CLCN3_RAT
ID CLCN3_RAT Reviewed; 818 AA.
AC P51792; Q9R287;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 2.
DT 03-AUG-2022, entry version 154.
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;
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] (ISOFORM 2), AND FUNCTION (ISOFORM 2).
RC TISSUE=Kidney;
RX PubMed=8155321; DOI=10.1016/0896-6273(94)90215-1;
RA Kawasaki M., Uchida S., Monkawa T., Miyawaki A., Mikoshiba K., Marumo F.,
RA Sasaki S.;
RT "Cloning and expression of a protein kinase C-regulated chloride channel
RT abundantly expressed in rat brain neuronal cells.";
RL Neuron 12:597-604(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORM 2),
RP FUNCTION (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), AND
RP TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=10915634; DOI=10.1152/ajpgi.2000.279.2.g268;
RA Shimada K., Li X., Xu G., Nowak D.E., Showalter L.A., Weinman S.A.;
RT "Expression and canalicular localization of two isoforms of the ClC-3
RT chloride channel from rat hepatocytes.";
RL Am. J. Physiol. 279:G268-G276(2000).
RN [3]
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).
CC -!- FUNCTION: [Isoform 1]: Strongly outwardly rectifying, electrogenic
CC H(+)/Cl(-)exchanger which mediates the exchange of chloride ions
CC against protons (PubMed:10915634). 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:10915634}.
CC -!- FUNCTION: [Isoform 2]: Strongly outwardly rectifying, electrogenic
CC H(+)/Cl(-)exchanger which mediates the exchange of chloride ions
CC against protons (PubMed:10915634). May play an important role in
CC neuronal cell function through regulation of membrane excitability by
CC protein kinase C (PubMed:8155321). It could help neuronal cells to
CC establish short-term memory (PubMed:8155321).
CC {ECO:0000269|PubMed:10915634, ECO:0000269|PubMed:8155321}.
CC -!- SUBUNIT: [Isoform 1]: Monomer and homodimer (By similarity). Forms
CC heterodimers with CLCN4 (By similarity).
CC {ECO:0000250|UniProtKB:P51791}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Lysosome membrane
CC {ECO:0000250|UniProtKB:P51791}; Multi-pass membrane protein
CC {ECO:0000255}. Late endosome membrane {ECO:0000250|UniProtKB:P51791};
CC Multi-pass membrane protein {ECO:0000255}. Cell membrane
CC {ECO:0000269|PubMed:10915634}; Multi-pass membrane protein
CC {ECO:0000255}. Early endosome membrane {ECO:0000250|UniProtKB:P51790};
CC Multi-pass membrane protein {ECO:0000255}. Note=In hepatocytes found in
CC the canalicular membrane. {ECO:0000269|PubMed:10915634}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: 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}. Cell membrane
CC {ECO:0000269|PubMed:10915634}; Multi-pass membrane protein
CC {ECO:0000255}. Note=In hepatocytes found in the canalicular membrane.
CC {ECO:0000269|PubMed:10915634}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=long;
CC IsoId=P51792-1; Sequence=Displayed;
CC Name=2; Synonyms=short;
CC IsoId=P51792-2; Sequence=VSP_036900;
CC -!- TISSUE SPECIFICITY: Abundant in brain, especially in the olfactory
CC bulb, hippocampus, and cerebellum. A moderate expression is seen in the
CC lung, kidney and adrenal gland. {ECO:0000269|PubMed:10915634}.
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; D17521; BAA04471.1; -; mRNA.
DR EMBL; AF142778; AAD29440.1; -; mRNA.
DR RefSeq; NP_445815.2; NM_053363.2. [P51792-1]
DR AlphaFoldDB; P51792; -.
DR SMR; P51792; -.
DR STRING; 10116.ENSRNOP00000045523; -.
DR TCDB; 2.A.49.2.3; the chloride carrier/channel (clc) family.
DR GlyGen; P51792; 3 sites.
DR iPTMnet; P51792; -.
DR PhosphoSitePlus; P51792; -.
DR PaxDb; P51792; -.
DR PRIDE; P51792; -.
DR ABCD; P51792; 1 sequenced antibody.
DR GeneID; 84360; -.
DR KEGG; rno:84360; -.
DR UCSC; RGD:621219; rat. [P51792-1]
DR CTD; 1182; -.
DR RGD; 621219; Clcn3.
DR VEuPathDB; HostDB:ENSRNOG00000010682; -.
DR eggNOG; KOG0475; Eukaryota.
DR HOGENOM; CLU_003181_2_1_1; -.
DR InParanoid; P51792; -.
DR PRO; PR:P51792; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000010682; Expressed in Ammon's horn and 19 other tissues.
DR ExpressionAtlas; P51792; baseline and differential.
DR Genevisible; P51792; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0043679; C:axon terminus; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; ISO:RGD.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0098982; C:GABA-ergic synapse; ISO:RGD.
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; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; ISO:RGD.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; ISO:RGD.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0045335; C:phagocytic vesicle; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; ISS:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; ISO:RGD.
DR GO; GO:0030141; C:secretory granule; ISO:RGD.
DR GO; GO:0042581; C:specific granule; ISO:RGD.
DR GO; GO:0045202; C:synapse; IDA:GO_Central.
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; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005254; F:chloride channel activity; IDA:RGD.
DR GO; GO:0005216; F:ion channel activity; IDA:RGD.
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; IDA:UniProtKB.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IDA:RGD.
DR GO; GO:0072320; F:volume-sensitive chloride channel activity; ISO:RGD.
DR GO; GO:0008344; P:adult locomotory behavior; ISO:RGD.
DR GO; GO:1902476; P:chloride transmembrane transport; ISO:RGD.
DR GO; GO:0006821; P:chloride transport; IDA:RGD.
DR GO; GO:0006811; P:ion transport; IDA:RGD.
DR GO; GO:0045794; P:negative regulation of cell volume; ISO:RGD.
DR GO; GO:0070050; P:neuron cellular homeostasis; ISO:RGD.
DR GO; GO:0006911; P:phagocytosis, engulfment; ISO:RGD.
DR GO; GO:0045494; P:photoreceptor cell maintenance; ISO:RGD.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISO:RGD.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; ISO:RGD.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; ISO:RGD.
DR GO; GO:0097401; P:synaptic vesicle lumen acidification; 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; 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 2: Evidence at transcript level;
KW Alternative splicing; Antiport; ATP-binding; CBS domain; Cell membrane;
KW Chloride; Endosome; Glycoprotein; Ion transport; Lysosome; Membrane;
KW Nucleotide-binding; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..818
FT /note="H(+)/Cl(-) exchange transporter 3"
FT /id="PRO_0000094442"
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:0000250|UniProtKB:P51791"
FT MOTIF 46..47
FT /note="Di-leucine internalization motif; mediates targeting
FT to late endosome and lysosome membranes"
FT /evidence="ECO:0000250|UniProtKB:P51791"
FT MOTIF 71..75
FT /note="Di-leucine internalization motif; mediates targeting
FT to late endosome and lysosome membranes"
FT /evidence="ECO:0000250|UniProtKB:P51791"
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)"
FT /evidence="ECO:0000303|PubMed:8155321"
FT /id="VSP_036900"
FT CONFLICT 774
FT /note="I -> V (in Ref. 1; BAA04471)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 818 AA; 90855 MW; 0651B441484AAC6F 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
KKQEGVVGSS RVCFAQHTPS LPAESPRPLK LRSILDMSPF TVTDHTPMEI VVDIFRKLGL
RQCLVTHNGR LLGIITKKDI LRHMAQTANQ DPASIMFN