ID   AREG_MOUSE              Reviewed;         248 AA.
AC   P31955;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   24-JAN-2024, entry version 174.
DE   RecName: Full=Amphiregulin;
DE            Short=AR;
DE   AltName: Full=Schwannoma-derived growth factor;
DE            Short=SDGF;
DE   Flags: Precursor;
GN   Name=Areg; Synonyms=Sdgf;
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].
RX   PubMed=1318038; DOI=10.1016/s0006-291x(05)80961-1;
RA   Sonoda H., Yamaguchi T., Watanabe S.;
RT   "Androgen-responsive expression and mitogenic activity of schwannoma-
RT   derived growth factor on an androgen-dependent Shionogi mouse mammary
RT   carcinoma cell line.";
RL   Biochem. Biophys. Res. Commun. 185:103-109(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8592515; DOI=10.1210/mend.9.6.8592515;
RA   Das S.K., Chakraborty I., Paria B.C., Wang X.N., Plowman G.D., Dey S.K.;
RT   "Amphiregulin is an implantation-specific and progesterone-regulated gene
RT   in the mouse uterus.";
RL   Mol. Endocrinol. 9:691-705(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Cecum;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
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).
CC   -!- FUNCTION: Ligand of the EGF receptor/EGFR. Autocrine growth factor as
CC       well as a mitogen for a broad range of target cells including
CC       astrocytes, Schwann cells and fibroblasts.
CC   -!- SUBUNIT: The immature precursor interacts with CNIH. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein.
CC   -!- INDUCTION: Androgen-dependent.
CC   -!- SIMILARITY: Belongs to the amphiregulin family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; D12648; BAA02169.1; -; mRNA.
DR   EMBL; L41352; AAB00472.1; -; Genomic_DNA.
DR   EMBL; AK018590; BAB31296.1; -; mRNA.
DR   EMBL; BC009138; AAH09138.1; -; mRNA.
DR   CCDS; CCDS19421.1; -.
DR   PIR; JH0612; JH0612.
DR   RefSeq; NP_033834.1; NM_009704.4.
DR   AlphaFoldDB; P31955; -.
DR   SMR; P31955; -.
DR   STRING; 10090.ENSMUSP00000031325; -.
DR   GlyCosmos; P31955; 2 sites, No reported glycans.
DR   GlyGen; P31955; 2 sites.
DR   iPTMnet; P31955; -.
DR   PhosphoSitePlus; P31955; -.
DR   PaxDb; 10090-ENSMUSP00000031325; -.
DR   ProteomicsDB; 277271; -.
DR   Antibodypedia; 1919; 635 antibodies from 35 providers.
DR   DNASU; 11839; -.
DR   Ensembl; ENSMUST00000031325.6; ENSMUSP00000031325.5; ENSMUSG00000029378.6.
DR   GeneID; 11839; -.
DR   KEGG; mmu:11839; -.
DR   UCSC; uc008ybt.1; mouse.
DR   AGR; MGI:88068; -.
DR   CTD; 374; -.
DR   MGI; MGI:88068; Areg.
DR   VEuPathDB; HostDB:ENSMUSG00000029378; -.
DR   eggNOG; ENOG502S0KA; Eukaryota.
DR   GeneTree; ENSGT00940000160696; -.
DR   HOGENOM; CLU_096527_1_0_1; -.
DR   InParanoid; P31955; -.
DR   OMA; CHHDYFG; -.
DR   OrthoDB; 4334035at2759; -.
DR   PhylomeDB; P31955; -.
DR   TreeFam; TF332773; -.
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-204005; COPII-mediated vesicle transport.
DR   Reactome; R-MMU-212718; EGFR interacts with phospholipase C-gamma.
DR   Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-MMU-5694530; Cargo concentration in the ER.
DR   Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR   Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR   Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR   BioGRID-ORCS; 11839; 2 hits in 80 CRISPR screens.
DR   ChiTaRS; Areg; mouse.
DR   PRO; PR:P31955; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; P31955; Protein.
DR   Bgee; ENSMUSG00000029378; Expressed in mucous cell of stomach and 35 other cell types or tissues.
DR   ExpressionAtlas; P31955; baseline and differential.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005615; C:extracellular space; IDA:MGI.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0005154; F:epidermal growth factor receptor binding; ISO:MGI.
DR   GO; GO:0008083; F:growth factor activity; ISO:MGI.
DR   GO; GO:0048018; F:receptor ligand activity; IGI:MGI.
DR   GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; IGI:MGI.
DR   GO; GO:0060598; P:dichotomous subdivision of terminal units involved in mammary gland duct morphogenesis; IMP:MGI.
DR   GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IGI:MGI.
DR   GO; GO:0060750; P:epithelial cell proliferation involved in mammary gland duct elongation; IMP:MGI.
DR   GO; GO:0038134; P:ERBB2-EGFR signaling pathway; ISO:MGI.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:MGI.
DR   GO; GO:0014009; P:glial cell proliferation; ISO:MGI.
DR   GO; GO:0060749; P:mammary gland alveolus development; IGI:MGI.
DR   GO; GO:0060744; P:mammary gland branching involved in thelarche; IMP:MGI.
DR   GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:MGI.
DR   GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR   GO; GO:0042327; P:positive regulation of phosphorylation; ISO:MGI.
DR   GO; GO:0051591; P:response to cAMP; IEA:Ensembl.
DR   GO; GO:0032355; P:response to estradiol; IDA:MGI.
DR   GO; GO:0051384; P:response to glucocorticoid; ISO:MGI.
DR   GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl.
DR   GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR   Gene3D; 2.10.25.10; Laminin; 1.
DR   InterPro; IPR000742; EGF-like_dom.
DR   PANTHER; PTHR10740:SF12; AMPHIREGULIN; 1.
DR   PANTHER; PTHR10740; TRANSFORMING GROWTH FACTOR ALPHA; 1.
DR   SUPFAM; SSF57196; EGF/Laminin; 1.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS50026; EGF_3; 1.
DR   Genevisible; P31955; MM.
PE   2: Evidence at transcript level;
KW   Cytokine; Disulfide bond; EGF-like domain; Glycoprotein; Growth factor;
KW   Membrane; Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   PROPEP          27..99
FT                   /id="PRO_0000007476"
FT   CHAIN           100..248
FT                   /note="Amphiregulin"
FT                   /id="PRO_0000007477"
FT   TRANSMEM        192..215
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          135..175
FT                   /note="EGF-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   REGION          29..48
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          57..77
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          100..136
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        58..72
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        100..117
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        118..136
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        106
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        241
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        139..152
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        147..163
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        165..174
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
SQ   SEQUENCE   248 AA;  27549 MW;  98C61A1B0E75A64E CRC64;
     MRTPLLPLAR SVLLLLVLGS GHYAAALELN DPSSGKGESL SGDHSAGGLE LSVGREVSTI
     SEMPSGSELS TGDYDYSEEY DNEPQISGYI IDDSVRVEQV IKPKKNKTEG EKSTEKPKRK
     KKGGKNGKGR RNKKKKNPCT AKFQNFCIHG ECRYIENLEV VTCNCHQDYF GERCGEKSMK
     THSEDDKDLS KIAVVAVTIF VSAIILAAIG IGIVITVHLW KRYFREYEGE TEERRRLRQE
     NGTVHAIA
//