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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
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  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 ]