CLCN3_MOUSE
ID CLCN3_MOUSE Reviewed; 818 AA.
AC P51791; Q3TF45; Q8K4X0; Q8K4X1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 3.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=H(+)/Cl(-) exchange transporter 3;
DE AltName: Full=Chloride channel protein 3;
DE Short=ClC-3;
DE AltName: Full=Chloride transporter ClC-3;
GN Name=Clcn3; Synonyms=Clc3;
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 [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Thymus;
RX PubMed=7665160; DOI=10.1006/geno.1995.1015;
RA Borsani G., Rugarli E.I., Taglialatela M., Wong C., Ballabio A.;
RT "Characterization of a human and murine gene (CLCN3) sharing similarities
RT to voltage-gated chloride channels and to a yeast integral membrane
RT protein.";
RL Genomics 27:131-141(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Lens epithelium;
RX PubMed=9678416; DOI=10.1080/02713689808951247;
RA Shepard A.R., Rae J.L.;
RT "Ion transporters and receptors in cDNA libraries from lens and cornea
RT epithelia.";
RL Curr. Eye Res. 17:708-719(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv;
RA Schutte B.C., Zimmerman C.K., Swarz S., Malik M.I., Barna T.J., Lamb F.S.;
RT "Diversity at the N- and C-termini for the predicted protein product of the
RT mouse Clcn3 chloride channel gene is caused by alternative splicing.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Bone, and Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP FUNCTION (ISOFORM 2).
RX PubMed=15504734; DOI=10.1074/jbc.m407030200;
RA Hara-Chikuma M., Yang B., Sonawane N.D., Sasaki S., Uchida S.,
RA Verkman A.S.;
RT "ClC-3 chloride channels facilitate endosomal acidification and chloride
RT accumulation.";
RL J. Biol. Chem. 280:1241-1247(2005).
RN [8]
RP SUBCELLULAR LOCATION (ISOFORM 2).
RX PubMed=16222710; DOI=10.1002/jcp.20516;
RA Suzuki T., Rai T., Hayama A., Sohara E., Suda S., Itoh T., Sasaki S.,
RA Uchida S.;
RT "Intracellular localization of ClC chloride channels and their ability to
RT form hetero-oligomers.";
RL J. Cell. Physiol. 206:792-798(2006).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=18923035; DOI=10.1523/jneurosci.3750-08.2008;
RA Maritzen T., Keating D.J., Neagoe I., Zdebik A.A., Jentsch T.J.;
RT "Role of the vesicular chloride transporter ClC-3 in neuroendocrine
RT tissue.";
RL J. Neurosci. 28:10587-10598(2008).
RN [10]
RP ALTERNATIVE SPLICING (ISOFORM 5), FUNCTION (ISOFORMS 2 AND 5), ACTIVITY
RP REGULATION (ISOFORMS 2 AND 5), SUBCELLULAR LOCATION (ISOFORM 5), TISSUE
RP SPECIFICITY (ISOFORM 5), AND MUTAGENESIS (ISOFORM 5).
RX PubMed=24603049; DOI=10.1159/000358633;
RA Okada T., Akita T., Sato-Numata K., Islam M.R., Okada Y.;
RT "A newly cloned ClC-3 isoform, ClC-3d, as well as ClC-3a mediates Cd-
RT sensitive outwardly rectifying anion currents.";
RL Cell. Physiol. Biochem. 33:539-556(2014).
RN [11]
RP ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3 AND 4), FUNCTION (ISOFORMS 1; 2 AND
RP 4), SUBCELLULAR LOCATION (ISOFORMS 1; 2 AND 4), TISSUE SPECIFICITY
RP (ISOFORMS 1; 2; 3 AND 4), DI-LEUCINE INTERNALIZATION MOTIF (ISOFORMS 1 AND
RP 2), AND IP MOTIF (ISOFORM 4).
RX PubMed=26342074; DOI=10.1074/jbc.m115.668186;
RA Guzman R.E., Miranda-Laferte E., Franzen A., Fahlke C.;
RT "Neuronal ClC-3 Splice Variants Differ in Subcellular Localizations, but
RT Mediate Identical Transport Functions.";
RL J. Biol. Chem. 290:25851-25862(2015).
RN [12]
RP FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORMS 1; 2 AND 4), AND
RP SUBUNIT (ISOFORM 1).
RX PubMed=28972156; DOI=10.1074/jbc.m117.801951;
RA Guzman R.E., Bungert-Pluemke S., Franzen A., Fahlke C.;
RT "Preferential association with ClC-3 permits sorting of ClC-4 into
RT endosomal compartments.";
RL J. Biol. Chem. 292:19055-19065(2017).
CC -!- FUNCTION: May influence large dense-core vesicle exocytosis in adrenal
CC chromaffin cells. {ECO:0000269|PubMed:16141072}.
CC -!- FUNCTION: [Isoform 1]: Strongly outwardly rectifying, electrogenic
CC H(+)/Cl(-)exchanger which mediates the exchange of chloride ions
CC against protons (PubMed:26342074). The CLC channel family contains both
CC chloride channels and proton-coupled anion transporters that exchange
CC chloride or another anion for protons (By similarity). The presence of
CC conserved gating glutamate residues is typical for family members that
CC function as antiporters (By similarity). {ECO:0000250|UniProtKB:P51790,
CC ECO:0000269|PubMed:26342074}.
CC -!- FUNCTION: [Isoform 2]: Strongly outwardly rectifying, electrogenic
CC H(+)/Cl(-)exchanger which mediates the exchange of chloride ions
CC against protons (PubMed:24603049, PubMed:26342074, PubMed:28972156).
CC Facilitates endosomal acidification and chloride accumulation in
CC hepatocytes (PubMed:15504734). {ECO:0000269|PubMed:15504734,
CC ECO:0000269|PubMed:24603049, ECO:0000269|PubMed:26342074,
CC ECO:0000269|PubMed:28972156}.
CC -!- FUNCTION: [Isoform 4]: Strongly outwardly rectifying, electrogenic
CC H(+)/Cl(-)exchanger which mediates the exchange of chloride ions
CC against protons. {ECO:0000269|PubMed:26342074}.
CC -!- ACTIVITY REGULATION: [Isoform 2]: Inhibited by Cd(2+).
CC {ECO:0000269|PubMed:24603049}.
CC -!- ACTIVITY REGULATION: [Isoform 5]: Inhibited by Cd(2+).
CC {ECO:0000269|PubMed:24603049}.
CC -!- SUBUNIT: [Isoform 1]: Monomer and homodimer (PubMed:28972156). Forms
CC heterodimers with CLCN4 (PubMed:28972156).
CC {ECO:0000269|PubMed:28972156}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle membrane
CC {ECO:0000269|PubMed:18923035}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Lysosome membrane
CC {ECO:0000269|PubMed:26342074, ECO:0000269|PubMed:28972156}; Multi-pass
CC membrane protein {ECO:0000255}. Late endosome membrane
CC {ECO:0000269|PubMed:28972156}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:P51792}; Multi-pass
CC membrane protein {ECO:0000255}. Early endosome membrane
CC {ECO:0000250|UniProtKB:P51790}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Early endosome membrane
CC {ECO:0000269|PubMed:16222710}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:26342074,
CC ECO:0000269|PubMed:28972156}; Multi-pass membrane protein
CC {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:16222710,
CC ECO:0000269|PubMed:28972156}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cell membrane
CC {ECO:0000269|PubMed:26342074}; Multi-pass membrane protein
CC {ECO:0000255}. Recycling endosome membrane
CC {ECO:0000269|PubMed:26342074, ECO:0000269|PubMed:28972156}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cell membrane
CC {ECO:0000269|PubMed:24603049}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=b {ECO:0000303|PubMed:26342074};
CC IsoId=P51791-1; Sequence=Displayed;
CC Name=2; Synonyms=a {ECO:0000303|PubMed:24603049,
CC ECO:0000303|PubMed:26342074};
CC IsoId=P51791-2; Sequence=VSP_036899;
CC Name=3; Synonyms=e {ECO:0000303|PubMed:26342074};
CC IsoId=P51791-3; Sequence=VSP_060628;
CC Name=4; Synonyms=c {ECO:0000303|PubMed:26342074};
CC IsoId=P51791-4; Sequence=VSP_060627;
CC Name=5; Synonyms=d {ECO:0000303|PubMed:24603049};
CC IsoId=P51791-5; Sequence=VSP_036899, VSP_060628;
CC -!- TISSUE SPECIFICITY: Detected in kidney, in the apical part of proximal
CC tubule cells (at protein level). Expressed at high levels in the kidney
CC while a low level expression is seen in the brain. Within the brain, it
CC is prominent in the hippocampus, cerebral cortex and olfactory bulb.
CC {ECO:0000269|PubMed:18923035, ECO:0000269|PubMed:7665160}.
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Brain, pancreas, kidney, liver, lung,
CC retina, olfactory bulb, and spinal cord. {ECO:0000269|PubMed:26342074}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Brain, pancreas, kidney, liver, lung,
CC retina, olfactory bulb, and spinal cord. {ECO:0000269|PubMed:26342074}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Pancreas, kidney, liver, lung and
CC retina. {ECO:0000269|PubMed:26342074}.
CC -!- TISSUE SPECIFICITY: [Isoform 4]: Brain, heart, pancreas, kidney, liver,
CC lung, retina, olfactory bulb, and spinal cord.
CC {ECO:0000269|PubMed:26342074}.
CC -!- TISSUE SPECIFICITY: [Isoform 5]: Expressed at high levels in the liver
CC and at low levels in the brain. {ECO:0000269|PubMed:24603049}.
CC -!- DEVELOPMENTAL STAGE: At 10.5 days of development it is expressed
CC throughout the embryo. Later in development (12.5 to 14.5 days of
CC gestation), expression is progressively up-regulated in neurons of the
CC brain and the spinal cord, in all cranial sensory ganglia and in the
CC sympathetic dorsal root ganglia. {ECO:0000269|PubMed:7665160}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P51790}.
CC -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClC-
CC 3/CLCN3 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X78874; CAA55476.1; -; mRNA.
DR EMBL; AF029347; AAB95162.1; -; mRNA.
DR EMBL; AF347688; AAM89113.1; -; Genomic_DNA.
DR EMBL; AF347682; AAM89113.1; JOINED; Genomic_DNA.
DR EMBL; AF347683; AAM89113.1; JOINED; Genomic_DNA.
DR EMBL; AF347684; AAM89113.1; JOINED; Genomic_DNA.
DR EMBL; AF347685; AAM89113.1; JOINED; Genomic_DNA.
DR EMBL; AF347686; AAM89113.1; JOINED; Genomic_DNA.
DR EMBL; AH011751; AAM89117.1; -; Genomic_DNA.
DR EMBL; AF347682; AAM89117.1; JOINED; Genomic_DNA.
DR EMBL; AF347683; AAM89117.1; JOINED; Genomic_DNA.
DR EMBL; AF347684; AAM89117.1; JOINED; Genomic_DNA.
DR EMBL; AF347685; AAM89117.1; JOINED; Genomic_DNA.
DR EMBL; AF347686; AAM89117.1; JOINED; Genomic_DNA.
DR EMBL; AF347687; AAM89117.1; JOINED; Genomic_DNA.
DR EMBL; AK141136; BAE24568.1; -; mRNA.
DR EMBL; AK159698; BAE35298.1; -; mRNA.
DR EMBL; AK162639; BAE37002.1; -; mRNA.
DR EMBL; AK150688; BAE29767.1; -; mRNA.
DR EMBL; AK169297; BAE41053.1; -; mRNA.
DR EMBL; AC114920; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466569; EDL28642.1; -; Genomic_DNA.
DR CCDS; CCDS22322.1; -. [P51791-4]
DR CCDS; CCDS52555.1; -. [P51791-3]
DR PIR; I48295; S55473.
DR RefSeq; NP_031737.1; NM_007711.3.
DR RefSeq; NP_776298.1; NM_173873.1.
DR RefSeq; NP_776299.1; NM_173874.1. [P51791-3]
DR RefSeq; XP_006509323.1; XM_006509260.2. [P51791-5]
DR RefSeq; XP_017168041.1; XM_017312552.1. [P51791-5]
DR AlphaFoldDB; P51791; -.
DR SMR; P51791; -.
DR STRING; 10090.ENSMUSP00000004430; -.
DR GlyGen; P51791; 3 sites.
DR iPTMnet; P51791; -.
DR PhosphoSitePlus; P51791; -.
DR EPD; P51791; -.
DR MaxQB; P51791; -.
DR PaxDb; P51791; -.
DR PeptideAtlas; P51791; -.
DR PRIDE; P51791; -.
DR ProteomicsDB; 283574; -. [P51791-1]
DR ProteomicsDB; 283575; -. [P51791-2]
DR ProteomicsDB; 332668; -.
DR ABCD; P51791; 1 sequenced antibody.
DR Antibodypedia; 28481; 257 antibodies from 22 providers.
DR DNASU; 12725; -.
DR Ensembl; ENSMUST00000004430; ENSMUSP00000004430; ENSMUSG00000004319. [P51791-3]
DR GeneID; 12725; -.
DR KEGG; mmu:12725; -.
DR UCSC; uc009ltl.2; mouse. [P51791-1]
DR UCSC; uc009ltm.2; mouse.
DR CTD; 1182; -.
DR MGI; MGI:103555; Clcn3.
DR VEuPathDB; HostDB:ENSMUSG00000004319; -.
DR eggNOG; KOG0475; Eukaryota.
DR GeneTree; ENSGT00940000153763; -.
DR HOGENOM; CLU_003181_2_1_1; -.
DR InParanoid; P51791; -.
DR OrthoDB; 271925at2759; -.
DR TreeFam; TF313867; -.
DR BioGRID-ORCS; 12725; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Clcn3; mouse.
DR PRO; PR:P51791; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P51791; protein.
DR Bgee; ENSMUSG00000004319; Expressed in rostral migratory stream and 265 other tissues.
DR ExpressionAtlas; P51791; baseline and differential.
DR Genevisible; P51791; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0043679; C:axon terminus; IDA:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0060077; C:inhibitory synapse; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0045335; C:phagocytic vesicle; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0030141; C:secretory granule; ISO:MGI.
DR GO; GO:0042581; C:specific granule; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0008021; C:synaptic vesicle; IDA:MGI.
DR GO; GO:0012506; C:vesicle membrane; ISS:UniProtKB.
DR GO; GO:0015297; F:antiporter activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005254; F:chloride channel activity; ISO:MGI.
DR GO; GO:0005216; F:ion channel activity; ISO:MGI.
DR GO; GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
DR GO; GO:0015299; F:solute:proton antiporter activity; IBA:GO_Central.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; ISS:UniProtKB.
DR GO; GO:0005244; F:voltage-gated ion channel activity; ISO:MGI.
DR GO; GO:0072320; F:volume-sensitive chloride channel activity; IEA:Ensembl.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:MGI.
DR GO; GO:1902476; P:chloride transmembrane transport; ISO:MGI.
DR GO; GO:0006821; P:chloride transport; ISO:MGI.
DR GO; GO:0006811; P:ion transport; ISO:MGI.
DR GO; GO:0045794; P:negative regulation of cell volume; ISO:MGI.
DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:MGI.
DR GO; GO:0006911; P:phagocytosis, engulfment; IMP:MGI.
DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:MGI.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; IMP:MGI.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; IMP:MGI.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IMP:MGI.
DR GO; GO:0097401; P:synaptic vesicle lumen acidification; IDA:SynGO.
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; IPR002245; Cl_channel-3.
DR Pfam; PF00571; CBS; 2.
DR Pfam; PF00654; Voltage_CLC; 1.
DR PRINTS; PR00762; CLCHANNEL.
DR PRINTS; PR01114; CLCHANNEL3.
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 Alternative splicing; Antiport; ATP-binding; CBS domain; Cell membrane;
KW Chloride; Cytoplasmic vesicle; Endosome; Glycoprotein; Ion transport;
KW Lysosome; Membrane; Nucleotide-binding; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..818
FT /note="H(+)/Cl(-) exchange transporter 3"
FT /id="PRO_0000094439"
FT TOPO_DOM 1..125
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 126..163
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 209..232
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 241..248
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 258..276
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 282..301
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 313..325
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 329..337
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 349..367
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 391..416
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 423..443
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 500..520
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 525..544
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 572..586
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 590..601
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 602..605
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 606..624
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 625..818
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT DOMAIN 658..722
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 755..812
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT MOTIF 28..29
FT /note="Di-leucine internalization motif; mediates targeting
FT to late endosome and lysosome membranes"
FT /evidence="ECO:0000305|PubMed:26342074"
FT MOTIF 46..47
FT /note="Di-leucine internalization motif; mediates targeting
FT to late endosome and lysosome membranes"
FT /evidence="ECO:0000305|PubMed:26342074"
FT MOTIF 71..75
FT /note="Di-leucine internalization motif; mediates targeting
FT to late endosome and lysosome membranes"
FT /evidence="ECO:0000305|PubMed:26342074"
FT MOTIF 238..242
FT /note="Selectivity filter part_1"
FT /evidence="ECO:0000250"
FT MOTIF 280..284
FT /note="Selectivity filter part_2"
FT /evidence="ECO:0000250"
FT MOTIF 525..529
FT /note="Selectivity filter part_3"
FT /evidence="ECO:0000250"
FT BINDING 239
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 527
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 630
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 689..691
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 796..799
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT SITE 282
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 339
FT /note="Mediates proton transfer from the protein to the
FT inner aqueous phase"
FT /evidence="ECO:0000250"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 451
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 479
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..58
FT /note="Missing (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:24603049,
FT ECO:0000303|PubMed:26342074, ECO:0000303|PubMed:7665160"
FT /id="VSP_036899"
FT VAR_SEQ 1..53
FT /note="MESEQLFHRGYYRNSYNSITSASSDEELLDGAGAIMDFQTSEDDNLLDGDTA
FT A -> MDASSDPYLPYDGGGDSIPLRELHKR (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:26342074"
FT /id="VSP_060627"
FT VAR_SEQ 799..818
FT /note="DILRHMAQTANQDPASIMFN -> NILEHLEQLKQHVEPLTPPWHYNKKRYP
FT PSYGPDGKPRPRFNNVQLSPVDEDREETEEEVRLLNSTIL (in isoform 3 and
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:24603049,
FT ECO:0000303|PubMed:26342074, ECO:0000303|Ref.3"
FT /id="VSP_060628"
FT CONFLICT 790..791
FT /note="IV -> RL (in Ref. 1; CAA55476, 2; AAB95162, 3;
FT AAM89113, 4; BAE24568/BAE35298/BAE37002 and 6; EDL28642)"
FT /evidence="ECO:0000305"
FT MOTIF P51791-2:13..17
FT /note="Di-leucine internalization motif; mediates targeting
FT to late endosome and lysosome membranes"
FT /evidence="ECO:0000269|PubMed:26342074"
FT MOTIF P51791-4:18..19
FT /note="IP motif; mediates targeting to recycling endosomes"
FT /evidence="ECO:0000269|PubMed:26342074"
FT MUTAGEN P51791-5:224
FT /note="E->A: Abolishes outwardly-rectifying currents."
FT /evidence="ECO:0000269|PubMed:24603049"
SQ SEQUENCE 818 AA; 90812 MW; 8DD21FCAEDAE199E CRC64;
MESEQLFHRG YYRNSYNSIT SASSDEELLD GAGAIMDFQT SEDDNLLDGD TAAGTHYTMT
NGGSINSSTH LLDLLDEPIP GVGTYDDFHT IDWVREKCKD RERHRRINSK KKESAWEMTK
SLYDAWSGWL VVTLTGLASG ALAGLIDIAA DWMTDLKEGI CLSALWYNHE QCCWGSNETT
FEERDKCPQW KTWAELIIGQ AEGPGSYIMN YIMYIFWALS FAFLAVSLVK VFAPYACGSG
IPEIKTILSG FIIRGYLGKW TLMIKTITLV LAVASGLSLG KEGPLVHVAC CCGNIFSYLF
PKYSTNEAKK REVLSAASAA GVSVAFGAPI GGVLFSLEEV SYYFPLKTLW RSFFAALVAA
FVLRSINPFG NSRLVLFYVE YHTPWYLFEL FPFILLGVFG GLWGAFFIRA NIAWCRRRKS
TKFGKYPVLE VIIVAAITAV IAFPNPYTRL NTSELIKELF TDCGPLESSS LCDYRNDMNA
SKIVDDIPDR PAGVGVYSAI WQLCLALIFK IIMTVFTFGI KVPSGLFIPS MAIGAIAGRI
VGIAVEQLAY YHHDWFIFKE WCEVGADCIT PGLYAMVGAA ACLGGVTRMT VSLVVIVFEL
TGGLEYIVPL MAAVMTSKWV GDAFGREGIY EAHIRLNGYP FLDAKEEFTH TTLAADVMRP
RRSDPPLAVL TQDNMTVDDI ENMINETSYN GFPVIMSKES QRLVGFALRR DLTIAIESAR
KKQEGIVGSS RVCFAQHTPS LPAESPRPLK LRSILDMSPF TVTDHTPMEI VVDIFRKLGL
RQCLVTHNGI VLGIITKKDI LRHMAQTANQ DPASIMFN
