CLCN2_RAT
ID CLCN2_RAT Reviewed; 907 AA.
AC P35525;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Chloride channel protein 2;
DE Short=ClC-2;
GN Name=Clcn2;
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], AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=1311421; DOI=10.1038/356057a0;
RA Thiemann A., Gruender S., Pusch M., Jentsch T.J.;
RT "A chloride channel widely expressed in epithelial and non-epithelial
RT cells.";
RL Nature 356:57-60(1992).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AND DEPHOSPHORYLATION.
RX PubMed=12163466; DOI=10.1083/jcb.200204142;
RA Rutledge E., Denton J., Strange K.;
RT "Cell cycle- and swelling-induced activation of a Caenorhabditis elegans
RT ClC channel is mediated by CeGLC-7alpha/beta phosphatases.";
RL J. Cell Biol. 158:435-444(2002).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-767, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Voltage-gated chloride channel (PubMed:1311421,
CC PubMed:12163466). Chloride channels have several functions including
CC the regulation of cell volume; membrane potential stabilization, signal
CC transduction and transepithelial transport (PubMed:1311421). Involved
CC in the regulation of aldosterone production. The opening of CLCN2
CC channels at hyperpolarized membrane potentials in the glomerulosa
CC causes cell membrane depolarization, activation of voltage-gated Ca2+
CC channels and increased expression of aldosterone synthase, the rate-
CC limiting enzyme for aldosterone biosynthesis (By similarity).
CC {ECO:0000250|UniProtKB:P51788, ECO:0000269|PubMed:12163466,
CC ECO:0000269|PubMed:1311421}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255,
CC ECO:0000269|PubMed:12163466}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- PTM: Phosphorylated. Activated by dephosphorylation.
CC {ECO:0000269|PubMed:12163466}.
CC -!- MISCELLANEOUS: The CLC channel family contains both chloride channels
CC and proton-coupled anion transporters that exchange chloride or another
CC anion for protons. The absence of conserved gating glutamate residues
CC is typical for family members that function as channels (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClC-
CC 2/CLCN2 subfamily. {ECO:0000305}.
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DR EMBL; X64139; CAA45500.1; -; mRNA.
DR PIR; S23399; S23399.
DR RefSeq; NP_058833.1; NM_017137.1.
DR RefSeq; XP_006248624.1; XM_006248562.3.
DR AlphaFoldDB; P35525; -.
DR SMR; P35525; -.
DR CORUM; P35525; -.
DR STRING; 10116.ENSRNOP00000050925; -.
DR TCDB; 2.A.49.2.6; the chloride carrier/channel (clc) family.
DR iPTMnet; P35525; -.
DR PhosphoSitePlus; P35525; -.
DR PaxDb; P35525; -.
DR Ensembl; ENSRNOT00000050927; ENSRNOP00000050925; ENSRNOG00000001742.
DR GeneID; 29232; -.
DR KEGG; rno:29232; -.
DR CTD; 1181; -.
DR RGD; 2361; Clcn2.
DR eggNOG; KOG0476; Eukaryota.
DR GeneTree; ENSGT00940000155439; -.
DR InParanoid; P35525; -.
DR OMA; ACFMFNN; -.
DR OrthoDB; 1131873at2759; -.
DR PhylomeDB; P35525; -.
DR TreeFam; TF300522; -.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR PRO; PR:P35525; -.
DR Proteomes; UP000002494; Chromosome 11.
DR Bgee; ENSRNOG00000001742; Expressed in duodenum and 17 other tissues.
DR ExpressionAtlas; P35525; baseline.
DR Genevisible; P35525; RN.
DR GO; GO:0015629; C:actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; IDA:RGD.
DR GO; GO:0090425; P:acinar cell differentiation; IEA:Ensembl.
DR GO; GO:0060689; P:cell differentiation involved in salivary gland development; ISO:RGD.
DR GO; GO:0006821; P:chloride transport; IDA:RGD.
DR GO; GO:0030324; P:lung development; IMP:RGD.
DR GO; GO:0032347; P:regulation of aldosterone biosynthetic process; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0060041; P:retina development in camera-type eye; ISO:RGD.
DR Gene3D; 3.10.580.10; -; 2.
DR InterPro; IPR046342; CBS_dom_sf.
DR InterPro; IPR002244; Cl-channel-2.
DR InterPro; IPR014743; Cl-channel_core.
DR InterPro; IPR001807; Cl-channel_volt-gated.
DR Pfam; PF00654; Voltage_CLC; 1.
DR PRINTS; PR00762; CLCHANNEL.
DR PRINTS; PR01113; CLCHANNEL2.
DR SUPFAM; SSF54631; SSF54631; 1.
DR SUPFAM; SSF81340; SSF81340; 1.
DR PROSITE; PS51371; CBS; 2.
PE 1: Evidence at protein level;
KW CBS domain; Cell membrane; Chloride; Chloride channel; Ion channel;
KW Ion transport; Membrane; Phosphoprotein; Reference proteome; Repeat;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..907
FT /note="Chloride channel protein 2"
FT /id="PRO_0000094436"
FT TOPO_DOM 1..93
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 94..127
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 136..161
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 170..177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 186..204
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 211..229
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 245..257
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 261..269
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 281..301
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 327..355
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 364..383
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 435..455
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TRANSMEM 463..486
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 503..517
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 518..519
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250"
FT INTRAMEM 520..531
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 532..536
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000250"
FT TRANSMEM 537..554
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 555..907
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 590..648
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 799..859
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 650..720
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 865..907
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 463..467
FT /note="Selectivity filter part_3"
FT /evidence="ECO:0000250"
FT COMPBIAS 660..691
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 866..880
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 26
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0A1"
FT MOD_RES 767
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 907 AA; 99328 MW; 6192EEB2EE0D6528 CRC64;
MAAATAAAAT VAGEGMEPRA LQYEQTLMYG RYTQELGAFA KEEAARIRLG GPEPWKGSPS
ARATPELLEY GQSRCARCRI CSVRCHKFLV SRVGEDWIFL VLLGLLMALV SWAMDYAIAV
CLQAQQWMSR GLNTNILLQY LAWVTYPVVL ITFSAGFTQI LAPQAVGSGI PEMKTILRGV
VLKEYLTLKT FVAKVIGLTC ALGSGMPLGK EGPFVHIASM CAALLSKFLS LFGGIYENES
RNTEMLAAAC AVGVGCCFAA PIGGVLFSIE VTSTFFAVRN YWRGFFAATF SAFIFRVLAV
WNRDEETITA LFKTRFRLDF PFDLQELPAF AVIGIASGFG GALFVYLNRK IVQVMRKQKT
INRFLMKKRL LFPALVTLLI STLTFPPGFG QFMAGQLSQK ETLVTLFDNR TWVRQGLVED
LGAPSTSQAW SPPRANVFLT LVIFILMKFW MSALATTIPV PCGAFMPVFV IGAAFGRLVG
ESMAAWFPDG IHTDSSTYRI VPGGYAVVGA AALAGAVTHT VSTAVIVFEL TGQIAHILPV
MIAVILANAV AQSLQPSLYD SIIRIKKLPY LPELGWGRHQ QYRVRVEDIM VRDVPHVALS
CTFRDLRLAL HRTKGRMLAL VESPESMILL GSIERSQVVA LLGAQLSPAR RRQHMQKLRK
AQMSPPSDQE SPPSSETSIR FQVNTEDSGF PGAHGQTHKP LKPALKRGPS NATSLQEGTT
GNMESAGIAL RSLFCGSPPL ESTTSELEKS ESCDKRKLKR VRISLASDSD LEGKMSPEEI
LEWEEQQLDE PVNFSDCKID PAPFQLVERT SLHKTHTIFS LLGVDHAYVT SIGRLIGIVT
LKELRKAIEG SVTAQGVKVR PPLASFRDSA TSSSDTETTE VHALWGPRSR HGLPREGTPS
DSDDKCQ
