CLH3_CAEEL
ID CLH3_CAEEL Reviewed; 1001 AA.
AC Q9BMK9; Q7KKH7;
DT 24-JUN-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Chloride channel protein clh-3 {ECO:0000305};
GN Name=clh-3 {ECO:0000312|WormBase:E04F6.11a};
GN Synonyms=clc-3 {ECO:0000312|WormBase:E04F6.11a};
GN ORFNames=E04F6.11 {ECO:0000312|WormBase:E04F6.11a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAF13165.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAF13165.1};
RX PubMed=10567397; DOI=10.1074/jbc.274.48.34238;
RA Schriever A.M., Friedrich T., Pusch M., Jentsch T.J.;
RT "CLC chloride channels in Caenorhabditis elegans.";
RL J. Biol. Chem. 274:34238-34244(1999).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=11078724; DOI=10.1152/ajpcell.2000.279.6.c2052;
RA Nehrke K., Begenisich T., Pilato J., Melvin J.E.;
RT "Into ion channel and transporter function. Caenorhabditis elegans ClC-type
RT chloride channels: novel variants and functional expression.";
RL Am. J. Physiol. 279:C2052-2066(2000).
RN [3] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=11231150; DOI=10.1016/s0960-9822(01)00051-3;
RA Rutledge E., Bianchi L., Christensen M., Boehmer C., Morrison R.,
RA Broslat A., Beld A.M., George A.L., Greenstein D., Strange K.;
RT "CLH-3, a ClC-2 anion channel ortholog activated during meiotic maturation
RT in C. elegans oocytes.";
RL Curr. Biol. 11:161-170(2001).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DEPHOSPHORYLATION BY GSP-1/2.
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 [6] {ECO:0000305}
RP FUNCTION, ACTIVATION MECHANISM, AND SUBCELLULAR LOCATION.
RX PubMed=14565992; DOI=10.1113/jphysiol.2003.053165;
RA Denton J., Nehrke K., Rutledge E., Morrison R., Strange K.;
RT "Alternative splicing of N- and C-termini of a C. elegans ClC channel
RT alters gating and sensitivity to external Cl- and H+.";
RL J. Physiol. (Lond.) 555:97-114(2004).
RN [7] {ECO:0000305}
RP FUNCTION, INTERACTION WITH GCK-3, AND SUBCELLULAR LOCATION.
RX PubMed=15684092; DOI=10.1085/jgp.200409215;
RA Denton J., Nehrke K., Yin X., Morrison R., Strange K.;
RT "GCK-3, a newly identified Ste20 kinase, binds to and regulates the
RT activity of a cell cycle-dependent ClC anion channel.";
RL J. Gen. Physiol. 125:113-125(2005).
RN [8] {ECO:0000305}
RP FUNCTION, ACTIVATION MECHANISM, SUBCELLULAR LOCATION, DOMAIN, AND
RP MUTAGENESIS OF GLU-167.
RX PubMed=16500974; DOI=10.1529/biophysj.105.078295;
RA He L., Denton J., Nehrke K., Strange K.;
RT "Carboxy terminus splice variation alters ClC channel gating and
RT extracellular cysteine reactivity.";
RL Biophys. J. 90:3570-3581(2006).
RN [9] {ECO:0000305}
RP FUNCTION.
RX PubMed=18049475; DOI=10.1038/sj.embor.7401128;
RA Hisamoto N., Moriguchi T., Urushiyama S., Mitani S., Shibuya H.,
RA Matsumoto K.;
RT "Caenorhabditis elegans WNK-STE20 pathway regulates tube formation by
RT modulating ClC channel activity.";
RL EMBO Rep. 9:70-75(2008).
RN [10] {ECO:0000305}
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-742 AND SER-747,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF SER-742; THR-744
RP AND SER-747.
RX PubMed=19088383; DOI=10.1085/jgp.200810080;
RA Falin R.A., Morrison R., Ham A.J., Strange K.;
RT "Identification of regulatory phosphorylation sites in a cell volume- and
RT Ste20 kinase-dependent ClC anion channel.";
RL J. Gen. Physiol. 133:29-42(2009).
RN [11] {ECO:0000305}
RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF GLU-167; PHE-559; LEU-833;
RP ALA-836 AND ILE-837.
RX PubMed=20581474; DOI=10.4161/chan.4.4.12445;
RA Dave S., Sheehan J.H., Meiler J., Strange K.;
RT "Unique gating properties of C. elegans ClC anion channel splice variants
RT are determined by altered CBS domain conformation and the R-helix linker.";
RL Channels 4:289-301(2010).
RN [12] {ECO:0000305}
RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF TYR-232; SER-742; SER-747
RP AND HIS-805.
RX PubMed=23083714; DOI=10.1016/j.bpj.2012.09.001;
RA Miyazaki H., Yamada T., Parton A., Morrison R., Kim S., Beth A.H.,
RA Strange K.;
RT "CLC anion channel regulatory phosphorylation and conserved signal
RT transduction domains.";
RL Biophys. J. 103:1706-1718(2012).
RN [13] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF VAL-495.
RX PubMed=24431435; DOI=10.1523/jneurosci.3112-13.2014;
RA Branicky R., Miyazaki H., Strange K., Schafer W.R.;
RT "The voltage-gated anion channels encoded by clh-3 regulate egg laying in
RT C. elegans by modulating motor neuron excitability.";
RL J. Neurosci. 34:764-775(2014).
CC -!- FUNCTION: [Isoform a]: Voltage-gated chloride channel (PubMed:10567397,
CC PubMed:11078724, PubMed:11231150, PubMed:12163466, PubMed:15684092).
CC Insensitive to depolarizing conditioning voltages, requires low
CC voltages for activation, insensitive to chloride levels and has a mild
CC sensitivity to low pH. Channel gating properties are conferred by the
CC cytoplasmic C-terminus (PubMed:14565992, PubMed:16500974). Plays a role
CC in egg laying by modulating hermaphrodite-specific neurons (HSN)
CC excitability and the ovulatory contractions of gap-junction-coupled
CC gonadal sheath cells (PubMed:11231150, PubMed:24431435). When active,
CC may prevent tubular formation of the excretory canals
CC (PubMed:18049475). Activated during oocyte meiotic maturation and by
CC membrane hyperpolarization and cell swelling (PubMed:11231150,
CC PubMed:14565992). Inhibited by Zn(2+) and to a lesser extent by
CC Cd(2+)(PubMed:11231150). {ECO:0000269|PubMed:10567397,
CC ECO:0000269|PubMed:11078724, ECO:0000269|PubMed:11231150,
CC ECO:0000269|PubMed:12163466, ECO:0000269|PubMed:14565992,
CC ECO:0000269|PubMed:15684092, ECO:0000269|PubMed:16500974,
CC ECO:0000269|PubMed:18049475, ECO:0000269|PubMed:24431435}.
CC -!- FUNCTION: [Isoform b]: Voltage-gated chloride channel (PubMed:10567397,
CC PubMed:11078724, PubMed:11231150). Sensitive to depolarizing
CC conditioning voltages, requires stronger voltages for activation and
CC activation is slower, is inhibited by low concentrations of chloride
CC and is activated by low pH. Channel gating properties are conferred by
CC the cytoplasmic C-terminus (PubMed:14565992, PubMed:16500974).
CC {ECO:0000269|PubMed:10567397, ECO:0000269|PubMed:11078724,
CC ECO:0000269|PubMed:11231150, ECO:0000269|PubMed:14565992,
CC ECO:0000269|PubMed:16500974}.
CC -!- SUBUNIT: Isoform a interacts (via RFLI motif) with gck-3 (via C-
CC terminus). {ECO:0000269|PubMed:15684092}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10567397,
CC ECO:0000269|PubMed:11078724, ECO:0000269|PubMed:11231150,
CC ECO:0000269|PubMed:12163466, ECO:0000269|PubMed:14565992,
CC ECO:0000269|PubMed:15684092, ECO:0000269|PubMed:16500974,
CC ECO:0000269|PubMed:19088383, ECO:0000269|PubMed:20581474,
CC ECO:0000269|PubMed:23083714, ECO:0000269|PubMed:24431435}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:E04F6.11a}; Synonyms=clh-3b
CC {ECO:0000303|PubMed:10567397};
CC IsoId=Q9BMK9-1; Sequence=Displayed;
CC Name=b {ECO:0000312|EMBL:AAF13165.1}; Synonyms=clh-3a
CC {ECO:0000303|PubMed:14565992};
CC IsoId=Q9BMK9-2; Sequence=VSP_057741, VSP_057742, VSP_057743,
CC VSP_057744;
CC -!- TISSUE SPECIFICITY: Expressed in excretory cell, 4 anterior epithelial
CC cells of the intestine, hermaphrodite-specific neurons and enteric
CC muscles (PubMed:11078724, PubMed:10567397). Expressed also in vulva and
CC uterus (PubMed:10567397). Isoform a is expressed in oocytes (at protein
CC level) (PubMed:11231150). {ECO:0000269|PubMed:10567397,
CC ECO:0000269|PubMed:11078724, ECO:0000269|PubMed:11231150}.
CC -!- DOMAIN: The CBS domains, the R-helix linker (543-562) and the C-
CC terminal domain (833-1001) regulate channel sensitivity to voltage, pH
CC and extracellular chloride concentrations, probably by altering the
CC outer pore structure (PubMed:16500974, PubMed:20581474). The region
CC (738-751) between the CBS domains is essential for channel activation
CC (PubMed:23083714). {ECO:0000269|PubMed:16500974,
CC ECO:0000269|PubMed:20581474, ECO:0000269|PubMed:23083714}.
CC -!- PTM: Phosphorylated by gck-3; phosphorylation at both Ser-742 and Ser-
CC 747 is required to inhibit channel activity (PubMed:19088383).
CC Dephosphorylated by gsp-1/2 during cell swelling and oocyte meiotic
CC maturation, which results in channel activation (PubMed:12163466).
CC {ECO:0000269|PubMed:12163466, ECO:0000269|PubMed:19088383}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in oocytes results in
CC inhibition of hyperpolarization-induced or swelling-induced current and
CC in premature ovulatory contractions of gonadal sheath cells. Normal
CC adaptive response to hypotonic swelling. {ECO:0000269|PubMed:11231150}.
CC -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family.
CC {ECO:0000305}.
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DR EMBL; AF173172; AAF13165.1; -; mRNA.
DR EMBL; AF319614; AAG49524.1; -; mRNA.
DR EMBL; BX284602; CCD65907.1; -; Genomic_DNA.
DR RefSeq; NP_001022060.1; NM_001026889.2. [Q9BMK9-1]
DR AlphaFoldDB; Q9BMK9; -.
DR SMR; Q9BMK9; -.
DR STRING; 6239.E04F6.11a; -.
DR ChEMBL; CHEMBL2268011; -.
DR TCDB; 2.A.49.2.13; the chloride carrier/channel (clc) family.
DR iPTMnet; Q9BMK9; -.
DR PaxDb; Q9BMK9; -.
DR PRIDE; Q9BMK9; -.
DR EnsemblMetazoa; E04F6.11a.1; E04F6.11a.1; WBGene00000530. [Q9BMK9-1]
DR EnsemblMetazoa; E04F6.11a.2; E04F6.11a.2; WBGene00000530. [Q9BMK9-1]
DR EnsemblMetazoa; E04F6.11a.3; E04F6.11a.3; WBGene00000530. [Q9BMK9-1]
DR EnsemblMetazoa; E04F6.11a.4; E04F6.11a.4; WBGene00000530. [Q9BMK9-1]
DR GeneID; 174187; -.
DR UCSC; E04F6.11a; c. elegans. [Q9BMK9-1]
DR CTD; 174187; -.
DR WormBase; E04F6.11a; CE27906; WBGene00000530; clh-3. [Q9BMK9-1]
DR eggNOG; KOG0476; Eukaryota.
DR GeneTree; ENSGT00940000168847; -.
DR HOGENOM; CLU_006904_1_1_1; -.
DR InParanoid; Q9BMK9; -.
DR PhylomeDB; Q9BMK9; -.
DR Reactome; R-CEL-2672351; Stimuli-sensing channels.
DR PRO; PR:Q9BMK9; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00000530; Expressed in adult organism and 3 other tissues.
DR ExpressionAtlas; Q9BMK9; baseline and differential.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:WormBase.
DR GO; GO:0005247; F:voltage-gated chloride channel activity; IDA:WormBase.
DR GO; GO:1902476; P:chloride transmembrane transport; IDA:WormBase.
DR GO; GO:0006821; P:chloride transport; IBA:GO_Central.
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 Pfam; PF00571; CBS; 1.
DR Pfam; PF00654; Voltage_CLC; 1.
DR PRINTS; PR00762; CLCHANNEL.
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 Alternative splicing; Cell membrane; Chloride; Coiled coil; Ion transport;
KW Membrane; Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..1001
FT /note="Chloride channel protein clh-3"
FT /evidence="ECO:0000305"
FT /id="PRO_0000433362"
FT TOPO_DOM 1..48
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 49..85
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 91..117
FT /note="Helical"
FT /evidence="ECO:0000305"
FT INTRAMEM 126..133
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 142..160
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 167..185
FT /note="Helical"
FT /evidence="ECO:0000305"
FT INTRAMEM 202..214
FT /note="Helical"
FT /evidence="ECO:0000305"
FT INTRAMEM 218..226
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 285..313
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 322..341
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 405..425
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 433..456
FT /note="Helical"
FT /evidence="ECO:0000305"
FT INTRAMEM 473..487
FT /note="Helical"
FT /evidence="ECO:0000305"
FT INTRAMEM 488..489
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000305"
FT INTRAMEM 490..501
FT /note="Helical"
FT /evidence="ECO:0000305"
FT INTRAMEM 502..506
FT /note="Note=Loop between two helices"
FT /evidence="ECO:0000305"
FT TRANSMEM 507..524
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 525..1001
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 560..619
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 788..845
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 634..662
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 625..657
FT /evidence="ECO:0000255"
FT MOTIF 123..127
FT /note="Selectivity filter part_1"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT MOTIF 165..169
FT /note="Selectivity filter part_2"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT MOTIF 433..437
FT /note="Selectivity filter part_3"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT COMPBIAS 634..661
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 124
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT BINDING 434
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT BINDING 435
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT BINDING 529
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P37019"
FT SITE 232
FT /note="Essential for gck-3-mediated inhibition of channel
FT activity"
FT /evidence="ECO:0000269|PubMed:23083714"
FT SITE 805
FT /note="Essential for gck-3-mediated inhibition of channel
FT activity"
FT /evidence="ECO:0000269|PubMed:23083714"
FT MOD_RES 742
FT /note="Phosphoserine; by gck-3"
FT /evidence="ECO:0000269|PubMed:19088383"
FT MOD_RES 747
FT /note="Phosphoserine; by gck-3"
FT /evidence="ECO:0000269|PubMed:19088383"
FT VAR_SEQ 1
FT /note="M -> MPSRTPLSKIEWQSLLPLPPEKSEKDATIENNEELEKIRMPAGKEYD
FT LQPGSHLGVYKTVRGLPIDEDSKSM (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057741"
FT VAR_SEQ 669..770
FT /note="FLIVPVAKNGPQVAKNETLTGLSEENARKILTVEEKQALFDAASLATPKREM
FT SGKTINPVHIESHHTIGDIFRSITHLSFGRQNFPKKNNHNEFDLFGEERT -> Y (in
FT isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057742"
FT VAR_SEQ 833..841
FT /note="LRLAIEYLQ -> VCFLISRKK (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057743"
FT VAR_SEQ 842..1001
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057744"
FT MUTAGEN 167
FT /note="E->A: Constitutive activation and loss of pH
FT sensitivity; in isoform a."
FT /evidence="ECO:0000269|PubMed:16500974"
FT MUTAGEN 167
FT /note="E->A: Constitutive activation, loss of pH
FT sensitivity, loss of sensitivity to chloride levels and
FT conditioning depolarizing voltages; in isoform b."
FT /evidence="ECO:0000269|PubMed:16500974"
FT MUTAGEN 167
FT /note="E->C: Increased sensitivity to MTSET-mediated
FT inhibition; in isoform a and isoform b. Inhibition is
FT slower; in isoform a. Reduced sensitivity to MTSET-mediated
FT inhibition; when associated with D-559; in isoform a."
FT /evidence="ECO:0000269|PubMed:16500974,
FT ECO:0000269|PubMed:19088383"
FT MUTAGEN 232
FT /note="Y->A: Loss of gck-3-mediated inhibition."
FT /evidence="ECO:0000269|PubMed:23083714"
FT MUTAGEN 495
FT /note="V->A: In n995; increase channel activity and
FT accumulation of eggs in the uterus resulting from a defect
FT in egg-laying. Reduced HSN activity. Reduced sensitivity to
FT gck-3-mediated inhibition; in isoform a."
FT /evidence="ECO:0000269|PubMed:24431435"
FT MUTAGEN 559
FT /note="F->D: Confers similar gating properties to isoform
FT b; in isoform a. Reduced sensitivity to MTSET-mediated
FT inhibition; when associated with C-167; in isoform a."
FT /evidence="ECO:0000269|PubMed:20581474"
FT MUTAGEN 742
FT /note="S->A: Constitutively active, loss of inhibition by
FT gck-3-mediated phosphorylation."
FT /evidence="ECO:0000269|PubMed:19088383"
FT MUTAGEN 742
FT /note="S->E: Phosphomimetic mutant whose activity is
FT sensitive to gck-3-mediated inhibition and to cell
FT swelling-induced activation. Severe reduction in channel
FT activity, loss of cell swelling-induced activation; when
FT associated with E-747."
FT /evidence="ECO:0000269|PubMed:19088383,
FT ECO:0000269|PubMed:23083714"
FT MUTAGEN 744
FT /note="T->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:19088383"
FT MUTAGEN 747
FT /note="S->A: Constitutively active, loss of inhibition by
FT gck-3-mediated phosphorylation."
FT /evidence="ECO:0000269|PubMed:19088383"
FT MUTAGEN 747
FT /note="S->E: Phosphomimetic mutant whose activity is
FT sensitive to gck-3-mediated inhibition but insensitive to
FT cell swelling-induced activation. Severe reduction in
FT channel activity, loss of cell swelling-induced activation;
FT when associated with E-742."
FT /evidence="ECO:0000269|PubMed:19088383,
FT ECO:0000269|PubMed:23083714"
FT MUTAGEN 805
FT /note="H->A: Loss of gck-3-mediated inhibition."
FT /evidence="ECO:0000269|PubMed:23083714"
FT MUTAGEN 833
FT /note="L->E: Confers similar gating properties to isoform
FT b; in isoform a."
FT /evidence="ECO:0000269|PubMed:20581474"
FT MUTAGEN 836
FT /note="A->K: Confers similar gating properties to isoform
FT b; in isoform a."
FT /evidence="ECO:0000269|PubMed:20581474"
FT MUTAGEN 837
FT /note="I->K: Confers similar gating properties to isoform
FT b; in isoform a."
FT /evidence="ECO:0000269|PubMed:20581474"
SQ SEQUENCE 1001 AA; 110787 MW; 8C6F38A1703DE350 CRC64;
MGIGTKILSK IEKNKTSDGL TIPLTPTTQK QSSSWCSFES IKTFFRTVIR DWIFLALLGF
IMASLSFGMD YAILNLQNGQ MRLFDLVKEY HFTLAYLVWV GYVVGLILLS AVCAHYIAPQ
AIGSGIPEMK TILRGVILKE YLSVRTLLSK MIGLTLSLGS GLPMGKEGPF VHVASVVASQ
LTRLVHGSSG GIFENESRSG EMLAAGCAVG VACTFSAPIG GVLFSIEVTS VYFAVRNYWR
GFFAATCSAT LFRILRMFSV SAAVTVEAHY QTNFPPQNVF LPQELPIFAL IGLVCGLAGS
IFVYLHRRTV LFLRRNWLAK MIFQKYWLIY PIFIATFISS LSFPLGLGKF MGGEERFSHT
MKEFFVDCAW TAPPNDSYAC PMPTSNATSS DSFDIRHWKG DNYDYSPFVT LSSFQVVYFF
LAILASTLPV PSGIFMPVFV LGAAFGRLVG EGVFSLDPYG HISGDIQFFV RPGVYAVVGA
AAFCGAVTHT VSVAVIVFEL TGQLCHLLPV MIAVLIANAV ASYLQPSIYD SIIRIKNLPY
LPDIPHTTSL YHQMLIEQFM ISPLVYIAKD STVGDIKRAL ETKTRIRAFP LVENMESLAL
VGSVSRSQLQ RYVDSQIGTK ARFAEATRRI KQRLEDEESE RKRREESKSD DTEDSLETTG
AGERRASRFL IVPVAKNGPQ VAKNETLTGL SEENARKILT VEEKQALFDA ASLATPKREM
SGKTINPVHI ESHHTIGDIF RSITHLSFGR QNFPKKNNHN EFDLFGEERT EWEDMMLNQK
LDLSQLDIDS TPFQLSEYTS LFKAHSLFSL LGLNRAYVTK KGQLIGVVAL KELRLAIEYL
QSGKVPTPGM SIFNEPPTEQ SIYEKSARLE SGRATGDAQN AAFVTDNGED DAQNDYIQPP
LEVVRRGALT PNRMSELTRL ENVRTTPESP HFEVSSPSTS SSCVSIDFSP LDAANSENGS
VGGLVLNVPS LPTRARSANE LTRQNTHVQI NLPDDVHDEK F
