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ER membrane protein insertase complex of ten recognized proteins, EMC1 - 10 (Guna et al. 2018).  Inserts C-terminal moderately hydrophobic TMSs of tail anchored (TA) proteins into the endoplasmic reticular membrane (Guna et al. 2018). EMC also inserts the first N-terminal TMS of G-proteins and some receptors co-translationally and cooperates with the Sec61 translocon to ensure accurate topogenesis of many membrane proteins (Chitwood et al. 2018). Disrupted ER membrane protein complex-mediated topogenesis drives congenital neural crest defects (Marquez et al. 2020). The high resolution 3-d structure of this EMC complex has been determined (O'Donnell et al. 2020). EMC10 plays a regulatory role in the ER membrane complex, opposing the transmembrane-domain insertion activity of the complex (Coukos et al. 2021). Inherited retinal dystrophies (IRDs) are a heterogeneous group of visual disorders caused by different pathogenic mutations in genes and regulatory sequences. The endoplasmic reticulum (ER) membrane protein complex (EMC) subunit 3 (EMC3) is the core unit of the EMC insertase that integrates transmembrane peptides into lipid bilayers (Li et al. 2023).  The C-terminus of EMC3 is essential for EMC functions, and EMC3 may be the gene for retinal degenerative diseases (Li et al. 2023).

Metazoa, Chordata
EMC1 - 10 of Homo sapiens
EMC1, Q8N766, 993 aas and 1 C-terminal TMS
EMC2, Q15006, 297 aas and 0 TMSs
EMC3, Q9P0I2, 261 aas and 3 TMSs; may be a member of the YidC family (see EMC family description)
EMC4, Q5J8M3, 183 aas and 2 TMSs
EMC5 (MMGT1; TMEM32), Q8N4V1, 131 aas and 2 TMSs.  This protein is a member of the MMgT family (TC# 1.A.67)
EMC6 (TMEM93), Q9BV81, 110 aas and 2 TMSs
EMC7, Q9NPA0, 242 aas and 2 TMSs, one N-terminal and one near the C-terminus
EMC8, O43402, 210 aas and 0 - 2 TMSs; homologous to EMC9
EMC9, Q9Y3B6, 208 aas and 0 - 2 TMSs; homologous to EMC8
EMC10, Q5UCC4, 262 aas and 2 TMSs, one N-terminal and one C-terminal

ER membrane protein insertase complex of eight recognized proteins, EMC1 - 7 + EMC10 (Bai et al. 2020). These authors have determined the high resolution structure of the complex.  It co-translationally inserts TMSs of many multi-pass integral membrane proteins into the ER membrane, and it is also responsible for inserting the TMSs of some tail-anchored proteins. Bai et al. 2020 reported theCryoEM structure. The Saccharomyces cerevisiae EMC contains eight subunits (Emc1-6, Emc7 and Emc10), has a large lumenal region and a smaller cytosolic region, and has a transmembrane region formed by Emc4, Emc5 and Emc6 plus the transmembrane domains of Emc1 and Emc3. They identified a five-TMS fold centred around Emc3 that resembles the prokaryotic YidC insertase and that delineates a largely hydrophilic protein pocket. The transmembrane domain of Emc4 tilts away from the main transmembrane region of EMC and is partially mobile. The flexibility of Emc4 and the hydrophilicity of the pocket are required for EMC function. The structure reveals notable evolutionary conservation with prokaryotic insertases, suggesting that eukaryotic TMS insertion involves a similar mechanism (Bai et al. 2020).

Fungi, Ascomycota
EMC of Saccharomyces cerevisiae
EMC1, 760 aas and 2 TMSs, N- and C-terminal (P25574)
EMC2, 292 aas and 0 TMSs (P47133)
EMC3, 253 aas and 3 TMSs in a 1 + 2 TMS arrangement. (P36039). It resembles CLAC Ca2+ channels (see TC# 1.A.106.2.1).
EMC4, 190 aas and 2 TMSs in the C-terminal half of the protein. (P53073) It resembles MMgT Mg2+ channels and is identical to the channel protein with TC# 1.A.67.1.7.
EMC5, 141 aas and 2 TMSs in the N-terminal half of the protein. (P40540)
MEC6, 108 aas and 3 TMSs in a 2 + 1 TMS arrangement (Q12431)
MEC7 or Sop4 of 234 aas and 2 TMSs, N- and C-terminal (NP_012343.1)
MEC10, 205 aas and 1 N-terminal TMS (Q12025)