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| Class:Id | ReferenceGeneProduct:381525 |
|---|---|
| _chainChangeLog | signal peptide:1-27 added on Fri February 6 2015;chain:28-291 added on Fri February 6 2015 |
| _displayName | UniProt:P17936 IGFBP3 |
| _timestamp | 2025-02-21 19:18:39 |
| chain | signal peptide:1-27 chain:28-291 |
| checksum | A9682065AB266586 |
| comment | FUNCTION Multifunctional protein that plays a critical role in regulating the availability of IGFs such as IGF1 and IGF2 to their receptors and thereby regulates IGF-mediated cellular processes including proliferation, differentiation, and apoptosis in a cell-type specific manner (PubMed:10874028, PubMed:19556345). Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by its receptor TMEM219/IGFBP-3R (PubMed:20353938). Inhibits the positive effect of humanin on insulin sensitivity (PubMed:19623253). Promotes testicular germ cell apoptosis (PubMed:19952275). Acts via LRP-1/alpha2M receptor, also known as TGF-beta type V receptor, to mediate cell growth inhibition independent of IGF1 (PubMed:9252371). Mechanistically, induces serine-specific dephosphorylation of IRS1 or IRS2 upon ligation to its receptor, leading to the inhibitory cascade (PubMed:15371331). In the nucleus, interacts with transcription factors such as retinoid X receptor-alpha/RXRA to regulate transcriptional signaling and apoptosis (PubMed:10874028).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) (PubMed:35907924). Interacts with humanin; humanin competes with importin KPNB1 for binding to IGFBP3, blocking IGFBP3 nuclear import and IGFBP3-mediated apoptosis (PubMed:14561895, PubMed:19623253, PubMed:26216267). Interacts with TMEM219. Interacts with RXRA; this interaction modulates the transcriptional activity of RXRA (PubMed:10874028). Interacts with LRP1; this interaction mediates cell growth inhibition independent of IGF1 (PubMed:9252371).INTERACTION 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 Phosphorylated by FAM20C in the extracellular medium. Phosphorylated by CK2; resulting in decreased nuclear localization (PubMed:19556345). |
| created | [InstanceEdit:381505] May, B, 2008-11-19 20:29:10 |
| description | recommendedName: Insulin-like growth factor-binding protein 3 shortName: IBP-3 shortName: IGF-binding protein 3 shortName: IGFBP-3 |
| geneName | IGFBP3 IBP3 |
| identifier | P17936 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Apoptosis Direct protein sequencing Disulfide bond Glycoprotein Growth factor binding Nucleus Phosphoprotein Proteomics identification Reference proteome Secreted Signal |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | IGFBP3 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:6800041] ENSEMBL:ENSG00000146674 IGFBP3 [Homo sapiens] |
| secondaryIdentifier | IBP3_HUMAN A4D2F5 D3DVM0 Q2V509 Q6P1M6 Q9UCL4 |
| sequenceLength | 291 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8964817] UniProt:P17936-1 IGFBP3 [Homo sapiens] [ReferenceIsoform:8964818] UniProt:P17936-2 IGFBP3 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:381410] IGFBP3(187-291) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:381454] IGFBP3(28-186) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:381455] IGFBP3(127-291) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:381465] IGFBP3(125-233) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:381471] IGFBP3(188-291) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:381489] IGFBP3(28-168) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:381499] IGFBP3(169-226) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:381507] IGFBP3(125-187) [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:381512] IGFBP3 [extracellular region] [Homo sapiens] [EntityWithAccessionedSequence:381534] IGFBP3(28-126) [extracellular region] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:8952315] phosphorylated residue at unknown position [ModifiedResidue:8957039] phosphorylated residue at unknown position |
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