TRPM8_HUMAN
ID TRPM8_HUMAN Reviewed; 1104 AA.
AC Q7Z2W7; A0AVG2; Q3YFM7; Q6QNH9; Q8TAC3; Q8TDX8; Q9BVK1;
DT 21-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Transient receptor potential cation channel subfamily M member 8;
DE AltName: Full=Long transient receptor potential channel 6;
DE Short=LTrpC-6;
DE Short=LTrpC6;
DE AltName: Full=Transient receptor potential p8;
DE Short=Trp-p8;
GN Name=TRPM8; Synonyms=LTRPC6, TRPP8;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Prostate;
RX PubMed=11325849;
RA Tsavaler L., Shapero M.H., Morkowski S., Laus R.;
RT "Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer
RT and other malignancies and shares high homology with transient receptor
RT potential calcium channel proteins.";
RL Cancer Res. 61:3760-3769(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Prostate, and Prostate cancer;
RX PubMed=16174775; DOI=10.1074/jbc.m503544200;
RA Thebault S., Lemonnier L., Bidaux G., Flourakis M., Bavencoffe A.,
RA Gordienko D., Roudbaraki M., Delcourt P., Panchin Y., Shuba Y., Skryma R.,
RA Prevarskaya N.;
RT "Novel role of cold/menthol-sensitive transient receptor potential
RT melastatine family member 8 (TRPM8) in the activation of store-operated
RT channels in LNCaP human prostate cancer epithelial cells.";
RL J. Biol. Chem. 280:39423-39435(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), FUNCTION, SUBUNIT,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Prostate cancer;
RX PubMed=22128173; DOI=10.1074/jbc.m111.270256;
RA Bidaux G., Beck B., Zholos A., Gordienko D., Lemonnier L., Flourakis M.,
RA Roudbaraki M., Borowiec A.S., Fernandez J., Delcourt P., Lepage G.,
RA Shuba Y., Skryma R., Prevarskaya N.;
RT "Regulation of activity of transient receptor potential melastatin 8
RT (TRPM8) channel by its short isoforms.";
RL J. Biol. Chem. 287:2948-2962(2012).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4).
RC TISSUE=Skin;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-1104 (ISOFORM 1).
RA Sano Y., Inamura K., Miyake A., Mochizuki S., Yokoi H., Kitada C.,
RA Nozawa K., Matsushime H., Furuichi K.;
RT "Molecular cloning of a novel member of LTRP channel family, LTRPC6.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP TISSUE SPECIFICITY, AND EPITOPE MAPPING.
RX PubMed=12858355; DOI=10.1002/pros.10265;
RA Kiessling A., Fuessel S., Schmitz M., Stevanovic S., Meye A., Weigle B.,
RA Klenk U., Wirth M.P., Rieber E.P.;
RT "Identification of an HLA-A*0201-restricted T-cell epitope derived from the
RT prostate cancer-associated protein trp-p8.";
RL Prostate 56:270-279(2003).
RN [9]
RP FUNCTION.
RX PubMed=15306801; DOI=10.1038/nature02732;
RA Voets T., Droogmans G., Wissenbach U., Janssens A., Flockerzi V.,
RA Nilius B.;
RT "The principle of temperature-dependent gating in cold- and heat-sensitive
RT TRP channels.";
RL Nature 430:748-754(2004).
RN [10]
RP GLYCOSYLATION AT ASN-934, MUTAGENESIS OF ASN-821; ASN-934; HIS-946 AND
RP LEU-1089, AND ROLE OF COILED COIL DOMAIN.
RX PubMed=17065148; DOI=10.1074/jbc.m607756200;
RA Erler I., Al-Ansary D.M., Wissenbach U., Wagner T.F., Flockerzi V.,
RA Niemeyer B.A.;
RT "Trafficking and assembly of the cold-sensitive TRPM8 channel.";
RL J. Biol. Chem. 281:38396-38404(2006).
RN [11]
RP FUNCTION, AND INTERACTION WITH TCAF1 AND TCAF2.
RX PubMed=25559186; DOI=10.1083/jcb.201402076;
RA Gkika D., Lemonnier L., Shapovalov G., Gordienko D., Poux C.,
RA Bernardini M., Bokhobza A., Bidaux G., Degerny C., Verreman K., Guarmit B.,
RA Benahmed M., de Launoit Y., Bindels R.J., Fiorio Pla A., Prevarskaya N.;
RT "TRP channel-associated factors are a novel protein family that regulates
RT TRPM8 trafficking and activity.";
RL J. Cell Biol. 208:89-107(2015).
CC -!- FUNCTION: Receptor-activated non-selective cation channel involved in
CC detection of sensations such as coolness, by being activated by cold
CC temperature below 25 degrees Celsius. Activated by icilin, eucalyptol,
CC menthol, cold and modulation of intracellular pH. Involved in menthol
CC sensation. Permeable for monovalent cations sodium, potassium, and
CC cesium and divalent cation calcium. Temperature sensing is tightly
CC linked to voltage-dependent gating. Activated upon depolarization,
CC changes in temperature resulting in graded shifts of its voltage-
CC dependent activation curves. The chemical agonist menthol functions as
CC a gating modifier, shifting activation curves towards physiological
CC membrane potentials. Temperature sensitivity arises from a tenfold
CC difference in the activation energies associated with voltage-dependent
CC opening and closing. In prostate cancer cells, shows strong inward
CC rectification and high calcium selectivity in contrast to its behavior
CC in normal cells which is characterized by outward rectification and
CC poor cationic selectivity. Plays a role in prostate cancer cell
CC migration (PubMed:25559186). Isoform 2 and isoform 3 negatively
CC regulate menthol- and cold-induced channel activity by stabilizing the
CC closed state of the channel. {ECO:0000269|PubMed:15306801,
CC ECO:0000269|PubMed:16174775, ECO:0000269|PubMed:22128173,
CC ECO:0000269|PubMed:25559186}.
CC -!- SUBUNIT: Homotetramer (By similarity). Isoform 2 and isoform 3 interact
CC with the C-terminus of isoform 1 in a thermosensitive manner with
CC decreased interaction at 21 degrees Celsius compared to 37 degrees
CC Celsius. Interacts (via N-terminus and C-terminus domains) with TCAF1;
CC the interaction stimulates TRPM8 channel activity (PubMed:25559186).
CC Interacts (via N-terminus and C-terminus domains) with TCAF2 isoform 2;
CC the interaction inhibits TRPM8 channel activity (PubMed:25559186).
CC {ECO:0000250, ECO:0000269|PubMed:22128173,
CC ECO:0000269|PubMed:25559186}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC Membrane raft. Endoplasmic reticulum membrane. Note=Localizes to
CC membrane rafts but is also located in the cell membrane outside of
CC these regions where channel response to cold is enhanced compared to
CC membrane rafts (By similarity). Located in the endoplasmic reticulum in
CC prostate cancer cells. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q7Z2W7-1; Sequence=Displayed;
CC Name=2; Synonyms=sTRPM8-18, sM8-18;
CC IsoId=Q7Z2W7-2; Sequence=VSP_053268, VSP_012332, VSP_012333;
CC Name=3; Synonyms=sTRPM8-6, sM8-6;
CC IsoId=Q7Z2W7-3; Sequence=VSP_012330, VSP_012332, VSP_012333;
CC Name=4;
CC IsoId=Q7Z2W7-4; Sequence=VSP_054505, VSP_054506, VSP_054507;
CC -!- TISSUE SPECIFICITY: Expressed in prostate. Also expressed in prostate
CC tumors and in non-prostatic primary tumors such as colon, lung, breast
CC and skin tumors. {ECO:0000269|PubMed:11325849,
CC ECO:0000269|PubMed:12858355, ECO:0000269|PubMed:16174775,
CC ECO:0000269|PubMed:22128173}.
CC -!- DOMAIN: The coiled coil region is required for multimerization.
CC {ECO:0000269|PubMed:17065148, ECO:0000269|PubMed:25559186}.
CC -!- MISCELLANEOUS: The sensation of coolness triggered by eucalyptol or
CC menthol may be explained by the fact that menthol and cool temperatures
CC sensations are detected by this protein.
CC -!- MISCELLANEOUS: Its expression in most prostate tumors as well as the
CC presence of an immunogenic epitope suggest that it may be suitable for
CC the design of peptide vaccination strategies for prostate cancers.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. LTrpC
CC subfamily. TRPM8 sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: The 192-residue sequence submitted as AAS45276 has been
CC confirmed by the authors of PubMed:22128173 to be incorrect as
CC translation starts from a downstream methionine. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH01135.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAS45276.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY090109; AAM10446.1; -; mRNA.
DR EMBL; AY328400; AAP92167.1; -; mRNA.
DR EMBL; DQ139309; AAZ73614.1; -; mRNA.
DR EMBL; AY532375; AAS45275.1; -; mRNA.
DR EMBL; AY532376; AAS45276.1; ALT_INIT; mRNA.
DR EMBL; AC005538; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471063; EAW71068.1; -; Genomic_DNA.
DR EMBL; BC001135; AAH01135.1; ALT_INIT; mRNA.
DR EMBL; BC126342; AAI26343.1; -; mRNA.
DR EMBL; AB061779; BAB86335.1; -; mRNA.
DR CCDS; CCDS33407.1; -. [Q7Z2W7-1]
DR RefSeq; NP_076985.4; NM_024080.4. [Q7Z2W7-1]
DR AlphaFoldDB; Q7Z2W7; -.
DR SMR; Q7Z2W7; -.
DR BioGRID; 122512; 17.
DR IntAct; Q7Z2W7; 6.
DR STRING; 9606.ENSP00000323926; -.
DR BindingDB; Q7Z2W7; -.
DR ChEMBL; CHEMBL1075319; -.
DR DrugBank; DB11345; (S)-camphor.
DR DrugBank; DB01744; Camphor.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB00825; Levomenthol.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB11755; Tetrahydrocannabivarin.
DR DrugCentral; Q7Z2W7; -.
DR GuidetoPHARMACOLOGY; 500; -.
DR TCDB; 1.A.4.5.7; the transient receptor potential ca(2+) channel (trp-cc) family.
DR GlyGen; Q7Z2W7; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q7Z2W7; -.
DR PhosphoSitePlus; Q7Z2W7; -.
DR BioMuta; TRPM8; -.
DR DMDM; 143811469; -.
DR EPD; Q7Z2W7; -.
DR MassIVE; Q7Z2W7; -.
DR PaxDb; Q7Z2W7; -.
DR PeptideAtlas; Q7Z2W7; -.
DR PRIDE; Q7Z2W7; -.
DR ProteomicsDB; 18; -.
DR ProteomicsDB; 68976; -. [Q7Z2W7-1]
DR ProteomicsDB; 68977; -. [Q7Z2W7-2]
DR ProteomicsDB; 68978; -. [Q7Z2W7-3]
DR Antibodypedia; 20244; 502 antibodies from 37 providers.
DR DNASU; 79054; -.
DR Ensembl; ENST00000324695.9; ENSP00000323926.4; ENSG00000144481.17. [Q7Z2W7-1]
DR Ensembl; ENST00000409625.1; ENSP00000386771.1; ENSG00000144481.17. [Q7Z2W7-3]
DR GeneID; 79054; -.
DR KEGG; hsa:79054; -.
DR MANE-Select; ENST00000324695.9; ENSP00000323926.4; NM_024080.5; NP_076985.4.
DR UCSC; uc002vvi.4; human. [Q7Z2W7-1]
DR CTD; 79054; -.
DR DisGeNET; 79054; -.
DR GeneCards; TRPM8; -.
DR HGNC; HGNC:17961; TRPM8.
DR HPA; ENSG00000144481; Group enriched (liver, prostate).
DR MIM; 606678; gene.
DR neXtProt; NX_Q7Z2W7; -.
DR OpenTargets; ENSG00000144481; -.
DR PharmGKB; PA38270; -.
DR VEuPathDB; HostDB:ENSG00000144481; -.
DR eggNOG; KOG3614; Eukaryota.
DR GeneTree; ENSGT00940000160270; -.
DR HOGENOM; CLU_1414730_0_0_1; -.
DR InParanoid; Q7Z2W7; -.
DR OMA; SFWKEER; -.
DR OrthoDB; 738147at2759; -.
DR PhylomeDB; Q7Z2W7; -.
DR TreeFam; TF314204; -.
DR PathwayCommons; Q7Z2W7; -.
DR Reactome; R-HSA-3295583; TRP channels.
DR SABIO-RK; Q7Z2W7; -.
DR SignaLink; Q7Z2W7; -.
DR BioGRID-ORCS; 79054; 17 hits in 1078 CRISPR screens.
DR ChiTaRS; TRPM8; human.
DR GeneWiki; TRPM8; -.
DR GenomeRNAi; 79054; -.
DR Pharos; Q7Z2W7; Tclin.
DR PRO; PR:Q7Z2W7; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q7Z2W7; protein.
DR Bgee; ENSG00000144481; Expressed in right lobe of liver and 97 other tissues.
DR ExpressionAtlas; Q7Z2W7; baseline and differential.
DR Genevisible; Q7Z2W7; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0005262; F:calcium channel activity; TAS:Reactome.
DR GO; GO:0005261; F:cation channel activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0099604; F:ligand-gated calcium channel activity; IBA:GO_Central.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0098655; P:cation transmembrane transport; IBA:GO_Central.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0016048; P:detection of temperature stimulus; IEA:InterPro.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0009409; P:response to cold; IEA:Ensembl.
DR GO; GO:0050955; P:thermoception; IEA:Ensembl.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR029603; TRPM8.
DR InterPro; IPR041491; TRPM_SLOG.
DR PANTHER; PTHR13800:SF9; PTHR13800:SF9; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF18139; LSDAT_euk; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Coiled coil; Endoplasmic reticulum;
KW Glycoprotein; Ion channel; Ion transport; Membrane; Reference proteome;
KW Sensory transduction; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1104
FT /note="Transient receptor potential cation channel
FT subfamily M member 8"
FT /id="PRO_0000215333"
FT TOPO_DOM 1..691
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 692..712
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 713..734
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 735..755
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 756..759
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 760..780
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 781..794
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 795..815
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 816..829
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 830..850
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 851..958
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 959..979
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 980..1104
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 187..195
FT /note="Epitope; activates specific cytotoxic T lymphocytes"
FT COILED 1071..1104
FT /evidence="ECO:0000255"
FT CARBOHYD 934
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:17065148"
FT VAR_SEQ 1..188
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:22128173"
FT /id="VSP_053268"
FT VAR_SEQ 1..77
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:22128173"
FT /id="VSP_012330"
FT VAR_SEQ 1..2
FT /note="MS -> MQ (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054505"
FT VAR_SEQ 3..314
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054506"
FT VAR_SEQ 234..242
FT /note="GYFLAQYLM -> VPVGQEEVC (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:22128173"
FT /id="VSP_012332"
FT VAR_SEQ 243..1104
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:22128173"
FT /id="VSP_012333"
FT VAR_SEQ 675..784
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054507"
FT VARIANT 247
FT /note="R -> T (in dbSNP:rs13004520)"
FT /id="VAR_052383"
FT VARIANT 251
FT /note="Y -> C (in dbSNP:rs17868387)"
FT /id="VAR_052384"
FT VARIANT 419
FT /note="S -> N (in dbSNP:rs7593557)"
FT /id="VAR_059837"
FT VARIANT 462
FT /note="M -> T (in dbSNP:rs28902173)"
FT /id="VAR_052385"
FT VARIANT 732
FT /note="T -> I (in dbSNP:rs17862932)"
FT /id="VAR_052386"
FT VARIANT 821
FT /note="N -> S (in dbSNP:rs28902201)"
FT /id="VAR_052387"
FT MUTAGEN 821
FT /note="N->Q: No effect on glycosylation or ability to form
FT functional channels."
FT /evidence="ECO:0000269|PubMed:17065148"
FT MUTAGEN 934
FT /note="N->Q: Abolishes glycosylation."
FT /evidence="ECO:0000269|PubMed:17065148"
FT MUTAGEN 946
FT /note="H->N: No effect on glycosylation or channel
FT activity."
FT /evidence="ECO:0000269|PubMed:17065148"
FT MUTAGEN 1089
FT /note="L->P: Abolishes multimerization and channel
FT activity. Reduces cell surface expression."
FT /evidence="ECO:0000269|PubMed:17065148"
FT CONFLICT 58
FT /note="T -> I (in Ref. 1; AAM10446)"
FT /evidence="ECO:0000305"
FT CONFLICT 693
FT /note="W -> R (in Ref. 7; BAB86335)"
FT /evidence="ECO:0000305"
FT CONFLICT 795
FT /note="T -> A (in Ref. 2; AAP92167)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1104 AA; 127685 MW; 5D88F5081EDFA632 CRC64;
MSFRAARLSM RNRRNDTLDS TRTLYSSASR STDLSYSESD LVNFIQANFK KRECVFFTKD
SKATENVCKC GYAQSQHMEG TQINQSEKWN YKKHTKEFPT DAFGDIQFET LGKKGKYIRL
SCDTDAEILY ELLTQHWHLK TPNLVISVTG GAKNFALKPR MRKIFSRLIY IAQSKGAWIL
TGGTHYGLMK YIGEVVRDNT ISRSSEENIV AIGIAAWGMV SNRDTLIRNC DAEGYFLAQY
LMDDFTRDPL YILDNNHTHL LLVDNGCHGH PTVEAKLRNQ LEKYISERTI QDSNYGGKIP
IVCFAQGGGK ETLKAINTSI KNKIPCVVVE GSGQIADVIA SLVEVEDALT SSAVKEKLVR
FLPRTVSRLP EEETESWIKW LKEILECSHL LTVIKMEEAG DEIVSNAISY ALYKAFSTSE
QDKDNWNGQL KLLLEWNQLD LANDEIFTND RRWESADLQE VMFTALIKDR PKFVRLFLEN
GLNLRKFLTH DVLTELFSNH FSTLVYRNLQ IAKNSYNDAL LTFVWKLVAN FRRGFRKEDR
NGRDEMDIEL HDVSPITRHP LQALFIWAIL QNKKELSKVI WEQTRGCTLA ALGASKLLKT
LAKVKNDINA AGESEELANE YETRAVELFT ECYSSDEDLA EQLLVYSCEA WGGSNCLELA
VEATDQHFIA QPGVQNFLSK QWYGEISRDT KNWKIILCLF IIPLVGCGFV SFRKKPVDKH
KKLLWYYVAF FTSPFVVFSW NVVFYIAFLL LFAYVLLMDF HSVPHPPELV LYSLVFVLFC
DEVRQWYVNG VNYFTDLWNV MDTLGLFYFI AGIVFRLHSS NKSSLYSGRV IFCLDYIIFT
LRLIHIFTVS RNLGPKIIML QRMLIDVFFF LFLFAVWMVA FGVARQGILR QNEQRWRWIF
RSVIYEPYLA MFGQVPSDVD GTTYDFAHCT FTGNESKPLC VELDEHNLPR FPEWITIPLV
CIYMLSTNIL LVNLLVAMFG YTVGTVQENN DQVWKFQRYF LVQEYCSRLN IPFPFIVFAY
FYMVVKKCFK CCCKEKNMES SVCCFKNEDN ETLAWEGVMK ENYLVKINTK ANDTSEEMRH
RFRQLDTKLN DLKGLLKEIA NKIK
