CLCN4_RAT
ID CLCN4_RAT Reviewed; 747 AA.
AC P51794;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 127.
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=Clcn4-2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=7730971; DOI=10.1113/jphysiol.1995.sp020560;
RA Jentsch T.J., Guenther W., Pusch M., Schwappach B.;
RT "Properties of voltage-gated chloride channels of the ClC gene family.";
RL J. Physiol. (Lond.) 482:19-25(1995).
RN [2]
RP SUBCELLULAR LOCATION.
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).
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:0000269|PubMed:16222710}; Multi-pass membrane protein
CC {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:16222710};
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: Strongly expressed in liver and brain, but also in
CC heart, muscle, kidney and spleen. {ECO:0000269|PubMed:7730971}.
CC -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClC-
CC 4/CLCN4 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; Z36944; CAA85406.1; -; mRNA.
DR PIR; S47327; S47327.
DR AlphaFoldDB; P51794; -.
DR SMR; P51794; -.
DR STRING; 10116.ENSRNOP00000056037; -.
DR PaxDb; P51794; -.
DR PeptideAtlas; P51794; -.
DR PRIDE; P51794; -.
DR RGD; 708381; Clcn4.
DR eggNOG; KOG0475; Eukaryota.
DR InParanoid; P51794; -.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR PRO; PR:P51794; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0097546; C:ciliary base; ISO:RGD.
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:0005254; F:chloride channel activity; ISO:RGD.
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; ISO:RGD.
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_0000094445"
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 684..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"
SQ SEQUENCE 747 AA; 83701 MW; E86B5732248BA0C3 CRC64;
MDFLDEPFPD 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 LWGTVFTRCN IAWCRRRKTT RLGKYPVLEV
IVVTAITAII 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 FPVVVSRDSE RLIGFAQRRE LILAIKNARQ RQEGIVSNSI
MYFTEEPPEL PANSPHPLKL RRILNLSPFT VTDHTPMETV VDIFRKLGLR QCLVTRSGRL
LGIITKKDVL RHMAQMANQD PESIIFN
