| 2010 |
Pom33 (yeast TMEM33 ortholog) is an integral transmembrane protein dynamically associated with nuclear pore complexes (NPCs) in budding yeast. Loss of Pom33 impairs NPC distribution and NPC density in the daughter nucleus, and Pom33 becomes essential for viability in the absence of the Nup84 complex or Ndc1 interaction network. Pom33 associates physically with the reticulon Rtn1. |
Yeast genetics (synthetic lethality, deletion mutants), co-immunoprecipitation, fluorescence microscopy of NPC distribution |
The Journal of cell biology |
High |
20498018
|
| 2014 |
Nuclear pore targeting of yeast Pom33 requires two redundant mechanisms: direct interaction of its C-terminal domain (CTD) with the karyopherin Kap123 (identified by Co-IP/MS and confirmed by in vitro binding assay), and membrane association via amphipathic α-helices in the CTD that preferentially bind highly curved lipid membranes (shown by circular dichroism and liposome co-flotation assays). Combined impairment of both lipid-binding and Kap123-binding abolishes NPC targeting. |
Co-immunoprecipitation/mass spectrometry, in vitro protein-protein binding, circular dichroism, liposome co-flotation, yeast mutant analysis |
Journal of cell science |
High |
25413348
|
| 2014 |
Fission yeast Tts1 (TMEM33 ortholog) localizes to high-curvature ER domains via an amphipathic helix in its C-terminus and functions in two distinct processes during closed mitosis: (1) promoting spindle pole body (SPB) insertion into the nuclear envelope (NE), dependent on conserved residues at the luminal interface of the third transmembrane region; and (2) modulating NPC distribution during mitotic NE expansion, dependent on the amphipathic helix. |
Fluorescence microscopy, domain mutagenesis, yeast deletion mutants, live-cell imaging |
Molecular biology of the cell |
High |
25103238
|
| 2014 |
Human TMEM33 was identified as a reticulon-binding protein by affinity chromatography. TMEM33 binds reticulon 4C, reticulon 1A, reticulon 2B, reticulon 3C, and the reticulon homology domain protein Arl6IP1. TMEM33 localizes to the ER membrane and nuclear envelope, co-localizes with reticulon 4C at ER sheets and partially at ER tubules, and exogenous TMEM33 expression suppresses reticulon 4C-induced ER tubulation. |
Affinity chromatography, co-immunoprecipitation, immunofluorescence microscopy, ER morphology assay |
The Kobe journal of medical sciences |
Medium |
25612671
|
| 2015 |
TMEM33 is an ER stress-inducible transmembrane protein that localizes to the ER and physically binds PERK (an ER transmembrane kinase). Exogenous TMEM33 expression increases phosphorylation of eIF2α and IRE1α and elevates their downstream effectors ATF4-CHOP and XBP1-S, as well as apoptotic markers (cleaved caspase-7, cleaved PARP) and autophagosome marker LC3II. |
Immunoprecipitation, immunofluorescence, subcellular fractionation, immunoblotting, transient transfection |
Breast cancer research and treatment |
Medium |
26268696
|
| 2019 |
TMEM33 localizes to the ER in zebrafish endothelial cells and is required for cytosolic calcium oscillations in response to VEGF-A. Global or endothelial-specific knockdown of tmem33 impairs ERK phosphorylation, Notch signaling, tip cell filopodia formation, endothelial cell migration, and embryonic vascular development. |
Zebrafish genetic knockdown (morpholino/CRISPR), live calcium imaging, siRNA knockdown in human ECs, immunofluorescence, in vivo vascular development assays |
Nature communications |
High |
30760708
|
| 2019 |
TMEM33 interacts with the ion channel polycystin-2 (PC2) at the ER membrane, enhancing PC2 channel opening across the physiological calcium range (demonstrated in ER liposomes fused to planar bilayers). Consequently, TMEM33 reduces intracellular calcium content in a PC2-dependent manner, impairs lysosomal calcium refilling, causes cathepsin translocation, inhibits autophagic flux upon ER stress, and sensitizes cells to apoptosis. TMEM33 invalidation in mice protects against renal ER stress. |
Co-immunoprecipitation, ER liposome-planar bilayer electrophysiology, mouse TMEM33 knockout, siRNA knockdown, calcium imaging, autophagy and apoptosis assays |
Nature communications |
High |
31048699
|
| 2021 |
TMEM33 acts as a negative regulator of virus-triggered interferon induction via two mechanisms: (1) it promotes K48-linked ubiquitination and degradation of MAVS; (2) it acts as a decoy substrate for TBK1, reducing phosphorylation of MITA/IRF3. TMEM33 co-localizes with and interacts with RLR cascade components at the ER. The N-terminal TM1 and TM2 domains of TMEM33 are required for IFN suppression. |
Co-immunoprecipitation, ubiquitination assays, kinase phosphorylation assays, domain deletion mutants, IFN promoter reporter assay, siRNA knockdown, zebrafish cell line overexpression |
PLoS pathogens |
High |
33600488
|
| 2021 |
TMEM33 functions as a downstream effector of PKM2 in controlling lipid homeostasis. Loss of PKM2 upregulates TMEM33, which recruits the E3 ubiquitin ligase RNF5 to promote proteasomal degradation of SCAP (SREBP-cleavage activating protein), thereby reducing SREBP activation and lipid synthesis. TMEM33 transcription is controlled by NRF1, whose cleavage and activation are regulated by PKM2 levels. |
Co-immunoprecipitation, ubiquitination assay, protein stability assay, siRNA/shRNA knockdown, mouse PKM2 knockout, transcriptional reporter assays, immunoblotting |
The EMBO journal |
High |
34487377
|
| 2025 |
TMEM33 physically interacts with RAB22A and binds the TM2 domain of ER-shaping protein RTN4, forming a RAB22A/TMEM33/RTN4 complex. This assembly promotes RTN4 homo-oligomerization, generating RTN4-enriched microdomains of high ER curvature that drive bud scission of RTN4-positive vesicles. These vesicles develop into noncanonical autophagosomes that are secreted as extracellular vesicles via the Rafeesome pathway, constituting a secretory ER-phagy route that bypasses lysosomal degradation. |
Co-immunoprecipitation, domain mapping (TM2 binding), fluorescence microscopy, vesicle biogenesis assays, extracellular vesicle isolation, autophagy flux assays |
Cell discovery |
Medium |
40301304
|
| 2026 |
TMEM33 deletion in CD8+ T cells enhances their anti-tumor function. Tmem33 knockout mice show delayed melanoma growth and increased CD8+ T cell infiltration. TMEM33 acts cell-intrinsically in CD8+ T cells to constrain TCF-1+PD-1+ progenitor-exhausted T cell (Tpex) maintenance; its deletion promotes Tpex accumulation, elevated effector function, and reduced exhaustion. Ex vivo deletion also enhanced polyclonal activation of naïve CD8+ T cells. |
Murine constitutive knockout, adoptive cell transfer (OT-I cells), flow cytometry, ex vivo T cell activation assays, B16F10-OVA tumor model |
bioRxivpreprint |
Medium |
41509280
|