This gene encodes a secreted peptide hormone and member of the epidermal growth factor (EGF) family of proteins. The encoded protein is a ligand of the epidermal growth factor receptor (EGFR) and the structurally related erb-b2 receptor tyrosine kinase 4 (ERBB4). The encoded protein may be involved in a wide range of biological processes including inflammation, wound healing, o... See more...

Aliases for EREG Gene

Aliases for EREG Gene

  • Epiregulin 2 3 5
  • Proepiregulin 3 4
  • EPR 3
  • ER 3
  • Ep 3

External Ids for EREG Gene

Previous GeneCards Identifiers for EREG Gene

  • GC04P075220
  • GC04P075470
  • GC04P075631
  • GC04P075697
  • GC04P075595
  • GC04P071043

Summaries for EREG Gene

Entrez Gene Summary for EREG Gene

  • This gene encodes a secreted peptide hormone and member of the epidermal growth factor (EGF) family of proteins. The encoded protein is a ligand of the epidermal growth factor receptor (EGFR) and the structurally related erb-b2 receptor tyrosine kinase 4 (ERBB4). The encoded protein may be involved in a wide range of biological processes including inflammation, wound healing, oocyte maturation, and cell proliferation. Additionally, the encoded protein may promote the progression of cancers of various human tissues. [provided by RefSeq, Jul 2015]

CIViC Summary for EREG Gene

GeneCards Summary for EREG Gene

EREG (Epiregulin) is a Protein Coding gene. Diseases associated with EREG include Squamous Blepharitis and Malignant Fibroxanthoma. Among its related pathways are RET signaling and Downstream signaling events of B Cell Receptor (BCR). Gene Ontology (GO) annotations related to this gene include growth factor activity and epidermal growth factor receptor binding. An important paralog of this gene is EPGN.

UniProtKB/Swiss-Prot Summary for EREG Gene

  • 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).

Gene Wiki entry for EREG Gene

Additional gene information for EREG Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for EREG Gene

Genomics for EREG Gene

GeneHancer (GH) Regulatory Elements for EREG Gene

Promoters and enhancers for EREG Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J074363 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE dbSUPER 506 +1.5 1480 5.8 EP300 TCF12 ZBTB5 POLR2A ZNF263 ZBTB26 CTBP1 EZH2 KDM5B KDM1A EREG PARM1-AS1 EPGN AREG piR-33422-319
GH04J074107 Promoter/Enhancer 1.8 FANTOM5 Ensembl ENCODE dbSUPER 38.6 -251.7 -251672 11.5 TCF12 JUND TEAD4 FOS POLR2A RFX1 EP300 NR2F2 NEUROD1 MYNN MTHFD2L CXCL2 EREG CXCL8 CXCL3 CXCL1 AREG HSALNG0035194 lnc-MTHFD2L-3 LOC105377277
GH04J074326 Enhancer 1.3 FANTOM5 ENCODE dbSUPER 43.8 -35.3 -35339 5.7 GTF2E2 AFF1 NFRKB RBM25 NCOR1 KDM5B RELA TRIM24 TRIM28 CEBPG LOC105377276 lnc-CXCL2-1 EREG CXCL2 CXCL3 RASSF6 MTHFD2L lnc-EPGN-1
GH04J074228 Enhancer 1.3 FANTOM5 Ensembl ENCODE dbSUPER 27.5 -134.3 -134328 4.4 CTCF TCF12 REST MYC RAD21 EP300 TRIM22 SMC3 GABPA CEBPG CXCL8 EREG CXCL2 CXCL3 EPGN MTHFD2L ENSG00000269559
GH04J074092 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 13.2 -268.3 -268253 8.6 CTCF TCF12 GTF2E2 PHF8 ZIC2 POLR2A ZBTB10 ZBTB11 TCF7 TAF7 CXCL2 CXCL3 ANKRD17 ENSG00000250220 CXCL8 EREG MTHFD2L AREG HMGA1P2 lnc-CXCL3-3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around EREG on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for EREG

Top Transcription factor binding sites by QIAGEN in the EREG gene promoter:
  • AML1a
  • FOXO1
  • FOXO1a
  • HOXA9
  • HOXA9B
  • IRF-1
  • Meis-1
  • Meis-1b
  • Nkx2-5
  • p53

Genomic Locations for EREG Gene

Genomic Locations for EREG Gene
chr4:74,365,143-74,388,760
(GRCh38/hg38)
Size:
23,618 bases
Orientation:
Plus strand
chr4:75,230,860-75,254,477
(GRCh37/hg19)
Size:
23,618 bases
Orientation:
Plus strand

Genomic View for EREG Gene

Genes around EREG on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EREG Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EREG Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EREG Gene

Proteins for EREG Gene

  • Protein details for EREG Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O14944-EREG_HUMAN
    Recommended name:
    Proepiregulin
    Protein Accession:
    O14944
    Secondary Accessions:
    • B2RC66
    • Q6FH69

    Protein attributes for EREG Gene

    Size:
    169 amino acids
    Molecular mass:
    19044 Da
    Quaternary structure:
    • Interacts with EGFR and ERBB4.

    Three dimensional structures from OCA and Proteopedia for EREG Gene

neXtProt entry for EREG Gene

Post-translational modifications for EREG Gene

  • Glycosylation at Asn47
  • Modification sites at PhosphoSitePlus

Other Protein References for EREG Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for EREG Gene

Domains & Families for EREG Gene

Gene Families for EREG Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for EREG Gene

Blocks:
  • Type I EGF
  • Type I EGF signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for EREG Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ95874, Homo sapiens epiregulin (EREG), mRNA (B2RC66_HUMAN)
  • Proepiregulin (EREG_HUMAN)
genes like me logo Genes that share domains with EREG: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for EREG Gene

Function for EREG Gene

Molecular function for EREG Gene

UniProtKB/Swiss-Prot Function:
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).

Phenotypes From GWAS Catalog for EREG Gene

Gene Ontology (GO) - Molecular Function for EREG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005154 epidermal growth factor receptor binding IBA,TAS 10681561
GO:0005515 protein binding IPI 9419975
GO:0008083 growth factor activity IBA 21873635
genes like me logo Genes that share ontologies with EREG: view
genes like me logo Genes that share phenotypes with EREG: view

Animal Models for EREG Gene

MGI Knock Outs for EREG:

Animal Model Products

  • Taconic Biosciences Mouse Models for EREG

miRNA for EREG Gene

miRTarBase miRNAs that target EREG

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for EREG Gene

Localization for EREG Gene

Subcellular locations from UniProtKB/Swiss-Prot for EREG Gene

[Epiregulin]: Secreted, extracellular space.
[Proepiregulin]: Cell membrane; Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for EREG gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytoskeleton 2
nucleus 2
cytosol 2
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for EREG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IDA,IBA 9337852
GO:0005886 plasma membrane IEA --
GO:0005887 integral component of plasma membrane TAS 9337852
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with EREG: view

Pathways & Interactions for EREG Gene

PathCards logo

SuperPathways for EREG Gene

SuperPathway Contained pathways
1 RET signaling
2 Signaling by ERBB2
3 GAB1 signalosome
4 ErbB signaling pathway
5 Signaling by ERBB4
genes like me logo Genes that share pathways with EREG: view

Pathways by source for EREG Gene

2 GeneGo (Thomson Reuters) pathways for EREG Gene
  • Development EGFR signaling pathway
  • Development ERBB-family signaling
1 Qiagen pathway for EREG Gene
  • ErbB Family Pathway
1 Cell Signaling Technology pathway for EREG Gene

SIGNOR curated interactions for EREG Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for EREG Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0001525 angiogenesis IEA --
GO:0001550 ovarian cumulus expansion ISS,IEA --
GO:0001556 oocyte maturation ISS,IEA --
GO:0001819 positive regulation of cytokine production ISS,IEA --
genes like me logo Genes that share ontologies with EREG: view

Drugs & Compounds for EREG Gene

(7) Drugs for EREG Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(2) Additional Compounds for EREG Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with EREG: view

Transcripts for EREG Gene

mRNA/cDNA for EREG Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for EREG Gene

No ASD Table

Relevant External Links for EREG Gene

GeneLoc Exon Structure for
EREG

Expression for EREG Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for EREG Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for EREG Gene

This gene is overexpressed in Esophagus - Mucosa (x10.3), Skin - Sun Exposed (Lower leg) (x7.1), Skin - Not Sun Exposed (Suprapubic) (x5.7), and Whole Blood (x4.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for EREG Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for EREG

SOURCE GeneReport for Unigene cluster for EREG Gene:

Hs.115263

mRNA Expression by UniProt/SwissProt for EREG Gene:

O14944-EREG_HUMAN
Tissue specificity: In normal adults, expressed predominantly in the placenta and peripheral blood leukocytes. High levels were detected in carcinomas of the bladder, lung, kidney and colon.

Evidence on tissue expression from TISSUES for EREG Gene

  • Bone marrow(2.1)
  • Intestine(2)
genes like me logo Genes that share expression patterns with EREG: view

No data available for Protein differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for EREG Gene

Orthologs for EREG Gene

This gene was present in the common ancestor of chordates.

Orthologs for EREG Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia EREG 31 30
  • 99.21 (n)
OneToOne
cow
(Bos Taurus)
Mammalia EREG 31 30
  • 87.63 (n)
OneToOne
dog
(Canis familiaris)
Mammalia EREG 31 30
  • 87.32 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Ereg 17 31 30
  • 82.63 (n)
rat
(Rattus norvegicus)
Mammalia Ereg 30
  • 81.46 (n)
oppossum
(Monodelphis domestica)
Mammalia EREG 31
  • 63 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia EREG 31
  • 53 (a)
OneToOne
chicken
(Gallus gallus)
Aves EREG 31 30
  • 60.4 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia EREG 31
  • 49 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ereg 30
  • 57.76 (n)
Species where no ortholog for EREG was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for EREG Gene

ENSEMBL:
Gene Tree for EREG (if available)
TreeFam:
Gene Tree for EREG (if available)
Aminode:
Evolutionary constrained regions (ECRs) for EREG: view image

Paralogs for EREG Gene

Paralogs for EREG Gene

genes like me logo Genes that share paralogs with EREG: view

Variants for EREG Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for EREG Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
790002 Benign: not provided 74,384,738(+) G/A MISSENSE_VARIANT
VAR_035833 A breast cancer sample p.Gly42Ala
rs35275884 - p.Arg147Gln

Additional dbSNP identifiers (rs#s) for EREG Gene

Structural Variations from Database of Genomic Variants (DGV) for EREG Gene

Variant ID Type Subtype PubMed ID
nsv1009099 CNV gain 25217958
nsv290978 CNV deletion 16902084
nsv525980 CNV gain 19592680

Variation tolerance for EREG Gene

Residual Variation Intolerance Score: 39.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.32; 26.25% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for EREG Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
EREG

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EREG Gene

Disorders for EREG Gene

MalaCards: The human disease database

(9) MalaCards diseases for EREG Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
squamous blepharitis
malignant fibroxanthoma
  • fibrous histiocytoma, malignant
colorectal cancer
  • crc
breast cancer
  • breast cancer, familial
vallecula cancer
  • malignant tumor of vallecula
- elite association - COSMIC cancer census association via MalaCards
Search EREG in MalaCards View complete list of genes associated with diseases

Additional Disease Information for EREG

genes like me logo Genes that share disorders with EREG: view

No data available for UniProtKB/Swiss-Prot and Genatlas for EREG Gene

Publications for EREG Gene

  1. Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family. (PMID: 9337852) Toyoda H … Morimoto S (The Biochemical journal 1997) 2 3 4 23 54
  2. Solution structure of epiregulin and the effect of its C-terminal domain for receptor binding affinity. (PMID: 14572630) Sato K … Kawano K (FEBS letters 2003) 3 4 23 54
  3. 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: 9419975) Komurasaki T … Morimoto S (Oncogene 1997) 3 4 23 54
  4. Epiregulin: roles in normal physiology and cancer. (PMID: 24631357) Riese DJ … Cullum RL (Seminars in cell & developmental biology 2014) 3 4 54
  5. Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. (PMID: 18821565) Lasky-Su J … Faraone SV (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2008) 3 41 54

Products for EREG Gene

Sources for EREG Gene