The architecture of EMC reveals a path for membrane protein insertion.

Gene Ontology annotation through association of InterPro records with GO terms

Annotation inferences using phylogenetic trees

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

PMID:22119785

Defining human ERAD networks through an integrative mapping strategy.

Affinity-MS ERAD-network mapping that first identified the EMC (including EMC3) in human cells and localized it to the ER membrane.

PMID:26496610

A human interactome in three quantitative dimensions organized by stoichiometries and abundances.

PMID:29242231

The ER membrane protein complex is a transmembrane domain insertase.

EMC is a transmembrane domain insertase that post-translationally inserts tail-anchored membrane proteins; EMC3 is a distant homolog of the Get1 insertase.

PMID:29809151

The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins.

The EMC engages multipass membrane protein clients cotranslationally to enable their biogenesis.

PMID:30415835

EMC Is Required to Initiate Accurate Membrane Protein Topogenesis.

The EMC sets the N-exo topology of the first TMD of GPCRs and other multipass proteins, initiating accurate topogenesis in cooperation with Sec61.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32439656

Structural basis for membrane insertion by the human ER membrane protein complex.

Cryo-EM structure of the human EMC; substrate insertion occurs via an enclosed hydrophilic vestibule formed by the subunits EMC3 and EMC6 and requires a methionine-rich cytosolic loop.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

file:human/EMC3/EMC3-uniprot.txt

UniProt entry Q9P0I2 (EMC3_HUMAN), ER membrane protein complex subunit 3

Multipass ER membrane catalytic insertase subunit of the EMC (YidC/Oxa1/Get1 superfamily); with EMC6 forms the insertase vestibule; EMC3 vestibule/Met-rich-loop mutations reduce client insertion without affecting assembly.

PMID:37199759

A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER.

Two conserved positively charged EMC3 residues (R31 and R180) at the hydrophilic-vestibule entrance form a charge-repulsion selectivity filter that rejects mitochondrial tail-anchored proteins and enforces the positive-inside topology rule; introducing negative charge into the vestibule increases ER misinsertion, defining EMC3 as a fidelity determinant of insertion.

PMID:37957425

EMC rectifies the topology of multipass membrane proteins.

The EMC post-translationally inserts C-terminal transmembrane domains of multipass membrane proteins to rectify topology after ribosome release; the EMC cytosol-facing hydrophilic vestibule (formed by EMC3/EMC6) is adjacent to the pre-translocated C-terminal tail, and this mechanism may apply to ~250 diverse multipass proteins.

PMID:38517390

Structural insights into human EMC and its interaction with VDAC.

Cryo-EM of human EMC in apo and VDAC-bound states identifies a gating plug within the EMC3/EMC6 hydrophilic vestibule (substrate-binding pocket); conformational changes of the gating plug between states suggest the EMC is not insertion-competent in the VDAC1-bound state, indicating state-dependent regulation of the insertase vestibule.

PMID:31263175

ER complex proteins are required for rhodopsin biosynthesis and photoreceptor survival in Drosophila and mice.

Loss-of-function of emc3 (and emc5, emc6) in Drosophila causes defective phototransduction and photoreceptor degeneration with reduced rhodopsin, independent of ERAD; conditional Emc3 knockout in mice causes rhodopsin mislocalization and death of rod and cone photoreceptors, establishing a conserved in vivo requirement for EMC3 in rhodopsin (a multipass GPCR-like client) biogenesis.