| Aspect | Key findings | Supporting citations |
|---|---|---|
| Identity / aliases | Human **EMC2** encodes **ER membrane protein complex subunit 2**, also known as **TTC35/KIAA0103**; literature consistently identifies it as a **cytosolic EMC subunit** in the human ER membrane protein complex, matching UniProt Q15006. It is ~35 kDa and part of the conserved EMC core. | (pqac-00000001, pqac-00000015, pqac-00000020) |
| Localization | EMC2 is **cytosolic-facing** but tightly associated with the **ER-resident EMC** rather than being a free soluble factor. It sits in the **cytosolic domain/vestibule** of the complex adjacent to membrane subunits that form the insertase core. | (pqac-00000000, pqac-00000017, pqac-00000021) |
| Complex membership | Human EMC is a **9-10 subunit** complex depending on annotation/study context; EMC2 associates with membrane subunits plus **EMC8 or EMC9** in a mutually exclusive or paralog-substitutable manner. EMC2 knockdown destabilizes other EMC components, supporting a core assembly role. | (pqac-00000002, pqac-00000003, pqac-00000018) |
| Structural role | EMC2 forms an **α-solenoid/TPR-like helical scaffold** that organizes the cytosolic region. It contacts **EMC3, EMC5, EMC1, and EMC8/9**, and mutations at these interfaces disrupt assembly, showing EMC2 is primarily an **architectural scaffold** rather than the membrane-embedded catalytic insertase element. | (pqac-00000000, pqac-00000015, pqac-00000019) |
| Mechanistic role in insertion | EMC as a whole is a **co- and post-translational insertase** for selected low/moderate-hydrophobicity TMDs; EMC2 helps form the **cytosolic vestibule** that initially receives substrate TMDs before transfer to the **EMC3/EMC6 hydrophilic vestibule** in the membrane. Conserved basic residues at/near the EMC2-containing vestibule likely contribute to substrate filtering against positively charged segments. | (pqac-00000015, pqac-00000017, pqac-00000021) |
| Recent 2023-2024 developments | **2023:** EMC was shown to contain a **selectivity filter** that limits ER misinsertion, using a positively charged vestibule and methionine-rich capture loops; EMC4’s EMC2-binding site was functionally important for assembly. **2024:** EMC was shown to **rectify topology post-translationally** for some multipass proteins, with an estimated **~250 new putative substrates**. | (pqac-00000007, pqac-00000009, pqac-00000008) |
| Known client protein classes / examples | EMC-dependent proteins are enriched for **multipass transporters**, **ATPases**, some **tail-anchored proteins**, and selected **type III membrane proteins**. Example clients/contexts include **SQS/FDFT1**, **ATP6V0A1**, **FZD family proteins**, **CB5**, **SGPL1**, and viral or host type III TMPs such as **HIV Vpu**, **SMAGP**, **BCMA**, **Syt1**; flaviviral **NS4A/NS4B** biogenesis also depends on EMC contextually. | (pqac-00000018, pqac-00000027, pqac-00000033, pqac-00000036) |
| Quantitative stats | In unbiased mammalian proteomics, **36 of 971** transmembrane proteins were classified as EMC-dependent (~**3.7%**), while **171 of 971** were EMC-independent (~**17.6%**). Tian et al. identified **5,570** proteins total, retained **4,446** for analysis, with **81** significantly changed in EMC6-KO vs WT (**17 up**, **64 down**). Shurtleff et al. found **37** decreased proteins, and among **11** proteins decreased ≥2-fold in both EMC2- and EMC4-depleted cells, **10** were transmembrane proteins. | (pqac-00000027, pqac-00000028, pqac-00000026) |
| Experimental systems | EMC2/EMC function has been studied using **cryo-EM**, **mutagenesis**, **co-immunoprecipitation**, **SEC-MALS**, **site-specific crosslinking**, **reconstituted proteoliposome insertion assays**, **split-GFP topology reporters**, **glycosylation assays**, **SILAC/TMT proteomics**, **ribosome profiling**, and **siRNA/CRISPRi depletion** in human cell systems plus in vitro rough microsomes/reticulocyte lysates. | (pqac-00000000, pqac-00000011, pqac-00000026, pqac-00000028, pqac-00000033) |
| Disease / phenotype associations | Direct, gene-specific human disease causality for **EMC2** remains limited relative to complex-level biology, but EMC perturbation affects membrane-protein homeostasis, ER stress, and client stability. Experimental evidence links EMC biology to **viral infection** (e.g., DENV NS4A/NS4B, HIV Vpu), **proteostasis**, and cancer-related phenotypes in broader EMC studies; Open Targets lists low-to-moderate evidence associations for EMC2 to traits/diseases such as **neurodegenerative disease**, **asthma**, and **gastroesophageal reflux disease**, which should be interpreted cautiously as association-level rather than definitive mechanism. | (pqac-00000018, pqac-00000022, pqac-00000036) |


*Table: This table summarizes the verified identity, localization, structural role, mechanism, recent advances, client scope, quantitative data, methods, and disease relevance of human EMC2 (UniProt Q15006). It is useful as a compact evidence map linking EMC2 specifically to the ER membrane protein complex and membrane-protein biogenesis.*