The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Human EMC10 encodes ER membrane protein complex subunit 10, a single-pass, ER-associated protein that forms part of the endoplasmic reticulum membrane protein complex (EMC), a conserved membrane-protein biogenesis machine that facilitates insertion/topogenesis and quality control of select membrane-protein transmembrane domains (TMDs). Structural work places EMC10 in the ER-lumenal module of the complex (with EMC1/EMC4/EMC7), with a flexible single TMD that is not part of the catalytic insertase core. Separately, multiple studies report secreted/soluble EMC10-related products (notably HSS1/EMC10-2) with paracrine signaling activities in cancer and cardiac repair contexts. Recent 2023–2024 cryo-EM studies significantly advanced mechanistic understanding of EMC function and conformational states, providing the most current framework for interpreting EMC10’s role. (pleiner2020structuralbasisfor pages 1-3, volkmar2020squaringtheemc pages 10-11, pleiner2023aselectivityfilter pages 1-2, chen2023emcchaperone–cavstructure pages 1-3, li2024structuralinsightsinto pages 1-3)
The literature used here matches the requested target:
No conflicting gene symbol usage was encountered in retrieved materials; all “EMC10” references examined correspond to the human ER membrane protein complex subunit 10 context. (junesgill2014humanhematopoieticsignal pages 1-2, pleiner2020structuralbasisfor pages 1-3)
The EMC is an ER-resident multi-subunit assembly that acts as an insertase and chaperone/holdase supporting membrane-protein biogenesis, particularly for low-hydrophobicity TMDs (e.g., many tail-anchored proteins and certain multipass proteins). (pleiner2023aselectivityfilter pages 1-2, li2024structuralinsightsinto pages 1-3)
A key mechanistic concept is the hydrophilic vestibule within the membrane (primarily formed by core transmembrane subunits such as EMC3/EMC6, and supported by other subunits) that lowers the energetic barrier for integrating challenging TMDs and translocating short polar segments. (pleiner2020structuralbasisfor pages 1-3, pleiner2023aselectivityfilter pages 1-2)
EMC10 is best understood as an auxiliary/scaffold-like subunit in the lumenal module of the EMC, rather than as the catalytic insertase core.
Thus, for functional annotation, EMC10’s “primary function” is most defensibly described as participation in a membrane protein biogenesis/quality-control complex, not an enzyme reaction or substrate transporter in its own right. (pleiner2020structuralbasisfor pages 1-3, millervedam2020structuralandmechanistic pages 18-21)
Structural evidence places EMC10 on the ER-lumenal side of the EMC (i.e., lumen-facing domain) with a membrane anchor.
An improved cryo-EM model explicitly depicts the single-pass topology of EMC10:
No specific enzymatic or transporter activity is attributed to EMC10 itself in the cited primary structural studies. Instead, EMC10 is best classified as a non-catalytic structural subunit within a multi-subunit insertase/chaperone system.
A major 2023 mechanistic advance was identification of a selectivity filter at the EMC that helps prevent misinsertion and enforces correct topology.
Although this paper is not EMC10-specific mechanistically, it is directly relevant to EMC10 annotation because it employs an improved EMC structural model that includes EMC10 topology and emphasizes that certain subunits (including EMC10) have dynamic TMDs providing a protected environment during insertion decisions. (pleiner2023aselectivityfilter pages 10-11, pleiner2023aselectivityfilter media 41b09963)
A landmark 2023 Nature study solved cryo-EM structures of EMC bound to a voltage-gated calcium channel assembly intermediate, providing direct evidence for EMC’s holdase/chaperone roles.
This strengthens the interpretation that EMC10, as part of the lumenal module, may contribute to conformational coupling and/or stabilization during client engagement, even if it is not the catalytic insertase element. (chen2023emcchaperone–cavstructure pages 8-9, millervedam2020structuralandmechanistic pages 18-21)
A 2024 paper provided additional EMC structural states relevant to multifunctionality.
While not focused on EMC10 specifically, this contributes to current expert interpretation: EMC10 should be annotated within a complex that is conformationally and functionally versatile, with EMC10 embedded in the lumenal module that can move during client interactions. (li2024structuralinsightsinto pages 1-3, chen2023emcchaperone–cavstructure pages 8-9)
A recurring theme in EMC10 literature is the existence of secreted or soluble EMC10-related products, raising an annotation challenge: separating the EMC-bound subunit role from a secreted signaling factor.
A review synthesis reports that EMC10 exists both as a full-length, membrane-bound EMC subunit and as a splice variant EMC10-2 (HSS1) lacking a discernible TMD and being secreted. (volkmar2020squaringtheemc pages 10-11)
In glioma-derived cell models:
These results support biological activity of a secreted EMC10-related factor in vitro, but they do not establish the mechanism of action or receptor identity, and they likely relate specifically to the secreted HSS1/EMC10-2 product rather than the EMC-incorporated subunit. (volkmar2020squaringtheemc pages 10-11, junesgill2014humanhematopoieticsignal pages 1-2)
A key in vivo translational study reports secreted Emc10 after MI.
This study provides one of the strongest “real-world implementation” examples: recombinant protein delivery as a therapy concept in an animal model. (reboll2017emc10(endoplasmicreticulum pages 1-2, reboll2017emc10(endoplasmicreticulum pages 9-10)
Direct, EMC10-specific disease mechanisms are still emerging, but authoritative association resources implicate EMC10 in neurodevelopmental phenotypes.
These associations should be interpreted as gene–disease evidence links rather than definitive mechanistic proof; nonetheless, they prioritize EMC10 for deeper human genetics follow-up (variant interpretation, functional assays). (OpenTargets Search: -EMC10)
Consensus interpretation from structural and mechanistic studies: EMC10 is best annotated primarily as an ER membrane complex subunit contributing to EMC architecture and conformational states during client handling, rather than directly binding substrates as the catalytic insertase element.
Important caveat for annotation: A substantial portion of the EMC10 literature concerns secreted EMC10-related factors (HSS1/EMC10-2). Functional claims about angiogenesis or tumor suppression likely refer to soluble products and should not be conflated with the EMC-incorporated EMC10 subunit unless isoform usage is experimentally clarified. (volkmar2020squaringtheemc pages 10-11, junesgill2014humanhematopoieticsignal pages 1-2, reboll2017emc10(endoplasmicreticulum pages 1-2)
| 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 | (pleiner2020structuralbasisfor pages 1-3, volkmar2020squaringtheemc pages 10-11, junesgill2014humanhematopoieticsignal pages 1-2) |
| 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 | (pleiner2020structuralbasisfor pages 1-3, pleiner2023aselectivityfilter media 41b09963) |
| 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 | (millervedam2020structuralandmechanistic pages 18-21, pleiner2020structuralbasisfor pages 1-3) |
| 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 | (pleiner2020structuralbasisfor pages 1-3, li2024structuralinsightsinto pages 1-3) |
| 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 | (pleiner2023aselectivityfilter pages 1-2, pleiner2023aselectivityfilter pages 10-11, chen2023emcchaperone–cavstructure pages 1-3, chen2023emcchaperone–cavstructure pages 8-9, li2024structuralinsightsinto pages 1-3) |
| 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 | (junesgill2014humanhematopoieticsignal pages 1-2, reboll2017emc10(endoplasmicreticulum pages 1-2, reboll2017emc10(endoplasmicreticulum pages 9-10, volkmar2020squaringtheemc pages 10-11) |
| 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 | (reboll2017emc10(endoplasmicreticulum pages 1-2, reboll2017emc10(endoplasmicreticulum pages 9-10, junesgill2014humanhematopoieticsignal pages 1-2) |
| 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 | (OpenTargets Search: -EMC10, li2024structuralinsightsinto pages 1-3) |
| 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 | (junesgill2014humanhematopoieticsignal pages 1-2, reboll2017emc10(endoplasmicreticulum pages 9-10) |
| 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 | (pleiner2020structuralbasisfor pages 1-3, reboll2017emc10(endoplasmicreticulum pages 1-2, reboll2017emc10(endoplasmicreticulum pages 9-10) |
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.
Human EMC10 (UniProt Q5UCC4) is most strongly supported as a single-pass, ER-associated subunit of the EMC, residing in the lumenal module and contributing structurally to a versatile insertase/holdase machine that controls insertion and topology of select membrane proteins. The most important recent advances (2023–2024) strengthen a model in which EMC10 participates in client-induced conformational changes and a dynamic transmembrane environment, while core substrate discrimination is mediated by conserved charge features within the EMC’s hydrophilic vestibule. In parallel, secreted EMC10-related isoforms (e.g., HSS1/EMC10-2) have been implicated in signaling and tissue repair, including proof-of-concept recombinant protein therapy in a mouse MI model, but the relationship between these soluble forms and the canonical EMC subunit role remains an active area for clarification. (pleiner2023aselectivityfilter media 41b09963, chen2023emcchaperone–cavstructure pages 8-9, li2024structuralinsightsinto pages 1-3, reboll2017emc10(endoplasmicreticulum pages 1-2)
References
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(volkmar2020squaringtheemc pages 10-11): Norbert Volkmar and John C. Christianson. Squaring the emc – how promoting membrane protein biogenesis impacts cellular functions and organismal homeostasis. Journal of Cell Science, Apr 2020. URL: https://doi.org/10.1242/jcs.243519, doi:10.1242/jcs.243519. This article has 59 citations and is from a domain leading peer-reviewed journal.
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(chen2023emcchaperone–cavstructure pages 1-3): Zhou Chen, Abhisek Mondal, Fayal Abderemane-Ali, Seil Jang, Sangeeta Niranjan, José L. Montaño, Balyn W. Zaro, and Daniel L. Minor. Emc chaperone–cav structure reveals an ion channel assembly intermediate. Nature, 619:410-419, May 2023. URL: https://doi.org/10.1038/s41586-023-06175-5, doi:10.1038/s41586-023-06175-5. This article has 77 citations and is from a highest quality peer-reviewed journal.
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(reboll2017emc10(endoplasmicreticulum pages 9-10): Marc R. Reboll, Mortimer Korf-Klingebiel, Stefanie Klede, Felix Polten, Eva Brinkmann, Ines Reimann, Hans-Joachim Schönfeld, Maria Bobadilla, Jan Faix, George Kensah, Ina Gruh, Michael Klintschar, Matthias Gaestel, Hans W. Niessen, Andreas Pich, Johann Bauersachs, Joseph A. Gogos, Yong Wang, and Kai C. Wollert. Emc10 (endoplasmic reticulum membrane protein complex subunit 10) is a bone marrow–derived angiogenic growth factor promoting tissue repair after myocardial infarction. Circulation, 136:1809–1823, Nov 2017. URL: https://doi.org/10.1161/circulationaha.117.029980, doi:10.1161/circulationaha.117.029980. This article has 55 citations and is from a highest quality peer-reviewed journal.
(OpenTargets Search: -EMC10): Open Targets Query (-EMC10, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.