AREG_MOUSE
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 03-AUG-2022, entry version 166.
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}.
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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 GlyGen; P31955; 2 sites.
DR iPTMnet; P31955; -.
DR PhosphoSitePlus; P31955; -.
DR PaxDb; P31955; -.
DR PRIDE; P31955; -.
DR ProteomicsDB; 277271; -.
DR Antibodypedia; 1919; 522 antibodies from 35 providers.
DR DNASU; 11839; -.
DR Ensembl; ENSMUST00000031325; ENSMUSP00000031325; ENSMUSG00000029378.
DR GeneID; 11839; -.
DR KEGG; mmu:11839; -.
DR UCSC; uc008ybt.1; mouse.
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; 1444868at2759; -.
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 75 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 33 other tissues.
DR ExpressionAtlas; P31955; baseline and differential.
DR Genevisible; P31955; MM.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IBA:GO_Central.
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 InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR015497; EGF_rcpt_ligand.
DR PANTHER; PTHR10740; PTHR10740; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS50026; EGF_3; 1.
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
