Endoplasmic reticulum membrane protein complex

The endoplasmic reticulum membrane protein complex (EMC) is a putative endoplasmic reticulum-resident membrane protein (co-)chaperone. The EMC is evolutionarily conserved in eukaryotes (animals, plants, and fungi), and its initial appearance might reach back to the last eukaryotic common ancestor (LECA). Many aspects of mEMC biology and molecular function remain to be studied. The endoplasmic reticulum membrane protein complex (EMC) is a putative endoplasmic reticulum-resident membrane protein (co-)chaperone. The EMC is evolutionarily conserved in eukaryotes (animals, plants, and fungi), and its initial appearance might reach back to the last eukaryotic common ancestor (LECA). Many aspects of mEMC biology and molecular function remain to be studied. As of 2016, the structure of the EMC has not yet been resolved. The EMC consists of up to 10 subunits (EMC1 - EMC4, MMGT1, EMC6 - EMC10), of which only two (EMC8/9) are homologous proteins. Seven out of ten (EMC1, EMC3, EMC4, MMMGT1, EMC6, EMC7, EMC10) subunts are predicted to contain at least one transmembrane domain (TMD), whereas EMC2, EMC8 and EMC9 do not contain any predicted transmembrane domains are herefore likely to interact with the rest of the EMC on the cytosolic face of the endoplasmic reticulum (ER). EMC proteins are thought to be present in the mature complex in a 1:1 stoichiometry. The majority of EMC proteins (EMC1/3/4/MMGT1/6/7/10) contain at least one predicted TMD. EMC1, EMC5 and EMC10 contain an N-terminal signal sequence. EMC1, also known as KIAA0090, contains a single TMD (aa 959-979) and Pyrroloquinoline quinone (PQQ)-like repeats (aa 21-252), which could form a β-propeller domain. The TMD is part of a domain a larger domain (DUF1620). The functions of the PQQ and DUF1620 domains in EMC1 remain to be determined. EMC2 (TTC35) harbours three tetratricopeptide repeats (TPR1/2/3). TPRs have been shown to mediate protein-protein interactions and can be found in a large variety of proteins of diverse function. The function of TPRs in EMC2 is unknown. EMC8 and EMC9 show marked sequence identity (44.72%) on the amino acid level. Both proteins are members of the UPF0172 family, a member of which (e.g. TLA1) are unvolved in regulating the antenna size of chlorophyll-a. Several subunits of the mammalian EMC (mEMC) are posttranslationally modified. EMC1 contains three predicted N-glcosylation sites at positions 370, 818, and 913. EMC10 features a predicted N-glycosylation consensus motif at position 182. EMC proteins are evolutionarily conserved in eukaryotes. No homologues are reported in prokaryotes. Therefore, the EMC has been suggested to have its evolutionary roots in the last eukaryote common ancestor (LECA). The EMC was first identified in a genetic screen in yeast for factors involved in protein folding in the ER. Accordingly, deletion of individual EMC subunits correlates with the induction of an ER stress response in various model organisms. However, it is worth noting that in human osteosarcoma cells (U2OS cells), deletion of EMC6 does not appear to cause ER stress. When overexpressed, several subunits of the mammalian EMC orthologue (mEMC) have been found to physically interact with ERAD components (UBAC2, DER1, DER2) Genetic screens in yeast have shown EMC subunits to be enriched in alongside ERAD genes. Taken together, these findings imply a role of the mEMC in protein homeostasis.