Transient receptor potential cation channel subfamily M member 7 (TRPM7) is a unique ion channel-kinase fusion protein that functions as a calcium- and magnesium-permeable cation channel with an intrinsic serine/threonine protein kinase domain. Essential for cellular ion homeostasis, TRPM7 regulates Mg2+ and Ca2+ influx and is required for multiple developmental processes including melanophore survival, mechanosensory neuron function, dopaminergic neuron development, cardiac pacemaking, exocrine pancreas development, and skeletal mineralization. The protein localizes primarily to the plasma membrane where it forms homo-tetrameric channel complexes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004672 protein kinase activity | IBA GO_REF:0000033 | MODIFY | Summary: IBA annotation based on phylogenetic evidence. The deep research confirms TRPM7 contains a C-terminal alpha-kinase domain with serine/threonine kinase activity. However, this term is too general - the specific kinase type should be specified. Reason: While TRPM7 does have protein kinase activity, the more specific term GO:0004674 (protein serine/threonine kinase activity) better represents the actual molecular function of the alpha-kinase domain. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002674401 Β· TRPM channel-kinase ancestral node SUPPORTS TRANSFER Transfer is sound but 'protein kinase activity' is too generic; TRPM7's C-terminal alpha-kinase is a serine/threonine kinase (GO:0004674). UniProtKB:Q96QT4 Β· human TRPM7 SUPPORTS TRANSFER Ortholog's alpha-kinase domain has serine/threonine kinase activity, supporting the more specific replacement term. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md The C-terminal Ξ±-kinase domain of Trpm7 can phosphorylate itself and other substrates... Alpha-kinases are atypical serine/threonine kinases that phosphorylate substrates within alpha-helical regions. |
| GO:0005262 calcium channel activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation well-supported by experimental evidence. TRPM7 forms a calcium-permeable cation channel, though Ca2+ is actually one of the least permeable divalent cations compared to Mg2+, Co2+, and others. Reason: The deep research confirms TRPM7 functions as a calcium channel, mediating Ca2+ influx across membranes. This is a core molecular function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md Trpm7 forms a ion channel that mediates Ca^2+ influx... Mouse TRPM7 (mTRPM7) has been shown to best permeate zinc (Zn2+) and nickel (Ni2+), followed by barium (Ba2+), cobalt (Co2+), magnesium (Mg2+), manganese (Mn2+), strontium (Sr2+), cadmium (Cd2+) and calcium (Ca2+) PMID:27628598 TRPM7 exhibits an outwardly rectifying current-voltage relationship due to voltage-dependent block by Mg2+ and calcium (Ca2+) at negative voltages file:DANRE/trpm7/trpm7-deep-research-falcon.md TRPM7 forms a plasma-membrane cation channel permeable to **Mg2+**, **Ca2+**, and **Zn2+**, with broader permeability to other divalent cations |
| GO:0006816 calcium ion transport | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation correctly identifies TRPM7's role in calcium transport. The channel conducts Ca2+ ions across membranes as part of its divalent cation transport function. Reason: TRPM7 mediates calcium ion transport across the plasma membrane. This is a core biological process function, though the channel also transports other divalent cations. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md As an ion channel, TRPM7 mediates the influx of divalent cations (notably Ca^2+ and Mg^2+) across cell membranes, which is crucial for maintaining cellular ion homeostasis |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation strongly supported by experimental evidence. TRPM7 is an integral membrane protein that primarily localizes to the plasma membrane. Reason: Multiple lines of evidence confirm TRPM7 localizes to the plasma membrane where it functions as a transmembrane ion channel. This is a core cellular component. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md Trpm7 is an integral membrane protein that primarily localizes to the plasma membrane of cells... 'plasma membrane' is the key Gene Ontology cellular component term for Trpm7, reflecting its role as a transmembrane ion channel at the cell periphery |
| GO:0098655 monoatomic cation transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation correctly identifies TRPM7's broad cation transport function. The channel conducts various monoatomic cations including Ca2+, Mg2+, Zn2+, Ni2+, and others. Reason: TRPM7 functions as a non-selective cation channel that transports multiple monoatomic cations across membranes. This is a core biological process. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md Mouse TRPM7 (mTRPM7) has been shown to best permeate zinc (Zn2+) and nickel (Ni2+), followed by barium (Ba2+), cobalt (Co2+), magnesium (Mg2+), manganese (Mn2+), strontium (Sr2+), cadmium (Cd2+) and calcium (Ca2+) |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | MODIFY | Summary: IEA annotation based on keyword mapping. This general term is too vague - TRPM7 specifically binds ATP for its kinase activity. Reason: While TRPM7 does bind nucleotides, the more specific term GO:0005524 (ATP binding) better represents the actual molecular function, as the kinase domain utilizes ATP. Proposed replacements: ATP binding Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md It has catalytic activity (utilizing ATP to phosphorylate target proteins)... negatively regulated by intracellular magnesium (Mg2+), adenosine triphosphate (MgΒ·ATP) |
| GO:0004672 protein kinase activity | IEA GO_REF:0000117 | MODIFY | Summary: IEA annotation from ARBA machine learning. Duplicate of IBA annotation above, but less specific than needed. Reason: Same as above IBA annotation - should be more specific as protein serine/threonine kinase activity. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md Alpha-kinases are atypical serine/threonine kinases that phosphorylate substrates within alpha-helical regions |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation correctly identifies the specific kinase type. The alpha-kinase domain of TRPM7 has serine/threonine kinase activity. Reason: TRPM7 contains an alpha-kinase domain that phosphorylates serine/threonine residues. This is a core molecular function. Falcon deep research confirms the catalyzed reaction (phosphotransfer to Ser/Thr plus autophosphorylation), consistent with the UniProt EC 2.7.11.1 catalytic activity and the C-terminal alpha-kinase domain (residues 1503-1733). Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md the C-terminal Ξ±-kinase of Trpm7 phosphorylates serine/threonine residues on target proteins file:DANRE/trpm7/trpm7-deep-research-falcon.md Ξ±-kinase domain transfers phosphate from ATP to **serine/threonine residues** on protein substrates and on TRPM7 itself (autophosphorylation) |
| GO:0005216 monoatomic ion channel activity | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro. Correct general term for TRPM7's ion channel function. Reason: TRPM7 functions as an ion channel that conducts monoatomic cations. This is a core molecular function, though more specific terms also apply. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md It functions as a calcium- and magnesium-permeable cation channel... The channel's activity is negatively regulated by intracellular Mg^2+ and Mg-ATP levels file:DANRE/trpm7/trpm7-deep-research-falcon.md Channel opening requires **PIP2**; receptor pathways that deplete PIP2 reduce TRPM7 activity. |
| GO:0005261 monoatomic cation channel activity | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation from ARBA. Correctly identifies TRPM7 as a cation-selective channel. Reason: TRPM7 is a cation-selective channel that conducts various monoatomic cations. This is a core molecular function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md TRPM7 conducts Ca2+ ions across membranes as part of its divalent cation transport function... best permeate zinc (Zn2+) and nickel (Ni2+), followed by barium (Ba2+), cobalt (Co2+), magnesium (Mg2+) file:DANRE/trpm7/trpm7-deep-research-falcon.md A reported permeability ranking is **Zn2+ β Ni2+ >> Ba2+ > Co2+ > Mg2+ β₯ Mn2+ β₯ Sr2+ β₯ Cd2+ β₯ Ca2+**, and the channel is not permeable to the trivalent blockers **La3+** or **Gd3+**. |
| GO:0005262 calcium channel activity | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation from keyword mapping. Duplicate of IBA annotation above. Reason: TRPM7 has calcium channel activity, though Ca2+ is one of the least permeable divalents. Core function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md calcium (Ca2+)... Trpm7 forms a ion channel that mediates Ca^2+ influx |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation correctly identifies ATP binding for the kinase domain. Reason: The alpha-kinase domain of TRPM7 requires ATP binding for its catalytic activity. Core molecular function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md It has catalytic activity (utilizing ATP to phosphorylate target proteins) PMID:27628598 negatively regulated by intracellular magnesium (Mg2+), adenosine triphosphate (MgΒ·ATP) |
| GO:0005634 nucleus | IEA GO_REF:0000044 | REMOVE | Summary: IEA annotation based on subcellular location mapping. No evidence supports nuclear localization for TRPM7. Reason: TRPM7 is a plasma membrane protein with no documented nuclear localization. This appears to be an incorrect automated annotation. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md Trpm7 is an integral membrane protein that primarily localizes to the plasma membrane of cells... plasma membrane is the key Gene Ontology cellular component term for Trpm7 |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from subcellular location. Duplicate of IBA annotation above. Reason: Correctly identifies plasma membrane localization. Core cellular component. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md primarily localizes to the plasma membrane |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation correctly identifies general ion transport function. Reason: TRPM7 mediates transport of various monoatomic ions. Core biological process. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md mediates the influx of divalent cations (notably Ca^2+ and Mg^2+) across cell membranes |
| GO:0006816 calcium ion transport | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation from keyword mapping. Duplicate of IBA annotation above. Reason: TRPM7 mediates calcium ion transport. Core function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md mediates the influx of divalent cations (notably Ca^2+ and Mg^2+) |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation. Very general term - plasma membrane is more specific. Reason: TRPM7 is a membrane protein, though plasma membrane is more specific. Acceptable general annotation. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md integral membrane protein |
| GO:0016301 kinase activity | IEA GO_REF:0000043 | MODIFY | Summary: IEA annotation. Too general - protein serine/threonine kinase activity is more specific. Reason: While correct, more specific annotation GO:0004674 better describes the alpha-kinase activity. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md Alpha-kinases are atypical serine/threonine kinases |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MODIFY | Summary: IEA annotation. Extremely general term for kinase activity. Reason: Too general. The specific transferase activity is protein serine/threonine kinase. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md phosphorylates serine/threonine residues on target proteins |
| GO:0030001 metal ion transport | IEA GO_REF:0000117 | ACCEPT | Summary: IEA annotation correctly identifies metal ion transport function. Reason: TRPM7 transports various metal ions including Ca2+, Mg2+, Zn2+, Ni2+. Core biological process. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md best permeate zinc (Zn2+) and nickel (Ni2+), followed by barium (Ba2+), cobalt (Co2+), magnesium (Mg2+), manganese (Mn2+) |
| GO:0034220 monoatomic ion transmembrane transport | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation correctly identifies transmembrane ion transport. Reason: TRPM7 mediates transmembrane transport of monoatomic ions. Core function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md mediates the influx of divalent cations... across cell membranes |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation. General term that could apply to channel pore or regulatory sites. Reason: TRPM7 binds metal ions both in the channel pore and at regulatory sites (Mg2+ inhibition). Acceptable annotation. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md negatively regulated by intracellular Mg^2+ and Mg-ATP levels β high internal magnesium or ATP can inhibit TRPM7 channel currents |
| GO:0051262 protein tetramerization | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro. TRPM7 contains a coiled-coil tetramerization domain and forms homo-tetrameric complexes. Reason: TRPM7 forms tetrameric channel complexes via its coiled-coil domain. This is essential for channel assembly and function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md Trpm7 has a coiled-coil region (InterPro IPR032415) near the C-terminus that is crucial for subunit oligomerization and channel assembly... This coiled-coil helps four Trpm7 subunits come together to form a functional channel complex |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro. General term for transmembrane transport activity. Reason: TRPM7 mediates transmembrane transport of ions. Core function though more specific terms also apply. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md spans the membrane (with six transmembrane helices per subunit) and forms homo-tetrameric channel complexes in the lipid bilayer |
| GO:0070588 calcium ion transmembrane transport | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation from keyword mapping. More specific version of calcium ion transport. Reason: TRPM7 mediates calcium ion transport across membranes. Core function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md The channel is positioned such that its ion-conducting pore allows Ca^2+, Mg^2+, and other small cations to flow from the extracellular space or organelle lumen into the cytosol |
| GO:0001966 thigmotaxis | IMP PMID:38970357 Zebrafish trpm7 mutants show reduced motility in free moveme... | UNDECIDED | Summary: IMP evidence from 2024 study showing trpm7 mutants have reduced touch-evoked responses and altered movement patterns. However, the cited paper (PMID:38970357) measures movement distance and velocity, not thigmotaxis (wall-proximity/boundary-seeking behavior) specifically. Reason: PMID:38970357 reports reduced movement distance and swimming velocity in trpm7 mutants, supporting GO:0036269 swimming behavior but not thigmotaxis specifically. A dedicated thigmotaxis assay (e.g., center vs. periphery tracking) would be required to support this annotation. Supporting Evidence: PMID:38970357 Behavioral analyses revealed that trpm7 mutants showed compromised motility with their movement distance shorter than wild-type larvae file:DANRE/trpm7/trpm7-deep-research.md Mutant larvae exhibit a transient unresponsiveness to touch stimuli β for about 12 hours during early development, trpm7 mutants fail to perform the typical escape reflex when touched |
| GO:0036269 swimming behavior | IMP PMID:38970357 Zebrafish trpm7 mutants show reduced motility in free moveme... | ACCEPT | Summary: IMP evidence showing trpm7 mutants have reduced swimming velocity and movement distance. Reason: Experimental evidence demonstrates trpm7 is required for normal swimming behavior. Related to dopaminergic neuron defects. Supporting Evidence: PMID:38970357 The velocity of the movement was significantly reduced in trpm7 mutants than in wild-type larvae file:DANRE/trpm7/trpm7-deep-research.md Zebrafish lacking Trpm7 show reduced motility and abnormal swimming behavior. Even beyond the touch-response defect, mutants often have sluggish or uncoordinated movement |
| GO:0005886 plasma membrane | IDA PMID:27628598 The coiled-coil domain of zebrafish TRPM7 regulates MgΒ·nucle... | ACCEPT | Summary: IDA evidence from electrophysiology studies confirming plasma membrane localization of TRPM7. Reason: Direct experimental evidence shows TRPM7 localizes to plasma membrane where it functions as an ion channel. Core cellular component. Supporting Evidence: PMID:27628598 Patch-clamp experiments were performed in the tight-seal whole-cell configuration... HEK293 T-REx cells stably expressing HA-tagged Danio rerio TRPM7 (drTRPM7) file:DANRE/trpm7/trpm7-deep-research.md primarily localizes to the plasma membrane of cells file:DANRE/trpm7/trpm7-deep-research-falcon.md TRPM7 localizes to the **plasma membrane** and also to intracellular pools described as **tubulovesicular/synaptic vesicle-like compartments**. |
| GO:0010960 magnesium ion homeostasis | IDA PMID:27628598 The coiled-coil domain of zebrafish TRPM7 regulates MgΒ·nucle... | ACCEPT | Summary: IDA evidence from electrophysiology showing TRPM7 regulates Mg2+ homeostasis and is regulated by intracellular Mg2+. Reason: Direct experimental evidence shows TRPM7 is essential for magnesium homeostasis. This is a core function. Supporting Evidence: PMID:27628598 the channel's regulation by magnesium (Mg) and MgΒ·adenosine triphosphate (MgΒ·ATP)... A dose-response curve fit to averaged currents extracted at 200 s into the experiment revealed a half-maximal inhibitory concentration (IC50) of 778 Β± 291 ΞΌM file:DANRE/trpm7/trpm7-deep-research.md Based on this profile and the effects of divalent substitution/complementation experiments, the TRPM7 channel function is thought to serve as a primary mechanism for cellular Mg2+ homeostasis file:DANRE/trpm7/trpm7-deep-research-falcon.md reduced whole-embryo **total magnesium** and **total calcium** by early larval stages, consistent with TRPM7 acting as an in vivo regulator of organismal divalent-cation balance |
| GO:0030001 metal ion transport | IDA PMID:27628598 The coiled-coil domain of zebrafish TRPM7 regulates MgΒ·nucle... | ACCEPT | Summary: IDA evidence from electrophysiology demonstrating TRPM7 conducts various metal ions including Ca2+, Mg2+, Zn2+, Ni2+. Reason: Direct experimental evidence shows TRPM7 transports multiple metal ions. Core function. Supporting Evidence: PMID:27628598 TRPM7 conducted Ca2+ the least compared to other divalents, with cobalt and magnesium permeating the best file:DANRE/trpm7/trpm7-deep-research.md Mouse TRPM7 (mTRPM7) has been shown to best permeate zinc (Zn2+) and nickel (Ni2+), followed by barium (Ba2+), cobalt (Co2+), magnesium (Mg2+) |
| GO:0048066 developmental pigmentation | IMP PMID:9007256 Zebrafish pigmentation mutations and the processes of neural... | ACCEPT | Summary: IMP evidence from original touchtone/nutria mutant studies showing melanophore death and pigmentation defects. Reason: Strong experimental evidence shows trpm7 mutants have melanophore cell death leading to pigmentation defects. Core developmental function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md Trpm7 is required for the survival of embryonic melanophores (pigment cells). Zebrafish trpm7 mutants (e.g. touchtone and nutria alleles) show extensive melanophore cell death during development file:DANRE/trpm7/trpm7-deep-research-falcon.md In **trpm7 mutant embryos**, melanophore loss results from **cell death with necrotic features** (not caspase-dependent apoptosis). file:DANRE/trpm7/trpm7-uniprot.txt Zebrafish pigmentation mutations and the processes of neural crest development PMID:9007256 Zebrafish pigmentation mutations and the processes of neural crest development. |
| GO:0002027 regulation of heart rate | IMP PMID:23878236 Ion channel-kinase TRPM7 is required for maintaining cardiac... | ACCEPT | Summary: IMP evidence showing trpm7 mutants develop bradycardia and sinoatrial node dysfunction. Reason: Experimental evidence demonstrates TRPM7 is required for normal cardiac pacemaking and heart rate regulation. Important physiological function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md Zebrafish trpm7 mutants exhibit bradycardia (slower than normal heart rate) during larval stages... Trpm7 knockdown has been used as a model of sinoatrial node dysfunction PMID:23878236 Ion channel-kinase TRPM7 is required for maintaining cardiac automaticity. |
| GO:0003014 renal system process | IMP PMID:20881241 trpm7 regulation of in vivo cation homeostasis and kidney fu... | ACCEPT | Summary: IMP evidence showing trpm7 mutants develop kidney stones and have abnormal renal ion homeostasis. Reason: Experimental evidence shows TRPM7 is required for normal kidney function and prevention of stone formation. Important physiological role. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md mutants develop ectopic calcifications, such as kidney stones and aberrant bone calcification, due to improper calcium handling... Trpm7 is highly expressed in the zebrafish Corpuscles of Stannius β specialized endocrine glands in the kidney PMID:20881241 Sep 29. trpm7 regulation of in vivo cation homeostasis and kidney function involves stanniocalcin 1 and fgf23. file:DANRE/trpm7/trpm7-deep-research-falcon.md Mutants also exhibit **kidney stone formation** and altered endocrine programs involving **stanniocalcin 1 (stc1)** and **fgf23**; mechanistically, **fgf23 knockdown reduces kidney stones** |
| GO:0055080 monoatomic cation homeostasis | IMP PMID:20881241 trpm7 regulation of in vivo cation homeostasis and kidney fu... | ACCEPT | Summary: IMP evidence showing trpm7 regulates systemic Ca2+ and Mg2+ homeostasis, with mutants having dysregulated ion levels. Reason: Experimental evidence demonstrates TRPM7 is essential for maintaining organismal cation homeostasis. Core function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md Zebrafish trpm7 mutants have dysregulated Ca^2+ and Mg^2+ levels in bodily fluids, leading to abnormal mineralization of skeletal tissues PMID:20881241 Sep 29. trpm7 regulation of in vivo cation homeostasis and kidney function involves stanniocalcin 1 and fgf23. file:DANRE/trpm7/trpm7-deep-research-falcon.md In zebrafish, **trpm7 mRNA is broadly expressed**, with particularly high abundance in **kidney tubules** (pronephric/mesonephric) and in the **corpuscles of Stannius** (an endocrine organ involved in ionic homeostasis), supporting a primary role in systemic divalent-cation regulation and renal physiology |
| GO:0007346 regulation of mitotic cell cycle | IMP PMID:21183474 Transient receptor potential ion channel Trpm7 regulates exo... | KEEP AS NON CORE | Summary: IMP evidence suggesting TRPM7 affects cell proliferation in pancreatic development through Mg2+-sensitive signaling. Reason: While TRPM7 affects cell proliferation, this is likely secondary to its primary ion homeostasis function. Not a core function but a downstream effect. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md Based on this profile and the effects of divalent substitution/complementation experiments, the TRPM7 channel function is thought to serve as a primary mechanism for cellular Mg2+ homeostasis and be essential for cell proliferation PMID:21183474 Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg2+-sensitive Socs3a signaling in development and cancer. |
| GO:0031017 exocrine pancreas development | IMP PMID:21183474 Transient receptor potential ion channel Trpm7 regulates exo... | ACCEPT | Summary: IMP evidence showing TRPM7 regulates pancreatic epithelial proliferation through Mg2+-sensitive Socs3a signaling. Reason: Experimental evidence demonstrates TRPM7 is required for normal exocrine pancreas development. Important developmental function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md Trpm7 has been implicated in the development of the exocrine pancreas in zebrafish... Expression is also observed in the exocrine pancreas and intestinal tract PMID:21183474 Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg2+-sensitive Socs3a signaling in development and cancer. |
| GO:0050678 regulation of epithelial cell proliferation | IMP PMID:21183474 Transient receptor potential ion channel Trpm7 regulates exo... | KEEP AS NON CORE | Summary: IMP evidence from pancreas study showing TRPM7 affects epithelial proliferation. Reason: TRPM7 affects epithelial proliferation through its ion homeostasis function, but this is a downstream effect rather than a core function. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md it may relate to Trpm7's role in regulating cellular proliferation or differentiation in endodermal tissues PMID:21183474 Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg2+-sensitive Socs3a signaling in development and cancer. |
| GO:0046928 regulation of neurotransmitter secretion | IMP PMID:21832193 TRPM7 is required within zebrafish sensory neurons for the a... | ACCEPT | Summary: IMP evidence showing TRPM7 in sensory neurons affects touch-evoked responses, likely through neurotransmitter release. Reason: TRPM7 in sensory neurons is required for proper neurotransmission during touch-evoked escape responses. Important neurological function. Falcon deep research reinforces that this behavior depends specifically on TRPM7 channel (divalent conductance) activity and not on kinase catalytic activity, and that elevated extracellular divalents can restore the escape response, supporting a divalent-dependent synaptic transmitter-release mechanism. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md This defect in touch-evoked escape behavior can be rescued by expressing Trpm7 specifically in primary sensory neurons... indicating the protein is required within sensory nerves for them to fire or develop properly PMID:21832193 TRPM7 is required within zebrafish sensory neurons for the activation of touch-evoked escape behaviors. file:DANRE/trpm7/trpm7-deep-research-falcon.md Elevated extracellular **divalent cations** can restore escape behavior, supporting a divalent-dependent synaptic mechanism. |
| GO:0006582 melanin metabolic process | IMP PMID:17290233 Cell death of melanophores in zebrafish trpm7 mutant embryos... | ACCEPT | Summary: IMP evidence showing melanophore death in trpm7 mutants depends on melanin synthesis, with toxic intermediates accumulating. Reason: TRPM7 is required to prevent toxic buildup of melanin intermediates in melanophores. Important for pigment cell survival. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md It is thought that Trpm7's absence leads to toxic build-up of melanin intermediates in melanophores, causing death PMID:17290233 2007 Feb 8. Cell death of melanophores in zebrafish trpm7 mutant embryos depends on melanin synthesis. file:DANRE/trpm7/trpm7-deep-research-falcon.md **inhibition of melanin synthesis largely prevents melanophore death**, supporting a model where Trpm7-dependent ionic homeostasis buffers pigment cells against toxic melanin-synthesis intermediates or associated stress |
| GO:0001503 ossification | IMP PMID:15823540 Defective skeletogenesis with kidney stone formation in dwar... | ACCEPT | Summary: IMP evidence from dwarf mutant study showing abnormal bone mineralization and skeletal defects. Reason: trpm7 mutants have defective skeletal mineralization due to disrupted calcium/magnesium homeostasis. Important developmental function. Supporting Evidence: PMID:15823540 Defective skeletogenesis with kidney stone formation in dwarf zebrafish mutant for trpm7 file:DANRE/trpm7/trpm7-deep-research.md mutants develop ectopic calcifications, such as kidney stones and aberrant bone calcification, due to improper calcium handling |
| GO:0030318 melanocyte differentiation | IMP PMID:15823540 Defective skeletogenesis with kidney stone formation in dwar... | ACCEPT | Summary: IMP evidence showing trpm7 is required for melanocyte survival and proper differentiation. Reason: TRPM7 is essential for melanocyte development and survival, with mutants showing extensive melanophore cell death. Core developmental function. Supporting Evidence: PMID:15823540 Defective skeletogenesis with kidney stone formation in dwarf zebrafish mutant for trpm7 file:DANRE/trpm7/trpm7-deep-research.md The melanin-producing cells die and their melanosomes (pigment organelles) are structurally abnormal in Trpm7 mutants... restoring Trpm7 specifically in melanophores rescues their survival |
| GO:0001501 skeletal system development | IMP PMID:15823540 Defective skeletogenesis with kidney stone formation in dwar... | ACCEPT | Summary: IMP evidence showing trpm7 mutants have skeletal defects and abnormal bone development. Reason: TRPM7 is required for normal skeletal development through regulation of calcium/magnesium homeostasis. Important developmental function. Supporting Evidence: PMID:15823540 Defective skeletogenesis with kidney stone formation in dwarf zebrafish mutant for trpm7 file:DANRE/trpm7/trpm7-deep-research.md affects bone mineralization and development (via calcium homeostasis)... They are generally growth-impaired (often developing a dwarf phenotype) |
| GO:0015095 magnesium ion transmembrane transporter activity | IEA | NEW | Summary: magnesium ion transmembrane transporter activity identified from core_functions analysis Reason: This molecular function term captures TRPM7's specific role in mediating magnesium ion transport across cell membranes along with other divalent cations. Supporting Evidence: file:DANRE/trpm7/trpm7-deep-research.md TRPM7 mediates the influx of divalent cations (notably Ca^2+ and Mg^2+) across cell membranes, with mouse TRPM7 showing permeability to zinc, nickel, barium, cobalt, and magnesium PMID:27628598 It is negatively regulated by intracellular magnesium (Mg2+), adenosine triphosphate (MgΒ·ATP) and other polyvalent molecules |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: How does TRPM7 integrate mechanosensing with magnesium homeostasis in zebrafish development?
Q: What determines the tissue-specific requirements for TRPM7 kinase versus channel activity?
Q: How does TRPM7 regulate cell migration and morphogenesis during gastrulation and organogenesis?
Q: What role does TRPM7 play in left-right asymmetry establishment in the zebrafish embryo?
Experiment: Generate separation-of-function trpm7 alleles (channel-dead pore mutant vs. kinase-dead alpha-kinase mutant) and assay rescue of melanophore survival, total Mg2+/Ca2+ levels, and kidney stone formation in trpm7 mutants.
Hypothesis: TRPM7 channel conductance, but not its kinase activity, is the primary determinant of melanophore survival and cation homeostasis in zebrafish.
Type: CRISPR knock-in / structure-function rescue
Experiment: Measure hcn4 transcript levels and the pacemaker current If in sinoatrial pacemaker cells of trpm7 mutant versus wild-type zebrafish, and test whether hcn4 overexpression rescues bradycardia.
Hypothesis: TRPM7 maintains cardiac automaticity in zebrafish by transcriptionally sustaining hcn4 expression in pacemaker cells, as shown in mouse SAN.
Type: qPCR / electrophysiology
Experiment: Express wild-type and C-terminal coiled-coil truncation drTRPM7 constructs in heterologous cells and patch-clamp the currents across a range of intracellular Mg2+ and Mg-ATP concentrations to map dose-response inhibition.
Hypothesis: The coiled-coil domain confers Mg/Mg-ATP sensitivity that tunes TRPM7 channel activity in a tissue-specific manner relevant to magnesium homeostasis.
Type: whole-cell patch-clamp electrophysiology
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)π View Pathway Visualization Interactive pathway diagram with detailed annotations