You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP08187
Secondary Accession Numbers
  • 13898
Name H(+)/Cl(-) exchange transporter 5
Synonyms
  1. Chloride channel protein 5
  2. Chloride transporter ClC-5
  3. ClC-5
Gene Name CLCN5
Protein Type Unknown
Biological Properties
General Function Involved in ion channel activity
Specific Function Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function.
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
endocytosis
excretion
Cellular Component
apical part of cell
endosome membrane
Golgi membrane
integral to plasma 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
antiporter activity
voltage-gated chloride channel activity
chloride channel activity
Process
establishment of localization
transport
chloride transport
transmembrane transport
anion transport
inorganic anion transport
ion transport
Cellular Location
  1. Cell membrane
  2. Golgi apparatus membrane
  3. Endosome membrane
  4. Multi-pass membrane protein
  5. Multi-pass membrane protein
  6. Multi-pass membrane protein
Gene Properties
Chromosome Location X
Locus Xp11.23-p11.22
SNPs CLCN5
Gene Sequence
>2241 bp
ATGGACTTCTTGGAGGAGCCAATCCCTGGTGTAGGGACCTATGATGATTTCAATACAATT
GATTGGGTGAGAGAGAAGTCTCGAGACCGGGATAGGCACCGAGAGATTACCAATAAAAGC
AAAGAGTCAACATGGGCCTTAATTCACAGTGTGAGTGATGCTTTTTCCGGCTGGTTGTTG
ATGCTCCTTATTGGGCTTTTATCAGGTTCGTTAGCTGGTTTGATAGACATCTCTGCTCAT
TGGATGACAGACTTAAAAGAAGGTATATGCACAGGGGGATTCTGGTTTAACCATGAACAT
TGTTGCTGGAACTCTGAGCATGTCACCTTTGAAGAGAGAGACAAATGTCCAGAGTGGAAT
AGTTGGTCCCAGCTTATCATCAGCACAGATGAGGGAGCCTTTGCCTACATAGTCAATTAT
TTCATGTACGTCCTCTGGGCTCTCCTATTTGCCTTCCTTGCCGTATCTCTTGTCAAGGTG
TTTGCGCCTTATGCCTGTGGCTCTGGAATCCCTGAGATAAAAACTATCTTGAGTGGTTTC
ATTATTAGGGGCTATTTGGGTAAGTGGACTCTGGTTATCAAAACCATCACCTTGGTGCTG
GCAGTGTCGTCTGGCTTGAGCCTGGGCAAAGAGGGCCCTCTAGTGCACGTGGCTTGCTGC
TGTGGGAACATCCTGTGCCACTGCTTCAACAAATACAGGAAGAATGAAGCCAAGCGCAGA
GAGGTCTTGTCGGCTGCAGCAGCAGCTGGTGTATCTGTAGCCTTTGGAGCACCTATAGGT
GGAGTATTATTCAGCCTTGAAGAGGTCAGCTACTATTTTCCCCTCAAAACATTGTGGCGT
TCATTCTTTGCTGCCTTGGTGGCAGCATTCACTCTACGCTCCATCAATCCATTTGGGAAC
AGCCGCCTGGTACTATTTTATGTGGAGTTTCACACCCCATGGCATCTCTTTGAGCTCGTG
CCATTCATTCTGCTGGGCATATTTGGTGGTCTGTGGGGAGCACTGTTTATCCGCACAAAC
ATTGCCTGGTGTCGGAAGCGAAAGACCACCCAGTTGGGCAAGTATCCTGTTATAGAGGTA
CTCGTCGTGACAGCCATCACTGCCATCCTGGCTTTCCCCAATGAATACACTCGGATGAGC
ACAAGTGAGCTCATTTCTGAGCTGTTTAATGACTGTGGCCTTCTGGACTCCTCCAAGCTC
TGTGATTATGAGAACCGTTTCAACACAAGCAAAGGGGGTGAACTGCCTGACAGACCGGCT
GGCGTGGGAGTCTACAGTGCAATGTGGCAGCTGGCTTTAACACTCATACTGAAAATTGTC
ATTACTATATTCACCTTTGGCATGAAGATCCCTTCTGGCCTCTTTATCCCTAGCATGGCT
GTTGGTGCTATAGCAGGTCGACTTCTAGGAGTAGGAATGGAACAGCTGGCTTATTACCAC
CAGGAATGGACCGTCTTCAATAGCTGGTGTAGTCAGGGAGCTGATTGCATCACCCCCGGC
CTTTATGCAATGGTTGGGGCTGCAGCCTGCTTAGGTGGGGTGACTCGGATGACTGTTTCT
CTTGTTGTCATAATGTTTGAACTGACTGGTGGCTTAGAATACATCGTGCCTCTGATGGCT
GCAGCCATGACAAGCAAGTGGGTGGCAGATGCTCTTGGGCGGGAGGGCATCTATGATGCC
CACATCCGTCTCAATGGATACCCCTTTCTTGAAGCCAAAGAAGAGTTTGCTCATAAGACC
CTGGCAATGGATGTGATGAAACCCCGGAGAAATGATCCTTTGTTGACTGTCCTTACTCAG
GACAGTATGACTGTGGAAGATGTAGAGACCATAATCAGTGAAACCACTTACAGTGGCTTC
CCAGTGGTGGTATCCCGGGAGTCCCAAAGACTTGTGGGCTTTGTCCTCCGAAGAGATCTC
ATTATTTCAATTGAAAATGCTCGAAAGAAACAGGATGGGGTTGTTAGCACTTCCATCATT
TATTTCACGGAGCATTCTCCTCCATTGCCACCATACACTCCACCCACTCTAAAGCTTCGG
AACATCCTCGATCTCAGCCCCTTCACTGTGACTGACCTTACACCCATGGAGATCGTAGTG
GATATTTTCCGAAAGCTGGGACTGCGGCAGTGCCTGGTTACACACAACGGGCGATTGCTT
GGAATCATTACCAAAAAGGATGTGTTAAAGCATATAGCACAGATGGCGAACCAAGATCCT
GATTCCATTCTCTTCAACTAG
Protein Properties
Number of Residues 746
Molecular Weight 83146.045
Theoretical pI 6.82
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>H(+)/Cl(-) exchange transporter 5
MDFLEEPIPGVGTYDDFNTIDWVREKSRDRDRHREITNKSKESTWALIHSVSDAFSGWLL
MLLIGLLSGSLAGLIDISAHWMTDLKEGICTGGFWFNHEHCCWNSEHVTFEERDKCPEWN
SWSQLIISTDEGAFAYIVNYFMYVLWALLFAFLAVSLVKVFAPYACGSGIPEIKTILSGF
IIRGYLGKWTLVIKTITLVLAVSSGLSLGKEGPLVHVACCCGNILCHCFNKYRKNEAKRR
EVLSAAAAAGVSVAFGAPIGGVLFSLEEVSYYFPLKTLWRSFFAALVAAFTLRSINPFGN
SRLVLFYVEFHTPWHLFELVPFILLGIFGGLWGALFIRTNIAWCRKRKTTQLGKYPVIEV
LVVTAITAILAFPNEYTRMSTSELISELFNDCGLLDSSKLCDYENRFNTSKGGELPDRPA
GVGVYSAMWQLALTLILKIVITIFTFGMKIPSGLFIPSMAVGAIAGRLLGVGMEQLAYYH
QEWTVFNSWCSQGADCITPGLYAMVGAAACLGGVTRMTVSLVVIMFELTGGLEYIVPLMA
AAMTSKWVADALGREGIYDAHIRLNGYPFLEAKEEFAHKTLAMDVMKPRRNDPLLTVLTQ
DSMTVEDVETIISETTYSGFPVVVSRESQRLVGFVLRRDLIISIENARKKQDGVVSTSII
YFTEHSPPLPPYTPPTLKLRNILDLSPFTVTDLTPMEIVVDIFRKLGLRQCLVTHNGRLL
GIITKKDVLKHIAQMANQDPDSILFN
GenBank ID Protein 1171562
UniProtKB/Swiss-Prot ID P51795
UniProtKB/Swiss-Prot Entry Name CLCN5_HUMAN
PDB IDs
GenBank Gene ID X91906
GeneCard ID CLCN5
GenAtlas ID CLCN5
HGNC ID HGNC:2023
References
General References
  1. 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. [PubMed:15489334 ]
  2. Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C, Bird CP, Frankish A, Lovell FL, Howe KL, Ashurst JL, Fulton RS, Sudbrak R, Wen G, Jones MC, Hurles ME, Andrews TD, Scott CE, Searle S, Ramser J, Whittaker A, Deadman R, Carter NP, Hunt SE, Chen R, Cree A, Gunaratne P, Havlak P, Hodgson A, Metzker ML, Richards S, Scott G, Steffen D, Sodergren E, Wheeler DA, Worley KC, Ainscough R, Ambrose KD, Ansari-Lari MA, Aradhya S, Ashwell RI, Babbage AK, Bagguley CL, Ballabio A, Banerjee R, Barker GE, Barlow KF, Barrett IP, Bates KN, Beare DM, Beasley H, Beasley O, Beck A, Bethel G, Blechschmidt K, Brady N, Bray-Allen S, Bridgeman AM, Brown AJ, Brown MJ, Bonnin D, Bruford EA, Buhay C, Burch P, Burford D, Burgess J, Burrill W, Burton J, Bye JM, Carder C, Carrel L, Chako J, Chapman JC, Chavez D, Chen E, Chen G, Chen Y, Chen Z, Chinault C, Ciccodicola A, Clark SY, Clarke G, Clee CM, Clegg S, Clerc-Blankenburg K, Clifford K, Cobley V, Cole CG, Conquer JS, Corby N, Connor RE, David R, Davies J, Davis C, Davis J, Delgado O, Deshazo D, Dhami P, Ding Y, Dinh H, Dodsworth S, Draper H, Dugan-Rocha S, Dunham A, Dunn M, Durbin KJ, Dutta I, Eades T, Ellwood M, Emery-Cohen A, Errington H, Evans KL, Faulkner L, Francis F, Frankland J, Fraser AE, Galgoczy P, Gilbert J, Gill R, Glockner G, Gregory SG, Gribble S, Griffiths C, Grocock R, Gu Y, Gwilliam R, Hamilton C, Hart EA, Hawes A, Heath PD, Heitmann K, Hennig S, Hernandez J, Hinzmann B, Ho S, Hoffs M, Howden PJ, Huckle EJ, Hume J, Hunt PJ, Hunt AR, Isherwood J, Jacob L, Johnson D, Jones S, de Jong PJ, Joseph SS, Keenan S, Kelly S, Kershaw JK, Khan Z, Kioschis P, Klages S, Knights AJ, Kosiura A, Kovar-Smith C, Laird GK, Langford C, Lawlor S, Leversha M, Lewis L, Liu W, Lloyd C, Lloyd DM, Loulseged H, Loveland JE, Lovell JD, Lozado R, Lu J, Lyne R, Ma J, Maheshwari M, Matthews LH, McDowall J, McLaren S, McMurray A, Meidl P, Meitinger T, Milne S, Miner G, Mistry SL, Morgan M, Morris S, Muller I, Mullikin JC, Nguyen N, Nordsiek G, Nyakatura G, O'Dell CN, Okwuonu G, Palmer S, Pandian R, Parker D, Parrish J, Pasternak S, Patel D, Pearce AV, Pearson DM, Pelan SE, Perez L, Porter KM, Ramsey Y, Reichwald K, Rhodes S, Ridler KA, Schlessinger D, Schueler MG, Sehra HK, Shaw-Smith C, Shen H, Sheridan EM, Shownkeen R, Skuce CD, Smith ML, Sotheran EC, Steingruber HE, Steward CA, Storey R, Swann RM, Swarbreck D, Tabor PE, Taudien S, Taylor T, Teague B, Thomas K, Thorpe A, Timms K, Tracey A, Trevanion S, Tromans AC, d'Urso M, Verduzco D, Villasana D, Waldron L, Wall M, Wang Q, Warren J, Warry GL, Wei X, West A, Whitehead SL, Whiteley MN, Wilkinson JE, Willey DL, Williams G, Williams L, Williamson A, Williamson H, Wilming L, Woodmansey RL, Wray PW, Yen J, Zhang J, Zhou J, Zoghbi H, Zorilla S, Buck D, Reinhardt R, Poustka A, Rosenthal A, Lehrach H, Meindl A, Minx PJ, Hillier LW, Willard HF, Wilson RK, Waterston RH, Rice CM, Vaudin M, Coulson A, Nelson DL, Weinstock G, Sulston JE, Durbin R, Hubbard T, Gibbs RA, Beck S, Rogers J, Bentley DR: The DNA sequence of the human X chromosome. Nature. 2005 Mar 17;434(7031):325-37. [PubMed:15772651 ]
  3. Hryciw DH, Ekberg J, Lee A, Lensink IL, Kumar S, Guggino WB, Cook DI, Pollock CA, Poronnik P: Nedd4-2 functionally interacts with ClC-5: involvement in constitutive albumin endocytosis in proximal tubule cells. J Biol Chem. 2004 Dec 31;279(53):54996-5007. Epub 2004 Oct 15. [PubMed:15489223 ]
  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. Fisher SE, van Bakel I, Lloyd SE, Pearce SH, Thakker RV, Craig IW: Cloning and characterization of CLCN5, the human kidney chloride channel gene implicated in Dent disease (an X-linked hereditary nephrolithiasis). Genomics. 1995 Oct 10;29(3):598-606. [PubMed:8575751 ]
  6. Fisher SE, Black GC, Lloyd SE, Hatchwell E, Wrong O, Thakker RV, Craig IW: Isolation and partial characterization of a chloride channel gene which is expressed in kidney and is a candidate for Dent's disease (an X-linked hereditary nephrolithiasis). Hum Mol Genet. 1994 Nov;3(11):2053-9. [PubMed:7874126 ]
  7. Meyer S, Savaresi S, Forster IC, Dutzler R: Nucleotide recognition by the cytoplasmic domain of the human chloride transporter ClC-5. Nat Struct Mol Biol. 2007 Jan;14(1):60-7. Epub 2006 Dec 31. [PubMed:17195847 ]
  8. Lloyd SE, Pearce SH, Fisher SE, Steinmeyer K, Schwappach B, Scheinman SJ, Harding B, Bolino A, Devoto M, Goodyer P, Rigden SP, Wrong O, Jentsch TJ, Craig IW, Thakker RV: A common molecular basis for three inherited kidney stone diseases. Nature. 1996 Feb 1;379(6564):445-9. [PubMed:8559248 ]
  9. Oudet C, Martin-Coignard D, Pannetier S, Praud E, Champion G, Hanauer A: A second family with XLRH displays the mutation S244L in the CLCN5 gene. Hum Genet. 1997 Jun;99(6):781-4. [PubMed:9187673 ]
  10. Lloyd SE, Gunther W, Pearce SH, Thomson A, Bianchi ML, Bosio M, Craig IW, Fisher SE, Scheinman SJ, Wrong O, Jentsch TJ, Thakker RV: Characterisation of renal chloride channel, CLCN5, mutations in hypercalciuric nephrolithiasis (kidney stones) disorders. Hum Mol Genet. 1997 Aug;6(8):1233-9. [PubMed:9259268 ]
  11. Lloyd SE, Pearce SH, Gunther W, Kawaguchi H, Igarashi T, Jentsch TJ, Thakker RV: Idiopathic low molecular weight proteinuria associated with hypercalciuric nephrocalcinosis in Japanese children is due to mutations of the renal chloride channel (CLCN5). J Clin Invest. 1997 Mar 1;99(5):967-74. [PubMed:9062355 ]
  12. Schurman SJ, Norden AG, Scheinman SJ: X-linked recessive nephrolithiasis: presentation and diagnosis in children. J Pediatr. 1998 May;132(5):859-62. [PubMed:9602200 ]
  13. Smith AJ, Reed AA, Loh NY, Thakker RV, Lippiat JD: Characterization of Dent's disease mutations of CLC-5 reveals a correlation between functional and cell biological consequences and protein structure. Am J Physiol Renal Physiol. 2009 Feb;296(2):F390-7. doi: 10.1152/ajprenal.90526.2008. Epub 2008 Nov 19. [PubMed:19019917 ]