| 2016 |
TMCO1 is an ER transmembrane protein that forms a Ca2+-selective ion channel ('Ca2+ load-activated Ca2+ channel', CLAC) on giant liposomes and undergoes reversible homotetramerization in response to ER Ca2+ overloading, dissociating upon Ca2+ depletion, thereby preventing ER Ca2+ overfilling. |
Giant liposome electrophysiology, co-immunoprecipitation of oligomeric complexes, TMCO1 knockout mouse model with ER Ca2+ measurement, in vitro reconstitution |
Cell |
High |
27212239
|
| 2020 |
TMCO1 protein from Dictyostelium discoideum (ortholog) contains three α-helical transmembrane regions as determined by solution NMR in DPC micelles; recombinant protein was successfully purified by affinity and size exclusion chromatography. |
Solution NMR spectroscopy in DPC micelles, recombinant protein expression and purification (E. coli and insect cells) |
Protein expression and purification |
Medium |
33253810
|
| 2018 |
TMCO1 is essential for ovarian follicle development; its ablation in granulosa cells causes supernormal Ca2+ signaling, ER stress-mediated apoptosis, and elevated ROS, while ER Ca2+ stores in oocytes remain normal, placing TMCO1 specifically in granulosa cell Ca2+ homeostasis. |
Tmco1-/- knockout mice, Ca2+ imaging in granulosa cells, RNA-sequencing, ER stress and ROS assays |
Cell death and differentiation |
High |
29467381
|
| 2022 |
TMCO1 is a substrate of the ER-associated degradation E3 ubiquitin ligase Gp78, which ubiquitinates TMCO1 at K186 to promote its degradation. The oncoprotein iASPP competitively binds Gp78, interfering with Gp78-mediated TMCO1 ubiquitination and thus stabilizing TMCO1 protein levels and reducing ER Ca2+ stores. |
Co-immunoprecipitation, ubiquitination assays, competitive binding assay, Ca2+ store measurements, in vitro and in vivo tumor models |
Proceedings of the National Academy of Sciences of the United States of America |
High |
35121659
|
| 2022 |
TMCO1 is required for normal corpus callosum development; TMCO1 deficiency causes excessive ER Ca2+ release leading to upregulation of FGFs, over-activation of ERK signaling, excess midline glial cell migration, and overproduction of Slit2, which repels neural fiber bundles from crossing the midline. Pharmacological MEK inhibition rescues corpus callosum formation in Tmco1-/- mice. |
Tmco1-/- knockout mice, ERK phosphorylation assays, FGF/Slit2 expression analysis, MEK inhibitor rescue experiments, brain histology |
Cell death & disease |
High |
35927240
|
| 2019 |
In TMCO1-deficient cells, ER stress causes ERAD-mediated degradation of diacylglycerol acyltransferase 2 (DGAT2), reducing triglyceride synthesis, causing non-esterified fatty acid accumulation, and resulting in decreased mitochondrial volume, enhanced mitophagy, and impaired oxidative phosphorylation. |
Tmco1-/- cells, lipid droplet quantification, triglyceride measurement, DGAT2 protein level analysis, mitochondrial morphology and function assays (OXPHOS) |
Biochemical and biophysical research communications |
Medium |
30929916
|
| 2024 |
TMCO1 promotes ferroptosis and ECM deposition in trabecular meshwork cells through ERK1/2 signaling; dexamethasone stimulation upregulates TMCO1, and ferroptosis inhibitor ferrostatin-1 reduces both ECM deposition and ferroptosis downstream of TMCO1. |
In vivo glaucoma model, HTM cell culture, dexamethasone stimulation, ferrostatin-1 treatment, ERK1/2 phosphorylation assays, ECM marker quantification |
Biochimica et biophysica acta. Molecular basis of disease |
Medium |
39343416
|
| 2024 |
TMCO1 regulates mitochondrial function in hepatocellular carcinoma cells via TOMM20; TMCO1 overexpression promotes ATP production, increases mitochondrial membrane potential, and inhibits mPTP opening and ROS, while TOMM20 knockdown blocks these TMCO1-mediated effects, placing TOMM20 epistatically downstream of TMCO1. |
TMCO1 overexpression and knockdown, TOMM20 knockdown epistasis, ROS assay, mPTP assay, MMP assay, ATP measurement, subcutaneous xenograft mouse model |
Biochemistry and cell biology |
Medium |
39566034
|
| 2024 |
TMCO1 interacts with CALR (calreticulin) in ovarian cancer cells; TMCO1 overexpression upregulates CALR and VDAC1 and elevates intracellular Ca2+, while TMCO1 knockout reduces CALR and VDAC1 expression and reverses the pro-metastatic effects of CALR recombinant protein. |
TMCO1 overexpression and knockout, CALR/VDAC1 knockdown epistasis, Fluo-4 Ca2+ assay, ER/mitochondrial fluorescent probes, Transwell assay, Western blot, xenograft mouse model |
Cellular and molecular biology |
Low |
38372107
|
| 2024 |
In breast cancer cells, TMCO1 interacting proteins include ER-resident Ca2+-regulatory proteins and nuclear transport proteins; TMCO1 localizes to both the nucleus and ER in MDA-MB-231 cells, and TMCO1 regulates sensitivity to BCL-2/MCL-1 inhibitors analogously to IP3 receptors. |
Interactome pulldown/MS for TMCO1 binding partners, immunofluorescence for localization, cell viability assays with BCL-2/MCL-1 inhibitors |
Cell death discovery |
Low |
39353922
|
| 2012 |
In human ocular tissues, endogenous TMCO1 protein localizes to the cytoplasm and nucleus (including nucleoli) in vivo and ex vivo, as determined by immunolabeling; GFP-fusion experiments confirm subcellular distribution. TMCO1 is expressed in trabecular meshwork and retina. |
Immunolabeling of human ocular tissues, GFP-fusion subcellular localization |
Investigative ophthalmology & visual science |
Low |
22714896
|
| 2025 |
KALRN depletion suppresses TMCO1 expression in trabecular meshwork cells, and TMCO1 depletion phenocopies KALRN loss (ER dysfunction, Ca2+ dysregulation, energy metabolism impairment, cell senescence) and reduces KALRN expression, establishing KALRN and TMCO1 as interdependent regulators of ER and Ca2+ homeostasis. In vivo TMCO1 depletion elevated intraocular pressure in mice. |
siRNA knockdown in primary TM cells, mouse IOP measurements, Ca2+ homeostasis assays, energy metabolism assays, senescence assays, epistatic mutual suppression analysis |
bioRxivpreprint |
Medium |
bio_10.1101_2025.09.19.677310
|