IBP3_HUMAN
ID IBP3_HUMAN Reviewed; 291 AA.
AC P17936; A4D2F5; D3DVM0; Q2V509; Q6P1M6; Q9UCL4;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 231.
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=IBP3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLY-32.
RX PubMed=2464130; DOI=10.1210/mend-2-12-1176;
RA Wood W.I., Cachianes G., Henzel W.J., Winslow G.A., Spencer S.A.,
RA Hellmiss R., Martin J.L., Baxter R.C.;
RT "Cloning and expression of the growth hormone-dependent insulin-like growth
RT factor-binding protein.";
RL Mol. Endocrinol. 2:1176-1185(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT GLY-32.
RX PubMed=1695633; DOI=10.1016/s0021-9258(19)38392-9;
RA Cubbage M.L., Suwanichkul A., Powell D.R.;
RT "Insulin-like growth factor binding protein-3. Organization of the human
RT chromosomal gene and demonstration of promoter activity.";
RL J. Biol. Chem. 265:12642-12649(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLY-32.
RC TISSUE=Skin;
RX PubMed=7508771; DOI=10.3109/10425179309015621;
RA Thweatt R., Fleischmann R., Goldstein S.;
RT "Analysis of the primary structure of insulin-like growth factor binding
RT protein-3 cDNA from Werner syndrome fibroblasts.";
RL DNA Seq. 4:43-46(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), AND VARIANTS THR-56 AND
RP SER-234.
RG NIEHS SNPs program;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney, and Spleen;
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 [9]
RP PROTEIN SEQUENCE OF 28-65.
RX PubMed=1697583; DOI=10.1016/s0021-9258(18)77200-1;
RA Zapf J., Kiefer M., Merryweather J., Musiarz F., Bauer D., Born W.,
RA Fischer J.A., Froesch E.R.;
RT "Isolation from adult human serum of four insulin-like growth factor (IGF)
RT binding proteins and molecular cloning of one of them that is increased by
RT IGF I administration and in extrapancreatic tumor hypoglycemia.";
RL J. Biol. Chem. 265:14892-14898(1990).
RN [10]
RP PROTEIN SEQUENCE OF 28-45, INTERACTION WITH IGF2, AND VARIANT GLY-32.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=1726837;
RA Roghani M., Segovia B., Whitechurch O., Binoux M.;
RT "Purification from human cerebrospinal fluid of insulin-like growth factor
RT binding proteins (IGFBPs). Isolation of IGFBP-2, an altered form of IGFBP-3
RT and a new IGFBP species.";
RL Growth Regul. 1:125-130(1991).
RN [11]
RP PROTEIN SEQUENCE OF 28-42.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [12]
RP INTERACTION WITH HUMANIN.
RX PubMed=14561895; DOI=10.1073/pnas.2135111100;
RA Ikonen M., Liu B., Hashimoto Y., Ma L., Lee K.W., Niikura T., Nishimoto I.,
RA Cohen P.;
RT "Interaction between the Alzheimer's survival peptide humanin and insulin-
RT like growth factor-binding protein 3 regulates cell survival and
RT apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13042-13047(2003).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-136.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-136 AND ASN-199.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-136.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [16]
RP GLYCOSYLATION AT ASN-116; ASN-136 AND ASN-199.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TMEM219.
RX PubMed=20353938; DOI=10.1074/jbc.m110.122226;
RA Ingermann A.R., Yang Y.F., Han J., Mikami A., Garza A.E., Mohanraj L.,
RA Fan L., Idowu M., Ware J.L., Kim H.S., Lee D.Y., Oh Y.;
RT "Identification of a novel cell death receptor mediating IGFBP-3-induced
RT anti-tumor effects in breast and prostate cancer.";
RL J. Biol. Chem. 285:30233-30246(2010).
RN [18]
RP PHOSPHORYLATION AT SER-148 AND SER-201.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [19]
RP VARIANTS [LARGE SCALE ANALYSIS] MET-7 AND CYS-252.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [20]
RP FUNCTION, AND INTERACTION WITH HUMANIN.
RX PubMed=19623253; DOI=10.1371/journal.pone.0006334;
RA Muzumdar R.H., Huffman D.M., Atzmon G., Buettner C., Cobb L.J., Fishman S.,
RA Budagov T., Cui L., Einstein F.H., Poduval A., Hwang D., Barzilai N.,
RA Cohen P.;
RT "Humanin: a novel central regulator of peripheral insulin action.";
RL PLoS ONE 4:e6334-e6334(2009).
RN [21]
RP FUNCTION.
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).
RN [22]
RP INTERACTION WITH HUMANIN.
RX PubMed=26216267; DOI=10.2174/0929866522666150728114955;
RA Njomen E., Evans H.G., Gedara S.H., Heyl D.L.;
RT "Humanin Peptide Binds to Insulin-Like Growth Factor-Binding Protein 3
RT (IGFBP3) and Regulates Its Interaction with Importin-beta.";
RL Protein Pept. Lett. 22:869-876(2015).
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. Inhibits the positive effect of humanin on insulin
CC sensitivity (PubMed:19623253). Promotes testicular germ cell apoptosis
CC (PubMed:19952275). {ECO:0000269|PubMed:19623253,
CC ECO:0000269|PubMed:19952275, ECO:0000269|PubMed:20353938}.
CC -!- SUBUNIT: Interacts with XLKD1 (By similarity). Binds IGF2 more than
CC IGF1. Forms a ternary complex of about 140 to 150 kDa with IGF1 or IGF2
CC and a 85 kDa glycoprotein (ALS). Interacts with humanin; humanin
CC competes with importin KPNB1 for binding to IGFBP3, blocking IGFBP3
CC nuclear import and IGFBP3-mediated apoptosis (PubMed:14561895,
CC PubMed:19623253, PubMed:26216267). Interacts with TMEM219.
CC {ECO:0000250, ECO:0000269|PubMed:14561895, ECO:0000269|PubMed:1726837,
CC ECO:0000269|PubMed:19623253, ECO:0000269|PubMed:20353938,
CC ECO:0000269|PubMed:26216267}.
CC -!- INTERACTION:
CC P17936; P00533: EGFR; NbExp=3; IntAct=EBI-715709, EBI-297353;
CC P17936; Q92993: KAT5; NbExp=3; IntAct=EBI-715709, EBI-399080;
CC P17936; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-715709, EBI-11742507;
CC P17936; Q8IVG9: MT-RNR2; NbExp=7; IntAct=EBI-715709, EBI-8643752;
CC P17936; P17252: PRKCA; NbExp=3; IntAct=EBI-715709, EBI-1383528;
CC P17936; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-715709, EBI-9090795;
CC P17936; Q86XT9: TMEM219; NbExp=8; IntAct=EBI-715709, EBI-20264080;
CC P17936; P61981: YWHAG; NbExp=3; IntAct=EBI-715709, EBI-359832;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20353938}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P17936-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P17936-2; Sequence=VSP_047293;
CC -!- TISSUE SPECIFICITY: Expressed by most tissues. Present in plasma.
CC -!- DEVELOPMENTAL STAGE: IGFBP3 levels are higher during extrauterine life
CC and peak during puberty.
CC -!- INDUCTION: Up-regulated in the presence of IGF1, insulin and other
CC growth-stimulating factors such as growth hormone, EGF and phorbol
CC esters.
CC -!- DOMAIN: The thyroglobulin type-1 domain mediates interaction with HN.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000269|PubMed:26091039}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/igfbp3/";
CC -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and
CC polymorphism database;
CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=C&genename=IGFBP3";
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DR EMBL; M31159; AAA52541.1; -; mRNA.
DR EMBL; M35878; AAA52706.1; -; Genomic_DNA.
DR EMBL; X64875; CAA46087.1; -; mRNA.
DR EMBL; DQ301819; ABB96247.1; -; Genomic_DNA.
DR EMBL; AC091524; AAS07554.1; -; Genomic_DNA.
DR EMBL; CH236958; EAL23801.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW61028.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW61029.1; -; Genomic_DNA.
DR EMBL; BC000013; AAH00013.1; -; mRNA.
DR EMBL; BC018962; AAH18962.1; -; mRNA.
DR EMBL; BC064987; AAH64987.1; -; mRNA.
DR CCDS; CCDS34632.1; -. [P17936-2]
DR CCDS; CCDS5505.1; -. [P17936-1]
DR PIR; A36578; IOHU3.
DR RefSeq; NP_000589.2; NM_000598.4. [P17936-1]
DR RefSeq; NP_001013416.1; NM_001013398.1. [P17936-2]
DR RefSeq; XP_016867641.1; XM_017012152.1.
DR AlphaFoldDB; P17936; -.
DR SMR; P17936; -.
DR BioGRID; 109707; 51.
DR CORUM; P17936; -.
DR DIP; DIP-40786N; -.
DR IntAct; P17936; 32.
DR MINT; P17936; -.
DR STRING; 9606.ENSP00000370473; -.
DR BindingDB; P17936; -.
DR ChEMBL; CHEMBL3997; -.
DR DrugBank; DB00523; Alitretinoin.
DR DrugBank; DB01277; Mecasermin.
DR MEROPS; I31.952; -.
DR GlyConnect; 1945; 6 N-Linked glycans (3 sites).
DR GlyGen; P17936; 5 sites, 8 N-linked glycans (3 sites), 2 O-linked glycans (2 sites).
DR iPTMnet; P17936; -.
DR PhosphoSitePlus; P17936; -.
DR BioMuta; IGFBP3; -.
DR DMDM; 146327827; -.
DR EPD; P17936; -.
DR jPOST; P17936; -.
DR MassIVE; P17936; -.
DR MaxQB; P17936; -.
DR PaxDb; P17936; -.
DR PeptideAtlas; P17936; -.
DR PRIDE; P17936; -.
DR ProteomicsDB; 53527; -. [P17936-1]
DR Antibodypedia; 872; 731 antibodies from 43 providers.
DR DNASU; 3486; -.
DR Ensembl; ENST00000381083.9; ENSP00000370473.4; ENSG00000146674.16. [P17936-2]
DR Ensembl; ENST00000613132.5; ENSP00000477772.2; ENSG00000146674.16. [P17936-1]
DR GeneID; 3486; -.
DR KEGG; hsa:3486; -.
DR MANE-Select; ENST00000613132.5; ENSP00000477772.2; NM_000598.5; NP_000589.2.
DR UCSC; uc003tnr.4; human. [P17936-1]
DR CTD; 3486; -.
DR DisGeNET; 3486; -.
DR GeneCards; IGFBP3; -.
DR HGNC; HGNC:5472; IGFBP3.
DR HPA; ENSG00000146674; Tissue enhanced (placenta).
DR MIM; 146732; gene.
DR neXtProt; NX_P17936; -.
DR OpenTargets; ENSG00000146674; -.
DR PharmGKB; PA29705; -.
DR VEuPathDB; HostDB:ENSG00000146674; -.
DR eggNOG; ENOG502QWC0; Eukaryota.
DR GeneTree; ENSGT00940000158092; -.
DR InParanoid; P17936; -.
DR OMA; ALEQCKP; -.
DR OrthoDB; 979270at2759; -.
DR PhylomeDB; P17936; -.
DR TreeFam; TF331211; -.
DR PathwayCommons; P17936; -.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-6803211; TP53 Regulates Transcription of Death Receptors and Ligands.
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; P17936; -.
DR SIGNOR; P17936; -.
DR BioGRID-ORCS; 3486; 12 hits in 1074 CRISPR screens.
DR ChiTaRS; IGFBP3; human.
DR GeneWiki; IGFBP3; -.
DR GenomeRNAi; 3486; -.
DR Pharos; P17936; Tchem.
DR PRO; PR:P17936; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P17936; protein.
DR Bgee; ENSG00000146674; Expressed in decidua and 198 other tissues.
DR ExpressionAtlas; P17936; baseline and differential.
DR Genevisible; P17936; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0016942; C:insulin-like growth factor binding protein complex; IC:BHF-UCL.
DR GO; GO:0042567; C:insulin-like growth factor ternary complex; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0001968; F:fibronectin binding; IBA:GO_Central.
DR GO; GO:0005520; F:insulin-like growth factor binding; NAS:UniProtKB.
DR GO; GO:0031994; F:insulin-like growth factor I binding; IPI:BHF-UCL.
DR GO; GO:0031995; F:insulin-like growth factor II binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; NAS:UniProtKB.
DR GO; GO:0008160; F:protein tyrosine phosphatase activator activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:0009968; P:negative regulation of signal transduction; NAS:UniProtKB.
DR GO; GO:0014912; P:negative regulation of smooth muscle cell migration; IDA:BHF-UCL.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043568; P:positive regulation of insulin-like growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0001558; P:regulation of cell growth; IEA:Ensembl.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IEA:Ensembl.
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; IEA:Ensembl.
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 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Growth factor binding; Phosphoprotein; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000269|PubMed:15340161,
FT ECO:0000269|PubMed:1697583, ECO:0000269|PubMed:1726837"
FT CHAIN 28..291
FT /note="Insulin-like growth factor-binding protein 3"
FT /id="PRO_0000014378"
FT DOMAIN 36..117
FT /note="IGFBP N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00653"
FT DOMAIN 210..285
FT /note="Thyroglobulin type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT REGION 28..134
FT /note="IGF-binding"
FT /evidence="ECO:0000255"
FT REGION 130..162
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 189..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 190..206
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 148
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 201
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:19139490"
FT CARBOHYD 136
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19139490,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19139490"
FT DISULFID 213..240
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT DISULFID 251..262
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT DISULFID 264..285
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00500"
FT VAR_SEQ 135
FT /note="G -> GEPPAPG (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_047293"
FT VARIANT 7
FT /note="T -> M (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036279"
FT VARIANT 32
FT /note="A -> G (in dbSNP:rs2854746)"
FT /evidence="ECO:0000269|PubMed:1695633,
FT ECO:0000269|PubMed:1726837, ECO:0000269|PubMed:2464130,
FT ECO:0000269|PubMed:7508771"
FT /id="VAR_025262"
FT VARIANT 56
FT /note="A -> T (in dbSNP:rs34257987)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_025263"
FT VARIANT 158
FT /note="H -> P (in dbSNP:rs9282734)"
FT /id="VAR_021974"
FT VARIANT 234
FT /note="G -> S (in dbSNP:rs35712717)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_025264"
FT VARIANT 252
FT /note="R -> C (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs538312081)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036280"
SQ SEQUENCE 291 AA; 31674 MW; A9682065AB266586 CRC64;
MQRARPTLWA AALTLLVLLR GPPVARAGAS SAGLGPVVRC EPCDARALAQ CAPPPAVCAE
LVREPGCGCC LTCALSEGQP CGIYTERCGS GLRCQPSPDE ARPLQALLDG RGLCVNASAV
SRLRAYLLPA PPAPGNASES EEDRSAGSVE SPSVSSTHRV SDPKFHPLHS KIIIIKKGHA
KDSQRYKVDY ESQSTDTQNF SSESKRETEY GPCRREMEDT LNHLKFLNVL SPRGVHIPNC
DKKGFYKKKQ CRPSKGRKRG FCWCVDKYGQ PLPGYTTKGK EDVHCYSMQS K
