| Publication | Date | URL / DOI | Study type | EMC6-relevant findings | Quantitative data |
|---|---|---|---|---|---|
| Pleiner et al., 2020, *Science* | Jul 2020 | https://doi.org/10.1126/science.abb5008 | Human cryo-EM structure / mechanism | Human EMC6 is an integral membrane subunit with **3 transmembrane helices**; EMC6 and EMC3 form an enclosed **hydrophilic vestibule** within the membrane that supports substrate insertion. EMC6 TM1 is unusually weakly hydrophobic and inserts efficiently only upon assembly with EMC5, linking EMC6 to EMC assembly/stability. Figure summaries identify EMC6 in the core TM module and vestibule with EMC3. (pqac-00000002, pqac-00000004, pqac-00000008) | Cryo-EM resolution **~3.4 Å**; EMC particle **~200 × 70 × 100 Å**; EMC6 TM1 predicted insertion **ΔG = 3.8**; structure **PDB 6WW7**. (pqac-00000002) |
| O'Donnell et al., 2020, *eLife* | May 2020 | https://doi.org/10.7554/elife.57887 | Architecture / biochemical mechanism | Places EMC6 among the mammalian EMC membrane subunits in a stable ER insertase complex. EMC contains a cytosolic vestibule leading into a lumenally sealed, lipid-exposed intramembrane groove for TMD insertion; EMC6 contributes as part of the membrane subcomplex required for overall EMC integrity and function. Purified EMC is sufficient for insertion of terminal TMDs in vitro. (pqac-00000005, pqac-00000006) | Mammalian EMC described as **10 subunits** with **7 membrane subunits** including EMC6 and **12 predicted TM helices** across the membrane subcomplex. (pqac-00000005) |
| Bai et al., 2020, *Nature* | Jun 2020 | https://doi.org/10.1038/s41586-020-2389-3 | Cryo-EM structure / insertase mechanism | In yeast EMC, Emc6 is a transmembrane scaffold subunit contributing to the membrane region of the insertase. The EMC transmembrane region includes Emc4, Emc5 and Emc6 plus TMDs of Emc1 and Emc3, supporting evolutionary conservation of EMC6’s role in the insertase membrane core relevant to human EMC6. (pqac-00000001) | EMC knockout phenotypes: knockout of any single Emc subunit recapitulated EMC-null growth defect at **37°C**; proteomics of **Emc3/4/6 KO** cells found **38** significantly reduced membrane proteins, with **9** validated as markedly downregulated in Emc3 KO; structure **PDB 6WB9 / EMD-21587**. (pqac-00000001) |
| Bai & Li, 2022, *FEBS Journal* | Mar 2022 | https://doi.org/10.1111/febs.15786 | Review | Review synthesizing EMC structural work and current model: EMC is a membrane insertase for less-hydrophobic/amphipathic helices, with a consensus substrate-binding pocket and architectural conservation from yeast to humans. For EMC6 specifically, the review supports its placement in the conserved membrane-embedded insertase core. (paper search result) | Review notes mammalian EMC as a **9-subunit complex (EMC1–7, 8/9, 10 context-dependent naming in review summary)** and emphasizes the conserved client TMH-binding pocket; no EMC6-specific numerical assay readout provided in gathered evidence. (paper search result) |
| Pleiner et al., 2023, *Journal of Cell Biology* | May 2023 | https://doi.org/10.1083/jcb.202212007 | Mechanistic / selectivity filter | Defines a **selectivity filter** in EMC that limits protein misinsertion at the ER and enforces topology of multipass membrane proteins. The EMC3/6 insertase core remains central, but the gathered evidence indicates **mutations in EMC6 had only mild effects** relative to stronger EMC3 effects in the tested selectivity-filter context. EMC6 remains part of the partially enclosed vestibule with surrounding dynamic subunits. (paper search result) | Improved human EMC cryo-EM reconstruction reported; exact numerical resolution and EMC6-specific effect sizes not available in gathered evidence. EMC6 mutation effects described qualitatively as **mild**. (paper search result) |
| Chen et al., 2023, *Nature* | May 2023 | https://doi.org/10.1038/s41586-023-06175-5 | Client-bound structure / chaperone mechanism | EMC–CaV structure reveals a membrane-protein assembly intermediate and supports an EMC **chaperone** mode in addition to insertase activity. Gathered evidence specifically notes an **EMC6-gated transmembrane cavity** proposed to participate in client engagement during CaV biogenesis, placing EMC6 directly in the client-handling path. (paper search result) | The study reports an **~0.6 MDa** EMC–client complex. Additional EMC6-specific interface measurements were not available in gathered evidence. (paper search result) |
| Li et al., 2024, *Aging (Albany NY)* | Mar 2024 | https://doi.org/10.18632/aging.205660 | Human cryo-EM structure / interaction with VDAC | Human EMC structures in apo and VDAC-bound states identify a conserved EMC–VDAC interaction at **mitochondria–ER contact sites (MERCs)**. EMC6 is part of the **EMC3–EMC6 core**; an ordered EMC4 three-TMH bundle sits adjacent to this core to form a sidewall of the hydrophilic vestibule. The reported **gating plug** is assigned to EMC3 rather than EMC6, so EMC6’s role here is structural/core rather than the plug itself. (pqac-00000007) | Apo structure **3.47 Å**; VDAC-bound structure **3.32 Å**. No EMC6-specific buried surface area or mutation phenotype was provided in gathered evidence. (pqac-00000007) |
| Klose et al., 2025, *Nature Communications* | Aug 2025 | https://doi.org/10.1038/s41467-025-62109-x | Chaperone mechanism / interactomics | Although outside the user-prioritized 2023–2024 window, this recent mechanistic study is useful context: EMC6 is named as part of a **lipid-filled cavity** formed by EMC1, EMC3, EMC5 and EMC6, distinct from the canonical insertase site, supporting a broader EMC chaperone/quality-control role. (pqac-00000003) | Crosslinking IP–MS found **506** enriched interactors, including **>200** transmembrane proteins; about **50%** of single-pass hits had signal peptides, **~1/3** had terminal TM helices, and **~2/3** of multipass hits had predicted Ncyto orientation. (pqac-00000003) |


*Table: This table summarizes key structural and mechanistic studies relevant to human EMC6/TMEM93 within the ER membrane protein complex, emphasizing recent 2023–2024 work while anchoring interpretations in foundational 2020 structures. It highlights EMC6’s role in the EMC3/EMC6 insertase core, assembly/stability, client handling, and emerging interaction contexts such as VDAC at MERCs.*