CLCN5_RAT
ID CLCN5_RAT Reviewed; 816 AA.
AC P51796; A0A0G2K839; P70642;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 2.
DT 03-AUG-2022, entry version 153.
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 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).
RC TISSUE=Brain;
RX PubMed=8537381; DOI=10.1074/jbc.270.52.31172;
RA Steinmeyer K., Schwappach B., Bens M., Vandewalle A., Jentsch T.J.;
RT "Cloning and functional expression of rat CLC-5, a chloride channel related
RT to kidney disease.";
RL J. Biol. Chem. 270:31172-31177(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
RX PubMed=8626585; DOI=10.1074/jbc.271.17.10210;
RA Sakamoto H., Kawasaki M., Uchida S., Sasaki S., Marumo F.;
RT "Identification of a new outwardly rectifying Cl- channel that belongs to a
RT subfamily of the ClC Cl- channels.";
RL J. Biol. Chem. 271:10210-10216(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [4]
RP FUNCTION.
RX PubMed=19261613; DOI=10.1074/jbc.m901170200;
RA Bergsdorf E.-Y., Zdebik A.A., Jentsch T.J.;
RT "Residues important for nitrate/proton coupling in plant and mammalian CLC
RT transporters.";
RL J. Biol. Chem. 284:11184-11193(2009).
CC -!- FUNCTION: Proton-coupled chloride transporter. Functions as antiport
CC system and exchanges chloride ions against protons. Important for
CC normal acidification of the endosome lumen. May play an important role
CC in renal tubular function (By similarity). The CLC channel family
CC contains both chloride channels and proton-coupled anion transporters
CC that exchange chloride or another anion for protons. The absence of
CC conserved gating glutamate residues is typical for family members that
CC function as channels (Probable). {ECO:0000250|UniProtKB:P51795,
CC ECO:0000269|PubMed:19261613, 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P51796-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P51796-2; Sequence=VSP_060659;
CC -!- TISSUE SPECIFICITY: Kidney specific.
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; Z56277; CAA91216.1; -; mRNA.
DR EMBL; D50497; BAA09091.1; -; mRNA.
DR EMBL; AABR07037207; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07037208; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_058802.1; NM_017106.1. [P51796-2]
DR AlphaFoldDB; P51796; -.
DR SMR; P51796; -.
DR STRING; 10116.ENSRNOP00000003895; -.
DR PhosphoSitePlus; P51796; -.
DR PaxDb; P51796; -.
DR ABCD; P51796; 2 sequenced antibodies.
DR Ensembl; ENSRNOT00000003895; ENSRNOP00000003895; ENSRNOG00000002862. [P51796-2]
DR Ensembl; ENSRNOT00000079054; ENSRNOP00000074459; ENSRNOG00000002862. [P51796-1]
DR GeneID; 25749; -.
DR KEGG; rno:25749; -.
DR UCSC; RGD:2362; rat. [P51796-1]
DR CTD; 1184; -.
DR RGD; 2362; Clcn5.
DR eggNOG; KOG0475; Eukaryota.
DR GeneTree; ENSGT00940000153763; -.
DR HOGENOM; CLU_003181_2_1_1; -.
DR InParanoid; P51796; -.
DR OMA; CLDWTPW; -.
DR OrthoDB; 271925at2759; -.
DR PhylomeDB; P51796; -.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR PRO; PR:P51796; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000002862; Expressed in adult mammalian kidney and 19 other tissues.
DR ExpressionAtlas; P51796; baseline and differential.
DR Genevisible; P51796; RN.
DR GO; GO:0045177; C:apical part of cell; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; IBA:GO_Central.
DR GO; GO:0005768; C:endosome; IDA:RGD.
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:0016020; C:membrane; IDA:UniProtKB.
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; ISO:RGD.
DR GO; GO:0015299; F:solute:proton antiporter activity; IBA:GO_Central.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; IDA:RGD.
DR GO; GO:0006821; P:chloride transport; IDA:RGD.
DR GO; GO:0006897; P:endocytosis; ISO:RGD.
DR GO; GO:0003014; P:renal system process; 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; 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_0000094448"
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..811
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
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 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_060659"
FT CONFLICT 385
FT /note="H -> Y (in Ref. 2; BAA09091)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 816 AA; 90687 MW; 68AE3812E820141D CRC64;
MAMWQGAMDN RGFHQGSFSS FQSSSSDEDL MDIPGTAMDF SMRDDVPPLD REIEGNKSYN
GGGIGSSNRI MDFLEEPIPG VGTYDDFNTI DWVREKSRDR DRHREITNKS KESTWALIHS
VSDAFSGWLL MLLIGLLSGS LAGLIDISAH WMTDLKEGIC TGGFWFNHEH CCWNSEHVTF
EDRDKCPEWN SWSQLIISTD QGAFAYIVNY FMYVLWALLF AFLAVSLVKA FAPYACGSGI
PEIKTILSGF IIRGYLGKWT LVIKTITLVL AVSSGLSLGK EGPLVHVACC CGNILCHCFN
KYRKNEAKRR EVLSAAAAAG VSVAFGAPIG GVLFSLEEVS YYFPLKTLWR SFFAALVAAF
TLRSINPFGN SRLVLFYVEF HTPWHLFELV PFIVLGIFGG LWGALFIRTN IAWCRKRKTT
QLGKYPVVEV LIVTAITAIL AFPNEYTRMS TSELISELFN DCGLLDSSKL CDYENHFNTS
KGGELPDRPA GVGVYSAMWQ LALTLILKIV ITIFTFGMKI PSGLFIPSMA VGAIAGRLLG
VGMEQLAYYH HDWGIFNSWC SQGADCITPG LYAMVGAAAC LGGVTRMTVS LVVIMFELTG
GLEYIVPLMA AAMTSKWVAD ALGREGIYDA HIRLNGYPFL EAKEEFAHKT LAMDVMKPRR
NDPLLTVLTQ DSMTVEDVET IISETTYSGF PVVVSRESQR LVGFVLRRDL IISIENARKK
QDGVVSTSII YFTEHSPPMP PYTPPTLKLR NILDLSPFTV TDLTPMEIVV DIFRKLGLRQ
CLVTHNGRLL GIITKKDVLK HIAQMANQDP ESILFN
