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Database: UniProt
Entry: Q9Z0L5
LinkDB: Q9Z0L5
Original site: Q9Z0L5 
ID   EREG_RAT                Reviewed;         162 AA.
AC   Q9Z0L5;
DT   14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   13-FEB-2019, entry version 139.
DE   RecName: Full=Proepiregulin;
DE   Contains:
DE     RecName: Full=Epiregulin;
DE              Short=EPR;
DE   Flags: Precursor;
GN   Name=Ereg;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 56-75, FUNCTION, AND
RP   INDUCTION.
RC   TISSUE=Aortic smooth muscle;
RX   PubMed=9990076; DOI=10.1073/pnas.96.4.1633;
RA   Taylor D.S., Cheng X., Pawlowski J.E., Wallace A.R., Ferrer P.,
RA   Molloy C.J.;
RT   "Epiregulin is a potent vascular smooth muscle cell-derived mitogen
RT   induced by angiotensin II, endothelin-1, and thrombin.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:1633-1638(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION.
RC   TISSUE=Liver;
RX   PubMed=12446600; DOI=10.1210/en.2002-220440;
RA   Sekiguchi T., Mizutani T., Yamada K., Yazawa T., Kawata H.,
RA   Yoshino M., Kajitani T., Kameda T., Minegishi T., Miyamoto K.;
RT   "Transcriptional regulation of the epiregulin gene in the rat ovary.";
RL   Endocrinology 143:4718-4729(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T.,
RA   Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A.,
RA   Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M.,
RA   Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K.,
RA   Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S.,
RA   Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J.,
RA   Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y.,
RA   Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A.,
RA   Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J.,
RA   D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R.,
RA   Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A.,
RA   Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E.,
RA   Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E.,
RA   Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D.,
RA   Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M.,
RA   Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O.,
RA   Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O.,
RA   Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H.,
RA   Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S.,
RA   Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J.,
RA   Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E.,
RA   Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F.,
RA   Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K.,
RA   Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S.,
RA   Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M.,
RA   Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M.,
RA   Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A.,
RA   Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S.,
RA   Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G.,
RA   Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H.,
RA   Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R.,
RA   Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M.,
RA   Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H.,
RA   Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S.,
RA   Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into
RT   mammalian evolution.";
RL   Nature 428:493-521(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
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
CC       EGFR and ERBB4 tyrosine phosphorylation (PubMed:9990076).
CC       Contributes to inflammation, wound healing, tissue repair, and
CC       oocyte maturation by regulating angiogenesis and vascular
CC       remodeling and by stimulating cell proliferation
CC       (PubMed:24631357). {ECO:0000269|PubMed:9990076,
CC       ECO:0000303|PubMed:24631357}.
CC   -!- SUBUNIT: Interacts with EGFR and ERBB4.
CC       {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
CC       protein {ECO:0000250|UniProtKB:O14944}.
CC   -!- INDUCTION: By angiotensin II, endothelin-1 and alpha-thrombin.
CC       Strongly induced in ovarian granulosa cells by FSH stimulation.
CC       {ECO:0000269|PubMed:12446600, ECO:0000269|PubMed:9990076}.
DR   EMBL; AF074952; AAD10631.1; -; mRNA.
DR   EMBL; AB078739; BAC44880.1; -; Genomic_DNA.
DR   EMBL; AABR07072382; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC108576; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH474060; EDL88580.1; -; Genomic_DNA.
DR   RefSeq; NP_067721.1; NM_021689.1.
DR   UniGene; Rn.42897; -.
DR   ProteinModelPortal; Q9Z0L5; -.
DR   SMR; Q9Z0L5; -.
DR   STRING; 10116.ENSRNOP00000003716; -.
DR   PhosphoSitePlus; Q9Z0L5; -.
DR   PaxDb; Q9Z0L5; -.
DR   PRIDE; Q9Z0L5; -.
DR   Ensembl; ENSRNOT00000003716; ENSRNOP00000003716; ENSRNOG00000002771.
DR   GeneID; 59325; -.
DR   KEGG; rno:59325; -.
DR   UCSC; RGD:620299; rat.
DR   CTD; 2069; -.
DR   RGD; 620299; Ereg.
DR   eggNOG; ENOG410IXV0; Eukaryota.
DR   eggNOG; ENOG410YNFA; LUCA.
DR   GeneTree; ENSGT00510000048748; -.
DR   HOGENOM; HOG000059635; -.
DR   HOVERGEN; HBG005601; -.
DR   InParanoid; Q9Z0L5; -.
DR   KO; K09784; -.
DR   OMA; CTALVQM; -.
DR   OrthoDB; 1420179at2759; -.
DR   PhylomeDB; Q9Z0L5; -.
DR   TreeFam; TF336145; -.
DR   Reactome; R-RNO-1227986; Signaling by ERBB2.
DR   Reactome; R-RNO-1236394; Signaling by ERBB4.
DR   Reactome; R-RNO-1250196; SHC1 events in ERBB2 signaling.
DR   Reactome; R-RNO-1250342; PI3K events in ERBB4 signaling.
DR   Reactome; R-RNO-1250347; SHC1 events in ERBB4 signaling.
DR   Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR   Reactome; R-RNO-177929; Signaling by EGFR.
DR   Reactome; R-RNO-179812; GRB2 events in EGFR signaling.
DR   Reactome; R-RNO-180292; GAB1 signalosome.
DR   Reactome; R-RNO-180336; SHC1 events in EGFR signaling.
DR   Reactome; R-RNO-182971; EGFR downregulation.
DR   Reactome; R-RNO-1963640; GRB2 events in ERBB2 signaling.
DR   Reactome; R-RNO-1963642; PI3K events in ERBB2 signaling.
DR   Reactome; R-RNO-212718; EGFR interacts with phospholipase C-gamma.
DR   Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-RNO-6785631; ERBB2 Regulates Cell Motility.
DR   Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-RNO-8847993; ERBB2 Activates PTK6 Signaling.
DR   Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR   Reactome; R-RNO-8863795; Downregulation of ERBB2 signaling.
DR   PRO; PR:Q9Z0L5; -.
DR   Proteomes; UP000002494; Chromosome 14.
DR   Bgee; ENSRNOG00000002771; Expressed in 2 organ(s), highest expression level in colon.
DR   Genevisible; Q9Z0L5; RN.
DR   GO; GO:0005615; C:extracellular space; IDA:RGD.
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; ISS:UniProtKB.
DR   GO; GO:0008083; F:growth factor activity; IDA:RGD.
DR   GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0008283; P:cell population proliferation; TAS:RGD.
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; ISS:UniProtKB.
DR   GO; GO:0007143; P:female meiotic nuclear division; IDA:UniProtKB.
DR   GO; GO:0043616; P:keratinocyte proliferation; ISS:UniProtKB.
DR   GO; GO:0042700; P:luteinizing hormone signaling pathway; IDA:UniProtKB.
DR   GO; GO:0009299; P:mRNA transcription; ISS:UniProtKB.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; ISS: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; IDA:UniProtKB.
DR   GO; GO:0001550; P:ovarian cumulus expansion; IDA:UniProtKB.
DR   GO; GO:0030728; P:ovulation; IDA:UniProtKB.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; TAS: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:RGD.
DR   GO; GO:0042108; P:positive regulation of cytokine biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0001819; P:positive regulation of cytokine production; ISS: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; IDA:UniProtKB.
DR   GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISS:UniProtKB.
DR   GO; GO:0045089; P:positive regulation of innate immune response; ISS:UniProtKB.
DR   GO; GO:0045410; P:positive regulation of interleukin-6 biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0045840; P:positive regulation of mitotic nuclear division; IDA:UniProtKB.
DR   GO; GO:0042327; P:positive regulation of phosphorylation; IDA: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; IDA:UniProtKB.
DR   GO; GO:0048160; P:primary follicle stage; IDA:UniProtKB.
DR   GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR   InterPro; IPR013032; EGF-like_CS.
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; Complete proteome; Developmental protein;
KW   Differentiation; Direct protein sequencing; Disulfide bond;
KW   EGF-like domain; Glycoprotein; Growth factor; Membrane; Mitogen;
KW   Reference proteome; Secreted; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL        1     22       {ECO:0000255}.
FT   CHAIN        23    162       Proepiregulin.
FT                                /FTId=PRO_5000054710.
FT   PROPEP       23     55       {ECO:0000269|PubMed:9990076}.
FT                                /FTId=PRO_0000433960.
FT   CHAIN        56    101       Epiregulin.
FT                                /FTId=PRO_5000054711.
FT   PROPEP      102    162       Removed in mature form. {ECO:0000250}.
FT                                /FTId=PRO_0000433961.
FT   TRANSMEM    113    133       Helical. {ECO:0000255}.
FT   DOMAIN       57     97       EGF-like. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   CARBOHYD     40     40       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     61     74       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID     69     85       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID     87     96       {ECO:0000255|PROSITE-ProRule:PRU00076}.
SQ   SEQUENCE   162 AA;  18404 MW;  EA660DE2B34990C4 CRC64;
     METFPAAWVL ALLCLGSHLL QAVISTTVIP SCIPEESEDN CTALVQMEDD PRVAQVLITK
     CSSDMDGYCL HGHCIYLVDM SEKYCRCEVG YTGLRCEHFF LTVHQPLSRE YVALTVILVF
     LFLIVTAGSM YYFCRWYRNR KSKKSREEYE RVTSGGPGLP QV
//
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