CLCKA_RAT
ID CLCKA_RAT Reviewed; 687 AA.
AC Q06393; P97709;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Chloride channel protein ClC-Ka;
DE Short=Chloride channel Ka;
DE AltName: Full=ClC-K1;
GN Name=Clcnka; Synonyms=Clcnk1;
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].
RC TISSUE=Kidney;
RX PubMed=7680033; DOI=10.1016/s0021-9258(18)53545-6;
RA Uchida S., Sasaki S., Furukawa T., Hiraoka M., Imai T., Hirata Y.,
RA Marumo F.;
RT "Molecular cloning of a chloride channel that is regulated by dehydration
RT and expressed predominantly in kidney medulla.";
RL J. Biol. Chem. 268:3821-3824(1993).
RN [2]
RP SEQUENCE REVISION.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=8034678; DOI=10.1016/s0021-9258(17)32293-7;
RA Uchida S., Sasaki S., Furukawa T., Hiraoka M., Imai T., Hirata Y.,
RA Marumo F.;
RT "Molecular cloning of a chloride channel that is regulated by dehydration
RT and expressed predominantly in kidney medulla.";
RL J. Biol. Chem. 269:19192-19192(1994).
RN [3]
RP SEQUENCE REVISION.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RA Uchida S.;
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=8041726; DOI=10.1073/pnas.91.15.6943;
RA Kieferle S., Fong P., Bens M., Vandewalle A., Jentsch T.;
RT "Two highly homologous members of the ClC chloride channel family in both
RT rat and human kidney.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:6943-6947(1994).
RN [5]
RP INTERACTION WITH BSND.
RX PubMed=12111250; DOI=10.1007/s00424-002-0819-8;
RA Waldegger S., Jeck N., Barth P., Peters M., Vitzthum H., Wolf K., Kurtz A.,
RA Konrad M., Seyberth H.W.;
RT "Barttin increases surface expression and changes current properties of
RT ClC-K channels.";
RL Pflugers Arch. 444:411-418(2002).
RN [6]
RP DOWN-REGULATION BY FUROSEMIDE.
RX PubMed=12759757; DOI=10.1007/s00424-003-1098-8;
RA Wolf K., Meier-Meitinger M., Bergler T., Castrop H., Vitzthum H.,
RA Riegger G.A.J., Kurtz A., Kraemer B.K.;
RT "Parallel down-regulation of chloride channel CLC-K1 and barttin mRNA in
RT the thin ascending limb of the rat nephron by furosemide.";
RL Pflugers Arch. 446:665-671(2003).
CC -!- FUNCTION: Voltage-gated chloride channel. Chloride channels have
CC several functions including the regulation of cell volume; membrane
CC potential stabilization, signal transduction and transepithelial
CC transport. May be important in urinary concentrating mechanisms.
CC -!- SUBUNIT: Homodimer. Interacts with BSND. Forms heteromers with BSND in
CC the thin ascending limb of Henle (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in the kidney. Expressed
CC strongly in the cortical thick ascending limb and the distal convoluted
CC tubule, with minor expression in the S3 segment of the proximal tubule
CC and the cortical collecting tubule.
CC -!- INDUCTION: Regulated in parallel with BSND under furosemide treatment.
CC Decreased to half in the inner medulla under furosemide treatment. In
CC the renal cortex and outer medulla levels were weak and did not change.
CC Regulation with BSND in inner medulla is limited to the thin limb;
CC levels in collecting ducts were not affected by furosemide treatment.
CC During furosemide treatment selective down-regulation with BSND in thin
CC limb plays a role in maintaining salt and water homeostasis.
CC -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. CLCNKA
CC 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; D13927; BAA03026.1; -; mRNA.
DR EMBL; Z34291; CAA84064.1; -; mRNA.
DR PIR; A45483; A45483.
DR PIR; A57713; A57713.
DR RefSeq; NP_445779.1; NM_053327.1.
DR AlphaFoldDB; Q06393; -.
DR SMR; Q06393; -.
DR STRING; 10116.ENSRNOP00000013103; -.
DR TCDB; 2.A.49.2.4; the chloride carrier/channel (clc) family.
DR PhosphoSitePlus; Q06393; -.
DR PaxDb; Q06393; -.
DR GeneID; 79425; -.
DR KEGG; rno:79425; -.
DR UCSC; RGD:68435; rat.
DR CTD; 1187; -.
DR RGD; 68435; Clcnka.
DR eggNOG; KOG0476; Eukaryota.
DR InParanoid; Q06393; -.
DR PhylomeDB; Q06393; -.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR PRO; PR:Q06393; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:RGD.
DR GO; GO:0005254; F:chloride channel activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; IBA:GO_Central.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IDA:RGD.
DR GO; GO:0007589; P:body fluid secretion; IEP:RGD.
DR GO; GO:0006821; P:chloride transport; IBA:GO_Central.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0050878; P:regulation of body fluid levels; ISO:RGD.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0070293; P:renal absorption; TAS:UniProtKB.
DR GO; GO:0072053; P:renal inner medulla development; ISO:RGD.
DR GO; GO:0051592; P:response to calcium ion; IEP:RGD.
DR GO; GO:0009268; P:response to pH; IEP:RGD.
DR GO; GO:0009414; P:response to water deprivation; IEP:RGD.
DR GO; GO:0030321; P:transepithelial chloride transport; TAS:UniProtKB.
DR Gene3D; 3.10.580.10; -; 1.
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; IPR002250; Cl_channel-K.
DR Pfam; PF00571; CBS; 1.
DR Pfam; PF00654; Voltage_CLC; 1.
DR PRINTS; PR00762; CLCHANNEL.
DR PRINTS; PR01119; CLCHANNELKDY.
DR SMART; SM00116; CBS; 2.
DR SUPFAM; SSF54631; SSF54631; 1.
DR SUPFAM; SSF81340; SSF81340; 1.
DR PROSITE; PS51371; CBS; 2.
PE 1: Evidence at protein level;
KW Calcium; CBS domain; Chloride; Chloride channel; Ion channel;
KW Ion transport; Membrane; Metal-binding; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..687
FT /note="Chloride channel protein ClC-Ka"
FT /id="PRO_0000094458"
FT TRANSMEM 52..72
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 94..114
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 161..181
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 236..256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 282..302
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 325..345
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 396..416
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 417..437
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 458..478
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 486..506
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 507..687
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 551..609
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 626..687
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT BINDING 259
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P51800"
FT BINDING 261
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P51800"
FT BINDING 278
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P51800"
FT BINDING 281
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P51800"
FT CONFLICT 266
FT /note="I -> V (in Ref. 4; CAA84064)"
FT /evidence="ECO:0000305"
FT CONFLICT 534
FT /note="W -> R (in Ref. 4; CAA84064)"
FT /evidence="ECO:0000305"
FT CONFLICT 608..609
FT /note="AS -> TP (in Ref. 4; CAA84064)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 687 AA; 75569 MW; 41434F07E3E6E8AD CRC64;
MEELVGLREG SSGKPVTLQE LWGPCPRIRR GVRRGLEWLK ERLFRVGEDW HFLVALGVLM
ALISYAMNFA IGRVVRAHKW LYREVGDGHL LRYLSWTVYP VALLSFSSGF SQSISPFSGG
SGLPELKTML SGVVLEDYLD IKNFGAKVVG LSCTLATGST IFLGKVGPFV HLSVMISAYL
GRVRAKTIGE TENKAKEIEM LSAAAAVGVA TVFAAPFSGV LFSIEVMSSH FSVWNYWRGF
FAATCGAFMF RLLGVFNSEQ ETITSIYKTR FRVDVPFDLP EIFFFVALGF ICGVLSCAYL
FCQRTFLRFI KTNRYTSRLL ATSKPSYAAL VALVLASITY PPGVGRFMAS RLSMAEHLHS
LFDNNSWALM TRNSSPPWPA EPDPQNLWLE WCHPRFTIFG TLAFFLVMKF WMLILATTIP
MPAGYFMPIF IIGAAIGRLL GEALSVAFPE GIVAGREVNP IMPGGYALAG AAAFSGAVTH
TISTALLAFE LTGQIVHALP VLMAVLAANA ISQNCQPSFY DGTIMAKKLP YLPWIRGRQI
GSYPVTVEHF MNCNLTTLAK DTPLEEVVKV VTSTEVSQYP LVETRESQTL VGIVERTHLV
QALQTQPASW APGQERFLQD ILAGGCPTQP VTLQLSPETS LYQAHSLFER LTLQSLFVTS
RGKAVGSVSW AELKKAISTL INPPAPK
