EMC7 (ER membrane protein complex subunit 7) is a 242 aa single-pass type I ER membrane protein and a constitutive subunit of the ER membrane protein complex (EMC), a conserved transmembrane-domain insertase and membrane-protein chaperone of the endoplasmic reticulum. After cleavage of its N-terminal signal peptide, EMC7 presents a large lumenal beta-sandwich domain followed by a single transmembrane helix and a short, partly disordered cytoplasmic tail. EMC7 is a peripheral, non-catalytic architectural subunit; the catalytic insertase machinery (the membrane-embedded hydrophilic vestibule) is formed by EMC3 and EMC6. As part of the EMC, EMC7 contributes to the energy-independent insertion of newly synthesized membrane proteins into the ER membrane, with a preference for transmembrane domains that are weakly hydrophobic or contain destabilizing residues, including post-translational insertion of tail-anchored proteins and cotranslational insertion and topogenesis of multipass membrane proteins. EMC7 localizes to the ER membrane and is broadly expressed.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0072546 EMC complex | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic assignment of EMC complex membership, consistent with direct experimental and structural identification of EMC7 in the EMC. This is the core structural identity of EMC7. Reason: EMC complex membership is the core cellular-component identity of EMC7; supported by IDA, cryo-EM, and the conserved EMC7 family. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt Component of the ER membrane protein complex (EMC). |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic transfer of the ER membrane subcellular location from UniProt; the correct and core compartment for EMC7. Reason: Correct core location; redundant with experimental EXP/IDA evidence. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0030246 carbohydrate binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro fold-homology assignment derived from the lumenal beta-sandwich resembling a starch-binding/carbohydrate-binding-like domain. There is no experimental evidence that EMC7 binds carbohydrate; the fold is structural and the assignment is an over-propagated electronic inference. Reason: Fold-similarity-only IEA with no supporting evidence that EMC7 actually binds carbohydrate; the beta-sandwich is structural and serves complex architecture. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt Starch-binding domain-like |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: High-throughput interactome capture (with PDIA4). Bare protein binding is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative per guidelines. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt P13667: PDIA4 |
| GO:0005515 protein binding | IPI PMID:28734904 Identifying novel members of the Wntless interactome through... | KEEP AS NON CORE | Summary: Interaction with WLS (Wntless), itself an EMC client, identified in a Wntless-interactome screen. The interaction plausibly reflects EMC client engagement, but bare protein binding is uninformative. Reason: Likely reflects client engagement, but the bare term is uninformative and not core. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt Q5T9L3-1: WLS |
| GO:0005515 protein binding | IPI PMID:31286866 Alternative splicing of the Wnt trafficking protein, Wntless... | KEEP AS NON CORE | Summary: Interaction with WLS from a Wntless splicing/PPI study. WLS is an EMC client; bare protein binding is uninformative. Reason: Likely client engagement; bare term uninformative, not core. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt Q5T9L3-1: WLS |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: High-throughput binary (HuRI) interactome captures (CYSRT1, NOTCH2NLC, keratin-associated proteins, MEOX2); several are likely sticky Y2H hits. Bare protein binding is uninformative. Reason: High-throughput binary interactions of uncertain biological relevance; bare term uninformative. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt A8MQ03: CYSRT1 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex affinity-MS interactome capture (with PDIA4). Bare protein binding is uninformative. Reason: High-throughput interaction; bare term uninformative, not core. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt P13667: PDIA4 |
| GO:0005789 endoplasmic reticulum membrane | NAS PMID:29242231 The ER membrane protein complex is a transmembrane domain in... | ACCEPT | Summary: ComplexPortal NAS annotation of ER membrane localization for the EMC, consistent with experimental evidence. Core compartment. Reason: Correct core location; consistent with EXP/IDA evidence. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0045050 protein insertion into ER membrane by stop-transfer membrane-anchor sequence | IDA PMID:29242231 The ER membrane protein complex is a transmembrane domain in... | ACCEPT | Summary: The EMC inserts transmembrane domains, including stop-transfer membrane-anchor sequences of multipass proteins; EMC7 participates as an EMC subunit. A genuine EMC-mediated process, though EMC7 is non-catalytic. Reason: Correct EMC-mediated process EMC7 is involved in as a complex subunit; non-core relative to complex membership. Supporting Evidence: PMID:29242231 EMC is a transmembrane domain insertase |
| GO:0071816 tail-anchored membrane protein insertion into ER membrane | IDA PMID:29242231 The ER membrane protein complex is a transmembrane domain in... | ACCEPT | Summary: The EMC mediates post-translational insertion of tail-anchored proteins; EMC7 participates as an EMC subunit. Genuine EMC-mediated process. Reason: Correct EMC-mediated process EMC7 participates in via membership. Supporting Evidence: PMID:29242231 tail-anchored membrane proteins with moderately hydrophobic transmembrane |
| GO:0072546 EMC complex | IPI PMID:32439656 Structural basis for membrane insertion by the human ER memb... | ACCEPT | Summary: ComplexPortal IPI assignment of EMC complex membership based on the cryo-EM structure of the human EMC. Core structural identity of EMC7. Reason: Structurally demonstrated core EMC membership. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt Component of the ER membrane protein complex (EMC). |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:22119785 Defining human ERAD networks through an integrative mapping ... | ACCEPT | Summary: Experimental ER membrane localization from the EMC-discovery ERAD-network study. Core compartment. Reason: Experimentally supported core location. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0032977 membrane insertase activity | IMP PMID:29809151 The ER membrane protein complex interacts cotranslationally ... | KEEP AS NON CORE | Summary: IMP evidence that EMC subunit depletion impairs membrane insertion; EMC7 contributes_to the complex insertase activity. The qualifier is appropriate, but as a peripheral lumenal subunit EMC7's role is via complex participation, not standalone catalysis. Reason: Whole-complex molecular function to which EMC7 contributes; EMC7 is non-catalytic (the EMC3/EMC6 vestibule is the catalytic core), so not EMC7's own core MF. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt enables the energy-independent insertion into endoplasmic |
| GO:0032977 membrane insertase activity | IMP PMID:30415835 EMC Is Required to Initiate Accurate Membrane Protein Topoge... | KEEP AS NON CORE | Summary: IMP evidence (topogenesis study) supporting the EMC's membrane insertase activity, to which EMC7 contributes as a complex subunit. Non-core for the non-catalytic EMC7. Reason: Whole-complex MF; EMC7 contributes via membership but is not the catalytic subunit. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt enables the energy-independent insertion into endoplasmic |
| GO:0045050 protein insertion into ER membrane by stop-transfer membrane-anchor sequence | IMP PMID:29809151 The ER membrane protein complex interacts cotranslationally ... | ACCEPT | Summary: The EMC is required for cotranslational insertion of multipass proteins in which stop-transfer membrane-anchor sequences become membrane-spanning helices; EMC7 participates as a subunit. Genuine EMC process. Reason: Correct EMC-mediated process EMC7 participates in. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt stop-transfer membrane-anchor sequences become ER membrane spanning |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:32439656 Structural basis for membrane insertion by the human ER memb... | ACCEPT | Summary: Direct (structural) evidence placing EMC7 in the ER membrane. Core compartment. Reason: Experimentally supported core location. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0045050 protein insertion into ER membrane by stop-transfer membrane-anchor sequence | IMP PMID:30415835 EMC Is Required to Initiate Accurate Membrane Protein Topoge... | ACCEPT | Summary: IMP (topogenesis study) supporting the EMC's role in insertion of stop-transfer membrane-anchor sequences and N-exo topogenesis; EMC7 participates as a subunit. Genuine EMC process. Reason: Correct EMC-mediated process EMC7 participates in. Supporting Evidence: PMID:30415835 G protein-coupled receptors (GPCRs) |
| GO:0016020 membrane | IDA PMID:22119785 Defining human ERAD networks through an integrative mapping ... | KEEP AS NON CORE | Summary: Direct generic membrane localization from the EMC-discovery study; a parent of the specific ER membrane term. Reason: Correct but generic; the ER membrane term captures the informative localization. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0072546 EMC complex | IDA PMID:22119785 Defining human ERAD networks through an integrative mapping ... | ACCEPT | Summary: Direct experimental identification of EMC7 in the EMC by the foundational ERAD-network mapping study. Core structural identity. Reason: Core EMC membership; directly demonstrated. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt Component of the ER membrane protein complex (EMC). |
| GO:0016020 membrane | NAS PMID:12975309 The secreted protein discovery initiative (SPDI), a large-sc... | KEEP AS NON CORE | Summary: Generic membrane localization asserted (NAS) in the secreted-protein discovery initiative bioinformatics survey that first catalogued this transmembrane protein. Correct but generic and superseded by the specific ER membrane localization. Reason: Correct but generic and based on a bioinformatic transmembrane prediction; the ER membrane term is the informative localization. Supporting Evidence: file:human/EMC7/EMC7-uniprot.txt Single-pass type I membrane protein |
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Download this section (compressed HTML)Q: What specific structural or functional contribution does the lumenal beta-sandwich domain of EMC7 make to EMC stability or substrate handling?
Q: Are the EMC7-WLS interactions reported in interactome screens a reflection of EMC client engagement rather than a standalone binding function?
Experiment: Test whether the EMC7 lumenal beta-sandwich domain binds any carbohydrate ligand in vitro to confirm or refute the InterPro-derived carbohydrate-binding annotation.
Experiment: Reconstitute EMC complexes lacking EMC7 to assess its contribution to complex assembly, stability, and insertion efficiency of representative tail-anchored and multipass substrates.
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