Epiregulin is a member of the epidermal growth factor family. It is made as proepiregulin, a single-pass type I membrane precursor whose EGF-like domain faces the extracellular space, and is then shed to release the soluble mature growth factor. Epiregulin binds and activates EGFR and ERBB4, inducing tyrosine phosphorylation of EGFR, ERBB2, ERBB3 and ERBB4 through receptor homodimers and heterodimers, and it stabilises a distinct EGFR dimer conformation from that induced by EGF, which gives it different signalling kinetics. It acts as an autocrine and paracrine mitogen for keratinocytes, fibroblasts and vascular smooth muscle cells, contributes to wound repair and inflammation, and in the ovary mediates luteinizing-hormone-driven cumulus expansion and oocyte maturation. Expression is low in normal adult tissues apart from placenta and peripheral blood leukocytes, and high in several carcinomas.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001550 ovarian cumulus expansion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Rodent EGF-like ovarian factors mediate luteinizing-hormone-driven cumulus expansion, transferred here from the mouse ortholog. Reason: The evidence is from the mouse and rat orthologs rather than human, and the role is a tissue-specific consequence of EGFR activation rather than the molecular core function of the growth factor. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0001550 ovarian cumulus expansion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same ovarian role. Reason: Same assessment as the Compara row. Plausible for human, demonstrated in rodents, and downstream of EGFR activation. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0001556 oocyte maturation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Epiregulin contributes to oocyte maturation, a role recorded by UniProt. Reason: The supporting experiments are rodent, and the function is an organ-level outcome of EGFR signalling rather than the core activity of the ligand. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0001556 oocyte maturation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same role. Reason: Same assessment as the Compara row. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0001819 positive regulation of cytokine production | IDA PMID:10681561 Epiregulin, a novel member of the epidermal growth factor fa... | KEEP AS NON CORE | Summary: Epiregulin treatment of keratinocytes changes cytokine output. Reason: A downstream transcriptional consequence of EGFR activation in a specific cell type, rather than the growth factor's own activity. Retained as non-core. Supporting Evidence: PMID:10681561 Epiregulin stimulated human keratinocyte proliferation under both subconfluent and confluent culture conditions in the absence of exogenous EGF family growth factors. |
| GO:0001819 positive regulation of cytokine production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog transfer of the same cytokine-production role. Reason: Consistent with the human experimental row and with the inflammatory role recorded by UniProt, but downstream of receptor activation. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0001819 positive regulation of cytokine production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same role. Reason: Same assessment as the other cytokine-production rows. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0005154 epidermal growth factor receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: Binding EGFR is the core molecular function of epiregulin. Reason: The ancestral EGF-family node is well placed, and human epiregulin has its own direct binding evidence, including a crystal structure of the EGFR extracellular region bound to epiregulin. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. PMID:28988771 Using crystallography and other approaches, we show how the EGFR ligands epiregulin (EREG) and epigen (EPGN) stabilize different dimeric conformations of the EGFR extracellular region. |
| GO:0005154 epidermal growth factor receptor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog transfer agreeing with direct human binding data. Reason: Human epiregulin binds EGFR directly, so the inferred row introduces no error. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0005154 epidermal growth factor receptor binding | ISS GO_REF:0000024 | ACCEPT | Summary: Curator-judged transfer of EGFR binding. Reason: Consistent with the direct human evidence. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0005154 epidermal growth factor receptor binding | TAS PMID:10681561 Epiregulin, a novel member of the epidermal growth factor fa... | ACCEPT | Summary: Author statement of EGFR binding in the keratinocyte autocrine study. Reason: Independently established by direct binding and structural work. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0005515 protein binding | IPI PMID:28988771 EGFR Ligands Differentially Stabilize Receptor Dimers to Spe... | MODIFY | Summary: The interactor is EGFR, characterised crystallographically. Reason: This study solves how epiregulin engages the EGFR extracellular region and stabilises a distinct dimer, so the informative replacement for the generic term is epidermal growth factor receptor binding. Proposed replacements: epidermal growth factor receptor binding Supporting Evidence: PMID:28988771 Using crystallography and other approaches, we show how the EGFR ligands epiregulin (EREG) and epigen (EPGN) stabilize different dimeric conformations of the EGFR extracellular region. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: A CXCL9 hit from a proteome-scale binary interactome map. Reason: The generic term carries no functional information and the pairing supports no specific molecular function for epiregulin. Removal does not assert that the interaction was not detected. Supporting Evidence: file:human/EREG/EREG-uniprot.txt O14944; Q07325 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: An MS4A13 hit from the same interactome map. Reason: Same assessment as the other high-throughput rows. Supporting Evidence: file:human/EREG/EREG-uniprot.txt O14944; Q5J8X5 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: An OLFM4 hit from the same interactome map. Reason: Same assessment as the other high-throughput rows. Supporting Evidence: file:human/EREG/EREG-uniprot.txt O14944; Q6UX06 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: A NINJ2 hit from the same interactome map. Reason: Same assessment as the other high-throughput rows. Supporting Evidence: file:human/EREG/EREG-uniprot.txt O14944; Q9NZG7 |
| GO:0005515 protein binding | IPI PMID:9419975 Epiregulin binds to epidermal growth factor receptor and Erb... | MODIFY | Summary: The interactor is EGFR, shown by direct binding and receptor phosphorylation. Reason: The paper demonstrates epiregulin binding to EGFR, so the specific receptor binding term replaces the uninformative generic one. Proposed replacements: epidermal growth factor receptor binding Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. |
| GO:0005515 protein binding | IPI PMID:9419975 Epiregulin binds to epidermal growth factor receptor and Erb... | MODIFY | Summary: The interactor is ERBB4, which epiregulin binds and activates. Reason: GO has no ERBB4-binding term, so the informative replacement is receptor ligand activity, which epiregulin already carries on direct evidence and which captures agonist binding to a receptor other than EGFR. Proposed replacements: receptor ligand activity Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. file:human/EREG/EREG-uniprot.txt Interacts with EGFR and ERBB4. |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: The mature growth factor acts outside the cell, after shedding from the membrane precursor. Reason: The EGF-family node correctly places these ligands in the extracellular space, and human epiregulin is secreted as a soluble form. Human EREG appears among the descendant evidences because it has its own experimental data. Supporting Evidence: PMID:9337852 Recombinant expression in mammalian cells also showed that human epiregulin was secreted as a soluble form of approx. |
| GO:0005576 extracellular region | IDA PMID:14581411 Epiregulin as a major autocrine/paracrine factor released fr... | ACCEPT | Summary: Epiregulin is released from activated vascular smooth muscle cells into the medium. Reason: The study detects epiregulin as a secreted autocrine and paracrine factor, which is direct evidence of an extracellular pool. Supporting Evidence: PMID:14581411 Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells. |
| GO:0005576 extracellular region | IDA PMID:28783046 Epiregulin and EGFR interactions are involved in pain proces... | ACCEPT | Summary: Epiregulin acts extracellularly on EGFR in this study. Reason: Applying the ligand to cells and tissue requires it to act from outside, which is where the mature growth factor functions. Supporting Evidence: PMID:28783046 Epiregulin and EGFR interactions are involved in pain processing. |
| GO:0005576 extracellular region | IDA PMID:9337852 Distribution of mRNA for human epiregulin, a differentially ... | ACCEPT | Summary: Recombinant human epiregulin is secreted as a soluble protein. Reason: Direct demonstration that the processed growth factor leaves the cell. Supporting Evidence: PMID:9337852 Recombinant expression in mammalian cells also showed that human epiregulin was secreted as a soluble form of approx. |
| GO:0005576 extracellular region | IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac... | ACCEPT | Summary: Soluble epiregulin activates ERBB4 on target cells. Reason: The hormone is applied to cells from outside, so the extracellular space is where it acts. Supporting Evidence: PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2. |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Automated mapping of the curated secreted location of the mature chain. Reason: UniProt records the epiregulin chain as secreted to the extracellular space on experimental evidence. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1225978 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1236398 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1250195 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1250220 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1250315 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1250346 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1250348 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1250353 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1250357 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1250370 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1250380 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1250383 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1306969 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1306972 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1306979 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177922 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177923 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177924 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177925 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177926 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177927 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177930 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177933 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177934 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177935 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177936 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177937 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177938 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177939 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177941 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177942 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177943 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177944 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-177945 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-182969 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-182986 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-182990 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-182993 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-182994 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-183002 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-183036 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-183051 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-183055 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-183058 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-183067 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-183072 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-183084 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-183089 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1963563 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1963581 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1963582 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1963586 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1963589 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1977958 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-1977959 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-212706 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-212710 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-212713 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2316434 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-2400009 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5672965 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6785636 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6785648 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8847995 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8848005 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8863804 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8866279 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8867041 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8867044 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8867047 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8951490 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9625482 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9625487 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region, where the shed growth factor engages its receptors. Reason: The compartment matches the curated secreted location of the epiregulin chain and the experimental demonstration that the protein is released as a soluble form. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005576 extracellular region | TAS Reactome:R-NUL-1251988 | ACCEPT | Summary: Reactome places mature epiregulin in the extracellular region in this cross-species reaction entry. Reason: The compartment matches the curated secreted location of the epiregulin chain. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Secreted, extracellular space |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Proepiregulin is a single-pass type I membrane protein before shedding. Reason: UniProt records a cell-membrane location for the proepiregulin form on experimental evidence, with the EGF-like domain facing the extracellular space. This is a genuine second location of the gene product, distinct from the secreted mature chain. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Single-pass type I membrane protein |
| GO:0005886 plasma membrane | TAS PMID:9337852 Distribution of mRNA for human epiregulin, a differentially ... | ACCEPT | Summary: The gene encodes a transmembrane precursor with an internal EGF-like domain. Reason: The precursor is membrane-anchored and only the processed form is released, so both the membrane and the extracellular locations are correct for this gene product. Supporting Evidence: PMID:9337852 The human epiregulin gene encoded a 163-residue putative transmembrane precursor containing an EGF-like domain in the internal segment |
| GO:0007143 female meiotic nuclear division | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Part of the rodent ovarian programme in which EGF-like factors drive oocyte meiotic resumption. Reason: Evidence is from the mouse ortholog, and the role is an organ-level consequence of EGFR activation in cumulus cells rather than the core ligand activity. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0007143 female meiotic nuclear division | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same ovarian role. Reason: Same assessment as the Compara row. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0007173 epidermal growth factor receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Epiregulin initiates EGFR signalling as the agonist ligand. Reason: The EGF-family node is well placed, and epiregulin itself performs the ligand step of the pathway, binding the receptor and driving its dimerisation and phosphorylation. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:28783046 Epiregulin and EGFR interactions are involved in pain proces... | ACCEPT | Summary: Epiregulin acts through EGFR in this study. Reason: The work characterises epiregulin and EGFR interactions and their signalling consequences directly. Supporting Evidence: PMID:28783046 Epiregulin and EGFR interactions are involved in pain processing. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac... | ACCEPT | Summary: Epiregulin activates EGFR-family receptors, with ErbB2 modulating the response. Reason: Direct receptor-activation experiments support participation in the pathway. Supporting Evidence: PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac... | ACCEPT | Summary: Same experimental basis as the companion row for this paper. Reason: Epiregulin is the agonist that initiates the pathway. Supporting Evidence: PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2. |
| GO:0007173 epidermal growth factor receptor signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: Automated inference agreeing with the direct evidence. Reason: Epiregulin is a canonical EGFR agonist. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0007173 epidermal growth factor receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Curator-judged transfer consistent with human data. Reason: The human protein has its own direct evidence for this pathway. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0007173 epidermal growth factor receptor signaling pathway | ISS PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived m... | ACCEPT | Summary: Epiregulin acts as an EGFR-dependent mitogen for vascular smooth muscle cells. Reason: The study identifies epiregulin as a potent smooth muscle mitogen induced by vasoactive agonists, acting through EGFR-family receptors. Supporting Evidence: PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. |
| GO:0007267 cell-cell signaling | IDA PMID:14581411 Epiregulin as a major autocrine/paracrine factor released fr... | ACCEPT | Summary: Epiregulin is released by one cell and acts on receptors of the same or neighbouring cells. Reason: The study characterises it as a major autocrine and paracrine factor from activated vascular smooth muscle cells, which is cell-cell signalling in the literal sense. Supporting Evidence: PMID:14581411 Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells. |
| GO:0008083 growth factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Epiregulin is a growth factor of the EGF family. Reason: The ancestral node is well placed and the human protein stimulates proliferation of keratinocytes, fibroblasts and smooth muscle cells directly. Supporting Evidence: PMID:10681561 Epiregulin stimulated human keratinocyte proliferation under both subconfluent and confluent culture conditions in the absence of exogenous EGF family growth factors. |
| GO:0008083 growth factor activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog transfer consistent with direct human evidence. Reason: Human epiregulin is a demonstrated mitogen. Supporting Evidence: PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. |
| GO:0008284 positive regulation of cell population proliferation | IBA GO_REF:0000033 | ACCEPT | Summary: Stimulating proliferation is the principal biological output of epiregulin. Reason: The inherited assertion matches direct human evidence in several cell types. Supporting Evidence: PMID:10681561 Epiregulin stimulated human keratinocyte proliferation under both subconfluent and confluent culture conditions in the absence of exogenous EGF family growth factors. |
| GO:0008284 positive regulation of cell population proliferation | IDA PMID:10681561 Epiregulin, a novel member of the epidermal growth factor fa... | ACCEPT | Summary: Epiregulin stimulates keratinocyte proliferation as an autocrine factor. Reason: Direct experimental demonstration in human cells. Supporting Evidence: PMID:10681561 Epiregulin stimulated human keratinocyte proliferation under both subconfluent and confluent culture conditions in the absence of exogenous EGF family growth factors. |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000120 | ACCEPT | Summary: Automated inference agreeing with the direct evidence. Reason: Consistent with the experimental rows. Supporting Evidence: PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. |
| GO:0008284 positive regulation of cell population proliferation | ISS GO_REF:0000024 | ACCEPT | Summary: Curator-judged transfer consistent with human data. Reason: Direct human evidence exists for the same claim. Supporting Evidence: PMID:10681561 Epiregulin stimulated human keratinocyte proliferation under both subconfluent and confluent culture conditions in the absence of exogenous EGF family growth factors. |
| GO:0008285 negative regulation of cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Epiregulin is bifunctional and inhibits growth of some cell types while stimulating others. Reason: The inhibitory effect is real but context-restricted, in contrast with the general mitogenic activity, so it is retained as a non-core role rather than as a core function. Supporting Evidence: PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2. |
| GO:0008285 negative regulation of cell population proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same bifunctional behaviour. Reason: Same assessment as the Compara row. Supporting Evidence: PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2. |
| GO:0009299 mRNA transcription | IDA PMID:10681561 Epiregulin, a novel member of the epidermal growth factor fa... | MARK AS OVER ANNOTATED | Summary: A secreted growth factor does not itself carry out mRNA transcription. Reason: The underlying observation is that epiregulin treatment changes transcript levels in keratinocytes, which is a downstream response to receptor activation. Annotating the ligand as involved in mRNA transcription attributes the nuclear process to the wrong entity; the transcriptional consequence is already captured by the regulation terms retained here. Supporting Evidence: PMID:10681561 Epiregulin stimulated human keratinocyte proliferation under both subconfluent and confluent culture conditions in the absence of exogenous EGF family growth factors. |
| GO:0009653 anatomical structure morphogenesis | TAS PMID:9337852 Distribution of mRNA for human epiregulin, a differentially ... | KEEP AS NON CORE | Summary: A broad developmental role asserted by the authors of the cloning paper. Reason: True at a general level given the expression pattern and the mitogenic activity, but uninformative about mechanism and peripheral to the ligand function. Supporting Evidence: PMID:9337852 Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family. |
| GO:0009887 animal organ morphogenesis | TAS PMID:9337852 Distribution of mRNA for human epiregulin, a differentially ... | KEEP AS NON CORE | Summary: A broad developmental role inferred from the expression survey. Reason: Consistent with the family's developmental roles but not a core function of epiregulin, and no specific organ programme is established in this paper. Supporting Evidence: PMID:9337852 Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family. |
| GO:0019221 cytokine-mediated signaling pathway | IDA PMID:9419975 Epiregulin binds to epidermal growth factor receptor and Erb... | MODIFY | Summary: The pathway demonstrated in this paper is receptor tyrosine kinase signalling through EGFR and ERBB4, not cytokine-receptor signalling. Reason: The experiments show epiregulin binding EGFR and ERBB4 and inducing their tyrosine phosphorylation. The specific and accurate term for that is the epidermal growth factor receptor signaling pathway, which the gene already carries on direct evidence. Proposed replacements: epidermal growth factor receptor signaling pathway Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 and induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4. |
| GO:0030216 keratinocyte differentiation | TAS PMID:10681561 Epiregulin, a novel member of the epidermal growth factor fa... | KEEP AS NON CORE | Summary: Epiregulin influences keratinocyte behaviour, including differentiation. Reason: The demonstrated effect in this paper is proliferation; the differentiation claim is an author statement and is a downstream tissue response. Retained as non-core. Supporting Evidence: PMID:10681561 Epiregulin, a novel member of the epidermal growth factor family, is an autocrine growth factor in normal human keratinocytes. |
| GO:0030297 transmembrane receptor protein tyrosine kinase activator activity | IDA PMID:28783046 Epiregulin and EGFR interactions are involved in pain proces... | ACCEPT | Summary: Epiregulin activates the EGFR receptor tyrosine kinase. Reason: This is the precise molecular function of the ligand, demonstrated by receptor activation assays. Supporting Evidence: PMID:28783046 Epiregulin and EGFR interactions are involved in pain processing. |
| GO:0030297 transmembrane receptor protein tyrosine kinase activator activity | IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac... | ACCEPT | Summary: Epiregulin activates ERBB4, with ErbB2 modulating the output. Reason: Direct demonstration of receptor kinase activation by the ligand. Supporting Evidence: PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868658 | KEEP AS NON CORE | Summary: Epiregulin is carried into clathrin-coated vesicles while bound to an internalising EGFR or ERBB4 receptor. Reason: The assignment is a consequence of ligand-bound receptor endocytosis rather than a site where epiregulin acts, so it is retained as non-core. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868659 | KEEP AS NON CORE | Summary: Epiregulin is carried into clathrin-coated vesicles while bound to an internalising EGFR or ERBB4 receptor. Reason: The assignment is a consequence of ligand-bound receptor endocytosis rather than a site where epiregulin acts, so it is retained as non-core. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868660 | KEEP AS NON CORE | Summary: Epiregulin is carried into clathrin-coated vesicles while bound to an internalising EGFR or ERBB4 receptor. Reason: The assignment is a consequence of ligand-bound receptor endocytosis rather than a site where epiregulin acts, so it is retained as non-core. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868661 | KEEP AS NON CORE | Summary: Epiregulin is carried into clathrin-coated vesicles while bound to an internalising EGFR or ERBB4 receptor. Reason: The assignment is a consequence of ligand-bound receptor endocytosis rather than a site where epiregulin acts, so it is retained as non-core. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8869438 | KEEP AS NON CORE | Summary: Epiregulin is carried into clathrin-coated vesicles while bound to an internalising EGFR or ERBB4 receptor. Reason: The assignment is a consequence of ligand-bound receptor endocytosis rather than a site where epiregulin acts, so it is retained as non-core. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8871193 | KEEP AS NON CORE | Summary: Epiregulin is carried into clathrin-coated vesicles while bound to an internalising EGFR or ERBB4 receptor. Reason: The assignment is a consequence of ligand-bound receptor endocytosis rather than a site where epiregulin acts, so it is retained as non-core. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8871194 | KEEP AS NON CORE | Summary: Epiregulin is carried into clathrin-coated vesicles while bound to an internalising EGFR or ERBB4 receptor. Reason: The assignment is a consequence of ligand-bound receptor endocytosis rather than a site where epiregulin acts, so it is retained as non-core. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0030728 ovulation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EGF-like ovarian factors mediate the ovulatory response to luteinizing hormone in rodents. Reason: Rodent-derived and organ-level, downstream of EGFR activation in the follicle. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0030728 ovulation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same ovarian role. Reason: Same assessment as the Compara row. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0032755 positive regulation of interleukin-6 production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: A specific instance of the cytokine-production response to epiregulin. Reason: Inferred from the ortholog, and downstream of receptor activation rather than an activity of the ligand. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0032755 positive regulation of interleukin-6 production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same response. Reason: Same assessment as the Compara row. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0038134 ERBB2-EGFR signaling pathway | IDA PMID:28783046 Epiregulin and EGFR interactions are involved in pain proces... | ACCEPT | Summary: Epiregulin drives signalling through EGFR-containing heterodimers. Reason: Epiregulin binding induces phosphorylation of EGFR and ERBB2, which is the heterodimer this term describes. Supporting Evidence: PMID:9419975 induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4 |
| GO:0038134 ERBB2-EGFR signaling pathway | IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac... | ACCEPT | Summary: ErbB2 modulates the receptor response to epiregulin. Reason: The study shows that ErbB2 regulates epiregulin-driven activation, consistent with signalling through ErbB2-containing heterodimers. Supporting Evidence: PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2. |
| GO:0038135 ERBB2-ERBB4 signaling pathway | IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac... | ACCEPT | Summary: Epiregulin activates ERBB4 in an ErbB2-dependent manner. Reason: This is the central result of the cited study. Supporting Evidence: PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2. |
| GO:0038135 ERBB2-ERBB4 signaling pathway | IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac... | ACCEPT | Summary: Same experimental basis as the companion row. Reason: Epiregulin is the agonist that initiates signalling through this receptor pair. Supporting Evidence: PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2. |
| GO:0038138 ERBB4-ERBB4 signaling pathway | IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac... | ACCEPT | Summary: Epiregulin is a direct ERBB4 agonist. Reason: Receptor activation by epiregulin was measured directly, and UniProt records binding to ERBB4. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Interacts with EGFR and ERBB4. |
| GO:0038138 ERBB4-ERBB4 signaling pathway | IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac... | ACCEPT | Summary: Same experimental basis as the companion row. Reason: Epiregulin binds and activates ERBB4. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0042060 wound healing | TAS PMID:12898511 Epiregulin is more potent than EGF or TGFalpha in promoting ... | KEEP AS NON CORE | Summary: Epiregulin promotes wound closure more strongly than EGF or TGF-alpha in vitro. Reason: A real and well-supported tissue-level role, recorded by UniProt, but it is an organismal outcome of the mitogenic and migratory response rather than a core activity of the ligand. Supporting Evidence: PMID:12898511 Epiregulin is more potent than EGF or TGFalpha in promoting in vitro wound closure due to enhanced ERK/MAPK activation. |
| GO:0042327 positive regulation of phosphorylation | IDA PMID:10681561 Epiregulin, a novel member of the epidermal growth factor fa... | MODIFY | Summary: The phosphorylation that epiregulin induces is specifically receptor tyrosine phosphorylation. Reason: Epiregulin binding induces tyrosine phosphorylation of EGFR, ERBB2, ERBB3 and ERBB4, so the specific descendant term is supported and more informative. Proposed replacements: positive regulation of peptidyl-tyrosine phosphorylation Supporting Evidence: PMID:9419975 induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4 |
| GO:0042327 positive regulation of phosphorylation | IDA PMID:9419975 Epiregulin binds to epidermal growth factor receptor and Erb... | MODIFY | Summary: Same refinement as the companion row, from the paper that measured the phosphorylation. Reason: The cited experiments measure receptor tyrosine phosphorylation directly, so the specific descendant should be used. Proposed replacements: positive regulation of peptidyl-tyrosine phosphorylation Supporting Evidence: PMID:9419975 induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4 |
| GO:0042700 luteinizing hormone signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Epiregulin is an intermediate in the ovarian response to luteinizing hormone. Reason: Rodent-derived, and the role is as an induced relay rather than a core activity. Retained as non-core. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0042700 luteinizing hormone signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same role. Reason: Same assessment as the Compara row. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0043434 response to peptide hormone | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: EREG expression is induced by hormones and vasoactive peptides. Reason: This describes regulation of the gene rather than an activity of the protein, although the induction by angiotensin II, endothelin-1 and thrombin is well documented. Retained as non-core. Supporting Evidence: PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. |
| GO:0043616 keratinocyte proliferation | IDA PMID:10681561 Epiregulin, a novel member of the epidermal growth factor fa... | ACCEPT | Summary: Epiregulin is an autocrine mitogen for normal human keratinocytes. Reason: Direct experimental demonstration in human cells, in the absence of other EGF family ligands. Supporting Evidence: PMID:10681561 Epiregulin stimulated human keratinocyte proliferation under both subconfluent and confluent culture conditions in the absence of exogenous EGF family growth factors. |
| GO:0045089 positive regulation of innate immune response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Consistent with the inflammatory role recorded by UniProt. Reason: Inferred from the ortholog and downstream of EGFR activation in epithelial and immune cells. Retained as non-core. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0045089 positive regulation of innate immune response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same role. Reason: Same assessment as the Compara row. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0045740 positive regulation of DNA replication | IDA PMID:10681561 Epiregulin, a novel member of the epidermal growth factor fa... | KEEP AS NON CORE | Summary: DNA synthesis assays are the readout of the mitogenic response to epiregulin. Reason: The gene product acts at the receptor, and the effect on replication is several steps downstream. The proliferation terms capture the same evidence more appropriately, so this is retained as non-core. Supporting Evidence: PMID:10681561 Epiregulin stimulated human keratinocyte proliferation under both subconfluent and confluent culture conditions in the absence of exogenous EGF family growth factors. |
| GO:0045740 positive regulation of DNA replication | IDA PMID:9337852 Distribution of mRNA for human epiregulin, a differentially ... | KEEP AS NON CORE | Summary: Same mitogenic readout in the cloning paper. Reason: Downstream of receptor activation, as for the other DNA replication rows. Supporting Evidence: PMID:9337852 Recombinant expression in mammalian cells also showed that human epiregulin was secreted as a soluble form of approx. |
| GO:0045740 positive regulation of DNA replication | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Automated inference of the same mitogenic readout. Reason: Consistent with the experimental rows and equally downstream. Supporting Evidence: PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. |
| GO:0045740 positive regulation of DNA replication | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same readout. Reason: Same assessment as the other DNA replication rows. Supporting Evidence: PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. |
| GO:0045740 positive regulation of DNA replication | ISS PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived m... | KEEP AS NON CORE | Summary: Smooth muscle DNA synthesis in response to epiregulin. Reason: Same assessment as the other DNA replication rows. Supporting Evidence: PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. |
| GO:0045840 positive regulation of mitotic nuclear division | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: A cell-cycle consequence of mitogenic signalling by EGF-family ligands. Reason: The ancestral assertion is reasonable for mitogens, but the gene product acts at the receptor and the effect on mitosis is indirect. Non-core. Supporting Evidence: PMID:10681561 Epiregulin stimulated human keratinocyte proliferation under both subconfluent and confluent culture conditions in the absence of exogenous EGF family growth factors. |
| GO:0045840 positive regulation of mitotic nuclear division | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Automated inference of the same downstream effect. Reason: Same assessment as the phylogenetic row. Supporting Evidence: PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. |
| GO:0045840 positive regulation of mitotic nuclear division | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same downstream effect. Reason: Same assessment as the other mitotic division rows. Supporting Evidence: PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. |
| GO:0045840 positive regulation of mitotic nuclear division | ISS PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived m... | KEEP AS NON CORE | Summary: Smooth muscle proliferation readout. Reason: Same assessment as the other mitotic division rows. Supporting Evidence: PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. |
| GO:0045860 positive regulation of protein kinase activity | IDA PMID:14581411 Epiregulin as a major autocrine/paracrine factor released fr... | ACCEPT | Summary: Epiregulin activates receptor tyrosine kinases and the downstream ERK and p38 kinases. Reason: Activating the receptor kinase is the immediate molecular consequence of ligand binding, so this process term is directly supported. Supporting Evidence: PMID:9419975 induces tyrosine phosphorylation of epidermal growth factor receptor, ErbB-2, ErbB-3 and ErbB-4 |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:14581411 Epiregulin as a major autocrine/paracrine factor released fr... | MARK AS OVER ANNOTATED | Summary: A secreted ligand does not act on transcription directly. Reason: The observation behind the row is that epiregulin treatment lowers expression of smooth muscle differentiation genes. That is a transcriptional response several steps downstream of receptor activation, and the specific biology is already captured by the negative regulation of smooth muscle cell differentiation row. Supporting Evidence: PMID:14581411 Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells. |
| GO:0048018 receptor ligand activity | IDA PMID:28783046 Epiregulin and EGFR interactions are involved in pain proces... | ACCEPT | Summary: Epiregulin is an agonist ligand of EGFR. Reason: This is the core molecular function, demonstrated by direct receptor binding and activation. Supporting Evidence: PMID:28783046 Epiregulin and EGFR interactions are involved in pain processing. |
| GO:0048018 receptor ligand activity | IDA PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth fac... | ACCEPT | Summary: Epiregulin is an agonist ligand of ERBB4. Reason: The hormone activates ERBB4 directly, so the ligand activity term applies to both receptors. Supporting Evidence: PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2. |
| GO:0048018 receptor ligand activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated inference agreeing with the direct evidence. Reason: Consistent with the experimental rows. Supporting Evidence: PMID:9419975 Epiregulin binds to epidermal growth factor receptor and ErbB-4 |
| GO:0048146 positive regulation of fibroblast proliferation | IDA PMID:12702554 Molecular characterization of human telomerase reverse trans... | KEEP AS NON CORE | Summary: EREG is activated in immortalised fibroblasts and promotes their growth. Reason: A cell-type-specific instance of the general mitogenic activity already accepted, so it is retained as non-core. Supporting Evidence: PMID:12702554 Molecular characterization of human telomerase reverse transcriptase-immortalized human fibroblasts by gene expression profiling, activation of the epiregulin gene. |
| GO:0048160 primary follicle stage | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Part of the rodent ovarian follicular programme. Reason: Inferred from the ortholog and organ-level. Retained as non-core. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0048160 primary follicle stage | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Curator-judged transfer of the same ovarian role. Reason: Same assessment as the Compara row. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
| GO:0048513 animal organ development | IEA GO_REF:0000117 | TOO GENERAL | Summary: A parent of the animal organ morphogenesis term retained in this review. Reason: The claim is true at a very high level but adds nothing beyond the morphogenesis row, which entails it. Supporting Evidence: PMID:9337852 Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family. |
| GO:0048661 positive regulation of smooth muscle cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Epiregulin is a potent vascular smooth muscle mitogen. Reason: Well supported in human cells, but a cell-type-specific instance of the general proliferative function already accepted. Supporting Evidence: PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. |
| GO:0048661 positive regulation of smooth muscle cell proliferation | ISS PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived m... | KEEP AS NON CORE | Summary: Same claim from the study that demonstrated it. Reason: Same assessment as the companion row. Supporting Evidence: PMID:9990076 Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. |
| GO:0050680 negative regulation of epithelial cell proliferation | TAS PMID:10681561 Epiregulin, a novel member of the epidermal growth factor fa... | KEEP AS NON CORE | Summary: Epiregulin inhibits growth of some epithelial tumour cell lines while stimulating normal keratinocytes. Reason: Consistent with the bifunctional behaviour of the ligand, but context-specific and opposite to its principal mitogenic role, so retained as non-core. Supporting Evidence: PMID:9556621 Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB2. |
| GO:0051151 negative regulation of smooth muscle cell differentiation | IDA PMID:14581411 Epiregulin as a major autocrine/paracrine factor released fr... | KEEP AS NON CORE | Summary: Autocrine epiregulin shifts vascular smooth muscle cells away from the differentiated phenotype. Reason: A real downstream effect of sustained EGFR signalling in this cell type, but secondary to the ligand activity itself. Supporting Evidence: PMID:14581411 Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells. |
| GO:0051240 positive regulation of multicellular organismal process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: A very high-level rule-based regulatory grouping. Reason: True given the roles in wound healing, ovulation and inflammation, but uninformative; the specific organismal roles are recorded separately. Retained as non-core rather than removed. Supporting Evidence: file:human/EREG/EREG-uniprot.txt Contributes to inflammation, wound healing, tissue repair, and oocyte maturation |
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Download this section (compressed HTML)Q: How much epiregulin signalling in vivo comes from the shed soluble ligand versus juxtacrine presentation by membrane-anchored proepiregulin?
Q: What determines whether epiregulin stimulates or inhibits proliferation in a given cell type, and how much of that is set by the ERBB2 and ERBB4 complement?
Q: Does the distinct EGFR dimer conformation stabilised by epiregulin explain its greater potency in wound closure relative to its lower receptor affinity?
Experiment: Express a shedding-resistant proepiregulin in co-culture with reporter cells lacking EREG and measure EGFR phosphorylation in the neighbours, with and without metalloprotease inhibition.
Hypothesis: Membrane-anchored proepiregulin signals juxtacrine to neighbouring cells independently of shedding.
Experiment: Compare receptor dimer lifetime by single-molecule imaging and ERK dynamics by live reporter in cells stimulated with equipotent doses of epiregulin and EGF.
Hypothesis: The epiregulin-specific EGFR dimer geometry produces sustained rather than transient ERK signalling.
Experiment: Titrate epiregulin on isogenic lines differing only in ERBB4 and ERBB2 expression and measure proliferation, receptor phosphorylation and target-gene output for each receptor combination.
Hypothesis: Epiregulin's growth-inhibitory effect on some epithelial cells requires ERBB4 rather than EGFR.
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