EMC1

EMC1 (ER membrane protein complex subunit 1) is the large lumenal scaffold subunit of the endoplasmic reticulum membrane protein complex (EMC), a conserved nine- to ten-subunit transmembrane-domain insertase and chaperone of the ER. The 993-residue protein has a cleaved N-terminal signal peptide, an extensive lumenal region (~residues 23-962) that folds into a GOLD-like/WD40-YVTN beta-propeller, a single C-terminal transmembrane helix, and a short cytoplasmic tail, making it a single-pass type I membrane protein. As part of the EMC it enables the energy-independent insertion of newly synthesized membrane proteins into the ER membrane, with a preference for transmembrane domains that are weakly hydrophobic or carry destabilizing charged or aromatic residues. The complex inserts tail-anchored proteins post-translationally and inserts the first transmembrane domains of multipass proteins such as G protein-coupled receptors co-translationally, setting their N-exo topology in cooperation with the Sec61 translocon. The catalytic insertion vestibule of the complex is formed by the EMC3 and EMC6 subunits; EMC1 itself is non-catalytic and serves as a lumenal structural scaffold and assembly platform. EMC1 is broadly expressed and resides in the ER membrane, and biallelic or monoallelic variants cause CAVIPMR (cerebellar atrophy, visual impairment, and psychomotor retardation), an autosomal recessive neurodegenerative disorder.