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   27-MAR-2024, entry version 165.
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   CCDS; CCDS92976.1; -. [Q7Z2W7-3]
DR   RefSeq; NP_076985.4; NM_024080.4. [Q7Z2W7-1]
DR   PDB; 8BDC; EM; 2.65 A; A/B/C/D=2-1104.
DR   PDBsum; 8BDC; -.
DR   AlphaFoldDB; Q7Z2W7; -.
DR   EMDB; EMD-15981; -.
DR   EMDB; EMD-15982; -.
DR   EMDB; EMD-15983; -.
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; DB14123; Menthol.
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 ca2+/cation channel (trp-cc) family.
DR   GlyCosmos; Q7Z2W7; 1 site, No reported glycans.
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; 9606-ENSP00000323926; -.
DR   PeptideAtlas; Q7Z2W7; -.
DR   ProteomicsDB; 18; -.
DR   ProteomicsDB; 68976; -. [Q7Z2W7-1]
DR   ProteomicsDB; 68977; -. [Q7Z2W7-2]
DR   ProteomicsDB; 68978; -. [Q7Z2W7-3]
DR   Antibodypedia; 20244; 569 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   AGR; HGNC:17961; -.
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; SLYCGRV; -.
DR   OrthoDB; 201873at2759; -.
DR   PhylomeDB; Q7Z2W7; -.
DR   TreeFam; TF314204; -.
DR   PathwayCommons; Q7Z2W7; -.
DR   Reactome; R-HSA-3295583; TRP channels.
DR   SABIO-RK; Q7Z2W7; -.
DR   SignaLink; Q7Z2W7; -.
DR   SIGNOR; Q7Z2W7; -.
DR   BioGRID-ORCS; 79054; 18 hits in 1164 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 98 other cell types or tissues.
DR   ExpressionAtlas; Q7Z2W7; baseline and differential.
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: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: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:0006874; P:intracellular calcium ion homeostasis; IEA:Ensembl.
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; IPR041491; TRPM_SLOG.
DR   PANTHER; PTHR13800:SF9; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL SUBFAMILY M MEMBER 8; 1.
DR   PANTHER; PTHR13800; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY M, MEMBER 6; 1.
DR   Pfam; PF00520; Ion_trans; 1.
DR   Pfam; PF18139; LSDAT_euk; 1.
DR   Genevisible; Q7Z2W7; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane; Coiled coil;
KW   Endoplasmic reticulum; Glycoprotein; Ion channel; Ion transport; Membrane;
KW   Reference proteome; Sensory transduction; Transmembrane;
KW   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
//