EMC9 (ER membrane protein complex subunit 9; also FAM158A) is a 208 aa cytosolic, peripheral subunit of the ER membrane protein complex (EMC), associated with the cytoplasmic face of the ER membrane. It belongs to the EMC8/EMC9 family and contains an MPN (Mpr1/Pad1 N-terminal) domain that is degenerate and lacks the catalytic residues of active JAMM/MPN metalloproteases, so EMC9 is not predicted to have intrinsic enzymatic activity. EMC9 and its paralog EMC8 are mutually exclusive subunits of the EMC, defining alternative complex variants; EMC9 docks into the complex primarily through binding to EMC2. The EMC is 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. As a peripheral, non-catalytic subunit, EMC9 participates in these processes through complex membership rather than direct catalysis; the membrane insertase activity resides in the EMC3/EMC6 core. EMC9 is broadly expressed and remains relatively weakly characterized.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0032977 membrane insertase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic propagation of membrane insertase activity across the EMC8/EMC9 family with the contributes_to qualifier. EMC9 is a peripheral, non-catalytic subunit and an EMC8 paralog; the insertase activity is a property of the EMC core (EMC3/EMC6), to which EMC9 contributes only via complex membership. Reason: contributes_to is appropriate at the complex level, but this is not EMC9's own enzymatic core function; EMC8 and EMC9 are interchangeable, so neither is individually required for the catalytic insertase reaction. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt energy-independent insertion into endoplasmic |
| GO:0045050 protein insertion into ER membrane by stop-transfer membrane-anchor sequence | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic propagation of the EMC stop-transfer insertion process. A genuine EMC whole-complex process in which EMC9 participates as a subunit. Reason: Correct EMC process but complex-level; EMC9's contribution is via membership, and the EMC8/EMC9 paralogs are interchangeable. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt stop-transfer membrane-anchor sequences become ER membrane spanning |
| GO:0071816 tail-anchored membrane protein insertion into ER membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic propagation of the EMC tail-anchored protein insertion process. A genuine EMC whole-complex process in which EMC9 participates as a subunit. Reason: Correct EMC process but complex-level; EMC9's contribution is via membership. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt post-translational insertion of tail- |
| GO:0072546 EMC complex | IBA GO_REF:0000033 | ACCEPT | Summary: EMC9 is a constitutive (variant) subunit of the ER membrane protein complex; phylogenetic assignment is consistent with direct experimental and structural evidence. Core structural identity of EMC9. Reason: EMC complex membership is the core cellular-component identity of EMC9; supported by IDA, the EMC9-EMC2 crystal structure, and cryo-EM of the EMC. Supporting Evidence: file:human/EMC9/EMC9-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; EMC9 is a peripheral protein on the cytoplasmic side of the ER membrane. Core compartment. Reason: Correct core location for an EMC subunit; consistent with the peripheral/cytoplasmic-side localization. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0072546 EMC complex | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic assignment of EMC complex membership, consistent with the experimental IDA annotation. Core structural identity. Reason: Correct core structural identity; redundant with IDA/IBA evidence. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt Component of the ER membrane protein complex (EMC) |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | KEEP AS NON CORE | Summary: High-throughput proteome-scale interaction capture. EMC9's most informative partner is EMC2 (it docks into the complex via EMC2), but bare protein binding is uninformative. Reason: Real but the bare protein binding term is uninformative per curation guidelines; the EMC complex membership term captures the informative content. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt Q9Y3B6; Q15006: EMC2 |
| GO:0005515 protein binding | IPI PMID:22119785 Defining human ERAD networks through an integrative mapping ... | KEEP AS NON CORE | Summary: Interaction capture from the foundational ERAD-network mapping study that first defined the EMC and placed FAM158A/EMC9 in it. Genuine EMC partnership; bare protein binding is uninformative. Reason: Real EMC partner interaction but the bare term is uninformative; EMC membership captures the content. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt Q9Y3B6; Q15006: EMC2 |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Proteome-scale interactome map capture. Bare protein binding is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative and not core. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt Q9Y3B6; Q15006: EMC2 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: BioPlex protein-community interactome capture. Bare protein binding is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative and not core. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt Q9Y3B6; Q15006: EMC2 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary (HuRI) interactome capture, including an interaction with an SCN5A isoform, a plausible EMC client. Bare protein binding is uninformative. Reason: High-throughput interaction partly reflecting client engagement; the bare term is uninformative and not core. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt Q9Y3B6; Q14524-3: SCN5A |
| GO:0005515 protein binding | IPI PMID:32439656 Structural basis for membrane insertion by the human ER memb... | KEEP AS NON CORE | Summary: Interaction evidence associated with the cryo-EM structural study of the human EMC, reflecting intra-complex partnerships (notably EMC2). Bare protein binding is uninformative. Reason: Real intra-complex interaction; the EMC complex membership term captures the informative content. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt Q9Y3B6; Q15006: EMC2 |
| 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. Bare protein binding is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative and not core. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt Q9Y3B6; Q15006: EMC2 |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: OpenCell endogenous-tagging interactome capture. Bare protein binding is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative and not core. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt Q9Y3B6; Q15006: EMC2 |
| GO:0005789 endoplasmic reticulum membrane | NAS PMID:29242231 The ER membrane protein complex is a transmembrane domain in... | ACCEPT | Summary: NAS annotation of ER membrane localization for the EMC, consistent with EMC9's peripheral/cytoplasmic-side ER membrane localization. Core compartment. Reason: Correct core location; consistent with experimental evidence. Supporting Evidence: file:human/EMC9/EMC9-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... | KEEP AS NON CORE | Summary: The EMC inserts transmembrane domains including stop-transfer membrane-anchor sequences; EMC9 participates as a (variant) subunit. A genuine EMC whole-complex process. Reason: Correct EMC process but complex-level; EMC9 is a peripheral subunit contributing via membership rather than catalysis. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt stop-transfer membrane-anchor sequences become ER membrane spanning |
| GO:0071816 tail-anchored membrane protein insertion into ER membrane | IDA PMID:29242231 The ER membrane protein complex is a transmembrane domain in... | KEEP AS NON CORE | Summary: The EMC mediates post-translational insertion of tail-anchored proteins; EMC9 participates as a subunit. A genuine EMC whole-complex process. Reason: Correct EMC process but complex-level; EMC9's contribution is via membership. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt post-translational insertion of tail- |
| 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; EMC9 contributes to the complex-level insertase activity but is not the catalytic subunit. Reason: contributes_to is appropriate at complex level; not EMC9's standalone enzymatic core MF. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt 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 EMC9 contributes as a subunit. Reason: contributes_to is appropriate at complex level; not EMC9's standalone enzymatic core MF. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt 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 ... | KEEP AS NON CORE | Summary: The EMC is required for cotranslational insertion of multipass proteins in which stop-transfer membrane-anchor sequences become membrane-spanning helices; EMC9 participates as a subunit. Reason: Correct EMC process but complex-level; EMC9's contribution is via membership. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt stop-transfer membrane-anchor sequences become ER membrane spanning |
| 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... | KEEP AS NON CORE | Summary: IMP (topogenesis study) supporting the EMC's role in insertion of stop-transfer membrane-anchor sequences; EMC9 participates as a subunit. Reason: Correct EMC process but complex-level; EMC9's contribution is via membership. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt stop-transfer membrane-anchor sequences become ER membrane spanning |
| GO:0005737 cytoplasm | IDA PMID:22119785 Defining human ERAD networks through an integrative mapping ... | KEEP AS NON CORE | Summary: Direct evidence that EMC9 is on the cytoplasmic side of the ER membrane; consistent with its peripheral membrane localization. The more informative compartment is the ER membrane. Reason: Accurate (EMC9 is cytoplasmic-side peripheral) but less specific than the ER membrane localization that captures its functional context. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt Cytoplasmic side |
| GO:0072546 EMC complex | IDA PMID:22119785 Defining human ERAD networks through an integrative mapping ... | ACCEPT | Summary: Direct experimental identification of FAM158A/EMC9 in the EMC by the foundational ERAD-network mapping study. Core structural identity. Reason: Core EMC membership; directly demonstrated and the best-supported EMC9-specific assertion. Supporting Evidence: file:human/EMC9/EMC9-uniprot.txt Component of the ER membrane protein complex (EMC) |
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Download this section (compressed HTML)Q: Do the EMC8- and EMC9-containing EMC variants differ in client specificity, tissue distribution, or regulation, and what determines which paralog is incorporated?
Q: Does the degenerate MPN domain of EMC9 retain any binding or regulatory activity, or is it purely a structural scaffold for docking onto EMC2?
Experiment: Compare client repertoires and insertion efficiencies of EMC8-only versus EMC9-only complexes using paralog-specific knockouts with quantitative membrane proteomics and reconstituted insertion assays.
Experiment: Solve or model the EMC9 MPN domain in the holo-complex and test by mutagenesis whether the EMC9-EMC2 interface is required for complex assembly and stability.
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