EREG (O14944) — curation notes

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Protein and localization

Epiregulin is made as proepiregulin, a type I single-pass membrane precursor (signal
1-29, chain 30-169, transmembrane 120-140) whose EGF-like domain (64-104) lies in the
extracellular segment; the mature chain 63-108 is shed as a soluble growth factor.
PMID:9337852
PMID:9337852
UniProt records both locations, by molecule.
[file:human/EREG/EREG-uniprot.txt "SUBCELLULAR LOCATION: [Epiregulin]: Secreted, extracellular space"]
[file:human/EREG/EREG-uniprot.txt "SUBCELLULAR LOCATION: [Proepiregulin]: Cell membrane"]

Localization conclusion: secreted/extracellular for the mature ligand (the dominant,
core location, 89 annotation rows), plus plasma membrane for the uncleaved precursor
with the EGF domain extracellular. The clathrin-coated-vesicle rows reflect ligand being
carried in with the internalising receptor and are kept as non-core.

Function

PMID:9419975
PMID:28988771
PMID:9556621
PMID:10681561
PMID:9990076
PMID:12898511

Review decisions of note

• GO:0009299 mRNA transcription (IDA) and GO:0045892 negative regulation of DNA-templated transcription (IDA) were marked as over-annotations: a secreted ligand
  does not perform nuclear transcription, and the underlying observations are
  transcriptional responses downstream of receptor activation.
• GO:0019221 cytokine-mediated signaling pathway was modified to the EGFR signaling
  pathway, which is what the cited experiments show.
• The two positive regulation of phosphorylation rows were refined to positive
  regulation of peptidyl-tyrosine phosphorylation.
• Bare protein-binding rows: EGFR rows modified to EGFR binding, the ERBB4 row to
  receptor ligand activity (GO has no ERBB4-binding term), and four high-throughput
  interactome hits (CXCL9, MS4A13, OLFM4, NINJ2) removed.
• Ovarian, immune and cell-type-specific proliferation rows, and the DNA-replication and
  mitotic-division readouts, were kept as non-core.