TRPM7 Membrane Protein Introduction

Introduction of TRPM7

Transient receptor potential cation channel subfamily M member 7 (TRPM7) is a protein encoded by the gene TRPM7, which is mapped to the chromosome 15q21.2. Similar to other TRPs, TRPM7 comprises tetrameric ion channels with each subunit containing six-transmembrane (6 TM) segments. Notably, TRPM7 a bifunctional protein with ion channel and kinase domains in its carboxyl terminus, so it can transport ions across the cell membrane as well as transduce signals to the cytosol. TRPM7 has a broad expression in thyroid, small intestine, colon, kidney, testis, adrenal, lymph node, ovary, and multiple other tissues.

Basic Information of TRPM7
Protein Name	Transient receptor potential cation channel subfamily M member 7
Gene Name	TRPM7
Aliases	ALSPDC, CHAK, CHAK1, LTRPC7, LTrpC-7, TRP-PLIK
Organism	Homo sapiens (Human)
UniProt ID	Q96QT4
Transmembrane Times	6
Length (aa)	1017
Sequence	MSQKSWIESTLTKRECVYIIPSSKDPHRCLPGCQICQQLVRCFCGRLVKQHACFTASLAMKYSDVKLGDHFNQAIEEWSVEKHTEQSPTDAYGVINFQGGSHSYRAKYVRLSYDTKPEVILQLLLKEWQMELPKLVISVHGGMQKFELHPRIKQLLGKGLIKAAVTTGAWILTGGVNTGVAKHVGDALKEHASRSSRKICTIGIAPWGVIENRNDLVGRDVVAPYQTLLNPLSKLNVLNNLHSHFILVDDGTVGKYGAEVRLRRELEKTINQQRIHARIGQGVPVVALIFEGGPNVILTVLEYLQESPPVPVVVCEGTGRAADLLAYIHKQTEEGGNLPDAAEPDIISTIKKTFNFGQNEALHLFQTLMECMKRKELITVFHIGSDEHQDIDVAILTALLKGTNASAFDQLILTLAWDRVDIAKNHVFVYGQQWLVGSLEQAMLDALVMDRVAFVKLLIENGVSMHKFLTIPRLEELYNTKQGPTNPMLFHLVRDVKQGNLPPGYKITLIDIGLVIEYLMGGTYRCTYTRKRFRLIYNSLGGNNRRSGRNTSSSTPQLRKSHESFGNRADKKEKMRHNHFIKTAQPYRPKIDTVMEEGKKKRTKDEIVDIDDPETKRFPYPLNELLIWACLMKRQVMARFLWQHGEESMAKALVACKIYRSMAYEAKQSDLVDDTSEELKQYSNDFGQLAVELLEQSFRQDETMAMKLLTYELKNWSNSTCLKLAVSSRLRPFVAHTCTQMLLSDMWMGRLNMRKNSWYKVILSILVPPAILLLEYKTKAEMSHIPQSQDAHQMTMDDSENNFQNITEEIPMEVFKEVRILDSNEGKNEMEIQMKSKKLPITRKFYAFYHAPIVKFWFNTLAYLGFLMLYTFVVLVQMEQLPSVQEWIVIAYIFTYAIEKVREIFMSEAGKVNQKIKVWFSDYFNISDTIAIISFFIGFGLRFGAKWNFANAYDNHVFVAGRLIYCLNIIFWYVRLLDFLAVNQQAGPYVMMIGKMVANMFYIVVIMALVLLSFGVPRKAILYPHEAPSWTLAKDIVFHPYWMIFGEVYAYEIDVCANDSVIPQICGPGTWLTPFLQAVYLFVQYIIMVNLLIAFFNNVYLQVKAISNIVWKYQRYHFIMAYHEKPVLPPPLIILSHIVSLFCCICKRRKKDKTSDGPKLFLTEEDQKKLHDFEEQCVEMYFNEKDDKFHSGSEERIRVTFERVEQMCIQIKEVGDRVNYIKRSLQSLDSQIGHLQDLSALTVDTLKTLTAQKASEASKVHNEITRELSISKHLAQNLIDDGPVRPSVWKKHGVVNTLSSSLPQGDLESNNPFHCNILMKDDKDPQCNIFGQDLPAVPQRKEFNFPEAGSSSGALFPSAVSPPELRQRLHGVELLKIFNKNQKLGSSSTSIPHLSSPPTKFFVSTPSQPSCKSHLETGTKDQETVCSKATEGDNTEFGAFVGHRDSMDLQRFKETSNKIKILSNNNTSENTLKRVSSLAGFTDCHRTSIPVHSKQAEKISRRPSTEDTHEVDSKAALIPDWLQDRPSNREMPSEEGTLNGLTSPFKPAMDTNYYYSAVERNNLMRLSQSIPFTPVPPRGEPVTVYRLEESSPNILNNSMSSWSQLGLCAKIEFLSKEEMGGGLRRAVKVQCTWSEHDILKSGHLYIIKSFLPEVVNTWSSIYKEDTVLHLCLREIQQQRAAQKLTFAFNQMKPKSIPYSPRFLEVFLLYCHSAGQWFAVEECMTGEFRKYNNNNGDEIIPTNTLEEIMLAFSHWTYEYTRGELLVLDLQGVGENLTDPSVIKAEEKRSCDMVFGPANLGEDAIKNFRAKHHCNSCCRKLKLPDLKRNDYTPDKIIFPQDEPSDLNLQPGNSTKESESTNSVRLML

Function of TRPM7 Membrane Protein

TRPM7 is an outwardly-rectifying divalent cation channel that is permeable to several divalent cations, including Zn²⁺, Mg²⁺, and Ca²⁺, as well as common monovalent cations such as Na⁺ and K⁺. TRPM7 activity is indispensable for the normal channel function, which is associated with the mediation of intracellular Ca²⁺ levels and Mg²⁺ homeostasis. So, TRPM7 is involved in multiple biological processes, such as cell adhesion, cytoskeletal organization, cell migration, embryonic development and organogenesis. It has been reported that TRPM7 is localized in the membrane of sympathetic neuronal acetylcholine (ACh)-secreting synaptic vesicles as part of a molecular complex of synaptic vesicle-specific proteins, where it participates in the regulation of anoxic neuronal cell death. Defects in TRPM7 gene have been associated with magnesium deficiency in human microvascular endothelial cells.

Fig.1 CryoEM structure of truncated mouse TRPM7. (Duan, 2018)

Application of TRPM7 Membrane Protein in Literature

Huang Y., et al. TRPM7 channels play a role in high glucose-induced endoplasmic reticulum stress and neuronal cell apoptosis. J Biol Chem. 2018, 293(37):14393-14406. PubMed ID: 30076216

This article suggests that TRPM7 channel activities play a key role in high-glucose-associated endoplasmic reticulum stress and cytotoxicity via an apoptosis-inducing signaling cascade involving high-glucose, inducible nitric oxide synthase, TRPM7, other endoplasmic reticulum stress proteins, and caspases.
Takahashi K., et al. TRPM7-mediated spontaneous Ca²⁺ entry regulates the proliferation and differentiation of human leukemia cell line K562. Physiol Rep. 2018, 6(14):e13796. PubMed ID: 30033625

This article reveals that spontaneous calcium ion influx through the constitutively active TRPM7 ion channels may significantly modulate both erythroid differentiation potentials and proliferative capacity of K562 cells.
Liu Y., et al. TRPM7 Is Required for Normal Synapse Density, Learning, and Memory at Different Developmental Stages. Cell Rep. 2018, 23(12):3480-3491. PubMed ID: 29924992

This article confirms that brain TRPM7 is essential for having normal cognitive and synaptic functions under physiological, non-pathological conditions.
Krishnamoorthy M., et al. The channel-kinase TRPM7 regulates antigen gathering and internalization in B cells. Sci Signal. 2018, 11(533). PubMed ID: 29871912

This report suggests that TRPM7 plays a crucial role in a process necessary for B cell affinity maturation and the secretion of high-affinity antibodies.
Kuipers A.J., et al. TRPM7 controls mesenchymal features of breast cancer cells by tensional regulation of SOX4. Biochim Biophys Acta. 2018, 1864(7):2409-2419. PubMed ID: 29684587

This article demonstrates that a transcription factor SOX4 is uniquely sensitive to cellular tension and suggests that TRPM7 may play a special role in the progression of breast cancer via tensional regulation of SOX4.

TRPM7 Preparation Options

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Reference

Duan J, et al. (2018). Structure of the mammalian TRPM7, a magnesium channel required during embryonic development. Proc Natl Acad Sci Usa.

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