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Protein / target

Proepiregulin

Encoded byEREGO14944Homo sapiensSwiss-Prot
UniProt: O14944Ensembl: ENSG00000124882HGNC: HGNC:3443NCBI Gene: 2069
Clinical-stage
Therapeutic maturity
1
Clinical candidates
Antibody-tractable
Druggability
Advanced Clinical
2
Research papers

Protein at a glance

Biological role

Epidermal growth factor receptor binding

Strongest disease association

Neoplasms

Via encoding gene EREG · Pathway evidence · score 0.60

Therapeutic position

Clinically advancing target

Antibodies

Research activity

Emerging research

2 papers · latest 2023

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Ligand of the EGF receptor/EGFR and ERBB4.

View complete UniProt function annotation

Ligand of the EGF receptor/EGFR and ERBB4. Stimulates EGFR and ERBB4 tyrosine phosphorylation (PubMed:9419975). Contributes to inflammation, wound healing, tissue repair, and oocyte maturation by regulating angiogenesis and vascular remodeling and by stimulating cell proliferation (PubMed:24631357)

Subcellular location

Secreted, extracellular spaceCell membrane
Domains and Gene Ontology detail (44)

Domains & features

EGF-like

Gene Ontology

  • Cclathrin-coated endocytic vesicle membrane
  • Cextracellular region
  • Cextracellular space
  • Cplasma membrane
  • Fepidermal growth factor receptor binding
  • Fgrowth factor activity
  • Freceptor ligand activity
  • Ftransmembrane receptor protein tyrosine kinase activator activity
  • Panatomical structure morphogenesis
  • Pangiogenesis
  • Panimal organ morphogenesis
  • Pcell-cell signaling

169 aa · 19 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Receptor tyrosine kinase signallingUniProt · GOGrowth-factor signallingGOCell proliferation & survivalGOImmune signallingGOTranscriptional regulationGO
View supporting evidence

Receptor tyrosine kinase signalling

  • ·Ligand of the EGF receptor/EGFR and ERBB4. Stimulates EGFR and ERBB4 tyrosine phosphoryl…
  • ·transmembrane receptor protein tyrosine kinase activator activity
  • ·ERBB2-EGFR signaling pathway
  • ·ERBB2-ERBB4 signaling pathway

Growth-factor signalling

  • ·epidermal growth factor receptor binding
  • ·epidermal growth factor receptor signaling pathway

Cell proliferation & survival

  • ·negative regulation of cell population proliferation
  • ·positive regulation of cell population proliferation

Immune signalling

  • ·cytokine-mediated signaling pathway
  • ·positive regulation of cytokine production
  • ·positive regulation of innate immune response
  • ·positive regulation of interleukin-6 production

Transcriptional regulation

  • ·mRNA transcription
  • ·negative regulation of DNA-templated transcription

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene EREG

Gene-level evidence surfaced through the gene EREGthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Neoplasms
0.46Preliminary

Pathway evidence dominant · Open Targets 0.60 · no direct causal or clinical evidence

Colorectal adenocarcinoma
0.28Preliminary

Pathway evidence dominant · Open Targets 0.19 · no direct causal or clinical evidence

Breast Neoplasms
0.23Preliminary

Literature evidence dominant · Open Targets 0.11 · no direct causal or clinical evidence

Squamous Cell Carcinoma of Head and Neck
0.13Preliminary

Literature evidence dominant · Open Targets 0.10 · no direct causal or clinical evidence

Colorectal Neoplasms
0.12Preliminary

Literature evidence dominant · Open Targets 0.10 · no direct causal or clinical evidence

View evidence synthesis (5)
NeoplasmsPreliminary
0.46
agreement 0.28–0.64
Pathway75%Literature25%

Open Targets aggregate 0.60 · 2 independent evidence families · no direct causal or clinical evidence

Colorectal adenocarcinomaPreliminary
0.28
agreement 0.13–0.43
Pathway83%RNA expression14%Literature3%

Open Targets aggregate 0.19 · 3 independent evidence families · no direct causal or clinical evidence

Breast NeoplasmsPreliminary
0.23
agreement 0.04–0.42
Literature50%RNA expression50%

Open Targets aggregate 0.11 · 2 independent evidence families · no direct causal or clinical evidence

Squamous Cell Carcinoma of Head and NeckPreliminary
0.13
agreement 0.00–0.40
Literature100%

Open Targets aggregate 0.10 · 1 independent evidence family · no direct causal or clinical evidence

Colorectal NeoplasmsPreliminary
0.12
agreement 0.00–0.40
Literature100%

Open Targets aggregate 0.10 · 1 independent evidence family · no direct causal or clinical evidence

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Neoplasms0.60
Colorectal adenocarcinoma0.19
Breast Neoplasms0.11
Squamous Cell Carcinoma of Head and Neck0.10
Colorectal Neoplasms0.10
Carcinoma, Non-Small-Cell Lung0.10
Osteoarthritis0.09

Drug development

1 compounds recorded · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (1)
FEPIXNEBARTPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Antibodies — Strong

Advanced Clinical and UniProt loc high conf support this modality.

View underlying tractability evidence (4)
AB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMM

Raw Open Targets tractability assessment buckets, by modality.

Research activity

2 papers · to 2023

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.852 cites

Khambata-Ford S · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2007

Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer.22 cites

Williams CJM · Clinical cancer research : an official journal of the American Association for Cancer Research · 2023

Recent

Associations between AI-Assisted Tumor Amphiregulin and Epiregulin IHC and Outcomes from Anti-EGFR Therapy in the Routine Management of Metastatic Colorectal Cancer.

Williams CJM · Clinical cancer research : an official journal of the American Association for Cancer Research · 2023

Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.

Khambata-Ford S · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2007

Europe PMC papers linked directly to this protein.