCCTGGTAAAGGTATTTGCTCCATATGCCTGTGGCTCTGGA
ATTCCAGAGATTAAAACTATTTTAAGTGGATTCATCATCAGAGGTTACTTGGGAAAATGG
ACTTTAATGATTAAAACCATCACATTAGTCCTGGCTGTGGCATCAGGTTTGAGTTTAGGA
AAAGAAGGTCCCCTGGTACATGTTGCCTGTTGCTGCGGAAATATCTTTTCCTACCTCTTT
CCAAAGTATAGCACAAACGAAGCTAAAAAAAGGGAGGTGCTATCAGCTGCCTCAGCTGCA
GGGGTTTCTGTAGCTTTTGGTGCACCAATTGGAGGAGTTCTTTTTAGCCTGGAAGAGGTT
AGCTATTATTTTCCTCTCAAAACTTTATGGAGATCATTTTTTGCTGCTTTAGTGGCTGCA
TTTGTTTTGAGGTCCATCAATCCATTTGGTAACAGCCGTCTGGTCCTTTTTTATGTGGAG
TATCATACACCATGGTACCTTTTTGAACTGTTTCCTTTTATTCTTCTAGGGGTATTTGGA
GGGCTTTGGGGAGCCTTTTTCATTAGGGCAAATATTGCCTGGTGTCGTCGACGCAAGTCC
ACGAAATTTGGAAAGTATCCCGTTCTGGAAGTCATTATTGTTGCAGCCATTACTGCTGTG
ATAGCCTTCCCTAATCCATACACTAGGCTAAACACCAGTGAACTGATCAAAGAGCTTTTT
ACAGACTGTGGTCCCCTGGAATCCTCTTCTCTTTGTGACTACAGAAATGACATGAATGCC
AGTAAAATTGTCGATGACATTCCTGATCGTCCAGCAGGCATTGGAGTATATTCAGCTATA
TGGCAGTTATGCCTGGCACTCATATTTAAAATCATAATGACAGTATTCACTTTTGGCATC
AAGGTTCCATCAGGCTTGTTCATCCCCAGCATGGCCATTGGAGCGATCGCAGGAAGGATT
GTGGGGATTGCGGTGGAGCAGCTTGCCTACTATCACCACGACTGGTTTATCTTTAAGGAG
TGGTGTGAGGTCGGGGCTGATTGCATTACACCTGGCCTTTATGCCATGGTTGGTGCTGCT
GCATGCTTAGGTGGTGTGACAAGAATGACTGTCTCCCTGGTGGTTATTGTTTTTGAGCTT
ACTGGAGGCTTGGAATATATTGTTCCCCTTATGGCTGCAGTCATGACCAGTAAATGGGTT
GGAGATGCCTTTGGCAGGGAAGGCATTTATGAAGCACACATCCGATTAAATGGATACCCT
TTCTTGGATGCAAAAGAAGAATTCACTCATACCACCCTGGCTGCTGACGTTATGAGACCT
CGAAGGAATGATCCTCCCTTAGCTGTCCTGACACAGGACAATATGACAGTGGATGATATA
GAAAACATGATTAATGAAACCAGCTACAATGGATTTCCTGTCATAATGTCAAAAGAATCT
CAGAGATTAGTGGGATTTGCCCTCAGAAGAGACCTGACAATTGCAATAGAAAGTGCCAGG
AAAAAACAAGAAGGTATCGTTGGCAGTTCTCGGGTGTGTTTTGCACAGCACACCCCATCT
CTTCCAGCAGAAAGTCCTCGGCCATTGAAGCTTCGAAGCATTCTTGACATGAGCCCTTTT
ACAGTGACAGACCACACCCCAATGGAGATCGTGGTGGATATTTTCCGAAAGCTGGGACTG
AGGCAGTGCCTTGTAACTCACAATGGGCGCCTCCTTGGCATTATAACAAAAAAAGATATC
CTCCGGCATATGGCCCAGACGGCAAACCAAGACCCCGCTTCAATAATGTTCAACTGA
Protein Properties
Number of Residues 818
Molecular Weight 88463.45
Theoretical pI 6.448
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>H(+)/Cl(-) exchange transporter 3
MESEQLFHRGYYRNSYNSITSASSDEELLDGAGVIMDFQTSEDDNLLDGDTAVGTHYTMT
NGGSINSSTHLLDLLDEPIPGVGTYDDFHTIDWVREKCKDRERHRRINSKKKESAWEMTK
SLYDAWSGWLVVTLTGLASGALAGLIDIAADWMTDLKEGICLSALWYNHEQCCWGSNETT
FEERDKCPQWKTWAELIIGQAEGPGSYIMNYIMYIFWALSFAFLAVSLVKVFAPYACGSG
IPEIKTILSGFIIRGYLGKWTLMIKTITLVLAVASGLSLGKEGPLVHVACCCGNIFSYLF
PKYSTNEAKKREVLSAASAAGVSVAFGAPIGGVLFSLEEVSYYFPLKTLWRSFFAALVAA
FVLRSINPFGNSRLVLFYVEYHTPWYLFELFPFILLGVFGGLWGAFFIRANIAWCRRRKS
TKFGKYPVLEVIIVAAITAVIAFPNPYTRLNTSELIKELFTDCGPLESSSLCDYRNDMNA
SKIVDDIPDRPAGIGVYSAIWQLCLALIFKIIMTVFTFGIKVPSGLFIPSMAIGAIAGRI
VGIAVEQLAYYHHDWFIFKEWCEVGADCITPGLYAMVGAAACLGGVTRMTVSLVVIVFEL
TGGLEYIVPLMAAVMTSKWVGDAFGREGIYEAHIRLNGYPFLDAKEEFTHTTLAADVMRP
RRNDPPLAVLTQDNMTVDDIENMINETSYNGFPVIMSKESQRLVGFALRRDLTIAIESAR
KKQEGIVGSSRVCFAQHTPSLPAESPRPLKLRSILDMSPFTVTDHTPMEIVVDIFRKLGL
RQCLVTHNGRLLGIITKKDILRHMAQTANQDPASIMFN
GenBank ID Protein 55770838
UniProtKB/Swiss-Prot ID P51790
UniProtKB/Swiss-Prot Entry Name CLCN3_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_001829.2
GeneCard ID CLCN3
GenAtlas ID CLCN3
HGNC ID HGNC:2021
References
General References
  1. 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. [PubMed:15815621 ]
  2. 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. [PubMed:17974005 ]
  3. 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. [PubMed:12471024 ]
  4. 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. [PubMed:10198195 ]
  5. 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. [PubMed:7665160 ]
  6. 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. [PubMed:9678416 ]
  7. 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. [PubMed:11274166 ]
  8. 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. [PubMed:11967229 ]