Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTFPVZO)

• DTT Name: Long transient receptor potential channel 7 (TRPM7)
• Synonyms: Transient receptor potential cation channel subfamily M member 7; LTrpC-7; LTRPC7; Channel-kinase 1; CHAK1
• Gene Name: TRPM7
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Transient receptor potential catioin channel
• UniProt ID: TRPM7_HUMAN
• TTD ID: T11906
• EC Number: EC 2.7.11.1
• Sequence:
  MSQKSWIESTLTKRECVYIIPSSKDPHRCLPGCQICQQLVRCFCGRLVKQHACFTASLAM
  KYSDVKLGDHFNQAIEEWSVEKHTEQSPTDAYGVINFQGGSHSYRAKYVRLSYDTKPEVI
  LQLLLKEWQMELPKLVISVHGGMQKFELHPRIKQLLGKGLIKAAVTTGAWILTGGVNTGV
  AKHVGDALKEHASRSSRKICTIGIAPWGVIENRNDLVGRDVVAPYQTLLNPLSKLNVLNN
  LHSHFILVDDGTVGKYGAEVRLRRELEKTINQQRIHARIGQGVPVVALIFEGGPNVILTV
  LEYLQESPPVPVVVCEGTGRAADLLAYIHKQTEEGGNLPDAAEPDIISTIKKTFNFGQNE
  ALHLFQTLMECMKRKELITVFHIGSDEHQDIDVAILTALLKGTNASAFDQLILTLAWDRV
  DIAKNHVFVYGQQWLVGSLEQAMLDALVMDRVAFVKLLIENGVSMHKFLTIPRLEELYNT
  KQGPTNPMLFHLVRDVKQGNLPPGYKITLIDIGLVIEYLMGGTYRCTYTRKRFRLIYNSL
  GGNNRRSGRNTSSSTPQLRKSHESFGNRADKKEKMRHNHFIKTAQPYRPKIDTVMEEGKK
  KRTKDEIVDIDDPETKRFPYPLNELLIWACLMKRQVMARFLWQHGEESMAKALVACKIYR
  SMAYEAKQSDLVDDTSEELKQYSNDFGQLAVELLEQSFRQDETMAMKLLTYELKNWSNST
  CLKLAVSSRLRPFVAHTCTQMLLSDMWMGRLNMRKNSWYKVILSILVPPAILLLEYKTKA
  EMSHIPQSQDAHQMTMDDSENNFQNITEEIPMEVFKEVRILDSNEGKNEMEIQMKSKKLP
  ITRKFYAFYHAPIVKFWFNTLAYLGFLMLYTFVVLVQMEQLPSVQEWIVIAYIFTYAIEK
  VREIFMSEAGKVNQKIKVWFSDYFNISDTIAIISFFIGFGLRFGAKWNFANAYDNHVFVA
  GRLIYCLNIIFWYVRLLDFLAVNQQAGPYVMMIGKMVANMFYIVVIMALVLLSFGVPRKA
  ILYPHEAPSWTLAKDIVFHPYWMIFGEVYAYEIDVCANDSVIPQICGPGTWLTPFLQAVY
  LFVQYIIMVNLLIAFFNNVYLQVKAISNIVWKYQRYHFIMAYHEKPVLPPPLIILSHIVS
  LFCCICKRRKKDKTSDGPKLFLTEEDQKKLHDFEEQCVEMYFNEKDDKFHSGSEERIRVT
  FERVEQMCIQIKEVGDRVNYIKRSLQSLDSQIGHLQDLSALTVDTLKTLTAQKASEASKV
  HNEITRELSISKHLAQNLIDDGPVRPSVWKKHGVVNTLSSSLPQGDLESNNPFHCNILMK
  DDKDPQCNIFGQDLPAVPQRKEFNFPEAGSSSGALFPSAVSPPELRQRLHGVELLKIFNK
  NQKLGSSSTSIPHLSSPPTKFFVSTPSQPSCKSHLETGTKDQETVCSKATEGDNTEFGAF
  VGHRDSMDLQRFKETSNKIKILSNNNTSENTLKRVSSLAGFTDCHRTSIPVHSKQAEKIS
  RRPSTEDTHEVDSKAALIPDWLQDRPSNREMPSEEGTLNGLTSPFKPAMDTNYYYSAVER
  NNLMRLSQSIPFTPVPPRGEPVTVYRLEESSPNILNNSMSSWSQLGLCAKIEFLSKEEMG
  GGLRRAVKVQCTWSEHDILKSGHLYIIKSFLPEVVNTWSSIYKEDTVLHLCLREIQQQRA
  AQKLTFAFNQMKPKSIPYSPRFLEVFLLYCHSAGQWFAVEECMTGEFRKYNNNNGDEIIP
  TNTLEEIMLAFSHWTYEYTRGELLVLDLQGVGENLTDPSVIKAEEKRSCDMVFGPANLGE
  DAIKNFRAKHHCNSCCRKLKLPDLKRNDYTPDKIIFPQDEPSDLNLQPGNSTKESESTNS
  VRLML
• Function: Essential ion channel and serine/threonine-protein kinase. Divalent cation channel permeable to calcium and magnesium. Has a central role in magnesium ion homeostasis and in the regulation of anoxic neuronal cell death. Involved in TNF-induced necroptosis downstream of MLKL by mediating calcium influx. The kinase activity is essential for the channel function. May be involved in a fundamental process that adjusts plasma membrane divalent cation fluxes according to the metabolic state of the cell. Phosphorylates annexin A1 (ANXA1).
• KEGG Pathway:
  Necroptosis (hsa04217)
  Cellular senescence (hsa04218)
  NOD-like receptor signaling pathway (hsa04621)
  Mineral absorption (hsa04978)
• Reactome Pathway: TRP channels (R-HSA-3295583)

Molecular Interaction Atlas (MIA) of This DTT

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-APB	DM9AKVR	Discovery agent	N.A.	Investigative	[2]
carvacrol	DMINM2D	Discovery agent	N.A.	Investigative	[3]
PIP2	DMOZV7N	Discovery agent	N.A.	Investigative	[1]
waixenicin A	DMB6H35	Discovery agent	N.A.	Investigative	[4]

References

• [1] The TRPM7 channel is inactivated by PIP(2) hydrolysis. Nat Cell Biol. 2002 May;4(5):329-36.
• [2] LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability. Nature. 2001 May 31;411(6837):590-5.
• [3] Carvacrol is a novel inhibitor of Drosophila TRPL and mammalian TRPM7 channels. Cell Calcium. 2009 Mar;45(3):300-9.
• [4] Waixenicin A inhibits cell proliferation through magnesium-dependent block of transient receptor potential melastatin 7 (TRPM7) channels. J Biol Chem. 2011 Nov 11;286(45):39328-35.