ID:IBP3_HUMAN DESCRIPTION: RecName: Full=Insulin-like growth factor-binding protein 3; Short=IBP-3; Short=IGF-binding protein 3; Short=IGFBP-3; Flags: Precursor; FUNCTION: IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by its receptor TMEM219/IGFBP-3R. SUBUNIT: Interacts with XLKD1 (By similarity). Binds IGF2 more than IGF1. Forms a ternary complex of about 140 to 150 kDa with IGF1 or IGF2 and a 85 kDa glycoprotein (ALS). Interacts with HN. Interacts with TMEM219. SUBCELLULAR LOCATION: Secreted. TISSUE SPECIFICITY: Expressed by most tissues. Present in plasma. DEVELOPMENTAL STAGE: IGFBP3 levels are higher during extrauterine life and peak during puberty. INDUCTION: Up-regulated in the presence of IGF1, insulin and other growth-stimulating factors such as growth hormone, EGF and phorbol esters. DOMAIN: The thyroglobulin type-1 domain mediates interaction with HN. PTM: Phosphorylation sites are present in the extracellular medium. SIMILARITY: Contains 1 IGFBP N-terminal domain. SIMILARITY: Contains 1 thyroglobulin type-1 domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/igfbp3/"; WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=IGFBP3";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P17936
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0001968 fibronectin binding GO:0005515 protein binding GO:0005520 insulin-like growth factor binding GO:0008160 protein tyrosine phosphatase activator activity GO:0019838 growth factor binding GO:0031994 insulin-like growth factor I binding GO:0031995 insulin-like growth factor II binding GO:0046872 metal ion binding
Biological Process: GO:0001558 regulation of cell growth GO:0001649 osteoblast differentiation GO:0001933 negative regulation of protein phosphorylation GO:0006468 protein phosphorylation GO:0006915 apoptotic process GO:0008285 negative regulation of cell proliferation GO:0009968 negative regulation of signal transduction GO:0010906 regulation of glucose metabolic process GO:0014912 negative regulation of smooth muscle cell migration GO:0040008 regulation of growth GO:0042981 regulation of apoptotic process GO:0043065 positive regulation of apoptotic process GO:0043410 positive regulation of MAPK cascade GO:0043567 regulation of insulin-like growth factor receptor signaling pathway GO:0043568 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043666 regulation of phosphoprotein phosphatase activity GO:0043687 post-translational protein modification GO:0044267 cellular protein metabolic process GO:0044342 type B pancreatic cell proliferation GO:0045663 positive regulation of myoblast differentiation GO:0048662 negative regulation of smooth muscle cell proliferation
Cellular Component: GO:0005576 extracellular region GO:0005615 extracellular space GO:0005634 nucleus GO:0005788 endoplasmic reticulum lumen GO:0016942 insulin-like growth factor binding protein complex GO:0042567 insulin-like growth factor ternary complex
Descriptions from all associated GenBank mRNAs
LF208998 - JP 2014500723-A/16501: Polycomb-Associated Non-Coding RNAs. BC018962 - Homo sapiens insulin-like growth factor binding protein 3, mRNA (cDNA clone MGC:19695 IMAGE:3506929), complete cds. BX640961 - Homo sapiens mRNA; cDNA DKFZp686J08132 (from clone DKFZp686J08132). AF370418 - Homo sapiens PP14214 mRNA, complete cds. BC000013 - Homo sapiens insulin-like growth factor binding protein 3, mRNA (cDNA clone MGC:2305 IMAGE:3506666), complete cds. BC064987 - Homo sapiens insulin-like growth factor binding protein 3, mRNA (cDNA clone MGC:71301 IMAGE:4850456), complete cds. LF213767 - JP 2014500723-A/21270: Polycomb-Associated Non-Coding RNAs. M31159 - Human growth hormone-dependent insulin-like growth factor-binding protein mRNA, complete cds. AK075483 - Homo sapiens cDNA PSEC0177 fis, clone OVARC1000287, highly similar to Insulin-like growth factor-binding protein 3 precursor. AK095991 - Homo sapiens cDNA FLJ38672 fis, clone HSYRA2000371, moderately similar to Insulin-like growth factor-binding protein 3 precursor. AK123735 - Homo sapiens cDNA FLJ41741 fis, clone HSYRA2003168, highly similar to Insulin-like growth factor-binding protein 3 precursor. AK055632 - Homo sapiens cDNA FLJ31070 fis, clone HSYRA2001332, highly similar to INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 3 PRECURSOR. AK056274 - Homo sapiens cDNA FLJ31712 fis, clone NT2RI2006445, highly similar to Insulin-like growth factor-binding protein 3 precursor. AK091706 - Homo sapiens cDNA FLJ34387 fis, clone HCHON1000191, highly similar to Insulin-like growth factor-binding protein 3 precursor. AK091745 - Homo sapiens cDNA FLJ34426 fis, clone HHDPC2008474, moderately similar to Insulin-like growth factor-binding protein 3 precursor. AK092447 - Homo sapiens cDNA FLJ35128 fis, clone PLACE6008768, moderately similar to Insulin-like growth factor-binding protein 3 precursor. AK095408 - Homo sapiens cDNA FLJ38089 fis, clone CTONG2020831. AK095864 - Homo sapiens cDNA FLJ38545 fis, clone HCHON2001604, weakly similar to INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 3 PRECURSOR. AK095869 - Homo sapiens cDNA FLJ38550 fis, clone HCHON2002123, highly similar to Insulin-like growth factor-binding protein 3 precursor. AK095900 - Homo sapiens cDNA FLJ38581 fis, clone HCHON2008672, highly similar to Insulin-like growth factor-binding protein 3 precursor. AK095907 - Homo sapiens cDNA FLJ38588 fis, clone HCHON2009795. AK095974 - Homo sapiens cDNA FLJ38655 fis, clone HHDPC2009208, highly similar to Insulin-like growth factor-binding protein 3 precursor. AK097201 - Homo sapiens cDNA FLJ39882 fis, clone SPLEN2016250. AK122873 - Homo sapiens cDNA FLJ16507 fis, clone HCHON2000364, highly similar to Insulin-like growth factor-binding protein 3 precursor. AK125224 - Homo sapiens cDNA FLJ43234 fis, clone HCHON2002964, highly similar to Insulin-like growth factor-binding protein 3 precursor. AK127537 - Homo sapiens cDNA FLJ45630 fis, clone CHONS2001287, moderately similar to INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN 3 PRECURSOR. AK129951 - Homo sapiens cDNA FLJ26441 fis, clone KDN02278, highly similar to Homo sapiens insulin-like growth factor binding protein 3 (IGFBP3). AK130884 - Homo sapiens cDNA FLJ27374 fis, clone UBA05872. AX747551 - Sequence 1076 from Patent EP1308459. X64875 - H.sapiens mRNA for insulin-like growth factor binding protein-3. S56205 - insulin-like growth factor binding protein 3 {3' region} [human, tuberous sclerosis cells, mRNA Partial, 704 nt]. LF324909 - JP 2014500723-A/132412: Polycomb-Associated Non-Coding RNAs. JD488357 - Sequence 469381 from Patent EP1572962. JD379316 - Sequence 360340 from Patent EP1572962. LF324910 - JP 2014500723-A/132413: Polycomb-Associated Non-Coding RNAs. LF324911 - JP 2014500723-A/132414: Polycomb-Associated Non-Coding RNAs. JD504317 - Sequence 485341 from Patent EP1572962. JD563906 - Sequence 544930 from Patent EP1572962. LF324912 - JP 2014500723-A/132415: Polycomb-Associated Non-Coding RNAs. JD491157 - Sequence 472181 from Patent EP1572962. JD297251 - Sequence 278275 from Patent EP1572962. JD074341 - Sequence 55365 from Patent EP1572962. JD206543 - Sequence 187567 from Patent EP1572962. JD442075 - Sequence 423099 from Patent EP1572962. JD103700 - Sequence 84724 from Patent EP1572962. LF324913 - JP 2014500723-A/132416: Polycomb-Associated Non-Coding RNAs. JD472765 - Sequence 453789 from Patent EP1572962. JD340293 - Sequence 321317 from Patent EP1572962. JD485990 - Sequence 467014 from Patent EP1572962. JD498818 - Sequence 479842 from Patent EP1572962. JD486847 - Sequence 467871 from Patent EP1572962. JD321382 - Sequence 302406 from Patent EP1572962. JD325797 - Sequence 306821 from Patent EP1572962. JD046932 - Sequence 27956 from Patent EP1572962. AK297767 - Homo sapiens cDNA FLJ52568 complete cds, highly similar to Insulin-like growth factor-binding protein 3 precursor. JD221296 - Sequence 202320 from Patent EP1572962. JD314083 - Sequence 295107 from Patent EP1572962. AK298143 - Homo sapiens cDNA FLJ53634 complete cds, highly similar to Insulin-like growth factor-binding protein 3 precursor. JD312838 - Sequence 293862 from Patent EP1572962. JD284052 - Sequence 265076 from Patent EP1572962. DQ884396 - Homo sapiens clone BFC06155 insulin-like growth factor binding protein 3 isoform b precursor mRNA, complete cds. DQ884397 - Homo sapiens clone BFC06158 insulin-like growth factor binding protein 3 mRNA, complete cds. DQ884398 - Homo sapiens clone BFC06160 insulin-like growth factor binding protein 3 isoform b precursor mRNA, complete cds. AK315668 - Homo sapiens cDNA, FLJ96761, highly similar to Homo sapiens insulin-like growth factor binding protein 3 (IGFBP3),mRNA. DQ895344 - Synthetic construct Homo sapiens clone IMAGE:100009804; FLH183463.01L; RZPDo839C10141D insulin-like growth factor binding protein 3 (IGFBP3) gene, encodes complete protein. AB590345 - Synthetic construct DNA, clone: pFN21AB6362, Homo sapiens IGFBP3 gene for insulin-like growth factor binding protein 3, without stop codon, in Flexi system. LF212377 - JP 2014500723-A/19880: Polycomb-Associated Non-Coding RNAs. JD070908 - Sequence 51932 from Patent EP1572962. JD538022 - Sequence 519046 from Patent EP1572962. JD086146 - Sequence 67170 from Patent EP1572962. JD523121 - Sequence 504145 from Patent EP1572962. MA560486 - JP 2018138019-A/132412: Polycomb-Associated Non-Coding RNAs. MA560487 - JP 2018138019-A/132413: Polycomb-Associated Non-Coding RNAs. MA560488 - JP 2018138019-A/132414: Polycomb-Associated Non-Coding RNAs. MA560489 - JP 2018138019-A/132415: Polycomb-Associated Non-Coding RNAs. MA560490 - JP 2018138019-A/132416: Polycomb-Associated Non-Coding RNAs. MA444575 - JP 2018138019-A/16501: Polycomb-Associated Non-Coding RNAs. MA449344 - JP 2018138019-A/21270: Polycomb-Associated Non-Coding RNAs. MA447954 - JP 2018138019-A/19880: Polycomb-Associated Non-Coding RNAs. MP202716 - Sequence 27 from Patent WO2019090263.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_ghrelinPathway - Ghrelin: Regulation of Food Intake and Energy Homeostasis h_p53hypoxiaPathway - Hypoxia and p53 in the Cardiovascular system
Reactome (by CSHL, EBI, and GO)
Protein P17936 (Reactome details) participates in the following event(s):
R-HSA-381466 Prostate-specific Antigen proteolyzes IGF:IGFBP3:ALS R-HSA-381435 Matrix metalloproteinase proteolyzes IGF:IGFBP3:ALS R-HSA-381446 Thrombin proteolyzes IGF:IGFBP3:ALS R-HSA-381461 Plasmin proteolyzes IGF:IGFBP-3:ALS R-HSA-381500 Cathepsin G proteolyzes IGF:IGFBP3:ALS R-HSA-381496 Formation of the IGF:IGFBP3:ALS complex R-HSA-6800035 IGFBP3 binds TMEM219 R-HSA-8952289 FAM20C phosphorylates FAM20C substrates R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-6803211 TP53 Regulates Transcription of Death Receptors and Ligands R-HSA-392499 Metabolism of proteins R-HSA-5633008 TP53 Regulates Transcription of Cell Death Genes R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-8957275 Post-translational protein phosphorylation R-HSA-212436 Generic Transcription Pathway R-HSA-597592 Post-translational protein modification R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)