TRPM7
entrez
54822
canonical
uniprot
Q96QT4
canonical
ensembl
ENSG00000092439
resolver
ensp
ENSP00000453277
resolver
ensp
ENSP00000495860
resolver
enst
ENST00000560955
resolver
enst
ENST00000646667
resolver
genesymbol
TRPM7
resolver
genesymbol_syn
CHAK1
resolver
genesymbol_syn
LTRPC7
resolver
hgnc
HGNC:17994
resolver
uniprot
H0YLN8
resolver
uniprot
Q6ZMF5
resolver
uniprot
Q86VJ4
resolver
uniprot
Q8NBW2
resolver
uniprot
Q9BXB2
resolver
uniprot
Q9NXQ2
resolver
uniprot_entry
H0YLN8_HUMAN
resolver
uniprot_entry
TRPM7_HUMAN
resolver
uniprot_sec
Q6ZMF5
resolver
uniprot_sec
Q86VJ4
resolver
uniprot_sec
Q8NBW2
resolver
uniprot_sec
Q9BXB2
resolver
uniprot_sec
Q9NXQ2
resolver
activity_regulation
ACTIVITY REGULATION: Channel displays constitutive activity. Channel activity is negatively regulated by cytosolic Mg(2+) and Mg-ATP (PubMed:11385574, PubMed:16051700). Channel activity is negatively regulated by low intracellular pH (By similarity). Resting free cytosolic Mg(2+) and Mg-ATP concentrations seem to be sufficient to block native TRPM7 channel activity (By similarity). TRPM7 channel activity is highly dependent on membrane levels of phosphatidylinositol 4,5 bisphosphate (PIP2). PIP2 hydrolysis negatively regulates TRPM7 channel activity (By similarity). TRPM7 kinase activity does not affect channel activity (By similarity). The kinase activity is controlled through the autophosphorylation of a serine/threonine-rich region located N-terminal to the catalytic domain (PubMed:18365021). {ECO:0000250|UniProtKB:Q923J1, ECO:0000250|UniProtKB:Q925B3, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:16051700, ECO:0000269|PubMed:18365021}.
uniprot
proteins
amino_acid_sequence
MSQKSWIESTLTKRECVYIIPSSKDPHRCLPGCQICQQLVRCFCGRLVKQHACFTASLAMKYSDVKLGDHFNQAIEEWSVEKHTEQSPTDAYGVINFQGGSHSYRAKYVRLSYDTKPEVILQLLLKEWQMELPKLVISVHGGMQKFELHPRIKQLLGKGLIKAAVTTGAWILTGGVNTGVAKHVGDALKEHASRSSRKICTIGIAPWGVIENRNDLVGRDVVAPYQTLLNPLSKLNVLNNLHSHFILVDDGTVGKYGAEVRLRRELEKTINQQRIHARIGQGVPVVALIFEGGPNVILTVLEYLQESPPVPVVVCEGTGRAADLLAYIHKQTEEGGNLPDAAEPDIISTIKKTFNFGQNEALHLFQTLMECMKRKELITVFHIGSDEHQDIDVAILTALLKGTNASAFDQLILTLAWDRVDIAKNHVFVYGQQWLVGSLEQAMLDALVMDRVAFVKLLIENGVSMHKFLTIPRLEELYNTKQGPTNPMLFHLVRDVKQGNLPPGYKITLIDIGLVIEYLMGGTYRCTYTRKRFRLIYNSLGGNNRRSGRNTSSSTPQLRKSHESFGNRADKKEKMRHNHFIKTAQPYRPKIDTVMEEGKKKRTKDEIVDIDDPETKRFPYPLNELLIWACLMKRQVMARFLWQHGEESMAKALVACKIYRSMAYEAKQSDLVDDTSEELKQYSNDFGQLAVELLEQSFRQDETMAMKLLTYELKNWSNSTCLKLAVSSRLRPFVAHTCTQMLLSDMWMGRLNMRKNSWYKVILSILVPPAILLLEYKTKAEMSHIPQSQDAHQMTMDDSENNFQNITEEIPMEVFKEVRILDSNEGKNEMEIQMKSKKLPITRKFYAFYHAPIVKFWFNTLAYLGFLMLYTFVVLVQMEQLPSVQEWIVIAYIFTYAIEKVREIFMSEAGKVNQKIKVWFSDYFNISDTIAIISFFIGFGLRFGAKWNFANAYDNHVFVAGRLIYCLNIIFWYVRLLDFLAVNQQAGPYVMMIGKMVANMFYIVVIMALVLLSFGVPRKAILYPHEAPSWTLAKDIVFHPYWMIFGEVYAYEIDVCANDSVIPQICGPGTWLTPFLQAVYLFVQYIIMVNLLIAFFNNVYLQVKAISNIVWKYQRYHFIMAYHEKPVLPPPLIILSHIVSLFCCICKRRKKDKTSDGPKLFLTEEDQKKLHDFEEQCVEMYFNEKDDKFHSGSEERIRVTFERVEQMCIQIKEVGDRVNYIKRSLQSLDSQIGHLQDLSALTVDTLKTLTAQKASEASKVHNEITRELSISKHLAQNLIDDGPVRPSVWKKHGVVNTLSSSLPQGDLESNNPFHCNILMKDDKDPQCNIFGQDLPAVPQRKEFNFPEAGSSSGALFPSAVSPPELRQRLHGVELLKIFNKNQKLGSSSTSIPHLSSPPTKFFVSTPSQPSCKSHLETGTKDQETVCSKATEGDNTEFGAFVGHRDSMDLQRFKETSNKIKILSNNNTSENTLKRVSSLAGFTDCHRTSIPVHSKQAEKISRRPSTEDTHEVDSKAALIPDWLQDRPSNREMPSEEGTLNGLTSPFKPAMDTNYYYSAVERNNLMRLSQSIPFTPVPPRGEPVTVYRLEESSPNILNNSMSSWSQLGLCAKIEFLSKEEMGGGLRRAVKVQCTWSEHDILKSGHLYIIKSFLPEVVNTWSSIYKEDTVLHLCLREIQQQRAAQKLTFAFNQMKPKSIPYSPRFLEVFLLYCHSAGQWFAVEECMTGEFRKYNNNNGDEIIPTNTLEEIMLAFSHWTYEYTRGELLVLDLQGVGENLTDPSVIKAEEKRSCDMVFGPANLGEDAIKNFRAKHHCNSCCRKLKLPDLKRNDYTPDKIIFPQDEPSDLNLQPGNSTKESESTNSVRLML
uniprot
proteins
disease_involvement
DISEASE: Amyotrophic lateral sclerosis-parkinsonism/dementia complex 1 (ALS-PDC1) [MIM:105500]: A neurodegenerative disorder characterized by chronic, progressive and uniformly fatal amyotrophic lateral sclerosis and parkinsonism-dementia. Both diseases are known to occur in the same kindred, the same sibship and even the same individual. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Note=TRPM7 variants have been identified as a potential cause of disease in patients suffering from seizures and muscle cramps due to magnesium deficiency and episodes of hypocalcemia. {ECO:0000269|PubMed:35561741}.
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Bifunctional protein that combines an ion channel with an intrinsic kinase domain, enabling it to modulate cellular functions either by conducting ions through the pore or by phosphorylating downstream proteins via its kinase domain. The channel is highly permeable to divalent cations, specifically calcium (Ca2+), magnesium (Mg2+) and zinc (Zn2+) and mediates their influx (PubMed:11385574, PubMed:12887921, PubMed:15485879, PubMed:24316671, PubMed:35561741, PubMed:36027648). Controls a wide range of biological processes such as Ca2(+), Mg(2+) and Zn(2+) homeostasis, vesicular Zn(2+) release channel and intracellular Ca(2+) signaling, embryonic development, immune responses, cell motility, proliferation and differentiation (By similarity). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:18365021). In vivo, TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways. In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (PubMed:15485879, PubMed:18394644). {ECO:0000250|UniProtKB:Q923J1, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:12887921, ECO:0000269|PubMed:15485879, ECO:0000269|PubMed:18365021, ECO:0000269|PubMed:18394644, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741, ECO:0000269|PubMed:36027648}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000250|UniProtKB:Q923J1}.; FUNCTION: [TRPM7 kinase, cleaved form]: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. In immune cells, the TRPM7 kinase domain is clipped from the channel domain by caspases in response to Fas-receptor stimulation. The cleaved kinase fragments can translocate to the nucleus, and bind chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones known to be functionally important for cell differentiation and embryonic development. {ECO:0000250|UniProtKB:Q923J1}.
uniprot
proteins
mass_dalton
212697
uniprot
proteins
mutagenesis
MUTAGEN 1648; /note="K->R: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:12887921"; MUTAGEN 1799; /note="G->D: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:12887921
uniprot
proteins
post_translational_modification
PTM: Palmitoylated; palmitoylation at Cys-1143, Cys-1144 and Cys-1146 promotes TRPM7 trafficking from the Golgi to the surface membrane. {ECO:0000269|PubMed:36027648}.; PTM: Autophosphorylated; autophosphorylation of C-terminus regulates TRPM7 kinase activity towards its substrates. {ECO:0000269|PubMed:18365021}.; PTM: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion. TRPM7 is cleaved by caspase-8, dissociating the kinase from the ion-conducting pore. The cleaved kinase fragments (M7CKs) can translocate to the cell nucleus and binds chromatin-remodeling complex proteins in a Zn(2+)-dependent manner to ultimately phosphorylate specific Ser/Thr residues of histones. {ECO:0000250|UniProtKB:Q923J1}.
uniprot
proteins
protein_family
ALPK subfamily; Transient receptor (TC 1.A.4) family
uniprot
proteins
protein_family
Alpha-type protein kinase family
uniprot
proteins
protein_family
LTrpC subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
TRPM7 sub-subfamily
uniprot
proteins
pubmed
11385574
uniprot
proteins
pubmed
12887921
uniprot
proteins
pubmed
14594813
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14976260
uniprot
proteins
pubmed
15485879
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16051700
uniprot
proteins
pubmed
16636202
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18365021
uniprot
proteins
pubmed
18394644
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24316671
uniprot
proteins
pubmed
35561741
uniprot
proteins
pubmed
36027648
uniprot
proteins
sequence_length
1865
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:35561741}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q923J1}. Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:Q923J1}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q923J1}. Note=Localized largely in intracellular Zn(2+)-storage vesicles. {ECO:0000250|UniProtKB:Q923J1}.; SUBCELLULAR LOCATION: [TRPM7 kinase, cleaved form]: Nucleus {ECO:0000250|UniProtKB:Q923J1}.
uniprot
proteins
transmembrane_region
TRANSMEM 851..876; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:Q923J1"; TRANSMEM 883..904; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:Q923J1"; TRANSMEM 924..943; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:Q923J1"; TRANSMEM 957..980; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:Q923J1"; TRANSMEM 1000..1023; /note="Helical; Name=5"; /evidence="ECO:0000250|UniProtKB:Q923J1"; TRANSMEM 1070..1098; /note="Helical; Name=6"; /evidence="ECO:0000250|UniProtKB:Q923J1
uniprot
proteins