EMC10 PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q5UCC4
- AIGR review status: COMPLETE
- Review batch: proteostasis-batch-2026-06-11
- Batch change status: added
Source Files Checked
Deep Research Files
AIGR Review Snapshot
- Description: 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.
- Existing/core annotation action counts: ACCEPT: 6; KEEP_AS_NON_CORE: 14
PN Consistency Summary
- Consistency: Deep research, review YAML, and PN annotation agree on the EMC role: EMC10 is a single-pass type I lumenal/peripheral, non-catalytic EMC subunit. The review additionally documents the secreted isoform 2 (HSS1/INM02) as an extracellular angiogenic growth factor (PMID:28931551, 20680400, 19570817) and biallelic-LoF NEDD (NEDDFAS) disease — a substantial moonlighting biology entirely outside the PN node's scope. Not a contradiction, but the PN row captures only the membrane-EMC facet.
- PN story / NEW pressure: PN asserts only EMC membership + import/insertion, already captured (GO:0072546 part_of; insertion/insertase terms KEEP_AS_NON_CORE). No NEW GO term needed for the PN claim. The secreted-form functions are already annotated (GO:0001938, GO:0010595, GO:0045766, GO:0005576) and correctly KEEP_AS_NON_CORE — they are not a PN/ER-proteostasis story.
- Evidence alignment: Core EMC papers overlap (22119785, 29242231, 32439656, 30415835); review adds EMC10-specific secreted-isoform and disease PMIDs absent from the PN row.
- Verdict: Consistent for the EMC facet; well-reviewed. Shared group→GO:0044743 mapping diverges from insertion semantics; note EMC10's secreted angiogenic moonlighting is correctly non-core and outside PN scope.
Full Consistency Review
- UniProt: Q5UCC4 · batch: proteostasis-batch-2026-06-11 · review status: COMPLETE
- PN placement:
ER proteostasis|Protein transport|Transmembrane protein import|EMC complex component ; PN-node mapping: type → GO:0072546 (EMC complex); group → GO:0044743 (protein transmembrane import into intracellular organelle); class → GO:0015031 (protein transport); branch=no_mapping.
- Consistency: Deep research, review YAML, and PN annotation agree on the EMC role: EMC10 is a single-pass type I lumenal/peripheral, non-catalytic EMC subunit. The review additionally documents the secreted isoform 2 (HSS1/INM02) as an extracellular angiogenic growth factor (PMID:28931551, 20680400, 19570817) and biallelic-LoF NEDD (NEDDFAS) disease — a substantial moonlighting biology entirely outside the PN node's scope. Not a contradiction, but the PN row captures only the membrane-EMC facet.
- PN story / NEW pressure: PN asserts only EMC membership + import/insertion, already captured (GO:0072546 part_of; insertion/insertase terms KEEP_AS_NON_CORE). No NEW GO term needed for the PN claim. The secreted-form functions are already annotated (GO:0001938, GO:0010595, GO:0045766, GO:0005576) and correctly KEEP_AS_NON_CORE — they are not a PN/ER-proteostasis story.
- Mapping strategy: EMC10 does not change the shared node mapping (EMC complex member → GO:0072546 stands). Same group-level concern as EMC7-9: GO:0044743 (lumenal import) mismatches EMC membrane-protein insertion; insertion terms are not subclasses of it. The secreted/angiogenic facet argues against treating this node as capturing all of EMC10's biology, but is out of PN scope.
- Evidence alignment: Core EMC papers overlap (22119785, 29242231, 32439656, 30415835); review adds EMC10-specific secreted-isoform and disease PMIDs absent from the PN row.
- Verdict: Consistent for the EMC facet; well-reviewed. Shared group→GO:0044743 mapping diverges from insertion semantics; note EMC10's secreted angiogenic moonlighting is correctly non-core and outside PN scope.
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-11
- review_yaml: genes/human/EMC10/EMC10-ai-review.yaml
- PN workbook rows: 1
PN row 1: ER proteostasis | Protein transport | Transmembrane protein import | EMC complex component
- UniProt: Q5UCC4
- In branches: ER
- PN-node mapping records (path + ancestors):
- [type] ER proteostasis|Protein transport|Transmembrane protein import|EMC complex component
status=mapped scope=ok_for_propagation_to_go GO=[GO:0072546 EMC complex]
rationale: This PN type denotes ER membrane protein complex components. The GO EMC complex cellular-component term is the direct target.
- [group] ER proteostasis|Protein transport|Transmembrane protein import
status=mapped scope=ok_for_propagation_to_go GO=[GO:0044743 protein transmembrane import into intracellular organelle]
rationale: This PN group covers ER transmembrane-protein insertion/import systems such as EMC- and PAT-related pathways. The local GO cache does not expose an ER-specific matching term, so the broader intracellular-organelle transmembrane-import process is the best supported propagation target.
- [class] ER proteostasis|Protein transport
status=mapped scope=ok_for_propagation_to_go GO=[GO:0015031 protein transport]
rationale: The PN ER Protein transport class groups ER-targeting and ER-insertion pathways. GO protein transport is the appropriate propagation target, while the source class remains ER-specific and broader than any single GO transport subtype.
- [branch] ER proteostasis
status=no_mapping scope= GO=[]
rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.
Projected GO annotations (3)
- GO:0015031 protein transport | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=ER proteostasis|Protein transport
- GO:0044743 protein transmembrane import into intracellular organelle | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=ER proteostasis|Protein transport|Transmembrane protein import
- GO:0072546 EMC complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=ER proteostasis|Protein transport|Transmembrane protein import|EMC complex component
Note
This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.