| Claim/insight about EMC8 | Evidence type | Key quantitative details | System/clients studied | Citation |
|---|---|---|---|---|
| EMC8 is a cytosolic subunit of the human ER membrane protein complex and is functionally redundant with EMC9 in mammals. | Cryo-EM/biochemical architecture | EMC8 is ~23 kDa and ~44% identical to EMC9; no free EMC subunits detected, indicating stable complex assembly. | Human EMC; general membrane protein biogenesis | O'Donnell et al., 2020, eLife, https://doi.org/10.7554/eLife.57887 (pqac-00000001, pqac-00000006) |
| EMC8 helps form the cytosolic vestibule/cap that engages substrate transmembrane domains during EMC-mediated insertion. | Cryo-EM/biochemical mechanism | EMC has a “large, moderately hydrophobic vestibule” leading to a lumenally sealed, lipid-exposed intramembrane groove; insertase reaction described as energy independent. | Human EMC; tail-anchored client SQS and terminal TMD substrates | O'Donnell et al., 2020, eLife, https://doi.org/10.7554/eLife.57887 (pqac-00000001, pqac-00000006) |
| EMC8 is a structural assembly factor in the human EMC cytosolic basket, binding EMC2 and contributing to complex stability. | Cryo-EM/structure-guided mutagenesis | Human EMC resolved at 3.4 Å; EMC2 clamps around EMC8 via an extensive hydrophobic surface, and mutations at EMC8/EMC2/EMC3/EMC5 interfaces disrupted subunit binding in vitro. | Human EMC reconstituted in lipid nanodiscs | Pleiner et al., 2020, Science, https://doi.org/10.1126/science.abb5008 (pqac-00000005) |
| In mammals, EMC8 is one of the soluble/cytosolic EMC components rather than a membrane-spanning subunit. | Quantitative proteomics/background functional study | Mammalian EMC described with 10 subunits; EMC2, EMC8, and EMC9 are cytosolic; Tian et al. defined 36 EMC-dependent versus 171 EMC-independent membrane proteins. | Mammalian EMC; broad membrane protein client sets | Tian et al., 2019, Cell Reports, https://doi.org/10.1016/j.celrep.2019.08.006 (pqac-00000002) |
| EMC dependency is linked to difficult transmembrane segments containing polar/charged residues, supporting an EMC8-containing cytosolic recognition/chaperoning role in the intact complex. | Proteomics/mutagenesis | 36 EMC-dependent and 171 EMC-independent membrane proteins identified; TMD mutagenesis could convert EMC dependency. | Diverse membrane proteins; disease-relevant examples include CFTR and connexin-32 at EMC-complex level | Tian et al., 2019, Cell Reports, https://doi.org/10.1016/j.celrep.2019.08.006 (pqac-00000002) |
| Reviews place EMC8 within the cytosolic subcomplex of EMC and interpret EMC as both an insertase and membrane-protein biogenesis factor/chaperone. | Authoritative review | EMC is considered a nine-protein complex in many species with EMC8/EMC9 as mutually exclusive paralogs; validated EMC-dependent proteins remain limited to roughly ~a dozen in the literature summarized. | EMC broadly; multipass membrane proteins and cotranslational biogenesis | Hegde, 2022, Annual Review of Biochemistry, https://doi.org/10.1146/annurev-biochem-032620-104553 (pqac-00000003, pqac-00000007, pqac-00000008) |
| Structure-function mapping places EMC8 near the cytoplasmic cap adjacent to EMC3, a region that influences client-specific biogenesis. | Cryo-EM/functional mutagenesis | Mutating the cytoplasmic cap near EMC8/9 increased SQS levels; distinct EMC regions separately affected tail-anchored, N-terminal, and polytopic clients. | SQS, B1AR, TMEM97 | Miller-Vedam et al., 2020, eLife preprint record, https://doi.org/10.1101/2020.09.02.280008 (pqac-00000004) |
| 2023 cryo-EM shows EMC8 directly contacts CaVβ3 in a client-bound EMC assembly intermediate, demonstrating a specific EMC8-dependent cytosolic docking role. | Cryo-EM/client-bound structure | Cyto dock area ~1,500 Å^2; EMC8-centered subsite 962 Å^2; adjacent EMC2 site ~550 Å^2; overall maps at 3.4 Å/3.3 Å with local 2.4–2.0 Å. | Human EMC–CaV1.2(ΔC)–CaVβ3 complex | Chen et al., 2023, Nature, https://doi.org/10.1038/s41586-023-06175-5 (pqac-00000009, pqac-00000011, pqac-00000012, pqac-00000013, pqac-00000014) |
| EMC8 binding stabilizes otherwise disordered regions of CaVβ3, supporting a chaperone/assembly role beyond simple TMD insertion. | Cryo-EM/client interaction analysis | Two CaVβ loops (β7–α4, Thr218–Ala243; β8–β9, Pro277–Lys282) bind the EMC8 site; a CaVβ region Lys225–Ser245 becomes ordered on EMC8 binding; seven conserved CaVβ residues participate in H-bond/salt-bridge networks. | Human CaV1.2/CaVβ3 assembly intermediate | Chen et al., 2023, Nature, https://doi.org/10.1038/s41586-023-06175-5 (pqac-00000009, pqac-00000011, pqac-00000012, pqac-00000013, pqac-00000014) |
| A 2024 structural study supports multifunctionality of human EMC and identifies a VDAC-bound state at mitochondria–ER contact sites, but the provided snippet does not assign a specific direct mechanistic role to EMC8. | Cryo-EM/structural study | Apo and VDAC1-bound human EMC structures at 3.47 Å and 3.32 Å; VDAC interaction observed at mitochondria-ER contact sites; gating-plug conformational change proposed to regulate function. | Human EMC; VDAC1 | Li et al., 2024, Aging (Albany NY), https://doi.org/10.18632/aging.205660 |
| Disease links for EMC8 specifically are currently weak/indirect in the provided evidence, with Open Targets listing only low-score associations and no literature details in the retrieved snippet. | Disease-target database association | Example association scores: jaw disease 0.07599; diverticular disease 0.03701; retinitis pigmentosa and erythrocytic microcytosis 0.03655; familial ocular anterior segment mesenchymal dysgenesis 0.03620; exfoliation syndrome 0.03484. | Human EMC8 disease associations | Open Targets platform result for EMC8 (context output) (pqac-00000000) |


*Table: This table compiles the main structural, mechanistic, proteomic, and disease-association evidence for human EMC8 from the provided sources. It highlights where EMC8 is best supported as a cytosolic structural/chaperone component of the ER membrane protein complex and where evidence remains indirect or limited.*