Trpm7
entrez
58800
canonical
uniprot
Q923J1
canonical
ensembl
ENSMUSG00000027365
resolver
ensp
ENSMUSP00000028843
resolver
ensp
ENSMUSP00000099513
resolver
enst
ENSMUST00000028843
resolver
enst
ENSMUST00000103224
resolver
genesymbol
Trpm7
resolver
genesymbol_syn
Chak
resolver
genesymbol_syn
Ltrpc7
resolver
uniprot
A2AI57
resolver
uniprot
A2AI58
resolver
uniprot
Q8C7S7
resolver
uniprot
Q8CE54
resolver
uniprot
Q921Y5
resolver
uniprot
Q925B2
resolver
uniprot
Q9CUT2
resolver
uniprot
Q9JLQ1
resolver
uniprot_entry
A2AI57_MOUSE
resolver
uniprot_entry
TRPM7_MOUSE
resolver
uniprot_sec
A2AI58
resolver
uniprot_sec
Q8C7S7
resolver
uniprot_sec
Q8CE54
resolver
uniprot_sec
Q921Y5
resolver
uniprot_sec
Q925B2
resolver
uniprot_sec
Q9CUT2
resolver
uniprot_sec
Q9JLQ1
resolver
activity_regulation
ACTIVITY REGULATION: Channel displays constitutive activity (PubMed:35389104). Channel activity is negatively regulated by cytosolic Mg(2+), Mg-ATP and low intracellular pH (PubMed:11385574, PubMed:16260839, PubMed:35389104). Resting free cytosolic Mg(2+) and Mg-ATP concentrations seem to be sufficient to block native TRPM7 channel activity (PubMed:21045827, PubMed:28821869, PubMed:29203869). 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 (PubMed:25030553, PubMed:29203869). The kinase activity is controlled through the autophosphorylation of a serine/threonine-rich region located N-terminal to the catalytic domain (PubMed:18974357). {ECO:0000250|UniProtKB:Q925B3, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:16260839, ECO:0000269|PubMed:18974357, ECO:0000269|PubMed:21045827, ECO:0000269|PubMed:25030553, ECO:0000269|PubMed:28821869, ECO:0000269|PubMed:29203869, ECO:0000269|PubMed:35389104}.
uniprot
proteins
amino_acid_sequence
MSQKSWIESTLTKRECVYIIPSSKDPHRCLPGCQICQQLVRCFCGRLVKQHACFTASLAMKYSDVKLGEHFNQAIEEWSVEKHTEQSPTDAYGVINFQGGSHSYRAKYVRLSYDTKPEIILQLLLKEWQMELPKLVISVHGGMQKFELHPRIKQLLGKGLIKAAVTTGAWILTGGVNTGVAKHVGDALKEHASRSSRKICTIGIAPWGVIENRNDLVGRDVVAPYQTLLNPLSKLNVLNNLHSHFILVDDGTVGKYGAEVRLRRELEKTINQQRIHARIGQGVPVVALIFEGGPNVILTVLEYLQESPPVPVVVCEGTGRAADLLAYIHKQTEEGGNLPDAAEPDIISTIKKTFNFGQSEAVHLFQTMMECMKKKELITVFHIGSEDHQDIDVAILTALLKGTNASAFDQLILTLAWDRVDIAKNHVFVYGQQWLVGSLEQAMLDALVMDRVSFVKLLIENGVSMHKFLTIPRLEELYNTKQGPTNPMLFHLIRDVKQGNLPPGYKITLIDIGLVIEYLMGGTYRCTYTRKRFRLIYNSLGGNNRRSGRNTSSSTPQLRKSHETFGNRADKKEKMRHNHFIKTAQPYRPKMDASMEEGKKKRTKDEIVDIDDPETKRFPYPLNELLIWACLMKRQVMARFLWQHGEESMAKALVACKIYRSMAYEAKQSDLVDDTSEELKQYSNDFGQLAVELLEQSFRQDETMAMKLLTYELKNWSNSTCLKLAVSSRLRPFVAHTCTQMLLSDMWMGRLNMRKNSWYKVILSILVPPAILMLEYKTKAEMSHIPQSQDAHQMTMEDSENNFHNITEEIPMEVFKEVKILDSSDGKNEMEIHIKSKKLPITRKFYAFYHAPIVKFWFNTLAYLGFLMLYTFVVLVKMEQLPSVQEWIVIAYIFTYAIEKVREVFMSEAGKISQKIKVWFSDYFNVSDTIAIISFFVGFGLRFGAKWNYINAYDNHVFVAGRLIYCLNIIFWYVRLLDFLAVNQQAGPYVMMIGKMVANMFYIVVIMALVLLSFGVPRKAILYPHEEPSWSLAKDIVFHPYWMIFGEVYAYEIDVCANDSTLPTICGPGTWLTPFLQAVYLFVQYIIMVNLLIAFFNNVYLQVKAISNIVWKYQRYHFIMAYHEKPVLPPPLIILSHIVSLFCCVCKRRKKDKTSDGPKLFLTEEDQKKLHDFEEQCVEMYFDEKDDKFNSGSEERIRVTFERVEQMSIQIKEVGDRVNYIKRSLQSLDSQIGHLQDLSALTVDTLKTLTAQKASEASKVHNEITRELSISKHLAQNLIDDVPVRPLWKKPSAVNTLSSSLPQGDRESNNPFLCNIFMKDEKDPQYNLFGQDLPVIPQRKEFNIPEAGSSCGALFPSAVSPPELRQRRHGVEMLKIFNKNQKLGSSPNSSPHMSSPPTKFSVSTPSQPSCKSHLESTTKDQEPIFYKAAEGDNIEFGAFVGHRDSMDLQRFKETSNKIRELLSNDTPENTLKHVGAAGYSECCKTSTSLHSVQAESCSRRASTEDSPEVDSKAALLPDWLRDRPSNREMPSEGGTLNGLASPFKPVLDTNYYYSAVERNNLMRLSQSIPFVPVPPRGEPVTVYRLEESSPSILNNSMSSWSQLGLCAKIEFLSKEEMGGGLRRAVKVLCTWSEHDILKSGHLYIIKSFLPEVINTWSSIYKEDTVLHLCLREIQQQRAAQKLTFAFNQMKPKSIPYSPRFLEVFLLYCHSAGQWFAVEECMTGEFRKYNNNNGDEIIPTNTLEEIMLAFSHWTYEYTRGELLVLDLQGVGENLTDPSVIKAEEKRSCDMVFGPANLGEDAIKNFRAKHHCNSCCRKLKLPDLKRNDYTPDKIIFPQDESSDLNLQSGNSTKESEATNSVRLML
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:11161216, PubMed:11385574, PubMed:28696294, PubMed:29343440). 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 (PubMed:18974357, PubMed:21045827, PubMed:22203997, PubMed:23878236, PubMed:28696294, PubMed:29203869, PubMed:29343440, PubMed:30770447). The C-terminal alpha-kinase domain autophosphorylates cytoplasmic residues of TRPM7 (PubMed:22222377). TRPM7 phosphorylates SMAD2, suggesting that TRPM7 kinase may play a role in activating SMAD signaling pathways (PubMed:29203869). In vitro, TRPM7 kinase phosphorylates ANXA1 (annexin A1), myosin II isoforms and a variety of proteins with diverse cellular functions (By similarity). {ECO:0000250|UniProtKB:Q96QT4, ECO:0000269|PubMed:11161216, ECO:0000269|PubMed:11385574, ECO:0000269|PubMed:18974357, ECO:0000269|PubMed:21045827, ECO:0000269|PubMed:22203997, ECO:0000269|PubMed:22222377, ECO:0000269|PubMed:23878236, ECO:0000269|PubMed:28696294, ECO:0000269|PubMed:29203869, ECO:0000269|PubMed:29343440, ECO:0000269|PubMed:30770447}.; FUNCTION: [TRPM7 channel, cleaved form]: The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling. {ECO:0000269|PubMed:22698280}.; 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:0000269|PubMed:22698280, ECO:0000269|PubMed:24855944}.
uniprot
proteins
mass_dalton
212399
uniprot
proteins
mutagenesis
MUTAGEN 1097; /note="N->Q: Abrogates the inhibitory action of physiological intracellular Mg(2+) concentration. Does not abrogates the inhibitory action of Mg-ATP and PIP2."; /evidence="ECO:0000269|PubMed:35389104"; MUTAGEN 1098; /note="N->Q: High constitutive activity. Abrogates the inhibitory action of intracellular Mg(2+). Abrogates the inhibitory action of Mg-ATP and PIP2."; /evidence="ECO:0000269|PubMed:35389104, ECO:0000269|PubMed:37156763"; MUTAGEN 1646; /note="K->R: Kinase-dead knockin mouse mice display normal development and no changes in serum Mg(2+) and Ca(2+) concentrations."; /evidence="ECO:0000269|PubMed:25030553, ECO:0000269|PubMed:29203869"; MUTAGEN 1797; /note="G->D: Severe reduction of kinase activity."; /evidence="ECO:0000269|PubMed:11161216"; MUTAGEN 1810; /note="C->A: Loss of kinase activity; when associated with A-1813."; /evidence="ECO:0000269|PubMed:11161216"; MUTAGEN 1813; /note="C->A: Loss of kinase activity; when associated with A-1820."; /evidence="ECO:0000269|PubMed:11161216
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:0000250|UniProtKB:Q96QT4}.; PTM: Autophosphorylated; autophosphorylation regulates TRPM7 kinase activity towards its substrates. {ECO:0000250|UniProtKB:Q96QT4}.; PTM: The C-terminal kinase domain can be cleaved from the channel segment in a cell-type-specific fashion (PubMed:22698280, PubMed:24855944). TRPM7 is cleaved by caspase-8, dissociating the kinase from the ion-conducting pore (PubMed:22698280). 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 (PubMed:24855944). {ECO:0000269|PubMed:22698280, ECO:0000269|PubMed:24855944}.
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
11161216
uniprot
proteins
pubmed
11385574
uniprot
proteins
pubmed
11389851
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16260839
uniprot
proteins
pubmed
18974357
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21045827
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22203997
uniprot
proteins
pubmed
22222377
uniprot
proteins
pubmed
22698280
uniprot
proteins
pubmed
23878236
uniprot
proteins
pubmed
24855944
uniprot
proteins
pubmed
25030553
uniprot
proteins
pubmed
28696294
uniprot
proteins
pubmed
28821869
uniprot
proteins
pubmed
29203869
uniprot
proteins
pubmed
29343440
uniprot
proteins
pubmed
30108148
uniprot
proteins
pubmed
30770447
uniprot
proteins
pubmed
34686339
uniprot
proteins
pubmed
35389104
uniprot
proteins
pubmed
37156763
uniprot
proteins
sequence_length
1863
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q96QT4}; Multi-pass membrane protein {ECO:0000269|PubMed:37156763}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:28696294}; Multi-pass membrane protein {ECO:0000269|PubMed:37156763}. Note=Localized largely in intracellular Zn(2+)-storage vesicles (PubMed:28696294). {ECO:0000269|PubMed:24855944, ECO:0000269|PubMed:28696294}.; SUBCELLULAR LOCATION: [TRPM7 kinase, cleaved form]: Nucleus {ECO:0000269|PubMed:24855944}.
uniprot
proteins
transmembrane_region
TRANSMEM 851..876; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:37156763, ECO:0007744|PDB:8SI2"; TRANSMEM 883..904; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:37156763, ECO:0007744|PDB:8SI2"; TRANSMEM 924..943; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:37156763, ECO:0007744|PDB:8SI2"; TRANSMEM 957..980; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:37156763, ECO:0007744|PDB:8SI2"; TRANSMEM 1000..1023; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:37156763, ECO:0007744|PDB:8SI2"; TRANSMEM 1070..1098; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:37156763, ECO:0007744|PDB:8SI2
uniprot
proteins