Human Gene IGFBP3 (ENST00000381083.9) from GENCODE V44
  Description: Homo sapiens insulin like growth factor binding protein 3 (IGFBP3), transcript variant 1, mRNA. (from RefSeq NM_001013398)
RefSeq Summary (NM_001013398): This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000381083.9
Gencode Gene: ENSG00000146674.16
Transcript (Including UTRs)
   Position: hg38 chr7:45,912,245-45,921,272 Size: 9,028 Total Exon Count: 5 Strand: -
Coding Region
   Position: hg38 chr7:45,914,820-45,921,140 Size: 6,321 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr7:45,912,245-45,921,272)mRNA (may differ from genome)Protein (297 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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";

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: IGFBP3
Diseases sorted by gene-association score: insulin-like growth factor i (30), laron dwarfism (16), acid-labile subunit, deficiency of (13), diffuse idiopathic skeletal hyperostosis (13), marasmus (11), slipped capital femoral epiphysis (11), acromegaly (11), complete androgen insensitivity syndrome (10), secondary adrenal insufficiency (10), turner syndrome (10), hyperinsulinism (10), diabetes mellitus, insulin-dependent (9), leprechaunism (9), growth hormone deficiency (9), hypopituitarism (8), avascular necrosis of the femoral head (8), breast disease (8), rabson-mendenhall syndrome (8), colorectal adenoma (7), fetal macrosomia (7), growth hormone deficiency, isolated, type ib (7), arthropathy, progressive pseudorheumatoid, of childhood (7), sotos syndrome 1 (7), recessive dystrophic epidermolysis bullosa (6), silver-russell syndrome (6), superficial urinary bladder cancer (6), ocular hyperemia (6), pituitary adenoma, growth hormone-secreting (6), penis agenesis (6), meninges hemangiopericytoma (6), lymph node cancer (6), nutritional deficiency disease (5), hyperpituitarism (5), idiopathic juvenile osteoporosis (5), localized osteosarcoma (5), noonan syndrome 1 (5), liver cirrhosis (4), colorectal cancer (4), prostate cancer (4), osteogenesis imperfecta, type iii (3), osteogenesis imperfecta, type i (3), osteoporosis (2), lung cancer (2), breast cancer (2), obesity (2), diabetes mellitus, noninsulin-dependent (2), premature ovarian failure 1 (2), eye disease (1), male reproductive organ cancer (1), endocrine gland cancer (1), rheumatoid arthritis, systemic juvenile (1), exudative vitreoretinopathy 1 (1), reproductive organ cancer (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 147.55 RPKM in Adipose - Visceral (Omentum)
Total median expression: 1963.57 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -48.30132-0.366 Picture PostScript Text
3' UTR -452.501605-0.282 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR009030 - Growth_fac_rcpt
IPR012211 - IGFBP-3
IPR000867 - IGFBP-like
IPR009168 - IGFBP1-6
IPR022321 - IGFBP_1-6_chordata
IPR017891 - Insulin_GF-bd_Cys-rich_CS
IPR000716 - Thyroglobulin_1

Pfam Domains:
PF00219 - Insulin-like growth factor binding protein
PF00086 - Thyroglobulin type-1 repeat

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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  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.
MA444575 - JP 2018138019-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.
MA449344 - JP 2018138019-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.
MA560486 - JP 2018138019-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.
MA560487 - JP 2018138019-A/132413: Polycomb-Associated Non-Coding RNAs.
LF324911 - JP 2014500723-A/132414: Polycomb-Associated Non-Coding RNAs.
MA560488 - JP 2018138019-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.
MA560489 - JP 2018138019-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.
MA560490 - JP 2018138019-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.
MA447954 - JP 2018138019-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.
MP202716 - Sequence 27 from Patent WO2019090263.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04115 - p53 signaling pathway

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)

-  Other Names for This Gene
  Alternate Gene Symbols: A4D2F5, D3DVM0, ENST00000381083.1, ENST00000381083.2, ENST00000381083.3, ENST00000381083.4, ENST00000381083.5, ENST00000381083.6, ENST00000381083.7, ENST00000381083.8, IBP3, IBP3_HUMAN, NM_001013398, P17936, Q2V509, Q6P1M6, Q9UCL4, uc003tnr.1, uc003tnr.2, uc003tnr.3, uc003tnr.4, uc003tnr.5
UCSC ID: ENST00000381083.9
RefSeq Accession: NM_001013398
Protein: P17936 (aka IBP3_HUMAN)
CCDS: CCDS5505.1, CCDS34632.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.