CLCN5_CAVPO
ID CLCN5_CAVPO Reviewed; 746 AA.
AC Q99P66;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 92.
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 Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11406114; DOI=10.1016/s0005-2736(01)00331-5;
RA Cornejo I., Niemeyer M.I., Sepulveda F.V., Cid L.P.;
RT "Cloning, cellular distribution and functional expression of small
RT intestinal epithelium guinea pig ClC-5 chloride channel.";
RL Biochim. Biophys. Acta 1512:367-374(2001).
CC -!- FUNCTION: Proton-coupled chloride transporter. Functions as antiport
CC system and exchanges chloride ions against protons (PubMed:11406114).
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:11406114,
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:0000250|UniProtKB:P51795}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P51795}. Endosome membrane
CC {ECO:0000250|UniProtKB:P51795}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P51795}. Cell membrane
CC {ECO:0000250|UniProtKB:P51795}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P51795}.
CC -!- TISSUE SPECIFICITY: Detected in duodenum, jejunum and ileum. Detected
CC in crypt and villus regions of the epithelium of the small intestine.
CC {ECO:0000269|PubMed:11406114}.
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}.
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; AF326968; AAG49590.1; -; mRNA.
DR RefSeq; NP_001166402.1; NM_001172931.1.
DR AlphaFoldDB; Q99P66; -.
DR SMR; Q99P66; -.
DR STRING; 10141.ENSCPOP00000019422; -.
DR GeneID; 100135502; -.
DR KEGG; cpoc:100135502; -.
DR CTD; 1184; -.
DR eggNOG; KOG0475; Eukaryota.
DR InParanoid; Q99P66; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0015297; F:antiporter activity; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; IEA:InterPro.
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 Antiport; ATP-binding; CBS domain; Cell membrane; Chloride; Endosome;
KW Golgi apparatus; Ion transport; Membrane; Nucleotide-binding;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation.
FT CHAIN 1..746
FT /note="H(+)/Cl(-) exchange transporter 5"
FT /id="PRO_0000305927"
FT TOPO_DOM 1..54
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 55..92
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 138..161
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 170..177
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 186..205
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 211..230
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 242..254
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 258..266
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 278..296
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 319..344
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 352..372
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 428..448
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 453..472
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 500..514
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 515..517
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250"
FT INTRAMEM 518..529
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 530..534
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250"
FT TRANSMEM 535..552
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 553..746
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 586..650
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 682..742
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
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 453..457
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 455
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 558
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250"
FT BINDING 596
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P51795"
FT BINDING 617..619
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P51795"
FT BINDING 724..727
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P51795"
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 746 AA; 83094 MW; 92FC8AFDC7D8D4A5 CRC64;
MDFLEEPIPG VGTYDDFNTI DWVREKSRDR DRHREITNRS KESTWALIHS VSDAFSGWLL
MLLIGLLSGS LAGLIDISAH WMTDLKEGIC TEGFWFNHEH CCWNSQQVTF EDRDKCPEWN
SWSQLIINMD EGAFAYIVNY FMYVLWALLF AFLAVSLVKV FAPYACGSGI PEIKTILSGF
IIRGYLGKWT LIIKTITLVL AVSSGLSLGK EGPLVHVACC CGNILCHCFN KYRENEAKRR
EVLSAAAAAG VSVAFGAPIG GVLFSLEEVS YYFPLKTLWR SFFAALVAAF TLRSINPFGN
SRLVLFYVEF HTPWHLFELV PFILLGIFGG LWGALFIRTN IAWCRKRKTT QLGKYPVIEV
LIVTAITAIL AFPNEYTRMS TSELISELFN DCGLLDSSKL CDYKNLSNTS KSGELPDRPA
GAGVSSAMWQ LALTLILKIV ITIFTFGMKI PSGLFIPSMA VGAIAGRLLG VGMEQLAYHH
RDWTIFNSWC SQGADCITPG LYAMVGAAAC LGGVTRMTVS LVVIMFELTG GLEYIVPLMA
AAMTSKWVAD ALGREGIYDA HIRLNGYPFL EAKEEFAHKT LAMDVMKPRR NDPLLTVLTQ
DSMTVEDVET IISETTYSGF PVVVSRESQR LVGFVLRRDL IISIENARKE QDGVVSTSII
YFTEHSPPVP PYTAPTLKLR NILDLSPFTV TDLTPMEIVV DIFRKLGLRQ CLVTHNGRLL
GIITKKDVLK HIAQMANQDP DSILFN
