TCDB is operated by the Saier Lab Bioinformatics Group
« See all members of the family


2.A.49.3.3
CLC-7 or Clcn7 Cl-:H+ antiporter; provides the primary Cl- permeation pathway in the lysosome (Graves et al., 2008). Cl- provides the counter ion for acidification of the lysosomal lumen via the V-type ATPase (Mindell, 2012). It is a slowly voltage-gated 2Cl-/1H+-exchanger and requires Ostm1 for transport activity (Leisle et al., 2011). Common gating (involving both of the two subunits) underlies the slow voltage activation dependent on the C-terminal CBS domain (Ludwig et al. 2013). Lethal CLCN7-related osteopetrosis has been described (Rössler et al. 2021).

Accession Number:P51798
Protein Name:Chloride channel protein 7 aka ClC-7
Length:805
Molecular Weight:88679.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:10
Location1 / Topology2 / Orientation3: Lysosome membrane1 / Multi-pass membrane protein2
Substrate chloride

Cross database links:

RefSeq: NP_001107803.1    NP_001278.1   
Entrez Gene ID: 1186   
Pfam: PF00571    PF00654   
OMIM: 166600  phenotype
602727  gene
611490  phenotype
KEGG: hsa:1186   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005765 C:lysosomal membrane
GO:0015297 F:antiporter activity
GO:0005524 F:ATP binding
GO:0005247 F:voltage-gated chloride channel activity
GO:0006821 P:chloride transport
GO:0055085 P:transmembrane transport

References (11)

[1] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[2] “The sequence and analysis of duplication-rich human chromosome 16.”  Martin J.et.al.   15616553
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “ClC-6 and ClC-7 are two novel broadly expressed members of the CLC chloride channel family.”  Brandt S.et.al.   8543009
[5] “The exon-intron architecture of human chloride channel genes is not conserved.”  Eggermont J.et.al.   9565675
[6] “Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.”  Olsen J.V.et.al.   17081983
[7] “The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes.”  Graves A.R.et.al.   18449189
[8] “Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man.”  Kornak U.et.al.   11207362
[9] “Albers-Schonberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene.”  Cleiren E.et.al.   11741829
[10] “Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis.”  Frattini A.et.al.   14584882
[11] “DNA-based diagnosis of malignant osteopetrosis by whole-genome scan using a single-nucleotide polymorphism microarray: standardization of molecular investigations of genetic diseases due to consanguinity.”  Lam C.-W.et.al.   17033731
Structure:
7BXU   7JM7     

External Searches:

Analyze:

Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence
1:	MANVSKKVSW SGRDRDDEEA APLLRRTARP GGGTPLLNGA GPGAARQSPR SALFRVGHMS 
61:	SVELDDELLD PDMDPPHPFP KEIPHNEKLL SLKYESLDYD NSENQLFLEE ERRINHTAFR 
121:	TVEIKRWVIC ALIGILTGLV ACFIDIVVEN LAGLKYRVIK GNIDKFTEKG GLSFSLLLWA 
181:	TLNAAFVLVG SVIVAFIEPV AAGSGIPQIK CFLNGVKIPH VVRLKTLVIK VSGVILSVVG 
241:	GLAVGKEGPM IHSGSVIAAG ISQGRSTSLK RDFKIFEYFR RDTEKRDFVS AGAAAGVSAA 
301:	FGAPVGGVLF SLEEGASFWN QFLTWRIFFA SMISTFTLNF VLSIYHGNMW DLSSPGLINF 
361:	GRFDSEKMAY TIHEIPVFIA MGVVGGVLGA VFNALNYWLT MFRIRYIHRP CLQVIEAVLV 
421:	AAVTATVAFV LIYSSRDCQP LQGGSMSYPL QLFCADGEYN SMAAAFFNTP EKSVVSLFHD 
481:	PPGSYNPLTL GLFTLVYFFL ACWTYGLTVS AGVFIPSLLI GAAWGRLFGI SLSYLTGAAI 
541:	WADPGKYALM GAAAQLGGIV RMTLSLTVIM MEATSNVTYG FPIMLVLMTA KIVGDVFIEG 
601:	LYDMHIQLQS VPFLHWEAPV TSHSLTAREV MSTPVTCLRR REKVGVIVDV LSDTASNHNG 
661:	FPVVEHADDT QPARLQGLIL RSQLIVLLKH KVFVERSNLG LVQRRLRLKD FRDAYPRFPP 
721:	IQSIHVSQDE RECTMDLSEF MNPSPYTVPQ EASLPRVFKL FRALGLRHLV VVDNRNQVVG 
781:	LVTRKDLARY RLGKRGLEEL SLAQT