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 27-MAR-2024, entry version 164. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 EMDB; EMD-7132; -. DR EMDB; EMD-7133; -. DR EMDB; EMD-7299; -. DR EMDB; EMD-8871; -. DR SMR; Q8TD43; -. DR BioGRID; 120154; 53. 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 ca2+/cation channel (trp-cc) family. DR GlyCosmos; Q8TD43; 1 site, No reported glycans. DR GlyGen; Q8TD43; 1 site. DR iPTMnet; Q8TD43; -. DR PhosphoSitePlus; Q8TD43; -. DR SwissPalm; Q8TD43; -. DR BioMuta; TRPM4; -. DR DMDM; 74715868; -. DR EPD; Q8TD43; -. DR jPOST; Q8TD43; -. DR MassIVE; Q8TD43; -. DR MaxQB; Q8TD43; -. DR PaxDb; 9606-ENSP00000252826; -. DR PeptideAtlas; Q8TD43; -. DR ProteomicsDB; 74233; -. [Q8TD43-1] DR ProteomicsDB; 74234; -. [Q8TD43-2] DR ProteomicsDB; 74235; -. [Q8TD43-3] DR Pumba; Q8TD43; -. DR ABCD; Q8TD43; 1 sequenced antibody. DR Antibodypedia; 31943; 360 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 AGR; HGNC:17993; -. 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; 201873at2759; -. 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; 14 hits in 1162 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 123 other cell types or tissues. DR ExpressionAtlas; Q8TD43; baseline and differential. 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:0016020; C:membrane; IDA:UniProtKB. 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:HPA. DR GO; GO:0034706; C:sodium channel complex; IDA:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0005227; F:calcium-activated cation channel activity; IDA:UniProtKB. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. 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: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 InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR041491; TRPM_SLOG. DR PANTHER; PTHR13800:SF6; TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL SUBFAMILY M MEMBER 4; 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 SUPFAM; SSF140860; Pseudo ankyrin repeat-like; 1. DR Genevisible; Q8TD43; HS. 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 //