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    IGFBP3 insulin like growth factor binding protein 3 [ Homo sapiens (human) ]

    Gene ID: 3486, updated on 2-Nov-2024

    Summary

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    Official Symbol
    IGFBP3provided by HGNC
    Official Full Name
    insulin like growth factor binding protein 3provided by HGNC
    Primary source
    HGNC:HGNC:5472
    See related
    Ensembl:ENSG00000146674 MIM:146732; AllianceGenome:HGNC:5472
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    IBP3; BP-53; IBP-3; IGFBP-3
    Summary
    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]
    Expression
    Biased expression in placenta (RPKM 686.3), endometrium (RPKM 259.6) and 7 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See IGFBP3 in Genome Data Viewer
    Location:
    7p12.3
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (45912245..45921272, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (46073961..46082986, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (45951844..45960871, complement)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene coiled-coil domain containing 201 Neighboring gene NANOG hESC enhancer GRCh37_chr7:45918149-45918667 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:45925716-45925933 Neighboring gene insulin like growth factor binding protein 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:45960674-45961254 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:45961255-45961835 Neighboring gene uncharacterized LOC102723446 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:45992471-45992971 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr7:46017226-46018425 Neighboring gene RNA, U7 small nuclear 76 pseudogene Neighboring gene uncharacterized LOC105375264 Neighboring gene ferritin light chain pseudogene 15

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Insulin-like-growth-factor-binding-protein-3 (IGFBP-3) contrasts melanoma progression in vitro and in vivo. Naspi A, et al. PLoS One, 2014. PMID 24905466, Free PMC Article
    2. Nonsecreted insulin-like growth factor binding protein-3 (IGFBP-3) can induce apoptosis in human prostate cancer cells by IGF-independent mechanisms without being concentrated in the nucleus. Bhattacharyya N, et al. J Biol Chem, 2006 Aug 25. PMID 16793770
    3. Growth inhibitory concentrations of androgens up-regulate insulin-like growth factor binding protein-3 expression via an androgen response element in LNCaP human prostate cancer cells. Peng L, et al. Endocrinology, 2006 Oct. PMID 16825320
    4. Pioglitazone restores IGFBP-3 levels through DNA PK in retinal endothelial cells cultured in hyperglycemic conditions. Thakran S, et al. Invest Ophthalmol Vis Sci, 2014 Dec 18. PMID 25525174, Free PMC Article
    5. Methylation status of IGFBP-3 as a useful clinical tool for deciding on a concomitant radiotherapy. Pernía O, et al. Epigenetics, 2014 Nov. PMID 25482372, Free PMC Article

    See all (756) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Discovering genes and microRNAs involved in human lung development unveils IGFBP3/miR-34a dynamics and their relevance for alveolar differentiation.
      Title: Discovering genes and microRNAs involved in human lung development unveils IGFBP3/miR-34a dynamics and their relevance for alveolar differentiation.
    2. IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome.
      Title: IGF2BP2 and IGFBP3 Genotypes, Haplotypes, and Genetic Models Studies in Polycystic Ovary Syndrome.
    3. Novel therapeutic targets, including IGFBP3, of umbilical cord mesenchymal stem-cell-conditioned medium in intrauterine adhesion.
      Title: Novel therapeutic targets, including IGFBP3, of umbilical cord mesenchymal stem-cell-conditioned medium in intrauterine adhesion.
    4. Insulin-like growth factor binding protein-3 mediates hyperosmolar stress-induced mitophagy through the mechanistic target of rapamycin.
      Title: Insulin-like growth factor binding protein-3 mediates hyperosmolar stress-induced mitophagy through the mechanistic target of rapamycin.
    5. Expression of insulin-like growth factor binding protein-3 in HELLP syndrome.
      Title: Expression of insulin-like growth factor binding protein-3 in HELLP syndrome.
    6. Insulin-like growth factor binding protein 3 promoter variant (rs2854744) is associated with nonalcoholic fatty liver disease.
      Title: Insulin-like growth factor binding protein 3 promoter variant (rs2854744) is associated with nonalcoholic fatty liver disease.
    7. MicroRNA-210-3p Regulates Endometriotic Lesion Development by Targeting IGFBP3 in Baboons and Women with Endometriosis.
      Title: MicroRNA-210-3p Regulates Endometriotic Lesion Development by Targeting IGFBP3 in Baboons and Women with Endometriosis.
    8. The relationship between serum leptin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels and clinical parameters in primary fibromyalgia patients.
      Title: The relationship between serum leptin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels and clinical parameters in primary fibromyalgia patients.
    9. Obese Asthma Phenotype Is Associated with hsa-miR-26a-1-3p and hsa-miR-376a-3p Modulating the IGF Axis.
      Title: Obese Asthma Phenotype Is Associated with hsa-miR-26a-1-3p and hsa-miR-376a-3p Modulating the IGF Axis.
    10. GATA4 inhibits odontoblastic differentiation of dental pulp stem cells through targeting IGFBP3.
      Title: GATA4 inhibits odontoblastic differentiation of dental pulp stem cells through targeting IGFBP3.
    Submit: New GeneRIF Correction See all GeneRIFs (618)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies novel loci associated with circulating IGF-I and IGFBP-3.
    EBI GWAS Catalog
    Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.
    EBI GWAS Catalog
    Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.
    EBI GWAS Catalog
    Genome-wide association analyses identify variants in developmental genes associated with hypospadias.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables fibronectin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables insulin-like growth factor I binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables insulin-like growth factor I binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables insulin-like growth factor II binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables insulin-like growth factor binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables metal ion binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein tyrosine phosphatase activator activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within negative regulation of cell population proliferation IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of signal transduction NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in negative regulation of smooth muscle cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of smooth muscle cell proliferation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in osteoblast differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of insulin-like growth factor receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of myoblast differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of cell growth IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of glucose metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of insulin-like growth factor receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in type B pancreatic cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in endoplasmic reticulum lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular region NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of insulin-like growth factor binding protein complex IC
    Inferred by Curator
    more info
    		 PubMed 
    part_of insulin-like growth factor ternary complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    insulin-like growth factor-binding protein 3
    Names
    IGF-binding protein 3
    acid stable subunit of the 140 K IGF complex
    binding protein 29
    binding protein 53
    growth hormone-dependent binding protein

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011508.1 RefSeqGene

      Range
      5001..14028
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_68

    mRNA and Protein(s)

    1. NM_000598.5 → NP_000589.2  insulin-like growth factor-binding protein 3 isoform b precursor

      See identical proteins and their annotated locations for NP_000589.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1, resulting in a shorter protein (isoform b).
      Source sequence(s)
      AI142967, AK056274, AU102436, BC064987
      Consensus CDS
      CCDS5505.1
      UniProtKB/Swiss-Prot
      A4D2F5, D3DVM0, P17936, Q2V509, Q6P1M6, Q9UCL4
      UniProtKB/TrEMBL
      B4DN53
      Related
      ENSP00000477772.2, ENST00000613132.5
      Conserved Domains (2) summary
      smart00121
      Location:38 → 115
      IB; Insulin growth factor-binding protein homologues
      pfam00086
      Location:213 → 285
      Thyroglobulin_1; Thyroglobulin type-1 repeat

    2. NM_001013398.2 → NP_001013416.1  insulin-like growth factor-binding protein 3 isoform a precursor

      See identical proteins and their annotated locations for NP_001013416.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).
      Source sequence(s)
      AC091524, AI142967, AL540642, BC064987, X64875
      Consensus CDS
      CCDS34632.1
      UniProtKB/TrEMBL
      B4DN53
      Related
      ENSP00000370473.4, ENST00000381083.9
      Conserved Domains (2) summary
      smart00121
      Location:38 → 115
      IB; Insulin growth factor-binding protein homologues
      pfam00086
      Location:219 → 291
      Thyroglobulin_1; Thyroglobulin type-1 repeat

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      45912245..45921272 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047420325.1 → XP_047276281.1  insulin-like growth factor-binding protein 3 isoform X1

      UniProtKB/Swiss-Prot
      A4D2F5, D3DVM0, P17936, Q2V509, Q6P1M6, Q9UCL4

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      46073961..46082986 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054358119.1 → XP_054214094.1  insulin-like growth factor-binding protein 3 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P17936.2 GenPept UniProtKB/Swiss-Prot:P17936

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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