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

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:22119785

Defining human ERAD networks through an integrative mapping strategy.

Affinity-MS ERAD-network mapping that first identified the EMC (including EMC6) in human cells and localized it to the ER membrane.

PMID:23182941

A novel ER-localized transmembrane protein, EMC6, interacts with RAB5A and regulates cell autophagy.

EMC6 interacts with RAB5A and BECN1, colocalizes with the omegasome marker ZFYVE1/DFCP1, and its deficiency impairs autophagosome formation.

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 with moderately hydrophobic TMDs.

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.

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 EMC3 and EMC6, and EMC6 D27/T31 mutants reduce insertion without disrupting assembly.

PMID:33961781

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

PMID:34918864

EMC is required for biogenesis of Xport-A, an essential chaperone of Rhodopsin-1 and the TRP channel.

In vivo Drosophila evidence that the EMC, including EMC6, is required for TMD membrane insertion of the tail-anchored client Xport-A.

PMID:37199759

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

An improved human EMC model defines a charge-based selectivity filter at the hydrophilic vestibule that rejects mitochondrial tail-anchored proteins and enforces the positive-inside rule; the EMC3/EMC6 vestibule remains the central insertion route.

PMID:37196677

EMC chaperone-Ca(V) structure reveals an ion channel assembly intermediate.

Cryo-EM of an EMC-bound CaV1.2 assembly intermediate shows the EMC acts as a holdase/chaperone during multipass channel assembly, defining TM and Cyto client-docking sites, supporting that EMC function extends beyond insertion to assembly of complex multipass clients.

PMID:38517390

Structural insights into human EMC and its interaction with VDAC.

Cryo-EM structures of human EMC in apo and VDAC-bound states place EMC6 in the EMC3-EMC6 core; a gating plug (assigned to EMC3) within the hydrophilic vestibule changes conformation between states, and the EMC engages VDAC at mitochondria-ER contact sites.

PMID:40753078

The EMC acts as a chaperone for membrane proteins.

The EMC has a chaperone function in addition to insertase activity; EMC6 is named as part of a lipid-filled cavity formed by EMC1/EMC3/EMC5/EMC6 distinct from the canonical insertase site, supporting a broader EMC quality-control/chaperone role.

file:human/EMC6/EMC6-uniprot.txt

UniProt entry Q9BV81 (EMC6_HUMAN), ER membrane protein complex subunit 6

Three-TM ER membrane subunit of the EMC; with EMC3 forms the insertase vestibule; EMC6 D27/T31 mutants reduce client insertion without affecting assembly.