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Details on Person UniProt:Q96QT4 TRPM7
| Class:Id | ReferenceGeneProduct:252750 |
|---|---|
| _chainChangeLog | chain:1-1865 added on Sat February 7 2015;chain:1- for 252750 added on Fri Feb 21 2025;chain:-1865 for 252750 added on Fri Feb 21 2025 |
| _displayName | UniProt:Q96QT4 TRPM7 |
| _timestamp | 2025-02-21 19:23:53 |
| chain | chain:1-1865 chain:1- chain:-1865 |
| checksum | BE732674D52D7485 |
| comment | 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).FUNCTION The cleaved channel exhibits substantially higher current and potentiates Fas receptor signaling.FUNCTION 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.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)CATALYTIC ACTIVITY Mg(2+)(in) = Mg(2+)(out)CATALYTIC ACTIVITY Ca(2+)(in) = Ca(2+)(out)CATALYTIC ACTIVITY Zn(2+)(in) = Zn(2+)(out)COFACTOR Binds 1 zinc ion per subunit.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).SUBUNIT Homotetramer (By similarity). Interacts with PLCB1 (By similarity). Forms heteromers with TRPM6; heteromeric channels are functionally different from the homomeric channels (PubMed:14976260, PubMed:16636202).SUBCELLULAR LOCATION Localized largely in intracellular Zn(2+)-storage vesicles.SUBCELLULAR LOCATION Palmitoylated; palmitoylation at Cys-1143, Cys-1144 and Cys-1146 promotes TRPM7 trafficking from the Golgi to the surface membrane.PTM Autophosphorylated; autophosphorylation of C-terminus regulates TRPM7 kinase activity towards its substrates.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.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE 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.SIMILARITY In the C-terminal section; belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.SIMILARITY In the N-terminal section; belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM7 sub-subfamily. |
| created | [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 |
| description | recommendedName: Transient receptor potential cation channel subfamily M member 7 ecNumber evidence="10 14 15"2.7.11.1 alternativeName: Channel-kinase 1 alternativeName: fullName evidence="19"Long transient receptor potential channel 7 shortName: LTrpC-7 shortName: LTrpC7 component recommendedName: fullName evidence="2"TRPM7 kinase, cleaved form shortName: M7CK /component component recommendedName: fullName evidence="2"TRPM7 channel, cleaved form /component |
| geneName | TRPM7 CHAK1 LTRPC7 |
| identifier | Q96QT4 |
| isSequenceChanged | FALSE |
| keyword | Acetylation Amyotrophic lateral sclerosis ATP-binding Calcium Calcium channel Calcium transport Cell membrane Coiled coil Cytoplasmic vesicle Disease variant Ion channel Ion transport Kinase Lipoprotein Membrane Metal-binding Necrosis Neurodegeneration Nucleotide-binding Nucleus Palmitate Parkinsonism Phosphoprotein Proteomics identification Reference proteome Serine/threonine-protein kinase Transferase Transmembrane Transmembrane helix Transport Zinc |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | TRPM7 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8991633] ENSEMBL:ENSG00000092439 TRPM7 [Homo sapiens] |
| secondaryIdentifier | TRPM7_HUMAN Q6ZMF5 Q86VJ4 Q8NBW2 Q9BXB2 Q9NXQ2 |
| sequenceLength | 1865 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:937281] TRPM7 [plasma membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:Q96QT4 TRPM7 (252750)
