CLCN1_CANLF
ID CLCN1_CANLF Reviewed; 976 AA.
AC Q9MZT1;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Chloride channel protein 1;
DE Short=ClC-1;
DE AltName: Full=Chloride channel protein, skeletal muscle;
GN Name=CLCN1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT MCR MET-268, INVOLVEMENT IN MCR,
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RC STRAIN=Miniature Schnauzer;
RX PubMed=10452529; DOI=10.1016/s0014-5793(99)00926-6;
RA Rhodes T.H., Vite C.H., Giger U., Patterson D.F., Fahlke C.,
RA George A.L. Jr.;
RT "A missense mutation in canine C1C-1 causes recessive myotonia congenita in
RT the dog.";
RL FEBS Lett. 456:54-58(1999).
CC -!- FUNCTION: Voltage-gated chloride channel. Plays an important role in
CC membrane repolarization in skeletal muscle cells after muscle
CC contraction. {ECO:0000269|PubMed:10452529}.
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:P51798};
CC -!- SUBUNIT: Homodimer. {ECO:0000305|PubMed:10452529}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10452529};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P35523}.
CC -!- DISEASE: Note=Defects in CLCN1 are the cause of autosomal recessive
CC myotonia congenita (MCR). MCR is a disorder of sarcolemmal excitation
CC leading to delayed relaxation of skeletal muscle following
CC contractions. The disease has been identified in the miniature
CC Schnauzer breed. {ECO:0000269|PubMed:10452529}.
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 1/CLCN1 subfamily. {ECO:0000305}.
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DR EMBL; AF162445; AAF82606.1; -; mRNA.
DR RefSeq; NP_001003124.1; NM_001003124.2.
DR AlphaFoldDB; Q9MZT1; -.
DR SMR; Q9MZT1; -.
DR STRING; 9612.ENSCAFP00000018866; -.
DR PaxDb; Q9MZT1; -.
DR Ensembl; ENSCAFT00030020703; ENSCAFP00030018053; ENSCAFG00030011180.
DR Ensembl; ENSCAFT00040009316; ENSCAFP00040008072; ENSCAFG00040004929.
DR Ensembl; ENSCAFT00845030053; ENSCAFP00845023575; ENSCAFG00845016951.
DR GeneID; 403723; -.
DR KEGG; cfa:403723; -.
DR CTD; 1180; -.
DR VEuPathDB; HostDB:ENSCAFG00845016951; -.
DR eggNOG; KOG0476; Eukaryota.
DR GeneTree; ENSGT00940000157383; -.
DR HOGENOM; CLU_006904_0_1_1; -.
DR InParanoid; Q9MZT1; -.
DR OMA; TYAQMQP; -.
DR OrthoDB; 1131873at2759; -.
DR TreeFam; TF352264; -.
DR Reactome; R-CFA-2672351; Stimuli-sensing channels.
DR Proteomes; UP000002254; Chromosome 16.
DR Bgee; ENSCAFG00000003619; Expressed in tongue and 29 other tissues.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; ISS:UniProtKB.
DR GO; GO:1902476; P:chloride transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006821; P:chloride transport; IBA:GO_Central.
DR GO; GO:0006936; P:muscle contraction; ISS:UniProtKB.
DR GO; GO:0019227; P:neuronal action potential propagation; IEA:Ensembl.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR Gene3D; 3.10.580.10; -; 2.
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; IPR002243; Cl_channel-1.
DR Pfam; PF00654; Voltage_CLC; 1.
DR PRINTS; PR00762; CLCHANNEL.
DR PRINTS; PR01112; CLCHANNEL1.
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; Disease variant;
KW Ion channel; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..976
FT /note="Chloride channel protein 1"
FT /id="PRO_0000094428"
FT TOPO_DOM 1..118
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 119..150
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 151..158
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 159..179
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 180..183
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 184..195
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 196..208
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 209..228
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 229..246
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 247..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 269..290
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 291..301
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 302..321
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 322..347
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 348..376
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 377..390
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 391..408
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 409..414
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 415..426
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 427..457
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 458..478
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TRANSMEM 479..498
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 499..521
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 522..554
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 555..557
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 558..578
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P35523"
FT TOPO_DOM 579..976
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 609..668
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 816..871
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 71..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 707..759
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 872..976
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 188..192
FT /note="Selectivity filter part_1"
FT /evidence="ECO:0000250"
FT MOTIF 230..234
FT /note="Selectivity filter part_2"
FT /evidence="ECO:0000250"
FT MOTIF 482..486
FT /note="Selectivity filter part_3"
FT /evidence="ECO:0000250"
FT COMPBIAS 718..732
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 911..927
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 189
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT BINDING 484
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT BINDING 578
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT MOD_RES 881
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64347"
FT VARIANT 268
FT /note="T -> M (in MCR; profound effect on the voltage-
FT dependence of activation such that mutant channels have a
FT greatly reduced open probability at voltages near the
FT resting membrane potential of skeletal muscle)"
FT /evidence="ECO:0000269|PubMed:10452529"
SQ SEQUENCE 976 AA; 108053 MW; 8F85593E7C858F6E CRC64;
MQPSQSLRRG GEQSWWGSAP QYQYMPFEHC TSYGLPSENG ALQHRLHRDA GLRANTRPTQ
IYGHYKQQFS DKEQDTGMSK KMGSSESMDS KDEDHYSKCQ GCVRRLGHVV RRKLGEDWIF
LVLLGLLMAL VSWSMDYVSA KSLQAYKWSY YQMQPNLPLQ YLVWVTFPLT LILFSAVFCH
LISPQAVGSG IPEMKTILRG VILKEYLTLK AFVAKVVALT AGLGSGIPVG KEGPFVHIAS
ICAAVLSKFM SMFCGVYEQP YYYTDMLTVG CAVGVGCCFG TPLGGVLFSI EVTSTYFAVR
NYWRGFFAAT FSAFVFRVLA VWNKDAVTIT ALFRTNFRMD FPFDLQELPA FAIIGICCGF
LGAVFVYLHR QVMLGVRKHK ALSQFLAKHR LLYPGIVTFI IASFTFPPGI GQFMAGELMP
REAISTLFDN NTWVKHVGDP ESLGRSAVWI HPRVNVIIII FLFFIMKFWM SIVATTMPIP
CGGFMPVFVL GAAFGRLVGE IMAMLFPDGI LFDDIIYKIL PGGYAVIGAA ALTGAVSHTV
STAVICFELT GQIAHILPMM VAVILANMVA QSLQPSLYDS IIQVKKLPYL PDLGWNQLSK
FTIFVEDIMV RDVKFVSATC TYGELRTLLQ TTTVKTLPLV DSKDSMILLG SVERSELQSL
LQRHLGPERR LRVAQDMARK LSELPYDGKG HQGISPEGRR ESFAFVDEDE DEDLSGKPEL
PPLPPPHPLP SAPLSSEESN GPLPSHKQQP EAPEPADQRP SVFRSLLRCL LGRPRPTKKK
TTQESMDLVD NMSPEEIEAW EQEQLSQPVC FDYCCIDQSP FQLVEQTSLH KTHTLFSLLG
LHLAYVTSMG KLRGVLALEE LQKAIEGHTK SGVQLRPPLA SFRSTTSTRK NPGGPPPPTE
AWSLPEDGTG APASPEPPAP SPSPAPLLSE APAKVEGELE ELELGESPGL EEELADILQG
PSLRSTDEED EDELIL
