EREG_MOUSE
ID EREG_MOUSE Reviewed; 162 AA.
AC Q61521; Q7M0A8;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Proepiregulin;
DE Contains:
DE RecName: Full=Epiregulin;
DE Short=EPR;
DE Flags: Precursor;
GN Name=Ereg;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=NIH Swiss; TISSUE=Fibroblast;
RX PubMed=8549764; DOI=10.1016/0014-5793(95)01403-9;
RA Toyoda H., Komurasaki T., Ikeda Y., Yoshimoto M., Morimoto S.;
RT "Molecular cloning of mouse epiregulin, a novel epidermal growth factor-
RT related protein, expressed in the early stage of development.";
RL FEBS Lett. 377:403-407(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 56-101.
RX PubMed=7706296; DOI=10.1074/jbc.270.13.7495;
RA Toyoda H., Komurasaki T., Uchida D., Takayama Y., Isobe T., Okuyama T.,
RA Hanada K.;
RT "Epiregulin, a novel epidermal growth factor with mitogenic activity for
RT rat primary hepatocytes.";
RL J. Biol. Chem. 270:7495-7500(1995).
RN [4]
RP REVIEW.
RX PubMed=24631357; DOI=10.1016/j.semcdb.2014.03.005;
RA Riese D.J. II, Cullum R.L.;
RT "Epiregulin: roles in normal physiology and cancer.";
RL Semin. Cell Dev. Biol. 28:49-56(2014).
CC -!- FUNCTION: Ligand of the EGF receptor/EGFR and ERBB4. Stimulates EGFR
CC and ERBB4 tyrosine phosphorylation (By similarity). Contributes to
CC inflammation, wound healing, tissue repair, and oocyte maturation by
CC regulating angiogenesis and vascular remodeling and by stimulating cell
CC proliferation (PubMed:24631357). {ECO:0000250|UniProtKB:O14944,
CC ECO:0000303|PubMed:24631357}.
CC -!- SUBUNIT: Interacts with EGFR and ERBB4. {ECO:0000250|UniProtKB:O14944}.
CC -!- SUBCELLULAR LOCATION: [Epiregulin]: Secreted, extracellular space
CC {ECO:0000250|UniProtKB:O14944}.
CC -!- SUBCELLULAR LOCATION: [Proepiregulin]: Cell membrane
CC {ECO:0000250|UniProtKB:O14944}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:O14944}.
CC -!- DEVELOPMENTAL STAGE: Expressed in 7-day-old embryos with levels then
CC falling to very low or undetectable amounts. Not detected in adult.
CC {ECO:0000269|PubMed:8549764}.
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DR EMBL; D30782; BAA06446.1; -; mRNA.
DR EMBL; BC027838; AAH27838.1; -; mRNA.
DR CCDS; CCDS19420.1; -.
DR PIR; JT0747; JT0747.
DR PIR; S68401; S68401.
DR RefSeq; NP_031976.1; NM_007950.2.
DR AlphaFoldDB; Q61521; -.
DR SMR; Q61521; -.
DR STRING; 10090.ENSMUSP00000031324; -.
DR GlyGen; Q61521; 1 site.
DR PhosphoSitePlus; Q61521; -.
DR PaxDb; Q61521; -.
DR PRIDE; Q61521; -.
DR ProteomicsDB; 275674; -.
DR ABCD; Q61521; 5 sequenced antibodies.
DR Antibodypedia; 24625; 287 antibodies from 30 providers.
DR Ensembl; ENSMUST00000031324; ENSMUSP00000031324; ENSMUSG00000029377.
DR GeneID; 13874; -.
DR KEGG; mmu:13874; -.
DR UCSC; uc008ybs.1; mouse.
DR CTD; 2069; -.
DR MGI; MGI:107508; Ereg.
DR VEuPathDB; HostDB:ENSMUSG00000029377; -.
DR eggNOG; ENOG502S5DM; Eukaryota.
DR GeneTree; ENSGT00510000048748; -.
DR HOGENOM; CLU_138015_0_0_1; -.
DR InParanoid; Q61521; -.
DR OMA; CTALVQM; -.
DR OrthoDB; 1420179at2759; -.
DR PhylomeDB; Q61521; -.
DR TreeFam; TF336145; -.
DR Reactome; R-MMU-1227986; Signaling by ERBB2.
DR Reactome; R-MMU-1236394; Signaling by ERBB4.
DR Reactome; R-MMU-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-MMU-1250342; PI3K events in ERBB4 signaling.
DR Reactome; R-MMU-1250347; SHC1 events in ERBB4 signaling.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-177929; Signaling by EGFR.
DR Reactome; R-MMU-179812; GRB2 events in EGFR signaling.
DR Reactome; R-MMU-180292; GAB1 signalosome.
DR Reactome; R-MMU-180336; SHC1 events in EGFR signaling.
DR Reactome; R-MMU-182971; EGFR downregulation.
DR Reactome; R-MMU-1963640; GRB2 events in ERBB2 signaling.
DR Reactome; R-MMU-1963642; PI3K events in ERBB2 signaling.
DR Reactome; R-MMU-212718; EGFR interacts with phospholipase C-gamma.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-6785631; ERBB2 Regulates Cell Motility.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-8847993; ERBB2 Activates PTK6 Signaling.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-MMU-8863795; Downregulation of ERBB2 signaling.
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR BioGRID-ORCS; 13874; 1 hit in 75 CRISPR screens.
DR PRO; PR:Q61521; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q61521; protein.
DR Bgee; ENSMUSG00000029377; Expressed in indifferent gonad and 54 other tissues.
DR Genevisible; Q61521; MM.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; ISO:MGI.
DR GO; GO:0048018; F:receptor ligand activity; IDA:MGI.
DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; IDA:MGI.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; ISS:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0038134; P:ERBB2-EGFR signaling pathway; ISO:MGI.
DR GO; GO:0038135; P:ERBB2-ERBB4 signaling pathway; ISO:MGI.
DR GO; GO:0038138; P:ERBB4-ERBB4 signaling pathway; ISO:MGI.
DR GO; GO:0007143; P:female meiotic nuclear division; ISS:UniProtKB.
DR GO; GO:0043616; P:keratinocyte proliferation; ISS:UniProtKB.
DR GO; GO:0042700; P:luteinizing hormone signaling pathway; ISS:UniProtKB.
DR GO; GO:0009299; P:mRNA transcription; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0051151; P:negative regulation of smooth muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0001556; P:oocyte maturation; ISS:UniProtKB.
DR GO; GO:0001550; P:ovarian cumulus expansion; ISS:UniProtKB.
DR GO; GO:0030728; P:ovulation; ISS:UniProtKB.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; IMP:UniProtKB.
DR GO; GO:0045740; P:positive regulation of DNA replication; IDA:UniProtKB.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; ISS:UniProtKB.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISS:UniProtKB.
DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:UniProtKB.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IDA:UniProtKB.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISS:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0048160; P:primary follicle stage; ISS:UniProtKB.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR015497; EGF_rcpt_ligand.
DR PANTHER; PTHR10740; PTHR10740; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Cell membrane; Developmental protein; Differentiation;
KW Direct protein sequencing; Disulfide bond; EGF-like domain; Glycoprotein;
KW Growth factor; Membrane; Mitogen; Reference proteome; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..162
FT /note="Proepiregulin"
FT /id="PRO_0000302801"
FT PROPEP 23..55
FT /evidence="ECO:0000269|PubMed:7706296"
FT /id="PRO_0000007559"
FT CHAIN 56..101
FT /note="Epiregulin"
FT /id="PRO_0000007560"
FT PROPEP 102..162
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000007561"
FT TOPO_DOM 53..112
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 113..133
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 134..162
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 57..97
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 61..74
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 69..85
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 87..96
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
SQ SEQUENCE 162 AA; 18474 MW; DA50A10C9386B97D CRC64;
METLPASWVL TLLCLGSHLL QAVISTTVIP SCIPGESEDN CTALVQMEDD PRVAQVQITK
CSSDMDGYCL HGQCIYLVDM REKFCRCEVG YTGLRCEHFF LTVHQPLSKE YVALTVILIF
LFLIITAGCI YYFCRWYKNR KSKKSREEYE RVTSGDPVLP QV
