Epiregulin

Epiregulin
NMR Structure of Human Epiregulin: by scheme of amino acid.[1] SCOP 103561
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1K36​, 1K37​
Identifiers
Symbols	EREG ; EPR; ER; Ep
External IDs	OMIM: 602061 MGI: 107508 HomoloGene: 1097 GeneCards: EREG Gene
Gene ontology Molecular function • epidermal growth factor receptor binding • protein binding • growth factor activity Cellular component • extracellular region • extracellular space • intracellular • integral component of plasma membrane Biological process • activation of MAPK activity • angiogenesis • ovarian cumulus expansion • oocyte maturation • positive regulation of cytokine production • female meiotic division • epidermal growth factor receptor signaling pathway • cell-cell signaling • positive regulation of cell proliferation • negative regulation of cell proliferation • fibroblast growth factor receptor signaling pathway • mRNA transcription • anatomical structure morphogenesis • organ morphogenesis • cytokine-mediated signaling pathway • keratinocyte differentiation • ovulation • Fc-epsilon receptor signaling pathway • wound healing • positive regulation of cytokine biosynthetic process • positive regulation of phosphorylation • luteinizing hormone signaling pathway • response to peptide hormone • keratinocyte proliferation • innate immune response • positive regulation of innate immune response • positive regulation of interleukin-6 biosynthetic process • positive regulation of DNA replication • positive regulation of epidermal growth factor-activated receptor activity • positive regulation of mitotic nuclear division • positive regulation of protein kinase activity • negative regulation of transcription, DNA-templated • neurotrophin TRK receptor signaling pathway • phosphatidylinositol-mediated signaling • positive regulation of fibroblast proliferation • primary follicle stage • positive regulation of smooth muscle cell proliferation • negative regulation of epithelial cell proliferation • negative regulation of smooth muscle cell differentiation Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2069	13874
Ensembl	ENSG00000124882	ENSMUSG00000029377
UniProt	O14944	Q61521
RefSeq (mRNA)	NM_001432	NM_007950
RefSeq (protein)	NP_001423	NP_031976
Location (UCSC)	Chr 4: 74.37 – 74.39 Mb	Chr 5: 91.07 – 91.09 Mb
PubMed search

Epiregulin (EPR) is a protein that in humans is encoded by the EREG gene.^[2][3]

Structure

Epiregulin consists of 46 amino acid residues. Its secondary structure contains approximately 30 percent of β-sheet in the strand.^[1] Some of the residues form loops and turns due to the hydrogen bonding.^[1] The percentage of β-sheet in epiregulin depends on the domain and the secondary structures that they occupy. The polymeric molecules of epiregulin has the formula weight of 5280.1 g/mol with a polypeptide(L), a polymer type.^[1]

Structural motifs in most proteins have typical connections in an all β motif. Meaning that the polypeptide chains do not make a crossover connection or in so far as this type of connection has not been observed. Epiregulin is one of the proteins that occupies a typical connection in all β motif. Furthermore, as the structure of epiregulin forms a chain in an all β motif, it also forms β hairpin structural motif. A β hairpin is when the two adjacent anti-parallel β strands connected by a β-turn.

Function

Epiregulin is a member of the epidermal growth factor family. Epiregulin can function as a ligand of epidermal growth factor receptor (EGFR), as well as a ligand of most members of the ERBB (v-erb-b2 oncogene homolog) family of tyrosine-kinase receptors.^[3] The secondary structure at the C-terminus epiregulin is different from other epidermal growth factor family ligands because of the lack of hydrogen bonds. The structural difference at the C-terminus may provide an explanation for the reduced binding affinity of epiregulin to the ERBB receptors.^[1]

References

1. PDB: 1K36​; Sato K, Nakamura T, Mizuguchi M, Miura K, Tada M, Aizawa T, Gomi T, Miyamoto K, Kawano K (October 2003). "Solution structure of epiregulin and the effect of its C-terminal domain for receptor binding affinity". FEBS Lett. 553 (3): 232–8. doi:10.1016/S0014-5793(03)01005-6. PMID 14572630.
2. Toyoda H, Komurasaki T, Uchida D, Morimoto S (August 1997). "Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family". Biochem. J. 326 (1): 69–75. PMC 1218638. PMID 9337852.
3. "Entrez Gene: epiregulin".

Further reading

• Yamamoto T, Akisue T, Marui T; et al. (2004). "Expression of betacellulin, heparin-binding epidermal growth factor and epiregulin in human malignant fibrous histiocytoma.". Anticancer Res. 24 (3b): 2007–10. PMID 15274392.
• Li S, Takeuchi F, Wang JA; et al. (2008). "Mesenchymal-epithelial interactions involving epiregulin in tuberous sclerosis complex hamartomas.". Proc. Natl. Acad. Sci. U.S.A. 105 (9): 3539–44. doi:10.1073/pnas.0712397105. PMC 2265180. PMID 18292222.
• Cho MC, Choi HS, Lee S; et al. (2008). "Epiregulin expression by Ets-1 and ERK signaling pathway in Ki-ras-transformed cells.". Biochem. Biophys. Res. Commun. 377 (3): 832–7. doi:10.1016/j.bbrc.2008.10.053. PMID 18948081.
• Lindvall C, Hou M, Komurasaki T; et al. (2003). "Molecular characterization of human telomerase reverse transcriptase-immortalized human fibroblasts by gene expression profiling: activation of the epiregulin gene.". Cancer Res. 63 (8): 1743–7. PMID 12702554.
• Morita S, Shirakata Y, Shiraishi A; et al. (2007). "Human corneal epithelial cell proliferation by epiregulin and its cross-induction by other EGF family members.". Mol. Vis. 13: 2119–28. PMID 18079685.
• Freimann S, Ben-Ami I, Dantes A; et al. (2004). "EGF-like factor epiregulin and amphiregulin expression is regulated by gonadotropins/cAMP in human ovarian follicular cells.". Biochem. Biophys. Res. Commun. 324 (2): 829–34. doi:10.1016/j.bbrc.2004.09.129. PMID 15474502.
• Ben-Ami I, Armon L, Freimann S; et al. (2009). "EGF-like growth factors as LH mediators in the human corpus luteum.". Hum. Reprod. 24 (1): 176–84. doi:10.1093/humrep/den359. PMID 18835871.
• Shigeishi H, Higashikawa K, Hiraoka M; et al. (2008). "Expression of epiregulin, a novel epidermal growth factor ligand associated with prognosis in human oral squamous cell carcinomas.". Oncol. Rep. 19 (6): 1557–64. doi:10.3892/or.19.6.1557. PMID 18497965.
• Taylor DS, Cheng X, Pawlowski JE; et al. (1999). "Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin.". Proc. Natl. Acad. Sci. U.S.A. 96 (4): 1633–8. doi:10.1073/pnas.96.4.1633. PMC 15542. PMID 9990076.
• Zhang J, Iwanaga K, Choi KC; et al. (2008). "Intratumoral epiregulin is a marker of advanced disease in non-small cell lung cancer patients and confers invasive properties on EGFR-mutant cells.". Cancer Prev Res (Phila) 1 (3): 201–7. doi:10.1158/1940-6207.CAPR-08-0014. PMC 3375599. PMID 19138957.
• Draper BK, Komurasaki T, Davidson MK, Nanney LB (2003). "Epiregulin is more potent than EGF or TGFalpha in promoting in vitro wound closure due to enhanced ERK/MAPK activation.". J. Cell. Biochem. 89 (6): 1126–37. doi:10.1002/jcb.10584. PMID 12898511.
• Révillion F, Lhotellier V, Hornez L, Bonneterre J, Peyrat JP (January 2008). "ErbB/HER ligands in human breast cancer, and relationships with their receptors, the bio-pathological features and prognosis". Ann. Oncol. 19 (1): 73–80. doi:10.1093/annonc/mdm431. PMID 17962208.
• Ben-Ami I, Freimann S, Armon L; et al. (2006). "PGE2 up-regulates EGF-like growth factor biosynthesis in human granulosa cells: new insights into the coordination between PGE2 and LH in ovulation.". Mol. Hum. Reprod. 12 (10): 593–9. doi:10.1093/molehr/gal068. PMID 16888076.
• Takahashi M, Hayashi K, Yoshida K; et al. (2003). "Epiregulin as a major autocrine/paracrine factor released from ERK- and p38MAPK-activated vascular smooth muscle cells.". Circulation 108 (20): 2524–9. doi:10.1161/01.CIR.0000096482.02567.8C. PMID 14581411.
• Lasky-Su J, Neale BM, Franke B; et al. (2008). "Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations.". Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B (8): 1345–54. doi:10.1002/ajmg.b.30867. PMID 18821565.
• Gupta GP, Nguyen DX, Chiang AC; et al. (2007). "Mediators of vascular remodelling co-opted for sequential steps in lung metastasis.". Nature 446 (7137): 765–70. doi:10.1038/nature05760. PMID 17429393.
• Shirakata Y, Komurasaki T, Toyoda H; et al. (2000). "Epiregulin, a novel member of the epidermal growth factor family, is an autocrine growth factor in normal human keratinocytes.". J. Biol. Chem. 275 (8): 5748–53. doi:10.1074/jbc.275.8.5748. PMID 10681561.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.