TRPM4_HUMAN
ID TRPM4_HUMAN Reviewed; 1214 AA.
AC Q8TD43; A2RU25; Q7Z5D9; Q96L84; Q9NXV1;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Transient receptor potential cation channel subfamily M member 4;
DE Short=hTRPM4;
DE AltName: Full=Calcium-activated non-selective cation channel 1;
DE AltName: Full=Long transient receptor potential channel 4;
DE Short=LTrpC-4;
DE Short=LTrpC4;
DE AltName: Full=Melastatin-4;
GN Name=TRPM4 {ECO:0000312|HGNC:HGNC:17993}; Synonyms=LTRPC4;
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 2), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=11535825; DOI=10.1073/pnas.191360198;
RA Xu X.-Z.S., Moebius F., Gill D.L., Montell C.;
RT "Regulation of melastatin, a TRP-related protein, through interaction with
RT a cytoplasmic isoform.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:10692-10697(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=12015988; DOI=10.1016/s0092-8674(02)00719-5;
RA Launay P., Fleig A., Perraud A.-L., Scharenberg A.M., Penner R.,
RA Kinet J.-P.;
RT "TRPM4 is a Ca2+-activated nonselective cation channel mediating cell
RT membrane depolarization.";
RL Cell 109:397-407(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RX PubMed=12842017; DOI=10.1016/s0960-9822(03)00431-7;
RA Hofmann T., Chubanov V., Gudermann T., Montell C.;
RT "TRPM5 is a voltage-modulated and Ca(2+)-activated monovalent selective
RT cation channel.";
RL Curr. Biol. 13:1153-1158(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Prostate;
RX PubMed=12799367; DOI=10.1074/jbc.m305127200;
RA Nilius B., Prenen J., Droogmans G., Voets T., Vennekens R., Freichel M.,
RA Wissenbach U., Flockerzi V.;
RT "Voltage dependence of the Ca2+-activated cation channel TRPM4.";
RL J. Biol. Chem. 278:30813-30820(2003).
RN [5]
RP ERRATUM OF PUBMED:12799367.
RA Nilius B., Prenen J., Droogmans G., Voets T., Vennekens R., Freichel M.,
RA Wissenbach U., Flockerzi V.;
RL J. Biol. Chem. 278:42728-42728(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Trachea;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15472118; DOI=10.1161/01.res.0000147311.54833.03;
RA Earley S., Waldron B.J., Brayden J.E.;
RT "Critical role for transient receptor potential channel TRPM4 in myogenic
RT constriction of cerebral arteries.";
RL Circ. Res. 95:922-929(2004).
RN [9]
RP FUNCTION.
RX PubMed=15121803; DOI=10.1113/jphysiol.2004.063974;
RA Guinamard R., Chatelier A., Demion M., Potreau D., Patri S., Rahmati M.,
RA Bois P.;
RT "Functional characterization of a Ca(2+)-activated non-selective cation
RT channel in human atrial cardiomyocytes.";
RL J. Physiol. (Lond.) 558:75-83(2004).
RN [10]
RP ACTIVITY REGULATION, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15331675; DOI=10.1113/jphysiol.2004.070839;
RA Nilius B., Prenen J., Janssens A., Voets T., Droogmans G.;
RT "Decavanadate modulates gating of TRPM4 cation channels.";
RL J. Physiol. (Lond.) 560:753-765(2004).
RN [11]
RP ATP-BINDING, ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=14758478; DOI=10.1007/s00424-003-1221-x;
RA Nilius B., Prenen J., Voets T., Droogmans G.;
RT "Intracellular nucleotides and polyamines inhibit the Ca2+-activated cation
RT channel TRPM4b.";
RL Pflugers Arch. 448:70-75(2004).
RN [12]
RP FUNCTION.
RX PubMed=15550671; DOI=10.1126/science.1098845;
RA Launay P., Cheng H., Srivatsan S., Penner R., Fleig A., Kinet J.-P.;
RT "TRPM4 regulates calcium oscillations after T cell activation.";
RL Science 306:1374-1377(2004).
RN [13]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP SER-1145 AND SER-1152, ATP-BINDING, CALMODULIN-BINDING, AND MUTAGENESIS OF
RP LEU-275; ILE-278; ASP-279; GLY-324; GLY-325; ARG-327; SER-1145 AND
RP SER-1152.
RX PubMed=15590641; DOI=10.1074/jbc.m411089200;
RA Nilius B., Prenen J., Tang J., Wang C., Owsianik G., Janssens A., Voets T.,
RA Zhu M.X.;
RT "Regulation of the Ca2+ sensitivity of the nonselective cation channel
RT TRPM4.";
RL J. Biol. Chem. 280:6423-6433(2005).
RN [14]
RP FUNCTION, AND MUTAGENESIS OF GLN-977; GLU-981; 981-GLU--ALA-986; ASP-982
RP AND ASP-984.
RX PubMed=15845551; DOI=10.1074/jbc.m501686200;
RA Nilius B., Prenen J., Janssens A., Owsianik G., Wang C., Zhu M.X.,
RA Voets T.;
RT "The selectivity filter of the cation channel TRPM4.";
RL J. Biol. Chem. 280:22899-22906(2005).
RN [15]
RP ACTIVITY REGULATION, PIP2-BINDING, AND FUNCTION.
RX PubMed=16186107; DOI=10.1074/jbc.m506965200;
RA Zhang Z., Okawa H., Wang Y., Liman E.R.;
RT "Phosphatidylinositol 4,5-bisphosphate rescues TRPM4 channels from
RT desensitization.";
RL J. Biol. Chem. 280:39185-39192(2005).
RN [16]
RP FUNCTION.
RX PubMed=16806463; DOI=10.1016/j.ceca.2006.04.032;
RA Cheng H., Beck A., Launay P., Gross S.A., Stokes A.J., Kinet J.-P.,
RA Fleig A., Penner R.;
RT "TRPM4 controls insulin secretion in pancreatic beta-cells.";
RL Cell Calcium 41:51-61(2007).
RN [17]
RP FUNCTION, ACTIVITY REGULATION, PIP2-BINDING, AND MUTAGENESIS OF LYS-1059;
RP ARG-1072 AND 1136-ARG--ARG-1141.
RX PubMed=16424899; DOI=10.1038/sj.emboj.7600963;
RA Nilius B., Mahieu F., Prenen J., Janssens A., Owsianik G., Vennekens R.,
RA Voets T.;
RT "The Ca2+-activated cation channel TRPM4 is regulated by
RT phosphatidylinositol 4,5-biphosphate.";
RL EMBO J. 25:467-478(2006).
RN [18]
RP TISSUE SPECIFICITY.
RX PubMed=16777713; DOI=10.1080/10799890600637506;
RA Fonfria E., Murdock P.R., Cusdin F.S., Benham C.D., Kelsell R.E.,
RA McNulty S.;
RT "Tissue distribution profiles of the human TRPM cation channel family.";
RL J. Recept. Signal Transduct. 26:159-178(2006).
RN [19]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=16407466; DOI=10.1124/mol.105.021154;
RA Takezawa R., Cheng H., Beck A., Ishikawa J., Launay P., Kubota H.,
RA Kinet J.-P., Fleig A., Yamada T., Penner R.;
RT "A pyrazole derivative potently inhibits lymphocyte Ca2+ influx and
RT cytokine production by facilitating transient receptor potential melastatin
RT 4 channel activity.";
RL Mol. Pharmacol. 69:1413-1420(2006).
RN [20]
RP SUBCELLULAR LOCATION.
RX PubMed=19945433; DOI=10.1016/j.bbrc.2009.11.142;
RA Yoo J.C., Yarishkin O.V., Hwang E.M., Kim E., Kim D.G., Park N., Hong S.G.,
RA Park J.Y.;
RT "Cloning and characterization of rat transient receptor potential-
RT melastatin 4 (TRPM4).";
RL Biochem. Biophys. Res. Commun. 391:806-811(2010).
RN [21]
RP FUNCTION.
RX PubMed=20625999; DOI=10.1002/jcp.22310;
RA Armisen R., Marcelain K., Simon F., Tapia J.C., Toro J., Quest A.F.,
RA Stutzin A.;
RT "TRPM4 enhances cell proliferation through up-regulation of the beta-
RT catenin signaling pathway.";
RL J. Cell. Physiol. 226:103-109(2011).
RN [22]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=20656926; DOI=10.4049/jimmunol.1000880;
RA Weber K.S., Hildner K., Murphy K.M., Allen P.M.;
RT "Trpm4 differentially regulates Th1 and th2 function by altering calcium
RT signaling and NFAT localization.";
RL J. Immunol. 185:2836-2846(2010).
RN [23] {ECO:0007744|PDB:5WP6}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.80 ANGSTROMS) IN COMPLEX WITH CALCIUM,
RP FUNCTION, ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=29211723; DOI=10.1038/nature24674;
RA Winkler P.A., Huang Y., Sun W., Du J., Lu W.;
RT "Electron cryo-microscopy structure of a human TRPM4 channel.";
RL Nature 552:200-204(2017).
RN [24] {ECO:0007744|PDB:6BQR, ECO:0007744|PDB:6BQV}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.10 ANGSTROMS) IN COMPLEX WITH CALCIUM,
RP SUBCELLULAR LOCATION, SUBUNIT, TOPOLOGY, GLYCOSYLATION AT ASN-992, AND
RP DISULFIDE BONDS.
RX PubMed=29217581; DOI=10.1126/science.aar4510;
RA Autzen H.E., Myasnikov A.G., Campbell M.G., Asarnow D., Julius D.,
RA Cheng Y.;
RT "Structure of the human TRPM4 ion channel in a lipid nanodisc.";
RL Science 359:228-232(2018).
RN [25]
RP VARIANT PFHB1B LYS-7, CHARACTERIZATION OF VARIANT PFHB1B LYS-7,
RP SUMOYLATION, AND TISSUE SPECIFICITY.
RX PubMed=19726882; DOI=10.1172/jci38292;
RA Kruse M., Schulze-Bahr E., Corfield V., Beckmann A., Stallmeyer B.,
RA Kurtbay G., Ohmert I., Schulze-Bahr E., Brink P., Pongs O.;
RT "Impaired endocytosis of the ion channel TRPM4 is associated with human
RT progressive familial heart block type I.";
RL J. Clin. Invest. 119:2737-2744(2009).
RN [26]
RP VARIANTS PFHB1B TRP-164; THR-432 AND ASP-844.
RX PubMed=20562447; DOI=10.1161/circgenetics.109.930867;
RA Liu H., El Zein L., Kruse M., Guinamard R., Beckmann A., Bozio A.,
RA Kurtbay G., Megarbane A., Ohmert I., Blaysat G., Villain E., Pongs O.,
RA Bouvagnet P.;
RT "Gain-of-function mutations in TRPM4 cause autosomal dominant isolated
RT cardiac conduction disease.";
RL Circ. Cardiovasc. Genet. 3:374-385(2010).
RN [27]
RP VARIANTS PFHB1B HIS-131; ARG-293; THR-432; SER-582; HIS-790; ASP-844;
RP ARG-914 AND SER-970, AND VARIANTS THR-101; CYS-103; HIS-252; LYS-487 DEL;
RP ALA-561; ARG-854 AND LEU-1204.
RX PubMed=21887725; DOI=10.1002/humu.21599;
RA Stallmeyer B., Zumhagen S., Denjoy I., Duthoit G., Hebert J.L., Ferrer X.,
RA Maugenre S., Schmitz W., Kirchhefer U., Schulze-Bahr E., Guicheney P.,
RA Schulze-Bahr E.;
RT "Mutational spectrum in the Ca(2+) -activated cation channel gene TRPM4 in
RT patients with cardiac conductance disturbances.";
RL Hum. Mutat. 33:109-117(2012).
RN [28]
RP FUNCTION, INVOLVEMENT IN EKVP6, TISSUE SPECIFICITY, VARIANTS EKVP6 MET-1033
RP AND THR-1040, AND CHARACTERIZATION OF VARIANTS EKVP6 MET-1033 AND THR-1040.
RX PubMed=30528822; DOI=10.1016/j.jid.2018.10.044;
RA Wang H., Xu Z., Lee B.H., Vu S., Hu L., Lee M., Bu D., Cao X., Hwang S.,
RA Yang Y., Zheng J., Lin Z.;
RT "Gain-of-Function Mutations in TRPM4 Activation Gate Cause Progressive
RT Symmetric Erythrokeratodermia.";
RL J. Invest. Dermatol. 139:1089-1097(2019).
CC -!- FUNCTION: Calcium-activated non selective (CAN) cation channel that
CC mediates membrane depolarization (PubMed:12015988, PubMed:29211723,
CC PubMed:30528822). While it is activated by increase in intracellular
CC Ca(2+), it is impermeable to it (PubMed:12015988). Mediates transport
CC of monovalent cations (Na(+) > K(+) > Cs(+) > Li(+)), leading to
CC depolarize the membrane. It thereby plays a central role in
CC cadiomyocytes, neurons from entorhinal cortex, dorsal root and
CC vomeronasal neurons, endocrine pancreas cells, kidney epithelial cells,
CC cochlea hair cells etc. Participates in T-cell activation by modulating
CC Ca(2+) oscillations after T lymphocyte activation, which is required
CC for NFAT-dependent IL2 production. Involved in myogenic constriction of
CC cerebral arteries. Controls insulin secretion in pancreatic beta-cells.
CC May also be involved in pacemaking or could cause irregular electrical
CC activity under conditions of Ca(2+) overload. Affects T-helper 1 (Th1)
CC and T-helper 2 (Th2) cell motility and cytokine production through
CC differential regulation of calcium signaling and NFATC1 localization.
CC Enhances cell proliferation through up-regulation of the beta-catenin
CC signaling pathway. Plays a role in keratinocyte differentiation
CC (PubMed:30528822). {ECO:0000269|PubMed:11535825,
CC ECO:0000269|PubMed:12015988, ECO:0000269|PubMed:12799367,
CC ECO:0000269|PubMed:14758478, ECO:0000269|PubMed:15121803,
CC ECO:0000269|PubMed:15331675, ECO:0000269|PubMed:15472118,
CC ECO:0000269|PubMed:15550671, ECO:0000269|PubMed:15590641,
CC ECO:0000269|PubMed:15845551, ECO:0000269|PubMed:16186107,
CC ECO:0000269|PubMed:16407466, ECO:0000269|PubMed:16424899,
CC ECO:0000269|PubMed:16806463, ECO:0000269|PubMed:20625999,
CC ECO:0000269|PubMed:20656926, ECO:0000269|PubMed:29211723,
CC ECO:0000269|PubMed:30528822}.
CC -!- ACTIVITY REGULATION: Gating is voltage-dependent and repressed by
CC decavanadate (PubMed:15331675, PubMed:29211723). Calmodulin-binding
CC confers the Ca(2+) sensitivity (PubMed:15590641). ATP is able to
CC restore Ca(2+) sensitivity after desensitization (PubMed:15590641). ATP
CC inhibits channel activity (PubMed:15331675, PubMed:14758478,
CC PubMed:29211723). Phosphatidylinositol 4,5-bisphosphate (PIP2)-binding
CC strongly enhances activity, by increasing the channel's Ca(2+)
CC sensitivity and shifting its voltage dependence of activation towards
CC negative potentials (PubMed:16186107, PubMed:16424899). Activity is
CC also enhanced by 3,5-bis(trifluoromethyl)pyrazole derivative (BTP2)
CC (PubMed:16407466). {ECO:0000269|PubMed:14758478,
CC ECO:0000269|PubMed:15331675, ECO:0000269|PubMed:15590641,
CC ECO:0000269|PubMed:16186107, ECO:0000269|PubMed:16407466,
CC ECO:0000269|PubMed:16424899, ECO:0000269|PubMed:29211723}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:29211723,
CC ECO:0000269|PubMed:29217581, ECO:0000305|PubMed:12015988}.
CC -!- INTERACTION:
CC Q8TD43; P60903: S100A10; NbExp=2; IntAct=EBI-11723041, EBI-717048;
CC Q8TD43; P31949: S100A11; NbExp=2; IntAct=EBI-11723041, EBI-701862;
CC Q8TD43; P29034: S100A2; NbExp=2; IntAct=EBI-11723041, EBI-752230;
CC Q8TD43; P33764: S100A3; NbExp=2; IntAct=EBI-11723041, EBI-1044747;
CC Q8TD43; P26447: S100A4; NbExp=2; IntAct=EBI-11723041, EBI-717058;
CC Q8TD43; P33763: S100A5; NbExp=3; IntAct=EBI-11723041, EBI-7211732;
CC Q8TD43; P06703: S100A6; NbExp=2; IntAct=EBI-11723041, EBI-352877;
CC Q8TD43; P05109: S100A8; NbExp=2; IntAct=EBI-11723041, EBI-355281;
CC Q8TD43-1; Q8TD43-1: TRPM4; NbExp=2; IntAct=EBI-20594601, EBI-20594601;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:12015988, ECO:0000269|PubMed:15331675,
CC ECO:0000269|PubMed:15590641, ECO:0000269|PubMed:19945433,
CC ECO:0000269|PubMed:29211723}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:29211723, ECO:0000269|PubMed:29217581}. Endoplasmic
CC reticulum {ECO:0000269|PubMed:19945433}. Golgi apparatus
CC {ECO:0000269|PubMed:19945433}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane
CC {ECO:0000269|PubMed:11535825}. Endoplasmic reticulum. Golgi apparatus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=TRPM4b;
CC IsoId=Q8TD43-1; Sequence=Displayed;
CC Name=2; Synonyms=TRPM4a;
CC IsoId=Q8TD43-2; Sequence=VSP_021442;
CC Name=3; Synonyms=TRPM4c;
CC IsoId=Q8TD43-3; Sequence=VSP_021443;
CC -!- TISSUE SPECIFICITY: Widely expressed with a high expression in
CC intestine and prostate. In brain, it is both expressed in whole
CC cerebral arteries and isolated vascular smooth muscle cells.
CC Prominently expressed in Purkinje fibers. Expressed at higher levels in
CC T-helper 2 (Th2) cells as compared to T-helper 1 (Th1) cells. Expressed
CC in keratocytes (PubMed:30528822). {ECO:0000269|PubMed:11535825,
CC ECO:0000269|PubMed:12015988, ECO:0000269|PubMed:12799367,
CC ECO:0000269|PubMed:15472118, ECO:0000269|PubMed:16777713,
CC ECO:0000269|PubMed:19726882, ECO:0000269|PubMed:20656926,
CC ECO:0000269|PubMed:30528822}.
CC -!- PTM: Phosphorylation by PKC leads to increase the sensitivity to
CC Ca(2+). {ECO:0000269|PubMed:15590641}.
CC -!- PTM: Sumoylated. Desumoylated by SENP1. {ECO:0000269|PubMed:19726882}.
CC -!- DISEASE: Progressive familial heart block 1B (PFHB1B) [MIM:604559]: A
CC cardiac bundle branch disorder characterized by progressive alteration
CC of cardiac conduction through the His-Purkinje system, with a pattern
CC of a right bundle-branch block and/or left anterior hemiblock occurring
CC individually or together. It leads to complete atrio-ventricular block
CC causing syncope and sudden death. {ECO:0000269|PubMed:19726882,
CC ECO:0000269|PubMed:20562447, ECO:0000269|PubMed:21887725}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Erythrokeratodermia variabilis et progressiva 6 (EKVP6)
CC [MIM:618531]: A form of erythrokeratodermia variabilis et progressiva,
CC a genodermatosis characterized by the coexistence of two independent
CC skin lesions: transient erythema and hyperkeratosis that is usually
CC localized but occasionally occurs in its generalized form. Clinical
CC presentation varies significantly within a family and from one family
CC to another. Palmoplantar keratoderma is present in around 50% of cases.
CC EKVP6 inheritance is autosomal dominant. {ECO:0000269|PubMed:30528822}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the transient receptor (TC 1.A.4) family. LTrpC
CC subfamily. TRPM4 sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA90907.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY046396; AAL02142.1; -; mRNA.
DR EMBL; AF497623; AAM18083.1; -; mRNA.
DR EMBL; AY297044; AAP44473.1; -; mRNA.
DR EMBL; AY297045; AAP44474.1; -; mRNA.
DR EMBL; AY297046; AAP44475.1; -; mRNA.
DR EMBL; AJ575813; CAE05941.1; -; mRNA.
DR EMBL; AK000048; BAA90907.1; ALT_SEQ; mRNA.
DR EMBL; AK292862; BAF85551.1; -; mRNA.
DR EMBL; BC132727; AAI32728.1; -; mRNA.
DR CCDS; CCDS33073.1; -. [Q8TD43-1]
DR CCDS; CCDS56098.1; -. [Q8TD43-3]
DR RefSeq; NP_001182156.1; NM_001195227.1. [Q8TD43-3]
DR RefSeq; NP_001308212.1; NM_001321283.1. [Q8TD43-2]
DR RefSeq; NP_060106.2; NM_017636.3. [Q8TD43-1]
DR PDB; 5WP6; EM; 3.80 A; A/B/C/D=1-1214.
DR PDB; 6BQR; EM; 3.20 A; A/B/C/D=75-1168.
DR PDB; 6BQV; EM; 3.10 A; A/B/C/D=2-1214.
DR PDB; 6BWI; EM; 3.70 A; A/B/C/D=395-1176.
DR PDBsum; 5WP6; -.
DR PDBsum; 6BQR; -.
DR PDBsum; 6BQV; -.
DR PDBsum; 6BWI; -.
DR AlphaFoldDB; Q8TD43; -.
DR SMR; Q8TD43; -.
DR BioGRID; 120154; 51.
DR IntAct; Q8TD43; 24.
DR MINT; Q8TD43; -.
DR STRING; 9606.ENSP00000252826; -.
DR BindingDB; Q8TD43; -.
DR ChEMBL; CHEMBL1628469; -.
DR DrugBank; DB01016; Glyburide.
DR DrugCentral; Q8TD43; -.
DR GuidetoPHARMACOLOGY; 496; -.
DR TCDB; 1.A.4.5.4; the transient receptor potential ca(2+) channel (trp-cc) family.
DR GlyGen; Q8TD43; 1 site.
DR iPTMnet; Q8TD43; -.
DR PhosphoSitePlus; Q8TD43; -.
DR BioMuta; TRPM4; -.
DR DMDM; 74715868; -.
DR EPD; Q8TD43; -.
DR jPOST; Q8TD43; -.
DR MassIVE; Q8TD43; -.
DR MaxQB; Q8TD43; -.
DR PaxDb; Q8TD43; -.
DR PeptideAtlas; Q8TD43; -.
DR PRIDE; Q8TD43; -.
DR ProteomicsDB; 74233; -. [Q8TD43-1]
DR ProteomicsDB; 74234; -. [Q8TD43-2]
DR ProteomicsDB; 74235; -. [Q8TD43-3]
DR ABCD; Q8TD43; 1 sequenced antibody.
DR Antibodypedia; 31943; 306 antibodies from 30 providers.
DR DNASU; 54795; -.
DR Ensembl; ENST00000252826.10; ENSP00000252826.4; ENSG00000130529.16. [Q8TD43-1]
DR Ensembl; ENST00000427978.6; ENSP00000407492.1; ENSG00000130529.16. [Q8TD43-3]
DR GeneID; 54795; -.
DR KEGG; hsa:54795; -.
DR MANE-Select; ENST00000252826.10; ENSP00000252826.4; NM_017636.4; NP_060106.2.
DR UCSC; uc002pmw.4; human. [Q8TD43-1]
DR CTD; 54795; -.
DR DisGeNET; 54795; -.
DR GeneCards; TRPM4; -.
DR GeneReviews; TRPM4; -.
DR HGNC; HGNC:17993; TRPM4.
DR HPA; ENSG00000130529; Low tissue specificity.
DR MalaCards; TRPM4; -.
DR MIM; 604559; phenotype.
DR MIM; 606936; gene.
DR MIM; 618531; phenotype.
DR neXtProt; NX_Q8TD43; -.
DR OpenTargets; ENSG00000130529; -.
DR Orphanet; 130; Brugada syndrome.
DR Orphanet; 871; Familial progressive cardiac conduction defect.
DR Orphanet; 316; Progressive symmetric erythrokeratodermia.
DR PharmGKB; PA38272; -.
DR VEuPathDB; HostDB:ENSG00000130529; -.
DR eggNOG; KOG3614; Eukaryota.
DR GeneTree; ENSGT00940000158693; -.
DR HOGENOM; CLU_001390_0_1_1; -.
DR InParanoid; Q8TD43; -.
DR OMA; LAVCCRM; -.
DR OrthoDB; 738147at2759; -.
DR PhylomeDB; Q8TD43; -.
DR TreeFam; TF314204; -.
DR PathwayCommons; Q8TD43; -.
DR Reactome; R-HSA-3295583; TRP channels.
DR Reactome; R-HSA-9717207; Sensory perception of sweet, bitter, and umami (glutamate) taste.
DR SignaLink; Q8TD43; -.
DR SIGNOR; Q8TD43; -.
DR BioGRID-ORCS; 54795; 13 hits in 1081 CRISPR screens.
DR ChiTaRS; TRPM4; human.
DR GeneWiki; TRPM4; -.
DR GenomeRNAi; 54795; -.
DR Pharos; Q8TD43; Tchem.
DR PRO; PR:Q8TD43; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8TD43; protein.
DR Bgee; ENSG00000130529; Expressed in mucosa of transverse colon and 121 other tissues.
DR ExpressionAtlas; Q8TD43; baseline and differential.
DR Genevisible; Q8TD43; HS.
DR GO; GO:0005829; C:cytosol; ISS:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; ISS:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0034706; C:sodium channel complex; IDA:BHF-UCL.
DR GO; GO:0089717; C:spanning component of membrane; IDA:UniProtKB.
DR GO; GO:0044214; C:spanning component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005227; F:calcium activated cation channel activity; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0005261; F:cation channel activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0099604; F:ligand-gated calcium channel activity; IBA:GO_Central.
DR GO; GO:0005272; F:sodium channel activity; TAS:Reactome.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0019722; P:calcium-mediated signaling; IDA:BHF-UCL.
DR GO; GO:0098655; P:cation transmembrane transport; IBA:GO_Central.
DR GO; GO:0071318; P:cellular response to ATP; IEA:Ensembl.
DR GO; GO:0002407; P:dendritic cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0098662; P:inorganic cation transmembrane transport; IDA:UniProtKB.
DR GO; GO:0086045; P:membrane depolarization during AV node cell action potential; IMP:BHF-UCL.
DR GO; GO:0086048; P:membrane depolarization during bundle of His cell action potential; IMP:BHF-UCL.
DR GO; GO:0086047; P:membrane depolarization during Purkinje myocyte cell action potential; IMP:BHF-UCL.
DR GO; GO:0030502; P:negative regulation of bone mineralization; ISS:BHF-UCL.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISS:BHF-UCL.
DR GO; GO:1904179; P:positive regulation of adipose tissue development; ISS:BHF-UCL.
DR GO; GO:1903949; P:positive regulation of atrial cardiac muscle cell action potential; ISS:BHF-UCL.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:BHF-UCL.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:BHF-UCL.
DR GO; GO:0010460; P:positive regulation of heart rate; ISS:BHF-UCL.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISS:BHF-UCL.
DR GO; GO:1904199; P:positive regulation of regulation of vascular associated smooth muscle cell membrane depolarization; ISS:BHF-UCL.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISS:BHF-UCL.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0016925; P:protein sumoylation; IDA:UniProtKB.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
DR GO; GO:0002724; P:regulation of T cell cytokine production; IDA:UniProtKB.
DR GO; GO:0098911; P:regulation of ventricular cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; IDA:BHF-UCL.
DR GO; GO:0042310; P:vasoconstriction; IEA:InterPro.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR029581; TRPM4.
DR InterPro; IPR041491; TRPM_SLOG.
DR PANTHER; PTHR13800:SF6; PTHR13800:SF6; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF18139; LSDAT_euk; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; ATP-binding;
KW Calcium; Calmodulin-binding; Cell membrane; Coiled coil; Disease variant;
KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Golgi apparatus;
KW Immunity; Ion channel; Ion transport; Membrane; Metal-binding;
KW Nucleotide-binding; Palmoplantar keratoderma; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation.
FT CHAIN 1..1214
FT /note="Transient receptor potential cation channel
FT subfamily M member 4"
FT /id="PRO_0000259529"
FT TOPO_DOM 1..782
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TRANSMEM 783..803
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TOPO_DOM 804..814
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TRANSMEM 815..835
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TOPO_DOM 836..863
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TRANSMEM 864..884
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TOPO_DOM 885..886
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TRANSMEM 887..910
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TOPO_DOM 911..930
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TRANSMEM 931..951
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TOPO_DOM 952..963
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT INTRAMEM 964..984
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TOPO_DOM 985..1019
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TRANSMEM 1020..1040
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT TOPO_DOM 1041..1214
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:29211723,
FT ECO:0000269|PubMed:29217581"
FT REGION 1076..1176
FT /note="Calmodulin-binding"
FT REGION 1136..1141
FT /note="Mediates modulation by decavanadate and PIP2-
FT binding"
FT /evidence="ECO:0000269|PubMed:16424899"
FT COILED 1134..1187
FT /evidence="ECO:0000255"
FT MOTIF 975..977
FT /note="Selectivity filter"
FT /evidence="ECO:0000305|PubMed:29211723"
FT BINDING 171
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:Q7TN37"
FT BINDING 421
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q7TN37"
FT BINDING 448
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q7TN37"
FT BINDING 828
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29217581,
FT ECO:0007744|PDB:6BQV"
FT BINDING 831
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29217581,
FT ECO:0007744|PDB:6BQV"
FT BINDING 865
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:29217581,
FT ECO:0007744|PDB:6BQV"
FT BINDING 868
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305|PubMed:29217581,
FT ECO:0007744|PDB:6BQV"
FT MOD_RES 1145
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000305|PubMed:15590641"
FT MOD_RES 1152
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000305|PubMed:15590641"
FT CARBOHYD 992
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:29217581"
FT DISULFID 993..1011
FT /evidence="ECO:0000269|PubMed:29217581,
FT ECO:0007744|PDB:6BQR"
FT VAR_SEQ 1..174
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11535825,
FT ECO:0000303|PubMed:12842017"
FT /id="VSP_021442"
FT VAR_SEQ 738..882
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12842017"
FT /id="VSP_021443"
FT VARIANT 7
FT /note="E -> K (in PFHB1B; attenuated desumoylation of TRPM4
FT resulting in constitutive sumoylation of the channel
FT leading to impaired endocytosis and elevated channel
FT density at the cell surface; dbSNP:rs267607142)"
FT /evidence="ECO:0000269|PubMed:19726882"
FT /id="VAR_064042"
FT VARIANT 101
FT /note="A -> T (in dbSNP:rs113984787)"
FT /evidence="ECO:0000269|PubMed:21887725"
FT /id="VAR_066761"
FT VARIANT 103
FT /note="Y -> C (in dbSNP:rs144781529)"
FT /evidence="ECO:0000269|PubMed:21887725"
FT /id="VAR_066762"
FT VARIANT 131
FT /note="Q -> H (in PFHB1B; incomplete right bundle-branch
FT block; dbSNP:rs172146854)"
FT /evidence="ECO:0000269|PubMed:21887725"
FT /id="VAR_066763"
FT VARIANT 164
FT /note="R -> W (in PFHB1B; dbSNP:rs387907216)"
FT /evidence="ECO:0000269|PubMed:20562447"
FT /id="VAR_066764"
FT VARIANT 252
FT /note="R -> H (in dbSNP:rs146564314)"
FT /evidence="ECO:0000269|PubMed:21887725"
FT /id="VAR_066765"
FT VARIANT 293
FT /note="Q -> R (in PFHB1B; right bundle-branch block;
FT dbSNP:rs172147855)"
FT /evidence="ECO:0000269|PubMed:21887725"
FT /id="VAR_066766"
FT VARIANT 432
FT /note="A -> T (in PFHB1B; atrioventricular block;
FT dbSNP:rs201907325)"
FT /evidence="ECO:0000269|PubMed:20562447,
FT ECO:0000269|PubMed:21887725"
FT /id="VAR_066767"
FT VARIANT 487..498
FT /note="Missing"
FT /id="VAR_066768"
FT VARIANT 561
FT /note="D -> A (in dbSNP:rs56355369)"
FT /evidence="ECO:0000269|PubMed:21887725"
FT /id="VAR_066769"
FT VARIANT 582
FT /note="G -> S (in PFHB1B; atrioventricular block;
FT dbSNP:rs172149856)"
FT /evidence="ECO:0000269|PubMed:21887725"
FT /id="VAR_066770"
FT VARIANT 790
FT /note="Y -> H (in PFHB1B; atrioventricular block;
FT dbSNP:rs172150857)"
FT /evidence="ECO:0000269|PubMed:21887725"
FT /id="VAR_066771"
FT VARIANT 844
FT /note="G -> D (in PFHB1B; right bundle-branch block;
FT dbSNP:rs200038418)"
FT /evidence="ECO:0000269|PubMed:20562447,
FT ECO:0000269|PubMed:21887725"
FT /id="VAR_066772"
FT VARIANT 854
FT /note="Q -> R (in dbSNP:rs172155862)"
FT /evidence="ECO:0000269|PubMed:21887725"
FT /id="VAR_066773"
FT VARIANT 914
FT /note="K -> R (in PFHB1B; atrioventricular block;
FT dbSNP:rs172151858)"
FT /evidence="ECO:0000269|PubMed:21887725"
FT /id="VAR_066774"
FT VARIANT 970
FT /note="P -> S (in PFHB1B; incomplete right bundle-branch
FT block; dbSNP:rs172152859)"
FT /evidence="ECO:0000269|PubMed:21887725"
FT /id="VAR_066775"
FT VARIANT 1033
FT /note="I -> M (in EKVP6; increased calcium activated cation
FT channel activity; increased keratinocytes proliferation and
FT differentiation; no effect on localization at cell
FT membrane; dbSNP:rs1278993777)"
FT /evidence="ECO:0000269|PubMed:30528822"
FT /id="VAR_083166"
FT VARIANT 1040
FT /note="I -> T (in EKVP6; increased calcium activated cation
FT channel activity; increased keratinocytes proliferation and
FT differentiation; no effect on localization at cell
FT membrane; dbSNP:rs1369949906)"
FT /evidence="ECO:0000269|PubMed:30528822"
FT /id="VAR_083167"
FT VARIANT 1204
FT /note="P -> L (in dbSNP:rs150391806)"
FT /evidence="ECO:0000269|PubMed:21887725"
FT /id="VAR_066776"
FT MUTAGEN 275
FT /note="L->A,C: Abolishes ability to restore sensitivity to
FT Ca(2+) after desensitization."
FT /evidence="ECO:0000269|PubMed:15590641"
FT MUTAGEN 278
FT /note="I->N: No effect."
FT /evidence="ECO:0000269|PubMed:15590641"
FT MUTAGEN 279
FT /note="D->N: No effect."
FT /evidence="ECO:0000269|PubMed:15590641"
FT MUTAGEN 324
FT /note="G->A: No effect."
FT /evidence="ECO:0000269|PubMed:15590641"
FT MUTAGEN 325
FT /note="G->A: Abolishes ability to restore sensitivity to
FT Ca(2+) after desensitization."
FT /evidence="ECO:0000269|PubMed:15590641"
FT MUTAGEN 327
FT /note="R->A: No effect."
FT /evidence="ECO:0000269|PubMed:15590641"
FT MUTAGEN 977
FT /note="Q->E: Alters the monovalent cation permeability
FT sequence and results in a pore with moderate Ca(2+)
FT permeability."
FT /evidence="ECO:0000269|PubMed:15845551"
FT MUTAGEN 981..986
FT /note="EDMDVA->TIIDGP: Induces a functional channel that
FT combines the gating hallmarks of TRPM4 (activation by
FT Ca(2+)) with TRPV6-like sensitivity to block by
FT extracellular Ca(2+) and Mg(2+) as well as Ca(2+)
FT permeation."
FT /evidence="ECO:0000269|PubMed:15845551"
FT MUTAGEN 981
FT /note="E->A: Results in a channel with normal permeability
FT properties but with a reduced sensitivity to block by
FT intracellular spermine."
FT /evidence="ECO:0000269|PubMed:15845551"
FT MUTAGEN 982
FT /note="D->A: Results in a functional channel that exhibits
FT extremely fast desensitization, possibly indicating
FT destabilization of the pore."
FT /evidence="ECO:0000269|PubMed:15845551"
FT MUTAGEN 984
FT /note="D->A: Results in a non-functional channel with a
FT dominant negative phenotype."
FT /evidence="ECO:0000269|PubMed:15845551"
FT MUTAGEN 1059
FT /note="K->Q: Does not affect PIP2-binding."
FT /evidence="ECO:0000269|PubMed:16424899"
FT MUTAGEN 1072
FT /note="R->Q: Does not affect PIP2-binding."
FT /evidence="ECO:0000269|PubMed:16424899"
FT MUTAGEN 1136..1141
FT /note="Missing: Results in a channel with very rapid
FT desensitization and highly reduced sensitivity to PIP2."
FT /evidence="ECO:0000269|PubMed:16424899"
FT MUTAGEN 1145
FT /note="S->A: Decreases the sensitivity to Ca(2+)."
FT /evidence="ECO:0000269|PubMed:15590641"
FT MUTAGEN 1152
FT /note="S->A: Decreases the sensitivity to Ca(2+)."
FT /evidence="ECO:0000269|PubMed:15590641"
FT CONFLICT 1149
FT /note="K -> E (in Ref. 6; BAA90907)"
FT /evidence="ECO:0000305"
FT CONFLICT 1207
FT /note="P -> L (in Ref. 6; BAA90907)"
FT /evidence="ECO:0000305"
FT CONFLICT 1210
FT /note="P -> H (in Ref. 6; BAA90907)"
FT /evidence="ECO:0000305"
FT CONFLICT 1214
FT /note="D -> E (in Ref. 6; BAA90907)"
FT /evidence="ECO:0000305"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 100..107
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 118..122
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 132..139
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 142..149
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 152..155
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 162..176
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 202..205
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 230..235
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:6BQR"
FT HELIX 245..259
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 260..263
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 273..277
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 282..293
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 298..301
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 308..315
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 319..326
FT /evidence="ECO:0007829|PDB:6BQR"
FT HELIX 331..338
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 344..357
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 359..364
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 373..385
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 395..397
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 398..402
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 406..414
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 415..417
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 422..434
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 438..446
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 451..454
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 457..465
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 469..473
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 474..480
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 504..509
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 560..568
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 572..578
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 579..581
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 585..601
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 608..633
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 635..642
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 648..651
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 654..660
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 664..667
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 670..680
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 681..683
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 690..697
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 700..704
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 705..708
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 768..776
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 779..803
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 807..809
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 812..829
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 830..834
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 852..859
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 863..883
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 888..909
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 914..916
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 917..920
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 921..926
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 927..951
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 959..965
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 968..972
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 973..975
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 980..983
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 985..987
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 995..998
FT /evidence="ECO:0007829|PDB:6BQV"
FT STRAND 1005..1008
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 1017..1030
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 1031..1033
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 1034..1070
FT /evidence="ECO:0007829|PDB:6BQV"
FT TURN 1080..1086
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 1087..1093
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 1115..1141
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 1144..1166
FT /evidence="ECO:0007829|PDB:6BQV"
FT HELIX 1168..1174
FT /evidence="ECO:0007829|PDB:6BQV"
SQ SEQUENCE 1214 AA; 134301 MW; 76ADA452690ED8F5 CRC64;
MVVPEKEQSW IPKIFKKKTC TTFIVDSTDP GGTLCQCGRP RTAHPAVAME DAFGAAVVTV
WDSDAHTTEK PTDAYGELDF TGAGRKHSNF LRLSDRTDPA AVYSLVTRTW GFRAPNLVVS
VLGGSGGPVL QTWLQDLLRR GLVRAAQSTG AWIVTGGLHT GIGRHVGVAV RDHQMASTGG
TKVVAMGVAP WGVVRNRDTL INPKGSFPAR YRWRGDPEDG VQFPLDYNYS AFFLVDDGTH
GCLGGENRFR LRLESYISQQ KTGVGGTGID IPVLLLLIDG DEKMLTRIEN ATQAQLPCLL
VAGSGGAADC LAETLEDTLA PGSGGARQGE ARDRIRRFFP KGDLEVLQAQ VERIMTRKEL
LTVYSSEDGS EEFETIVLKA LVKACGSSEA SAYLDELRLA VAWNRVDIAQ SELFRGDIQW
RSFHLEASLM DALLNDRPEF VRLLISHGLS LGHFLTPMRL AQLYSAAPSN SLIRNLLDQA
SHSAGTKAPA LKGGAAELRP PDVGHVLRML LGKMCAPRYP SGGAWDPHPG QGFGESMYLL
SDKATSPLSL DAGLGQAPWS DLLLWALLLN RAQMAMYFWE MGSNAVSSAL GACLLLRVMA
RLEPDAEEAA RRKDLAFKFE GMGVDLFGEC YRSSEVRAAR LLLRRCPLWG DATCLQLAMQ
ADARAFFAQD GVQSLLTQKW WGDMASTTPI WALVLAFFCP PLIYTRLITF RKSEEEPTRE
ELEFDMDSVI NGEGPVGTAD PAEKTPLGVP RQSGRPGCCG GRCGGRRCLR RWFHFWGAPV
TIFMGNVVSY LLFLLLFSRV LLVDFQPAPP GSLELLLYFW AFTLLCEELR QGLSGGGGSL
ASGGPGPGHA SLSQRLRLYL ADSWNQCDLV ALTCFLLGVG CRLTPGLYHL GRTVLCIDFM
VFTVRLLHIF TVNKQLGPKI VIVSKMMKDV FFFLFFLGVW LVAYGVATEG LLRPRDSDFP
SILRRVFYRP YLQIFGQIPQ EDMDVALMEH SNCSSEPGFW AHPPGAQAGT CVSQYANWLV
VLLLVIFLLV ANILLVNLLI AMFSYTFGKV QGNSDLYWKA QRYRLIREFH SRPALAPPFI
VISHLRLLLR QLCRRPRSPQ PSSPALEHFR VYLSKEAERK LLTWESVHKE NFLLARARDK
RESDSERLKR TSQKVDLALK QLGHIREYEQ RLKVLEREVQ QCSRVLGWVA EALSRSALLP
PGGPPPPDLP GSKD
