CLCN7_MOUSE
ID CLCN7_MOUSE Reviewed; 803 AA.
AC O70496;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=H(+)/Cl(-) exchange transporter 7;
DE AltName: Full=Chloride channel 7 alpha subunit;
DE AltName: Full=Chloride channel protein 7;
DE Short=ClC-7;
GN Name=Clcn7 {ECO:0000312|MGI:MGI:1347048}; Synonyms=Clc7;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=11207362; DOI=10.1016/s0092-8674(01)00206-9;
RA Kornak U., Kasper D., Boesl M.R., Kaiser E., Schweizer M., Schulz A.,
RA Friedrich W., Delling G., Jentsch T.J.;
RT "Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and
RT man.";
RL Cell 104:205-215(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, SUBUNIT, INTERACTION WITH OSTM1, AND SUBCELLULAR LOCATION.
RX PubMed=16525474; DOI=10.1038/nature04535;
RA Lange P.F., Wartosch L., Jentsch T.J., Fuhrmann J.C.;
RT "ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and
RT lysosomal function.";
RL Nature 440:220-223(2006).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19661288; DOI=10.1096/fj.09-130880;
RA Wartosch L., Fuhrmann J.C., Schweizer M., Stauber T., Jentsch T.J.;
RT "Lysosomal degradation of endocytosed proteins depends on the chloride
RT transport protein ClC-7.";
RL FASEB J. 23:4056-4068(2009).
RN [5]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-713.
RX PubMed=31155284; DOI=10.1016/j.ajhg.2019.04.008;
RG Undiagnosed Diseases Network;
RA Nicoli E.R., Weston M.R., Hackbarth M., Becerril A., Larson A., Zein W.M.,
RA Baker P.R. II, Burke J.D., Dorward H., Davids M., Huang Y., Adams D.R.,
RA Zerfas P.M., Chen D., Markello T.C., Toro C., Wood T., Elliott G., Vu M.,
RA Zheng W., Garrett L.J., Tifft C.J., Gahl W.A., Day-Salvatore D.L.,
RA Mindell J.A., Malicdan M.C.V.;
RT "Lysosomal Storage and Albinism Due to Effects of a De Novo CLCN7 Variant
RT on Lysosomal Acidification.";
RL Am. J. Hum. Genet. 104:1127-1138(2019).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
CC -!- FUNCTION: Slowly voltage-gated channel mediating the exchange of
CC chloride ions against protons (PubMed:16525474, PubMed:19661288).
CC Functions as antiporter and contributes to the acidification of the
CC lysosome lumen and may be involved in maintaining lysosomal pH
CC (PubMed:16525474, PubMed:19661288). The CLC channel family contains
CC both chloride channels and proton-coupled anion transporters that
CC exchange chloride or another anion for protons (By similarity). The
CC presence of conserved gating glutamate residues is typical for family
CC members that function as antiporters (By similarity).
CC {ECO:0000250|UniProtKB:P35523, ECO:0000269|PubMed:16525474,
CC ECO:0000269|PubMed:19661288}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 chloride(in) + H(+)(out) = 2 chloride(out) + H(+)(in);
CC Xref=Rhea:RHEA:29567, ChEBI:CHEBI:15378, ChEBI:CHEBI:17996;
CC Evidence={ECO:0000250|UniProtKB:P51798};
CC -!- SUBUNIT: Chloride channel 7 are heteromers of alpha (CLCN7) and beta
CC (OSTM1) subunits. {ECO:0000269|PubMed:16525474}.
CC -!- INTERACTION:
CC O70496; Q8BGT0: Ostm1; NbExp=7; IntAct=EBI-987482, EBI-987431;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:16525474,
CC ECO:0000269|PubMed:31155284}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16525474}.
CC -!- TISSUE SPECIFICITY: Liver, spleen, kidneys and brain.
CC {ECO:0000269|PubMed:31155284}.
CC -!- DISRUPTION PHENOTYPE: Accumulates undegraded endocyted material in
CC neurons or renal proximal tubular cells. Almost all ClC-7-deficient
CC neurons die. {ECO:0000269|PubMed:19661288}.
CC -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClC-
CC 7/CLCN7 subfamily. {ECO:0000305}.
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DR EMBL; AF063101; AAC18832.1; -; Genomic_DNA.
DR EMBL; AF063098; AAC18832.1; JOINED; Genomic_DNA.
DR EMBL; AF063099; AAC18832.1; JOINED; Genomic_DNA.
DR EMBL; AF063100; AAC18832.1; JOINED; Genomic_DNA.
DR EMBL; BC050907; AAH50907.1; -; mRNA.
DR EMBL; BC053049; AAH53049.1; -; mRNA.
DR EMBL; BC054799; AAH54799.1; -; mRNA.
DR CCDS; CCDS28509.1; -.
DR RefSeq; NP_036060.1; NM_011930.4.
DR AlphaFoldDB; O70496; -.
DR SMR; O70496; -.
DR BioGRID; 204933; 2.
DR IntAct; O70496; 1.
DR STRING; 10090.ENSMUSP00000035964; -.
DR iPTMnet; O70496; -.
DR PhosphoSitePlus; O70496; -.
DR SwissPalm; O70496; -.
DR EPD; O70496; -.
DR jPOST; O70496; -.
DR PaxDb; O70496; -.
DR PeptideAtlas; O70496; -.
DR PRIDE; O70496; -.
DR ProteomicsDB; 283282; -.
DR Antibodypedia; 23121; 200 antibodies from 27 providers.
DR DNASU; 26373; -.
DR Ensembl; ENSMUST00000040729; ENSMUSP00000035964; ENSMUSG00000036636.
DR GeneID; 26373; -.
DR KEGG; mmu:26373; -.
DR UCSC; uc008azv.1; mouse.
DR CTD; 1186; -.
DR MGI; MGI:1347048; Clcn7.
DR VEuPathDB; HostDB:ENSMUSG00000036636; -.
DR eggNOG; KOG0474; Eukaryota.
DR GeneTree; ENSGT00940000158458; -.
DR HOGENOM; CLU_003181_4_1_1; -.
DR InParanoid; O70496; -.
DR OrthoDB; 410280at2759; -.
DR PhylomeDB; O70496; -.
DR TreeFam; TF313867; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 26373; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Clcn7; mouse.
DR PRO; PR:O70496; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; O70496; protein.
DR Bgee; ENSMUSG00000036636; Expressed in superior surface of tongue and 255 other tissues.
DR ExpressionAtlas; O70496; baseline and differential.
DR Genevisible; O70496; MM.
DR GO; GO:0034707; C:chloride channel complex; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005765; C:lysosomal membrane; ISO:MGI.
DR GO; GO:0015297; F:antiporter activity; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0015108; F:chloride transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; IEA:InterPro.
DR GO; GO:0009268; P:response to pH; ISO:MGI.
DR GO; GO:0030321; P:transepithelial chloride transport; ISO:MGI.
DR Gene3D; 3.10.580.10; -; 1.
DR InterPro; IPR000644; CBS_dom.
DR InterPro; IPR046342; CBS_dom_sf.
DR InterPro; IPR014743; Cl-channel_core.
DR InterPro; IPR001807; Cl-channel_volt-gated.
DR InterPro; IPR002249; Cl_channel-7.
DR Pfam; PF00571; CBS; 2.
DR Pfam; PF00654; Voltage_CLC; 1.
DR PRINTS; PR00762; CLCHANNEL.
DR PRINTS; PR01118; CLCHANNEL7.
DR SMART; SM00116; CBS; 2.
DR SUPFAM; SSF54631; SSF54631; 1.
DR SUPFAM; SSF81340; SSF81340; 1.
DR PROSITE; PS51371; CBS; 2.
PE 1: Evidence at protein level;
KW Antiport; ATP-binding; CBS domain; Chloride; Ion transport; Lysosome;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..803
FT /note="H(+)/Cl(-) exchange transporter 7"
FT /id="PRO_0000094453"
FT TOPO_DOM 1..124
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 125..157
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 172..195
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 204..211
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 221..239
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 245..262
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 286..298
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 302..310
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 320..339
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 373..403
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 408..430
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 485..505
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 510..533
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 543..557
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 558..560
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250"
FT INTRAMEM 561..572
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 573..576
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250"
FT TRANSMEM 577..595
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 596..803
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 629..693
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 739..797
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 201..205
FT /note="Selectivity filter part_1"
FT /evidence="ECO:0000250"
FT MOTIF 243..247
FT /note="Selectivity filter part_2"
FT /evidence="ECO:0000250"
FT MOTIF 510..514
FT /note="Selectivity filter part_3"
FT /evidence="ECO:0000250"
FT COMPBIAS 9..26
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 202
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 512
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 600
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 656..658
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 781..784
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT SITE 245
FT /note="Mediates proton transfer from the outer aqueous
FT phase to the interior of the protein; involved in linking
FT H(+) and Cl(-) transport"
FT /evidence="ECO:0000250"
FT SITE 312
FT /note="Mediates proton transfer from the protein to the
FT inner aqueous phase"
FT /evidence="ECO:0000250"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 799
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51798"
FT MUTAGEN 713
FT /note="Y->C: Increased cytoplasmic vacuole size. Knockin
FT mice develop albinism and lysosomal-storage disease."
FT /evidence="ECO:0000269|PubMed:31155284"
SQ SEQUENCE 803 AA; 88713 MW; A7D6DA5791DAA48C CRC64;
MANVSKKVSW SGRDRDDEEG APLLRRTGQP DEETPLLNGA GPGARQSHSA LFRIGQMNNV
ELDDELLDPE VDPPHTFPKE IPHNEKLLSL KYESLDYDNS ENQLFLEEER RINHTAFRTV
EIKRWVICAL IGILTGLVAC FIDIVVENLA GLKYRVIKDN IDKFTEKGGL SFSLLLWATL
NSAFVLVGSV IVAFIEPVAA GSGIPQIKCF LNGVKIPHVV RLKTLVIKVS GVILSVVGGL
AVGKEGPMIH SGSVIAAGIS QGRSTSLKRD FKIFEYFRRD TEKRDFVSAG AAAGVSAAFG
APVGGVLFSL EEGASFWNQF LTWRIFFASM ISTFTLNFVL SIYHGNMWDL SSPGLINFGR
FDSEKMAYTI HEIPVFIAMG VVGGILGAVF NALNYWLTMF RIRYIHRPCL QVIEAMLVAA
VTATVAFVLI YSSRDCQPLQ GSSMSYPLQL FCADGEYNSM AAAFFNTPEK SVVSLFHDPP
GSYNPMTLGL FTLVYFFLAC WTYGLTVSAG VFIPSLLIGA AWGRLFGISL SYLTGAAIWA
DPGKYALMGA AAQLGGIVRM TLSLTVIMME ATSNVTYGFP IMLVLMTAKI VGDVFIEGLY
DMHIQLQSVP FLHWEAPVTS HSLTAREVMS TPVTCLRRRE KVGIIVDVLS DTASNHNGFP
VVEDVGDTQP ARLQGLILRS QLIVLLKHKV FVERSNMGLV QRRLRLKDFR DAYPRFPPIQ
SIHVSQDERE CTMDLSEFMN PSPYTVPQEA SLPRVFKLFR ALGLRHLVVV DNHNQVVGLV
TRKDLARYRL GKGGLEELSL AQT
