CLCN4_MOUSE
ID CLCN4_MOUSE Reviewed; 747 AA.
AC Q61418; Q2TAX6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=H(+)/Cl(-) exchange transporter 4;
DE AltName: Full=Chloride channel protein 4;
DE Short=ClC-4;
DE AltName: Full=Chloride transporter ClC-4;
GN Name=Clcn4; Synonyms=Clc4, Clcn4-2;
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].
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=7670496; DOI=10.1038/ng0895-466;
RA Rugarli E.I., Adler D.A., Borsani G., Tsuchiya K., Franco B., Hauge X.,
RA Disteche C., Chapman V., Ballabio A.;
RT "Different chromosomal localization of the Clcn4 gene in Mus spretus and
RT C57BL/6J mice.";
RL Nat. Genet. 10:466-471(1995).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium;
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=17023393; DOI=10.1096/fj.05-5588fje;
RA Okkenhaug H., Weylandt K.H., Carmena D., Wells D.J., Higgins C.F.,
RA Sardini A.;
RT "The human ClC-4 protein, a member of the CLC chloride channel/transporter
RT family, is localized to the endoplasmic reticulum by its N-terminus.";
RL FASEB J. 20:2390-2392(2006).
CC -!- FUNCTION: Strongly outwardly rectifying, electrogenic
CC H(+)/Cl(-)exchanger which mediates the exchange of chloride ions
CC against protons (By similarity). 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).
CC {ECO:0000250|UniProtKB:P51793}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane
CC {ECO:0000250|UniProtKB:P51794}; Multi-pass membrane protein
CC {ECO:0000255}. Late endosome membrane {ECO:0000250|UniProtKB:P51794};
CC Multi-pass membrane protein {ECO:0000255}. Endoplasmic reticulum
CC membrane {ECO:0000250|UniProtKB:P51793}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:P51793}; Multi-
CC pass membrane protein {ECO:0000255}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:P51793}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localizes to late endosome membrane, lysosome
CC membrane and recycling endosome membrane in the presence of CLCN3.
CC {ECO:0000250|UniProtKB:P51793}.
CC -!- TISSUE SPECIFICITY: Predominantly present in excitable tissues such as
CC nervous system and skeletal muscle. Not detected in heart.
CC {ECO:0000269|PubMed:17023393}.
CC -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClC-
CC 4/CLCN4 subfamily. {ECO:0000305}.
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DR EMBL; Z49916; CAA90150.1; -; mRNA.
DR EMBL; BC110668; AAI10669.1; -; mRNA.
DR EMBL; CH466983; EDL01090.1; -; Genomic_DNA.
DR CCDS; CCDS20786.1; -.
DR PIR; I48294; I48294.
DR RefSeq; NP_035464.3; NM_011334.4.
DR RefSeq; XP_006539564.1; XM_006539501.3.
DR RefSeq; XP_006539565.1; XM_006539502.3.
DR RefSeq; XP_011248728.1; XM_011250426.2.
DR AlphaFoldDB; Q61418; -.
DR SMR; Q61418; -.
DR BioGRID; 198737; 2.
DR STRING; 10090.ENSMUSP00000000619; -.
DR iPTMnet; Q61418; -.
DR PhosphoSitePlus; Q61418; -.
DR MaxQB; Q61418; -.
DR PaxDb; Q61418; -.
DR PRIDE; Q61418; -.
DR ProteomicsDB; 283376; -.
DR ABCD; Q61418; 1 sequenced antibody.
DR Antibodypedia; 23690; 180 antibodies from 30 providers.
DR DNASU; 12727; -.
DR Ensembl; ENSMUST00000000619; ENSMUSP00000000619; ENSMUSG00000000605.
DR GeneID; 12727; -.
DR KEGG; mmu:12727; -.
DR UCSC; uc009fcq.2; mouse.
DR CTD; 1183; -.
DR MGI; MGI:104571; Clcn4.
DR VEuPathDB; HostDB:ENSMUSG00000000605; -.
DR eggNOG; KOG0475; Eukaryota.
DR GeneTree; ENSGT00940000158265; -.
DR HOGENOM; CLU_003181_2_1_1; -.
DR InParanoid; Q61418; -.
DR OMA; KYAGLVH; -.
DR OrthoDB; 271925at2759; -.
DR PhylomeDB; Q61418; -.
DR TreeFam; TF313867; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 12727; 5 hits in 40 CRISPR screens.
DR ChiTaRS; Clcn4; mouse.
DR PRO; PR:Q61418; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q61418; protein.
DR Bgee; ENSMUSG00000000605; Expressed in barrel cortex and 258 other tissues.
DR ExpressionAtlas; Q61418; baseline and differential.
DR Genevisible; Q61418; MM.
DR GO; GO:0097546; C:ciliary base; IDA:MGI.
DR GO; GO:0005769; C:early endosome; IBA:GO_Central.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; ISS:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central.
DR GO; GO:0015297; F:antiporter activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0015299; F:solute:proton antiporter activity; IBA:GO_Central.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; IBA:GO_Central.
DR GO; GO:0006821; P:chloride transport; ISS:UniProtKB.
DR GO; GO:1905515; P:non-motile cilium assembly; IMP:MGI.
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; IPR002246; Cl_channel-4.
DR PANTHER; PTHR45711:SF2; PTHR45711:SF2; 1.
DR Pfam; PF00571; CBS; 2.
DR Pfam; PF00654; Voltage_CLC; 1.
DR PRINTS; PR00762; CLCHANNEL.
DR PRINTS; PR01115; CLCHANNEL4.
DR SMART; SM00116; CBS; 2.
DR SUPFAM; SSF54631; SSF54631; 1.
DR SUPFAM; SSF81340; SSF81340; 1.
DR PROSITE; PS51371; CBS; 2.
PE 2: Evidence at transcript level;
KW Antiport; ATP-binding; CBS domain; Chloride; Endoplasmic reticulum;
KW Endosome; Ion transport; Lysosome; Membrane; Nucleotide-binding;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..747
FT /note="H(+)/Cl(-) exchange transporter 4"
FT /id="PRO_0000094444"
FT TOPO_DOM 1..54
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 55..92
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 138..161
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 170..177
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 187..205
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 211..230
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 242..254
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 258..266
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 278..296
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 320..345
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 352..372
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 429..449
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 454..473
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 501..515
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 519..530
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT INTRAMEM 531..534
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 535..553
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 554..747
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT DOMAIN 587..653
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 680..742
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 1..50
FT /note="Required for localization in the endoplasmic
FT reticulum"
FT /evidence="ECO:0000250|UniProtKB:P51793"
FT REGION 654..683
FT /note="Required for localization in the endoplasmic
FT reticulum"
FT /evidence="ECO:0000250|UniProtKB:P51793"
FT MOTIF 167..171
FT /note="Selectivity filter part_1"
FT /evidence="ECO:0000250"
FT MOTIF 209..213
FT /note="Selectivity filter part_2"
FT /evidence="ECO:0000250"
FT MOTIF 454..458
FT /note="Selectivity filter part_3"
FT /evidence="ECO:0000250"
FT BINDING 168
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 456
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 559
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 597
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 618..620
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 725..728
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT SITE 211
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 268
FT /note="Mediates proton transfer from the protein to the
FT inner aqueous phase"
FT /evidence="ECO:0000250"
FT CONFLICT 284
FT /note="A -> R (in Ref. 1; CAA90150)"
FT /evidence="ECO:0000305"
FT CONFLICT 437
FT /note="I -> Y (in Ref. 1; CAA90150)"
FT /evidence="ECO:0000305"
FT CONFLICT 592
FT /note="G -> E (in Ref. 1; CAA90150)"
FT /evidence="ECO:0000305"
FT CONFLICT 684
FT /note="L -> F (in Ref. 1; CAA90150)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 747 AA; 83733 MW; F88340263F140E30 CRC64;
MDFLEEPFPD VGTYEDFHTI DWLREKSRDT DRHRKITSKS KESIWEFIKS LLDAWSGWVV
MLLIGLLAGT LAGVIDLAVD WMTDLKEGVC LSAFWYSHEQ CCWTSNETTF EDRDKCPLWQ
KWSELLLSQS EGASAYILNY LMYILWALLF AFLAVSLVRV FAPYACGSGI PEIKTILSGF
IIRGYLGKWT LLIKTVTLVL VVSSGLSLGK EGPLVHVACC CGNFFSSLFS KYSKNEGKRR
EVLSAAAAAG VSVAFGAPIG GVLFSLEEVS YYFPLKTLWR SFFAALVAAF TLRSINPFGN
SRLVLFYVEY HTPWYMAELF PFILLGVFGG LWGTLFTRCN IAWCRRRKTT RLGRYPVLEV
IAVTAVTAIV AYPNPYTRQS TSELISELFN DCGALESSQL CDYINDPNMT RPVDDIPDRP
AGVGVYTAMW QLALALIFKI VITIFTFGMK IPSGLFIPSM AVGAMAGRMV GIGVEQLAYH
HHDWIIFRNW CRPGADCVTP GLYAMVGAAA CLGGVTRMTV SLVVIMFELT GGLEYIVPLM
AAAVTSKWVA DAFGKEGIYE AHIHLNGYPF LDVKDEFTHR TLATDVMRPR RGEPPLSVLT
QDSMTVEDVE TLIKETDYNG FPVLVSRDSE RLIGFAQRRE LILAIKNARQ RQEGIVSNSI
MYFTEEPPEL PANSPHPLKL RRILNLSPFT VTDHTPMETV VDIFRKLGLR QCLVTRSGRL
LGIITKKDVL RHMAQMANQD PESIMFN
