BTC_MOUSE
ID BTC_MOUSE Reviewed; 177 AA.
AC Q05928;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Probetacellulin;
DE Contains:
DE RecName: Full=Betacellulin;
DE Short=BTC;
DE Flags: Precursor;
GN Name=Btc; Synonyms=Bcn;
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 PROTEIN SEQUENCE OF 32-54; 64-71 AND
RP 75-111.
RC TISSUE=Pancreas;
RX PubMed=8456283; DOI=10.1126/science.8456283;
RA Shing Y., Christofori G., Hanahan D., Ono Y., Sasada R., Igarashi K.,
RA Folkman J.;
RT "Betacellulin: a mitogen from pancreatic beta cell tumors.";
RL Science 259:1604-1607(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Skin;
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 [3]
RP FUNCTION.
RX PubMed=21897861; DOI=10.1371/journal.pone.0023894;
RA Oh Y.S., Shin S., Lee Y.J., Kim E.H., Jun H.S.;
RT "Betacellulin-induced beta cell proliferation and regeneration is mediated
RT by activation of ErbB-1 and ErbB-2 receptors.";
RL PLoS ONE 6:E23894-E23894(2011).
CC -!- FUNCTION: Growth factor that binds to EGFR, ERBB4 and other EGF
CC receptor family members. Potent mitogen for retinal pigment epithelial
CC cells and vascular smooth muscle cells. {ECO:0000269|PubMed:21897861}.
CC -!- SUBUNIT: Monomer. Interacts with EGFR and ERBB4.
CC -!- SUBCELLULAR LOCATION: [Betacellulin]: Secreted, extracellular space.
CC -!- SUBCELLULAR LOCATION: [Probetacellulin]: Cell membrane; Single-pass
CC type I membrane protein.
CC -!- TISSUE SPECIFICITY: Found in several mouse tissues including kidney,
CC uterus and liver, as well as in beta tumor cell line and MCF-7 cells.
CC It is not detected in the brain.
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DR EMBL; L08394; AAA40511.1; -; mRNA.
DR EMBL; AK076272; BAC36281.1; -; mRNA.
DR CCDS; CCDS19422.1; -.
DR PIR; A37408; A37408.
DR RefSeq; NP_031594.1; NM_007568.5.
DR AlphaFoldDB; Q05928; -.
DR SMR; Q05928; -.
DR BioGRID; 198395; 4.
DR STRING; 10090.ENSMUSP00000112765; -.
DR GlyGen; Q05928; 3 sites.
DR iPTMnet; Q05928; -.
DR PhosphoSitePlus; Q05928; -.
DR PaxDb; Q05928; -.
DR PeptideAtlas; Q05928; -.
DR PRIDE; Q05928; -.
DR ProteomicsDB; 273712; -.
DR Antibodypedia; 13367; 428 antibodies from 34 providers.
DR DNASU; 12223; -.
DR Ensembl; ENSMUST00000121044; ENSMUSP00000112765; ENSMUSG00000082361.
DR GeneID; 12223; -.
DR KEGG; mmu:12223; -.
DR UCSC; uc008ybv.2; mouse.
DR CTD; 685; -.
DR MGI; MGI:99439; Btc.
DR VEuPathDB; HostDB:ENSMUSG00000082361; -.
DR eggNOG; ENOG502RZHQ; Eukaryota.
DR GeneTree; ENSGT00940000160508; -.
DR HOGENOM; CLU_112513_1_0_1; -.
DR InParanoid; Q05928; -.
DR OMA; QPKRKGH; -.
DR OrthoDB; 1401257at2759; -.
DR PhylomeDB; Q05928; -.
DR TreeFam; TF332938; -.
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; 12223; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q05928; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q05928; protein.
DR Bgee; ENSMUSG00000082361; Expressed in metanephric cortical collecting duct and 94 other tissues.
DR ExpressionAtlas; Q05928; baseline and differential.
DR Genevisible; Q05928; MM.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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; IDA:MGI.
DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IDA:MGI.
DR GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:MGI.
DR GO; GO:1904019; P:epithelial cell apoptotic process; IDA:MGI.
DR GO; GO:0038134; P:ERBB2-EGFR signaling pathway; IDA:MGI.
DR GO; GO:0038138; P:ERBB4-ERBB4 signaling pathway; ISO:MGI.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IDA:MGI.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:MGI.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IBA:GO_Central.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:MGI.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISS:MGI.
DR GO; GO:0035810; P:positive regulation of urine volume; ISO:MGI.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR015497; EGF_rcpt_ligand.
DR PANTHER; PTHR10740; PTHR10740; 1.
DR Pfam; PF00008; EGF; 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 Cell membrane; Direct protein sequencing; Disulfide bond; EGF-like domain;
KW Glycoprotein; Growth factor; Membrane; Mitogen; Reference proteome;
KW Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..31
FT /evidence="ECO:0000269|PubMed:8456283"
FT CHAIN 32..177
FT /note="Probetacellulin"
FT /id="PRO_0000300686"
FT CHAIN 32..111
FT /note="Betacellulin"
FT /id="PRO_0000007492"
FT PROPEP 112..177
FT /note="Removed in mature form"
FT /id="PRO_0000007493"
FT TOPO_DOM 32..118
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 119..139
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 140..177
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 65..105
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 153..177
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 154..169
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 69..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 77..93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 95..104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
SQ SEQUENCE 177 AA; 19664 MW; 066BB34F0E13F82B CRC64;
MDPTAPGSSV SSLPLLLVLA LGLAILHCVV ADGNTTRTPE TNGSLCGAPG ENCTGTTPRQ
KVKTHFSRCP KQYKHYCIHG RCRFVVDEQT PSCICEKGYF GARCERVDLF YLQQDRGQIL
VVCLIVVMVV FIILVIGVCT CCHPLRKHRK KKKEEKMETL DKDKTPISED IQETNIA
