EMC10

EMC10 (ER membrane protein complex subunit 10; also C19orf63, INM02) is a 262 aa single-pass type I ER membrane glycoprotein with a cleavable N-terminal signal peptide, a large lumenal domain (N-glycosylated at Asn-182), a single transmembrane helix, and a short cytoplasmic tail. It is a constitutive lumenal/peripheral subunit of the ER membrane protein complex (EMC), a conserved transmembrane-domain insertase and membrane-protein chaperone that mediates energy-independent insertion of newly synthesized membrane proteins into the ER membrane, including post-translational insertion of tail-anchored proteins and cotranslational insertion and topogenesis of multipass membrane proteins such as G protein-coupled receptors. The membrane insertase activity resides in the EMC3/EMC6 membrane core; EMC10 is a non-catalytic structural subunit whose bulk projects into the ER lumen. An alternatively spliced isoform is secreted (HSS1) and circulates; secreted EMC10 has been characterized as a bone marrow-derived angiogenic growth factor that stimulates endothelial cell migration and outgrowth and promotes tissue repair after myocardial infarction. Biallelic loss-of-function variants in EMC10 cause a neurodevelopmental disorder with dysmorphic facies and variable seizures. EMC10 is broadly expressed, with the membrane form localizing to the ER membrane.