LRC8C_HUMAN
ID LRC8C_HUMAN Reviewed; 803 AA.
AC Q8TDW0; B3KXS9; Q29RV6; Q9H075;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Volume-regulated anion channel subunit LRRC8C {ECO:0000305};
DE AltName: Full=Factor for adipocyte differentiation 158 {ECO:0000303|PubMed:15564382};
DE AltName: Full=Leucine-rich repeat-containing protein 8C {ECO:0000303|PubMed:22532330};
GN Name=LRRC8C {ECO:0000303|PubMed:22532330, ECO:0000312|HGNC:HGNC:25075};
GN Synonyms=AD158 {ECO:0000303|PubMed:15564382},
GN FAD158 {ECO:0000303|PubMed:15564382};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT GLY-205.
RX PubMed=15564382; DOI=10.1242/jcs.01546;
RA Tominaga K., Johmura Y., Nishizuka M., Imagawa M.;
RT "Fad24, a mammalian homolog of Noc3p, is a positive regulator in adipocyte
RT differentiation.";
RL J. Cell Sci. 117:6217-6226(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-205.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-205.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 88-803, AND VARIANT GLY-205.
RC TISSUE=Uterus;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [6]
RP IDENTIFICATION.
RX PubMed=22532330; DOI=10.1002/bies.201100173;
RA Abascal F., Zardoya R.;
RT "LRRC8 proteins share a common ancestor with pannexins, and may form
RT hexameric channels involved in cell-cell communication.";
RL Bioessays 34:551-560(2012).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212, VARIANT [LARGE SCALE
RP ANALYSIS] GLY-205, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH LRRC8A, AND SUBCELLULAR
RP LOCATION.
RX PubMed=24790029; DOI=10.1126/science.1252826;
RA Voss F.K., Ullrich F., Muench J., Lazarow K., Lutter D., Mah N.,
RA Andrade-Navarro M.A., von Kries J.P., Stauber T., Jentsch T.J.;
RT "Identification of LRRC8 heteromers as an essential component of the
RT volume-regulated anion channel VRAC.";
RL Science 344:634-638(2014).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND MUTAGENESIS OF THR-44.
RX PubMed=26824658; DOI=10.1016/j.cell.2015.12.031;
RA Syeda R., Qiu Z., Dubin A.E., Murthy S.E., Florendo M.N., Mason D.E.,
RA Mathur J., Cahalan S.M., Peters E.C., Montal M., Patapoutian A.;
RT "LRRC8 proteins form volume-regulated anion channels that sense ionic
RT strength.";
RL Cell 164:499-511(2016).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=28193731; DOI=10.1242/jcs.196253;
RA Lutter D., Ullrich F., Lueck J.C., Kempa S., Jentsch T.J.;
RT "Selective transport of neurotransmitters and modulators by distinct
RT volume-regulated LRRC8 anion channels.";
RL J. Cell Sci. 130:1122-1133(2017).
RN [11]
RP DOMAIN, AND MUTAGENESIS OF GLU-6.
RX PubMed=29925591; DOI=10.1074/jbc.ra118.002853;
RA Zhou P., Polovitskaya M.M., Jentsch T.J.;
RT "LRRC8 N termini influence pore properties and gating of volume-regulated
RT anion channels (VRACs).";
RL J. Biol. Chem. 293:13440-13451(2018).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=33171122; DOI=10.1016/j.molcel.2020.10.021;
RA Lahey L.J., Mardjuki R.E., Wen X., Hess G.T., Ritchie C., Carozza J.A.,
RA Boehnert V., Maduke M., Bassik M.C., Li L.;
RT "LRRC8A:C/E heteromeric channels are ubiquitous transporters of cGAMP.";
RL Mol. Cell 0:0-0(2020).
CC -!- FUNCTION: Non-essential component of the volume-regulated anion channel
CC (VRAC, also named VSOAC channel), an anion channel required to maintain
CC a constant cell volume in response to extracellular or intracellular
CC osmotic changes (PubMed:24790029, PubMed:26824658, PubMed:28193731).
CC The VRAC channel conducts iodide better than chloride and can also
CC conduct organic osmolytes like taurine (PubMed:24790029,
CC PubMed:26824658, PubMed:28193731). Plays a redundant role in the efflux
CC of amino acids, such as aspartate and glutamate, in response to osmotic
CC stress (PubMed:24790029, PubMed:26824658, PubMed:28193731). The VRAC
CC channel also mediates transport of immunoreactive cyclic dinucleotide
CC GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA
CC virus in the cytosol (PubMed:33171122). Channel activity requires
CC LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or
CC LRRC8E); channel characteristics depend on the precise subunit
CC composition (PubMed:24790029, PubMed:26824658, PubMed:28193731).
CC {ECO:0000269|PubMed:24790029, ECO:0000269|PubMed:26824658,
CC ECO:0000269|PubMed:28193731, ECO:0000269|PubMed:33171122}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC ChEBI:CHEBI:17996; Evidence={ECO:0000305|PubMed:24790029};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=iodide(out) = iodide(in); Xref=Rhea:RHEA:66324,
CC ChEBI:CHEBI:16382; Evidence={ECO:0000305|PubMed:24790029};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=taurine(out) = taurine(in); Xref=Rhea:RHEA:66328,
CC ChEBI:CHEBI:507393; Evidence={ECO:0000305|PubMed:24790029};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2',3'-cGAMP(out) = 2',3'-cGAMP(in); Xref=Rhea:RHEA:66320,
CC ChEBI:CHEBI:143093; Evidence={ECO:0000269|PubMed:33171122};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66321;
CC Evidence={ECO:0000269|PubMed:33171122};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:66322;
CC Evidence={ECO:0000269|PubMed:33171122};
CC -!- SUBUNIT: Heterohexamer (By similarity). Oligomerizes with other LRRC8
CC proteins (LRRC8A, LRRC8B, LRRC8D and/or LRRC8E) to form a heterohexamer
CC (Probable). Detected in a channel complex that contains LRRC8A, LRRC8C
CC and LRRC8E (PubMed:28193731). In vivo, the subunit composition may
CC depend primarily on expression levels, and heterooligomeric channels
CC containing various proportions of the different LRRC8 proteins may
CC coexist (Probable). {ECO:0000250|UniProtKB:Q8R502,
CC ECO:0000269|PubMed:28193731, ECO:0000305|PubMed:24790029,
CC ECO:0000305|PubMed:26824658, ECO:0000305|PubMed:28193731}.
CC -!- INTERACTION:
CC Q8TDW0; Q8IWT6: LRRC8A; NbExp=2; IntAct=EBI-6916516, EBI-10970086;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24790029,
CC ECO:0000269|PubMed:28193731}; Multi-pass membrane protein
CC {ECO:0000305}. Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:24790029}. Note=In the absence of LRRC8A, resides
CC primarily in a cytoplasmic compartment, probably the endoplasmic
CC reticulum. Requires LRRC8A for expression at the cell membrane.
CC {ECO:0000269|PubMed:24790029}.
CC -!- TISSUE SPECIFICITY: Expressed at highest levels in skeletal muscle, and
CC at moderate levels in heart, lung and peripheral blood leukocytes.
CC {ECO:0000269|PubMed:15564382}.
CC -!- DOMAIN: The volume-regulated anion channel (VRAC) channel forms a
CC trimer of dimers, with symmetry mismatch between the pore-forming
CC domain and the cytosolic LRR repeats, a topology similar to gap
CC junction proteins. {ECO:0000250|UniProtKB:Q8IWT6}.
CC -!- DOMAIN: The cytoplasmic N-terminus preceding the first transmembrane
CC (residues 1-22) regulates volume-regulated anion channel (VRAC)
CC conductance, ion permeability and inactivation gating.
CC {ECO:0000269|PubMed:29925591}.
CC -!- SIMILARITY: Belongs to the LRRC8 family. {ECO:0000305}.
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DR EMBL; AB081509; BAB86303.1; -; mRNA.
DR EMBL; AK127881; BAG54591.1; -; mRNA.
DR EMBL; AC093423; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC113973; AAI13974.1; -; mRNA.
DR EMBL; AL136919; CAB66853.2; -; mRNA.
DR CCDS; CCDS725.1; -.
DR RefSeq; NP_115646.2; NM_032270.4.
DR RefSeq; XP_011540584.1; XM_011542282.2.
DR RefSeq; XP_016857992.1; XM_017002503.1.
DR AlphaFoldDB; Q8TDW0; -.
DR SMR; Q8TDW0; -.
DR BioGRID; 123963; 30.
DR CORUM; Q8TDW0; -.
DR DIP; DIP-61362N; -.
DR IntAct; Q8TDW0; 9.
DR STRING; 9606.ENSP00000359483; -.
DR TCDB; 1.A.25.3.1; the gap junction-forming innexin (innexin) family.
DR GlyGen; Q8TDW0; 4 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q8TDW0; -.
DR PhosphoSitePlus; Q8TDW0; -.
DR BioMuta; LRRC8C; -.
DR DMDM; 317373383; -.
DR EPD; Q8TDW0; -.
DR jPOST; Q8TDW0; -.
DR MassIVE; Q8TDW0; -.
DR MaxQB; Q8TDW0; -.
DR PaxDb; Q8TDW0; -.
DR PeptideAtlas; Q8TDW0; -.
DR PRIDE; Q8TDW0; -.
DR ProteomicsDB; 74345; -.
DR Antibodypedia; 33620; 24 antibodies from 15 providers.
DR DNASU; 84230; -.
DR Ensembl; ENST00000370454.9; ENSP00000359483.4; ENSG00000171488.15.
DR GeneID; 84230; -.
DR KEGG; hsa:84230; -.
DR MANE-Select; ENST00000370454.9; ENSP00000359483.4; NM_032270.5; NP_115646.3.
DR UCSC; uc001dnl.5; human.
DR CTD; 84230; -.
DR DisGeNET; 84230; -.
DR GeneCards; LRRC8C; -.
DR HGNC; HGNC:25075; LRRC8C.
DR HPA; ENSG00000171488; Low tissue specificity.
DR MIM; 612889; gene.
DR neXtProt; NX_Q8TDW0; -.
DR OpenTargets; ENSG00000171488; -.
DR PharmGKB; PA142671536; -.
DR VEuPathDB; HostDB:ENSG00000171488; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000159250; -.
DR HOGENOM; CLU_019019_0_0_1; -.
DR InParanoid; Q8TDW0; -.
DR OMA; LYIMYVR; -.
DR PhylomeDB; Q8TDW0; -.
DR TreeFam; TF331443; -.
DR PathwayCommons; Q8TDW0; -.
DR Reactome; R-HSA-5223345; Miscellaneous transport and binding events.
DR SignaLink; Q8TDW0; -.
DR BioGRID-ORCS; 84230; 13 hits in 1079 CRISPR screens.
DR ChiTaRS; LRRC8C; human.
DR GenomeRNAi; 84230; -.
DR Pharos; Q8TDW0; Tbio.
DR PRO; PR:Q8TDW0; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8TDW0; protein.
DR Bgee; ENSG00000171488; Expressed in sperm and 182 other tissues.
DR ExpressionAtlas; Q8TDW0; baseline and differential.
DR Genevisible; Q8TDW0; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0034702; C:ion channel complex; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005225; F:volume-sensitive anion channel activity; IMP:UniProtKB.
DR GO; GO:0098656; P:anion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0015810; P:aspartate transmembrane transport; IEA:Ensembl.
DR GO; GO:0071470; P:cellular response to osmotic stress; IEA:Ensembl.
DR GO; GO:0140361; P:cyclic-GMP-AMP transmembrane import across plasma membrane; IDA:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl.
DR GO; GO:0034214; P:protein hexamerization; ISS:UniProtKB.
DR GO; GO:0015734; P:taurine transport; IEA:Ensembl.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR026906; LRR_5.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR021040; LRRC8_Pannexin-like.
DR Pfam; PF13306; LRR_5; 1.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF12534; Pannexin_like; 1.
DR SMART; SM00369; LRR_TYP; 7.
DR PROSITE; PS51450; LRR; 7.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Ion channel; Ion transport; Leucine-rich repeat; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..803
FT /note="Volume-regulated anion channel subunit LRRC8C"
FT /id="PRO_0000076247"
FT TOPO_DOM 1..22
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 23..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..125
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 126..146
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 147..266
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..287
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 288..320
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 321..341
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 342..803
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 397..420
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 421..443
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 446..466
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 467..488
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 490..513
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 515..537
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT REPEAT 541..563
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT REPEAT 565..587
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT REPEAT 588..611
FT /note="LRR 9"
FT /evidence="ECO:0000255"
FT REPEAT 613..635
FT /note="LRR 10"
FT /evidence="ECO:0000255"
FT REPEAT 636..659
FT /note="LRR 11"
FT /evidence="ECO:0000255"
FT REPEAT 660..682
FT /note="LRR 12"
FT /evidence="ECO:0000255"
FT REPEAT 684..705
FT /note="LRR 13"
FT /evidence="ECO:0000255"
FT REPEAT 706..728
FT /note="LRR 14"
FT /evidence="ECO:0000255"
FT REPEAT 730..751
FT /note="LRR 15"
FT /evidence="ECO:0000255"
FT REPEAT 753..774
FT /note="LRR 16"
FT /evidence="ECO:0000255"
FT REPEAT 776..799
FT /note="LRR 17"
FT /evidence="ECO:0000255"
FT REGION 177..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 178..192
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 193..210
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q498T9"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..308
FT /evidence="ECO:0000250|UniProtKB:Q80WG5"
FT DISULFID 115..293
FT /evidence="ECO:0000250|UniProtKB:Q80WG5"
FT VARIANT 205
FT /note="D -> G (in dbSNP:rs474536)"
FT /evidence="ECO:0000269|PubMed:11230166,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15564382, ECO:0007744|PubMed:23186163"
FT /id="VAR_051129"
FT VARIANT 468
FT /note="N -> S (in dbSNP:rs12032393)"
FT /id="VAR_051130"
FT VARIANT 800
FT /note="M -> I (in dbSNP:rs12036569)"
FT /id="VAR_051131"
FT MUTAGEN 6
FT /note="E->C: Decreased amplitudes of swelling-activated
FT current."
FT /evidence="ECO:0000269|PubMed:29925591"
FT MUTAGEN 44
FT /note="T->C: Alters channel anion selectivity."
FT /evidence="ECO:0000269|PubMed:26824658"
FT CONFLICT 570
FT /note="M -> T (in Ref. 2; BAG54591)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 803 AA; 92450 MW; 95D179F028BF3F50 CRC64;
MIPVTEFRQF SEQQPAFRVL KPWWDVFTDY LSVAMLMIGV FGCTLQVMQD KIICLPKRVQ
PAQNHSSLSN VSQAVASTTP LPPPKPSPAN PITVEMKGLK TDLDLQQYSF INQMCYERAL
HWYAKYFPYL VLIHTLVFML CSNFWFKFPG SSSKIEHFIS ILGKCFDSPW TTRALSEVSG
EDSEEKDNRK NNMNRSNTIQ SGPEDSLVNS QSLKSIPEKF VVDKSTAGAL DKKEGEQAKA
LFEKVKKFRL HVEEGDILYA MYVRQTVLKV IKFLIIIAYN SALVSKVQFT VDCNVDIQDM
TGYKNFSCNH TMAHLFSKLS FCYLCFVSIY GLTCLYTLYW LFYRSLREYS FEYVRQETGI
DDIPDVKNDF AFMLHMIDQY DPLYSKRFAV FLSEVSENKL KQLNLNNEWT PDKLRQKLQT
NAHNRLELPL IMLSGLPDTV FEITELQSLK LEIIKNVMIP ATIAQLDNLQ ELSLHQCSVK
IHSAALSFLK ENLKVLSVKF DDMRELPPWM YGLRNLEELY LVGSLSHDIS RNVTLESLRD
LKSLKILSIK SNVSKIPQAV VDVSSHLQKM CIHNDGTKLV MLNNLKKMTN LTELELVHCD
LERIPHAVFS LLSLQELDLK ENNLKSIEEI VSFQHLRKLT VLKLWHNSIT YIPEHIKKLT
SLERLSFSHN KIEVLPSHLF LCNKIRYLDL SYNDIRFIPP EIGVLQSLQY FSITCNKVES
LPDELYFCKK LKTLKIGKNS LSVLSPKIGN LLFLSYLDVK GNHFEILPPE LGDCRALKRA
GLVVEDALFE TLPSDVREQM KTE
