| Aspect | Key findings | Evidence type | Key sources (date; URL) | Citeable context IDs |
|---|---|---|---|---|
| Identity / synonyms | • Verified target is **human EMC10** = **ER membrane protein complex subunit 10** • UniProt Q5UCC4 matches literature aliases **HSM1/HSS1/C19orf63** • Literature distinguishes membrane-bound EMC10 from secreted **HSS1/EMC10-2** splice product | Literature cross-mapping; review synthesis; structural papers | Pleiner et al., *Science* (2020 Jul); https://doi.org/10.1126/science.abb5008 • Volkmar & Christianson, *J Cell Sci* (2020 Apr); https://doi.org/10.1242/jcs.243519 • Junes-Gill et al., *BMC Cancer* (2014 Dec); http://www.biomedcentral.com/1471-2407/14/920 | (pqac-00000001, pqac-00000003, pqac-00000004) |
| Localization / topology | • EMC10 is an **ER-associated EMC subunit** positioned on the **ER-lumenal face** • Human cryo-EM places EMC10 in the **lumenal L-shaped region** with EMC1/EMC7 • EMC10 has a **single, flexible TMD**; improved cryo-EM explicitly visualized/labeled EMC10 TMD topology | Cryo-EM structure; image/figure inspection | Pleiner et al., *Science* (2020 Jul); https://doi.org/10.1126/science.abb5008 • Pleiner et al., *J Cell Biol* (2023 May); https://doi.org/10.1083/jcb.202212007 | (pqac-00000001, pqac-00000014) |
| Role in EMC complex | • EMC10 is a **non-catalytic accessory/scaffold-like lumenal subunit**, not the insertase core • Contacts/positions near EMC1 and EMC7 on the lumenal side • EMC7 loss can lead to loss of EMC10 from assembled complex, supporting an auxiliary stabilizing role | Cryo-EM; mutational/assembly analysis; review synthesis | Miller-Vedam et al., *eLife* (2020 Sep); https://doi.org/10.1101/2020.09.02.280008 • Pleiner et al., *Science* (2020 Jul); https://doi.org/10.1126/science.abb5008 | (pqac-00000002, pqac-00000001) |
| Primary molecular function | • No enzyme or transporter activity has been established for EMC10 itself • Best-supported primary function is as a **structural/auxiliary EMC subunit** supporting **membrane protein biogenesis** • Functional effect is indirect, through the EMC machinery that inserts or stabilizes select membrane-protein TMDs | Structural inference; complex-level functional studies | Pleiner et al., *Science* (2020 Jul); https://doi.org/10.1126/science.abb5008 • Bai & Li, *FEBS J* (2022 Mar); https://doi.org/10.1111/febs.15786 • Li et al., *Aging (Albany NY)* (2024 Mar 15); https://doi.org/10.18632/aging.205660 | (pqac-00000001, pqac-00000005) |
| Insertase / chaperone mechanism context | • EMC core insertase activity resides mainly in **EMC3/EMC6** hydrophilic vestibule, with EMC10 peripheral to this core • 2023 work defined a **selectivity filter** at the EMC that rejects misinserted positively charged TA substrates and enforces topology • 2023 client-bound structure supports EMC **holdase/chaperone** function for CaV channel assembly; lumenal module including EMC10 shifts during client engagement | Cryo-EM; mutagenesis; client-bound structural biology | Pleiner et al., *J Cell Biol* (2023 May); https://doi.org/10.1083/jcb.202212007 • Chen et al., *Nature* (2023 Jul); https://doi.org/10.1038/s41586-023-06175-5 • Li et al., *Aging (Albany NY)* (2024 Mar 15); https://doi.org/10.18632/aging.205660 | (pqac-00000007, pqac-00000009, pqac-00000010, pqac-00000011, pqac-00000005) |
| Secreted isoform / soluble form | • Alternative splice variant **EMC10-2 / HSS1** lacks a discernible TMD and is **secreted** • Secreted EMC10/HSS1 showed reported anti-glioma/anti-angiogenic effects in glioma assays • A separate cardiovascular study identified **secreted EMC10/Emc10** from bone marrow-derived monocytes/macrophages as a **pro-angiogenic growth factor** after MI, indicating context/isoform-dependent biology | Cell culture functional assays; recombinant protein; mouse MI models | Junes-Gill et al., *BMC Cancer* (2014 Dec); http://www.biomedcentral.com/1471-2407/14/920 • Reboll et al., *Circulation* (2017 Nov); https://doi.org/10.1161/CIRCULATIONAHA.117.029980 • Volkmar & Christianson, *J Cell Sci* (2020 Apr); https://doi.org/10.1242/jcs.243519 | (pqac-00000004, pqac-00000012, pqac-00000013, pqac-00000003) |
| Signaling linked to soluble EMC10 | • In endothelial/cardiac repair studies, Emc10 signaled via **small GTPases, PAK, p38 MAPK, and MK2** to promote actin polymerization and migration • In glioma-related studies, overexpression altered cell-cycle/tumorigenic transcriptional programs and reduced migration/invasion • These signaling findings concern the **soluble/secreted form**, not necessarily the EMC-bound ER subunit | Recombinant protein; cell migration assays; transcriptomics; mouse infarct explants | Reboll et al., *Circulation* (2017 Nov); https://doi.org/10.1161/CIRCULATIONAHA.117.029980 • Junes-Gill et al., *BMC Cancer* (2014 Dec); http://www.biomedcentral.com/1471-2407/14/920 | (pqac-00000012, pqac-00000013, pqac-00000004) |
| Disease / phenotype associations | • Open Targets lists associations with **neurodevelopmental disorder**, including **neurodevelopmental disorder with dysmorphic facies and variable seizures**, plus broader genetic disorder/hypertension links • EMC as a complex is implicated in neurological disease, diabetes, cancer, and membrane-protein proteostasis defects • Evidence is stronger at the **gene-disease association** level than for a fully resolved EMC10-specific molecular mechanism in these disorders | Database association; literature synthesis | Open Targets association context (retrieved current database evidence) • Li et al., *Aging (Albany NY)* (2024 Mar 15); https://doi.org/10.18632/aging.205660 | (pqac-00000000, pqac-00000005) |
| Quantitative phenotype highlights | • Glioma study: hHSS1 overexpression changed cell-cycle distribution (**G0/G1 down, S and G2/M up; P<0.05**) and reduced migration/invasion (**P<0.001 to P<0.01**) • TCGA correlations reported for **BRCA2 r = -0.224 (P<0.0005)**, **ADAMTS1 r = -0.132 (P<0.01)**, **endostatin r = 0.141 (P<0.005)** • MI study: **85±2%** of Emc10+ cells in infarct region coexpressed **F4/80** macrophage marker | Cell biology assays; TCGA correlation; mouse histology | Junes-Gill et al., *BMC Cancer* (2014 Dec); http://www.biomedcentral.com/1471-2407/14/920 • Reboll et al., *Circulation* (2017 Nov); https://doi.org/10.1161/CIRCULATIONAHA.117.029980 | (pqac-00000004, pqac-00000013) |
| Applications / translation | • EMC biology is relevant to **membrane-protein biogenesis**, affecting ion channels, receptors, transporters, and viral proteins—important because many drug targets are membrane proteins • Secreted Emc10 showed **proof-of-concept therapeutic benefit** in mouse post-MI repair when delivered by osmotic minipump • EMC machinery is being considered in virus-host biology and protein-quality-control research, but there is **no EMC10-targeted approved therapy** | Structural biology; translational mouse model; review | Pleiner et al., *Science* (2020 Jul); https://doi.org/10.1126/science.abb5008 • Reboll et al., *Circulation* (2017 Nov); https://doi.org/10.1161/CIRCULATIONAHA.117.029980 • Woo et al., *J Cell Sci* (2023 Jul); https://doi.org/10.1242/jcs.261121 | (pqac-00000001, pqac-00000012, pqac-00000013) |


*Table: This table summarizes the best-supported functional annotation for human EMC10/Q5UCC4, separating its likely primary role as an ER-lumenal accessory EMC subunit from reported biology of secreted EMC10/HSS1 isoforms. It also highlights recent 2023–2024 structural advances, disease links, and quantitative findings useful for downstream annotation.*