ID   IBP3_RAT                Reviewed;         292 AA.
AC   P15473;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 2.
DT   24-JAN-2024, entry version 173.
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2480787; DOI=10.1016/s0006-291x(89)80052-x;
RA   Shimasaki S., Koba A., Mercado M., Shimonaka M., Ling N.;
RT   "Complementary DNA structure of the high molecular weight rat insulin-like
RT   growth factor binding protein (IGF-BP3) and tissue distribution of its
RT   mRNA.";
RL   Biochem. Biophys. Res. Commun. 165:907-912(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RX   PubMed=1689154; DOI=10.1016/0006-291x(90)90894-s;
RA   Albiston A.L., Herington A.C.;
RT   "Cloning and characterization of the growth hormone-dependent insulin-like
RT   growth factor binding protein (IGFBP-3) in the rat.";
RL   Biochem. Biophys. Res. Commun. 166:892-897(1990).
RN   [3]
RP   PROTEIN SEQUENCE OF 28-68.
RX   PubMed=3190697; DOI=10.1016/s0006-291x(88)80758-7;
RA   Zapf J., Born W., Chang J.Y., James P., Froesch E.R., Fischer J.A.;
RT   "Isolation and NH2-terminal amino acid sequences of rat serum carrier
RT   proteins for insulin-like growth factors.";
RL   Biochem. Biophys. Res. Commun. 156:1187-1194(1988).
RN   [4]
RP   PROTEIN SEQUENCE OF 28-42.
RX   PubMed=2443135; DOI=10.1016/s0006-291x(87)80136-5;
RA   Baxter R.C., Martin J.L.;
RT   "Binding proteins for insulin-like growth factors in adult rat serum.
RT   Comparison with other human and rat binding proteins.";
RL   Biochem. Biophys. Res. Commun. 147:408-415(1987).
RN   [5]
RP   PROTEIN SEQUENCE OF 28-49.
RC   TISSUE=Serum;
RX   PubMed=2480123; DOI=10.1016/0006-291x(89)91053-x;
RA   Shimonaka M., Schroeder R., Shimasaki S., Ling N.;
RT   "Identification of a novel binding protein for insulin-like growth factors
RT   in adult rat serum.";
RL   Biochem. Biophys. Res. Commun. 165:189-195(1989).
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 (By
CC       similarity). {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}.
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DR   EMBL; M31837; AAA41383.1; -; mRNA.
DR   EMBL; M33300; AAB00989.1; -; mRNA.
DR   PIR; A36748; A36748.
DR   RefSeq; NP_036720.2; NM_012588.2.
DR   AlphaFoldDB; P15473; -.
DR   SMR; P15473; -.
DR   STRING; 10116.ENSRNOP00000073137; -.
DR   MEROPS; I31.952; -.
DR   GlyCosmos; P15473; 4 sites, No reported glycans.
DR   GlyGen; P15473; 4 sites.
DR   PhosphoSitePlus; P15473; -.
DR   PaxDb; 10116-ENSRNOP00000011678; -.
DR   DNASU; 24484; -.
DR   GeneID; 24484; -.
DR   KEGG; rno:24484; -.
DR   UCSC; RGD:2874; rat.
DR   AGR; RGD:2874; -.
DR   CTD; 3486; -.
DR   RGD; 2874; Igfbp3.
DR   eggNOG; ENOG502QWC0; Eukaryota.
DR   InParanoid; P15473; -.
DR   OrthoDB; 5394492at2759; -.
DR   PhylomeDB; P15473; -.
DR   Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR   PRO; PR:P15473; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005615; C:extracellular space; IDA:RGD.
DR   GO; GO:0000792; C:heterochromatin; IDA:RGD.
DR   GO; GO:0042568; C:insulin-like growth factor binary complex; IDA:RGD.
DR   GO; GO:0042567; C:insulin-like growth factor ternary complex; IDA:RGD.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0031091; C:platelet alpha granule; IDA:RGD.
DR   GO; GO:0001968; F:fibronectin binding; ISO:RGD.
DR   GO; GO:0005520; F:insulin-like growth factor binding; ISO:RGD.
DR   GO; GO:0031994; F:insulin-like growth factor I binding; ISO:RGD.
DR   GO; GO:0031995; F:insulin-like growth factor II binding; IPI:RGD.
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:0071392; P:cellular response to estradiol stimulus; IEP:RGD.
DR   GO; GO:1904017; P:cellular response to Thyroglobulin triiodothyronine; IEP:RGD.
DR   GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR   GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:RGD.
DR   GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:RGD.
DR   GO; GO:0014912; P:negative regulation of smooth muscle cell migration; ISO:RGD.
DR   GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:RGD.
DR   GO; GO:2000844; P:negative regulation of testosterone secretion; IMP:RGD.
DR   GO; GO:0001649; P:osteoblast differentiation; ISO:RGD.
DR   GO; GO:1902512; P:positive regulation of apoptotic DNA fragmentation; IMP:RGD.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR   GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IMP:RGD.
DR   GO; GO:0043568; P:positive regulation of insulin-like growth factor receptor signaling pathway; ISO:RGD.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR   GO; GO:0045663; P:positive regulation of myoblast differentiation; ISS:UniProtKB.
DR   GO; GO:0001558; P:regulation of cell growth; ISO:RGD.
DR   GO; GO:0010906; P:regulation of glucose metabolic process; ISO:RGD.
DR   GO; GO:0040008; P:regulation of growth; ISO:RGD.
DR   GO; GO:0043567; P:regulation of insulin-like growth factor receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0061771; P:response to caloric restriction; IEP:RGD.
DR   GO; GO:0060416; P:response to growth hormone; IEP:RGD.
DR   GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR   GO; GO:0032868; P:response to insulin; IEP:RGD.
DR   GO; GO:1990418; P:response to insulin-like growth factor stimulus; IEP:RGD.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR   GO; GO:0044342; P:type B pancreatic cell proliferation; ISO:RGD.
DR   CDD; cd00191; TY; 1.
DR   Gene3D; 4.10.40.20; -; 1.
DR   Gene3D; 4.10.800.10; Thyroglobulin type-1; 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; INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN; 1.
DR   PANTHER; PTHR11551:SF3; INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN 3; 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; Growth factor receptor domain; 1.
DR   SUPFAM; SSF57610; Thyroglobulin type-1 domain; 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   1: Evidence at protein level;
KW   Apoptosis; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Growth factor binding; Phosphoprotein; Reference proteome; Secreted;
KW   Signal.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000269|PubMed:2443135,
FT                   ECO:0000269|PubMed:2480123, ECO:0000269|PubMed:3190697"
FT   CHAIN           28..292
FT                   /note="Insulin-like growth factor-binding protein 3"
FT                   /id="PRO_0000014380"
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          127..161
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          191..211
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        127..160
FT                   /note="Polar residues"
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        124
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        40..69
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        43..71
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        51..72
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        60..75
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        83..96
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT   DISULFID        90..116
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
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        8
FT                   /note="Missing (in Ref. 2; AAB00989)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   292 AA;  31680 MW;  1887D5E2A528F3B2 CRC64;
     MHPARPALWA AALTALTLLR GPPVARAGAG AVGAGPVVRC EPCDARALAQ CAPPPTAPAC
     TELVREPGCG CCLTCALREG DACGVYTERC GTGLRCQPRP AEQYPLKALL NGRGFCANAS
     AASNLSAYLP SQPSPGNTTE SEEDHNAGSV ESQVVPSTHR VTDSKFHPLH SKMEVIIKGQ
     ARDSQRYKVD YESQSTDTQN FSSESKRETE YGPCRREMED TLNHLKFLNV LSPRGVHIPN
     CDKKGFYKKK QCRPSKGRKR GFCWCVDKYG QPLPGYDTKG KDDVHCLSVQ SQ
//