IBP3_MOUSE
ID IBP3_MOUSE Reviewed; 292 AA.
AC P47878; Q6PE62;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2013, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Insulin-like growth factor-binding protein 3;
DE Short=IBP-3;
DE Short=IGF-binding protein 3;
DE Short=IGFBP-3;
DE Flags: Precursor;
GN Name=Igfbp3; Synonyms=Igfbp-3;
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].
RC TISSUE=Liver;
RX PubMed=7529732; DOI=10.1016/0303-7207(94)90051-5;
RA Schuller A.G.P., Groffen C., van Neck J.W., Zwarthoff E.C., Drop S.L.S.;
RT "cDNA cloning and mRNA expression of the six mouse insulin-like growth
RT factor binding proteins.";
RL Mol. Cell. Endocrinol. 104:57-66(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=Mammary tumor;
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 [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=19952275; DOI=10.1210/en.2009-0577;
RA Lue Y., Swerdloff R., Liu Q., Mehta H., Hikim A.S., Lee K.W., Jia Y.,
RA Hwang D., Cobb L.J., Cohen P., Wang C.;
RT "Opposing roles of insulin-like growth factor binding protein 3 and humanin
RT in the regulation of testicular germ cell apoptosis.";
RL Endocrinology 151:350-357(2010).
CC -!- FUNCTION: IGF-binding proteins prolong the half-life of the IGFs and
CC have been shown to either inhibit or stimulate the growth promoting
CC effects of the IGFs on cell culture. They alter the interaction of IGFs
CC with their cell surface receptors. Also exhibits IGF-independent
CC antiproliferative and apoptotic effects mediated by its receptor
CC TMEM219/IGFBP-3R. Promotes testicular germ cell apoptosis.
CC {ECO:0000250|UniProtKB:P17936}.
CC -!- SUBUNIT: Interacts with XLKD1. Binds IGF2 more than IGF1. Forms a
CC ternary complex of about 140 to 150 kDa with IGF1 or IGF2 and a 85 kDa
CC glycoprotein (ALS). Interacts with TMEM219 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000250|UniProtKB:P17936}.
CC -!- DISRUPTION PHENOTYPE: No effect on baseline apoptosis in the testis but
CC germ cell apoptosis is dramatically reduced following treatment with a
CC gonadotropin-releasing hormone antagonist.
CC {ECO:0000269|PubMed:19952275}.
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DR EMBL; X81581; CAA57271.1; -; mRNA.
DR EMBL; AL607124; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC058261; AAH58261.1; -; mRNA.
DR CCDS; CCDS24428.1; -.
DR PIR; I48602; I48602.
DR RefSeq; NP_032369.2; NM_008343.2.
DR AlphaFoldDB; P47878; -.
DR SMR; P47878; -.
DR BioGRID; 200555; 1.
DR IntAct; P47878; 1.
DR STRING; 10090.ENSMUSP00000020702; -.
DR MEROPS; I31.952; -.
DR GlyGen; P47878; 3 sites.
DR iPTMnet; P47878; -.
DR PhosphoSitePlus; P47878; -.
DR CPTAC; non-CPTAC-3300; -.
DR PaxDb; P47878; -.
DR PeptideAtlas; P47878; -.
DR PRIDE; P47878; -.
DR ProteomicsDB; 267036; -.
DR Antibodypedia; 872; 731 antibodies from 43 providers.
DR DNASU; 16009; -.
DR Ensembl; ENSMUST00000020702; ENSMUSP00000020702; ENSMUSG00000020427.
DR Ensembl; ENSMUST00000135887; ENSMUSP00000131670; ENSMUSG00000020427.
DR GeneID; 16009; -.
DR KEGG; mmu:16009; -.
DR UCSC; uc007hzi.2; mouse.
DR CTD; 3486; -.
DR MGI; MGI:96438; Igfbp3.
DR VEuPathDB; HostDB:ENSMUSG00000020427; -.
DR eggNOG; ENOG502QWC0; Eukaryota.
DR GeneTree; ENSGT00940000158092; -.
DR HOGENOM; CLU_070833_1_1_1; -.
DR InParanoid; P47878; -.
DR OMA; ALEQCKP; -.
DR OrthoDB; 979270at2759; -.
DR PhylomeDB; P47878; -.
DR TreeFam; TF331211; -.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-6803211; TP53 Regulates Transcription of Death Receptors and Ligands.
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 16009; 2 hits in 73 CRISPR screens.
DR PRO; PR:P47878; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P47878; protein.
DR Bgee; ENSMUSG00000020427; Expressed in gonadal ridge and 265 other tissues.
DR Genevisible; P47878; MM.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0000792; C:heterochromatin; ISO:MGI.
DR GO; GO:0042568; C:insulin-like growth factor binary complex; ISO:MGI.
DR GO; GO:0042567; C:insulin-like growth factor ternary complex; ISS:BHF-UCL.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0031091; C:platelet alpha granule; ISO:MGI.
DR GO; GO:0001968; F:fibronectin binding; IDA:MGI.
DR GO; GO:0005520; F:insulin-like growth factor binding; IPI:MGI.
DR GO; GO:0031994; F:insulin-like growth factor I binding; ISO:MGI.
DR GO; GO:0031995; F:insulin-like growth factor II binding; ISO:MGI.
DR GO; GO:0008160; F:protein tyrosine phosphatase activator activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0000165; P:MAPK cascade; IGI:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:2000844; P:negative regulation of testosterone secretion; ISO:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IEP:BHF-UCL.
DR GO; GO:1902512; P:positive regulation of apoptotic DNA fragmentation; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0043568; P:positive regulation of insulin-like growth factor receptor signaling pathway; IGI:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IGI:MGI.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0001558; P:regulation of cell growth; IGI:MGI.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IGI:MGI.
DR GO; GO:0040008; P:regulation of growth; IGI:MGI.
DR GO; GO:0043567; P:regulation of insulin-like growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; IGI:MGI.
DR CDD; cd00191; TY; 1.
DR Gene3D; 4.10.800.10; -; 1.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR012211; IGFBP-3.
DR InterPro; IPR000867; IGFBP-like.
DR InterPro; IPR022321; IGFBP_1-6_chordata.
DR InterPro; IPR017891; Insulin_GF-bd_Cys-rich_CS.
DR InterPro; IPR000716; Thyroglobulin_1.
DR InterPro; IPR036857; Thyroglobulin_1_sf.
DR PANTHER; PTHR11551:SF3; PTHR11551:SF3; 1.
DR Pfam; PF00219; IGFBP; 1.
DR Pfam; PF00086; Thyroglobulin_1; 1.
DR PRINTS; PR01976; IGFBPFAMILY.
DR PRINTS; PR01979; IGFBPFAMILY3.
DR SMART; SM00121; IB; 1.
DR SMART; SM00211; TY; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR SUPFAM; SSF57610; SSF57610; 1.
DR PROSITE; PS00222; IGFBP_N_1; 1.
DR PROSITE; PS51323; IGFBP_N_2; 1.
DR PROSITE; PS00484; THYROGLOBULIN_1_1; 1.
DR PROSITE; PS51162; THYROGLOBULIN_1_2; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; Disulfide bond; Glycoprotein; Growth factor binding;
KW Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000250"
FT CHAIN 28..292
FT /note="Insulin-like growth factor-binding protein 3"
FT /id="PRO_0000014379"
FT DOMAIN 36..119
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 211..286
FT /note="Thyroglobulin type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT REGION 128..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 178..212
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 191..207
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17936"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P17936"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 214..241
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT DISULFID 252..263
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT DISULFID 265..286
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT CONFLICT 26..28
FT /note="RAG -> ELA (in Ref. 1; CAA57271)"
FT /evidence="ECO:0000305"
FT CONFLICT 34
FT /note="Missing (in Ref. 1; CAA57271)"
FT /evidence="ECO:0000305"
FT CONFLICT 48
FT /note="L -> V (in Ref. 1; CAA57271)"
FT /evidence="ECO:0000305"
FT CONFLICT 251
FT /note="Q -> R (in Ref. 1; CAA57271)"
FT /evidence="ECO:0000305"
FT CONFLICT 260..261
FT /note="RG -> QS (in Ref. 1; CAA57271)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="P -> R (in Ref. 1; CAA57271)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 292 AA; 31687 MW; 317F830AA843B73D CRC64;
MHPARPALWA AALTALTLLR GPPVARAGAG AVGAGPVVRC EPCDARALSQ CAPPPTAPAC
TELVREPGCG CCLTCALREG DACGVYTERC GTGLRCQPRP AEQYPLRALL NGRGFCANAS
AAGSLSTYLP SQPAPGNISE SEEEHNAGSV ESQVVPSTHR VTDSKFHPLH AKMDVIKKGH
ARDSQRYKVD YESQSTDTQN FSSESKRETE YGPCRREMED TLNHLKFLNV LSPRGVHIPN
CDKKGFYKKK QCRPSKGRKR GFCWCVDKYG QPLPGYDTKG KDDVHCLSVQ SQ
