CLCN5_PIG
ID CLCN5_PIG Reviewed; 816 AA.
AC Q9GKE7; A0A287BE85;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 2.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=H(+)/Cl(-) exchange transporter 5;
DE AltName: Full=Chloride channel protein 5;
DE Short=ClC-5;
DE AltName: Full=Chloride transporter ClC-5;
GN Name=CLCN5;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10978325; DOI=10.1074/jbc.m004840200;
RA Dowland L.K., Luyckx V.A., Enck A.H., Leclercq B., Yu A.S.L.;
RT "Molecular cloning and characterization of an intracellular chloride
RT channel in the proximal tubule cell line, LLC-PK1.";
RL J. Biol. Chem. 275:37765-37773(2000).
RN [2] {ECO:0000312|EMBL:HCZ85788.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=30723633; DOI=10.7717/peerj.6374;
RA Gilbert D.G.;
RT "Genes of the pig, Sus scrofa, reconstructed with EvidentialGene.";
RL PeerJ 7:E6374-E6374(2019).
RN [3] {ECO:0000312|Proteomes:UP000008227}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Proton-coupled chloride transporter. Functions as antiport
CC system and exchanges chloride ions against protons (PubMed:10978325).
CC Important for normal acidification of the endosome lumen. May play an
CC important role in renal tubular function (By similarity). The CLC
CC channel family contains both chloride channels and proton-coupled anion
CC transporters that exchange chloride or another anion for protons. The
CC absence of conserved gating glutamate residues is typical for family
CC members that function as channels (Probable).
CC {ECO:0000250|UniProtKB:P51795, ECO:0000269|PubMed:10978325,
CC ECO:0000305}.
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:P51795};
CC -!- SUBUNIT: Interacts with NEDD4 and NEDD4L.
CC {ECO:0000250|UniProtKB:P51795}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:10978325}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:10978325}. Endosome membrane
CC {ECO:0000269|PubMed:10978325}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:10978325}. Cell membrane
CC {ECO:0000250|UniProtKB:P51795}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P51795}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9GKE7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9GKE7-2; Sequence=VSP_060656;
CC -!- PTM: Ubiquitinated by NEDD4L in the presence of albumin; which promotes
CC endocytosis and proteasomal degradation.
CC {ECO:0000250|UniProtKB:P51795}.
CC -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClC-
CC 5/CLCN5 subfamily. {ECO:0000305}.
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DR EMBL; AF274055; AAG29104.1; -; mRNA.
DR EMBL; AEMK02000113; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DQIR01030313; HCZ85788.1; -; Transcribed_RNA.
DR RefSeq; NP_999304.1; NM_214139.1. [Q9GKE7-2]
DR AlphaFoldDB; Q9GKE7; -.
DR SMR; Q9GKE7; -.
DR STRING; 9823.ENSSSCP00000027416; -.
DR TCDB; 2.A.49.2.2; the chloride carrier/channel (clc) family.
DR PaxDb; Q9GKE7; -.
DR PRIDE; Q9GKE7; -.
DR Ensembl; ENSSSCT00000064514; ENSSSCP00000042280; ENSSSCG00000023026. [Q9GKE7-1]
DR Ensembl; ENSSSCT00025100441; ENSSSCP00025044337; ENSSSCG00025072959. [Q9GKE7-1]
DR Ensembl; ENSSSCT00030005600; ENSSSCP00030002301; ENSSSCG00030004195. [Q9GKE7-1]
DR Ensembl; ENSSSCT00035075084; ENSSSCP00035030521; ENSSSCG00035056248. [Q9GKE7-1]
DR Ensembl; ENSSSCT00045055218; ENSSSCP00045038497; ENSSSCG00045032335. [Q9GKE7-1]
DR Ensembl; ENSSSCT00050109186; ENSSSCP00050048637; ENSSSCG00050079073. [Q9GKE7-1]
DR Ensembl; ENSSSCT00055004384; ENSSSCP00055003367; ENSSSCG00055002299. [Q9GKE7-1]
DR Ensembl; ENSSSCT00060036495; ENSSSCP00060015534; ENSSSCG00060026931. [Q9GKE7-1]
DR Ensembl; ENSSSCT00070050001; ENSSSCP00070042232; ENSSSCG00070025014. [Q9GKE7-1]
DR Ensembl; ENSSSCT00070050003; ENSSSCP00070042234; ENSSSCG00070025014. [Q9GKE7-1]
DR GeneID; 397263; -.
DR KEGG; ssc:397263; -.
DR CTD; 1184; -.
DR eggNOG; KOG0475; Eukaryota.
DR GeneTree; ENSGT00940000153763; -.
DR HOGENOM; CLU_003181_2_1_1; -.
DR InParanoid; Q9GKE7; -.
DR OrthoDB; 271925at2759; -.
DR TreeFam; TF313867; -.
DR Reactome; R-SSC-2672351; Stimuli-sensing channels.
DR Proteomes; UP000008227; Chromosome X.
DR Proteomes; UP000314985; Unassembled WGS sequence.
DR Bgee; ENSSSCG00000023026; Expressed in metanephros cortex and 40 other tissues.
DR ExpressionAtlas; Q9GKE7; baseline and differential.
DR Genevisible; Q9GKE7; SS.
DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; IBA:GO_Central.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
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:0006897; P:endocytosis; IEA:Ensembl.
DR GO; GO:0003014; P:renal system process; IEA:Ensembl.
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; IPR002247; Cl_channel-5.
DR Pfam; PF00571; CBS; 2.
DR Pfam; PF00654; Voltage_CLC; 1.
DR PRINTS; PR00762; CLCHANNEL.
DR PRINTS; PR01116; CLCHANNEL5.
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; Golgi apparatus; Ion transport; Membrane;
KW Nucleotide-binding; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..816
FT /note="H(+)/Cl(-) exchange transporter 5"
FT /id="PRO_0000305928"
FT TOPO_DOM 1..124
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 125..162
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 208..231
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 240..247
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 256..275
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 281..300
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 312..324
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 328..336
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 348..366
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 389..414
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 422..442
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 498..518
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 523..542
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 570..584
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 585..587
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250"
FT INTRAMEM 588..599
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 600..604
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250"
FT TRANSMEM 605..622
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 623..816
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 656..720
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 752..812
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 237..241
FT /note="Selectivity filter part_1"
FT /evidence="ECO:0000250"
FT MOTIF 279..283
FT /note="Selectivity filter part_2"
FT /evidence="ECO:0000250"
FT MOTIF 523..527
FT /note="Selectivity filter part_3"
FT /evidence="ECO:0000250"
FT COMPBIAS 10..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 238
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 525
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 628
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 666
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P51795"
FT BINDING 687..689
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P51795"
FT BINDING 794..797
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P51795"
FT SITE 281
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 338
FT /note="Mediates proton transfer from the protein to the
FT inner aqueous phase"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..70
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_060656"
SQ SEQUENCE 816 AA; 90802 MW; 8B73E2E018DDEE5F CRC64;
MAMWQGAMDN RGFQQGSFNS FQSSSSDEDL MDIPGTAMDF SMRDDVPPLD GEIEEDKSYN
GGGLGSSYRM MDFLEEPIPG VGTYDDFNTI DWVREKSRDR DRHREITNKS KESTWALIHS
VSDAFSGWLL MLLIGLLSGS LAGLIDISAH WMTDLKEGIC TEGLWFNHEH CCWNSKHVTF
KDRDKCPEWN SWSQLIISAD EGAFAYIVNY FMYVLWALLF AFLAVSLVKV FAPYACGSGI
PEIKTILSGF IIRGYLGKWT LIIKTITLVL AVSSGLSLGK EGPLVHVACC CGNILCHCFN
KYRKNEAKRR EVLSAAAAAG VSVAFGAPIG GVLFSLEEVS YYFPLKTLWR SFFAALVAAF
TLRSINPFGN SRLVLFYVEF HTPWHLFELV PFILLGIFGG LWGALFIRTN IAWCRKRKTT
QLGKYPVIEV LVVTAITAIL AFPNEYTRMS TSELISELFN DCGLLDSSKL CDYENRFNTS
KAAELPDRPA GAGVYSAMWQ LALTLILKIV ITIFTFGMKI PSGLFIPSMA VGAIAGRLLG
VGMEQLAYYH HDWAIFNSWC SQGADCITPG LYAMVGAAAC LGGVTRMTVS LVVIMFELTG
GLEYIVPLMA AAMTSKWVAD ALGREGIYDA HIRLNGYPFL EAKEEFAHKT LAMDVMKPRR
NDPSLTVLTQ DSMTVEDVET IISETTYSGF PVVVSRESQR LVGFVLRRDL IISIENARKK
QDGVVSTSII YFTEHSPPMP PYTPPTLKLR NILDLSPFTV TDLTPMEIVV DIFRKLGLRQ
CLVTHNGRLL GIITKKDVLK HIAQMANQDP DSILFN
