Details for: IGFBP1

Gene ID: 3484

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: IGFBP1

Ensembl ID: ENSG00000146678

Description: insulin like growth factor binding protein 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • hepatocyte CL0000182
    CSI 11.31
    rCSI 20.25%
    PRS 96.61
  • endothelial cell of periportal hepatic sinusoid CL0019021
    CSI 7.63
    rCSI 35.02%
    PRS 98.13
  • hepatic stellate cell CL0000632
    CSI 6.92
    rCSI 25.91%
    PRS 96.85
  • centrilobular region hepatocyte CL0019029
    CSI 6.75
    rCSI 17.61%
    PRS 95.36
  • Kupffer cell CL0000091
    CSI 5.18
    rCSI 11.85%
    PRS 98.32
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 4.58
    rCSI 14.12%
    PRS 98.31
  • midzonal region hepatocyte CL0019028
    CSI 4.34
    rCSI 10.18%
    PRS 95.98
  • stromal cell CL0000499
    CSI 4.12
    rCSI 11.6%
    PRS 96.94
  • periportal region hepatocyte CL0019026
    CSI 3.32
    rCSI 12.93%
    PRS 95.62
  • intrahepatic cholangiocyte CL0002538
    CSI 2.95
    rCSI 7.08%
    PRS 97.67
  • macrophage CL0000235
    CSI 2.7
    rCSI 4.91%
    PRS 97.58
  • epithelial cell CL0000066
    CSI 2.7
    rCSI 4.14%
    PRS 92.01
  • cholangiocyte CL1000488
    CSI 1.4
    rCSI 8.41%
    PRS 96.64

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Insulin-like growth factor-binding protein 1, encoded by the [IGFBP1](/details-gene/3484) gene, is a secreted protein that plays a crucial role in regulating the bioavailability and activity of insulin-like growth factors (IGFs). It is a member of the IGFBP family and primarily functions by binding to IGF-I and IGF-II, thereby modulating their interaction with cell surface receptors. The expression profile of [IGFBP1](/details-gene/3484) is overwhelmingly localized to the liver, with particularly high significance in [hepatocytes](/details-cell/CL0000182), as well as other liver-resident cells such as [endothelial cells of periportal hepatic sinusoids](/details-cell/CL0019021) and [hepatic stellate cells](/details-cell/CL0000632). This specific expression pattern underscores its central role in systemic metabolic control, particularly in glucose homeostasis and growth regulation, which is further supported by early characterization studies [Link](https://pubmed.ncbi.nlm.nih.gov/2458522/). Dysregulation of [IGFBP1](/details-gene/3484) is associated with metabolic disorders, and it is linked to a clinical phenotype described in OMIM ([146730](https://omim.org/entry/146730)). ## Cellular Roles and Expression Landscape The expression data reveals that [IGFBP1](/details-gene/3484) is a hallmark gene of the liver microenvironment. **Overall**, its most significant expression is observed in [hepatocytes](/details-cell/CL0000182), including those in the [centrilobular](/details-cell/CL0019029), [midzonal](/details-cell/CL0019028), and [periportal](/details-cell/CL0019026) regions, consistent with the liver's role as the primary source of circulating IGFBPs. Beyond the liver parenchyma, [IGFBP1](/details-gene/3484) shows significant expression in several non-parenchymal cell types, suggesting complex paracrine roles within the liver. These include: * **Vascular cells:** High significance in [endothelial cells of periportal hepatic sinusoids](/details-cell/CL0019021) and [endothelial cells of pericentral hepatic sinusoids](/details-cell/CL0019022), suggesting a role in regulating IGF transport into and out of the liver. * **Fibrogenic cells:** Its prominence in [hepatic stellate cells](/details-cell/CL0000632) may indicate a function in modulating liver fibrosis or tissue remodeling. * **Immune cells:** Significant expression in liver-resident macrophages, known as [Kupffer cells](/details-cell/CL0000091), as well as the broader [macrophage](/details-cell/CL0000235) population, points towards a potential immunomodulatory role. * **Biliary cells:** The gene is also expressed in [intrahepatic cholangiocytes](/details-cell/CL0002538), suggesting a function related to the biliary system. The broad expression across multiple, functionally distinct liver cell types establishes [IGFBP1](/details-gene/3484) not just as a secreted product of [hepatocytes](/details-cell/CL0000182), but as an integral signaling molecule within the entire liver ecosystem. ## Pathways and Molecular Function The molecular functions of [IGFBP1](/details-gene/3484) are centered on its ability to bind IGFs, as annotated by its involvement in '[Insulin-like growth factor binding](/details-ontology/GO:0005520),' '[Insulin-like growth factor i binding](/details-ontology/GO:0031994),' and '[Insulin-like growth factor ii binding](/details-ontology/GO:0031995).' This binding capacity is the basis for its primary biological process: the '[Regulation of insulin-like growth factor receptor signaling pathway](/details-ontology/GO:0043567),' which in turn influences the broader '[Insulin receptor signaling pathway](/details-ontology/GO:0008286).' The protein is synthesized within the cell, passing through the '[Endoplasmic reticulum lumen](/details-ontology/GO:0005788)' before being secreted into the '[Extracellular space](/details-ontology/GO:0005615),' where it performs its regulatory function. Reactome pathway analysis corroborates and expands on this role, placing [IGFBP1](/details-gene/3484) within the '[Regulation of insulin-like growth factor (igf) transport and uptake by insulin-like growth factor binding proteins (igfbps)](https://reactome.org/content/detail/R-HSA-381426)' pathway. Interestingly, its expression appears to be regulated by transcription factors and cellular states associated with stress and metabolism. Its inclusion in '[Foxo-mediated transcription](https://reactome.org/content/detail/R-HSA-9614085)' and pathways related to the '[Unfolded protein response (upr)](https://reactome.org/content/detail/R-HSA-381119)' (e.g., '[Atf4 activates genes in response to endoplasmic reticulum stress](https://reactome.org/content/detail/R-HSA-380994)') is consistent with its known regulation by nutritional status and metabolic stress, particularly within [hepatocytes](/details-cell/CL0000182). ## Research Directions The specific and high-level expression of [IGFBP1](/details-gene/3484) within the liver niche, coupled with its function as a key metabolic regulator, provides a strong basis for further investigation into its role in both health and disease. **Proposed Hypotheses:** 1. Given its high expression in [hepatic stellate cells](/details-cell/CL0000632) and its role in regulating growth factors, [IGFBP1](/details-gene/3484) may function as a paracrine inhibitor of liver fibrosis. In a healthy liver, hepatocyte-secreted [IGFBP1](/details-gene/3484) could sequester pro-fibrotic IGFs, helping to maintain stellate cells in a quiescent state. A reduction in [IGFBP1](/details-gene/3484) during liver injury could contribute to stellate cell activation and the onset of fibrosis. 2. The significant expression of [IGFBP1](/details-gene/3484) in [Kupffer cells](/details-cell/CL0000091) suggests it plays a role in modulating the inflammatory response within the liver. [IGFBP1](/details-gene/3484) may act locally to dampen IGF-I-mediated pro-inflammatory signaling in [Kupffer cells](/details-cell/CL0000091), thereby preventing excessive inflammation during metabolic stress or infection. **Experimental Approach:** To test the hypothesis regarding the role of [IGFBP1](/details-gene/3484) in liver fibrosis (Hypothesis 1), a mouse model of liver injury (e.g., carbon tetrachloride or bile duct ligation) could be utilized. A liver-specific knockout of [IGFBP1](/details-gene/3484) could be generated using a Cre-Lox system. Following injury induction, the degree of fibrosis in knockout mice versus wild-type controls would be assessed via histology (Sirius Red staining), quantitative PCR for fibrotic markers (e.g., *Acta2*, *Col1a1*), and hydroxyproline assays. This would directly test whether the absence of hepatocyte-derived [IGFBP1](/details-gene/3484) exacerbates the fibrotic response to injury. **Therapeutic Potential:** As a secreted protein with a well-defined role in metabolic regulation, [IGFBP1](/details-gene/3484) presents considerable therapeutic potential. Its circulating levels are already used as a biomarker for insulin sensitivity and metabolic health. As a therapeutic agent, recombinant [IGFBP1](/details-gene/3484) could be administered to modulate IGF activity in diseases characterized by IGF excess. Conversely, in conditions such as cachexia or growth hormone insensitivity where increased IGF signaling may be beneficial, strategies to inhibit [IGFBP1](/details-gene/3484) function, such as neutralizing antibodies or small molecule inhibitors that disrupt its binding to IGFs, could be explored. Its liver-centric expression profile suggests that targeting this protein may have a potent systemic effect with potentially limited off-target effects in other tissues.

Genular Protein ID: 2938113013

Symbol: IBP1_HUMAN

Name: Insulin-like growth factor-binding protein 1

UniProtKB Accession Codes:

P08833 A4D2F4 D3DVL9 Q8IYP5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 18 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 15 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PIR 1 PRINTS 2 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 4 RefSeq 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 2461294

Title: Isolation and characterization of a cDNA encoding the low molecular weight insulin-like growth factor binding protein (IBP-1).

PubMed ID: 2461294

DOI: 10.1002/j.1460-2075.1988.tb03087.x

PubMed ID: 2454104

Title: Cloning, characterization, and expression of a human insulin-like growth factor binding protein.

PubMed ID: 2454104

DOI: 10.1016/s0006-291x(88)80425-x

PubMed ID: 3419931

Title: Cloning of cDNA encoding human placental protein 12 (PP12): binding protein for IGF I and somatomedin.

PubMed ID: 3419931

DOI: 10.1093/nar/16.17.8711

PubMed ID: 2457513

Title: Primary structure of human insulin-like growth factor-binding protein/placental protein 12 and tissue-specific expression of its mRNA.

PubMed ID: 2457513

DOI: 10.1016/0014-5793(88)80041-3

PubMed ID: 2458522

Title: Insulin-like growth factor (IGF) binding protein complementary deoxyribonucleic acid from human HEP G2 hepatoma cells: predicted protein sequence suggests an IGF binding domain different from those of the IGF-I and IGF-II receptors.

PubMed ID: 2458522

DOI: 10.1210/mend-2-5-404

PubMed ID: 2474129

Title: Structure of the human chromosomal gene for the 25 kilodalton insulin-like growth factor binding protein.

PubMed ID: 2474129

DOI: 10.1210/mend-3-5-846

PubMed ID: 2849945

Title: Organization of the gene encoding the insulin-like growth factor binding protein IBP-1.

PubMed ID: 2849945

DOI: 10.1016/s0006-291x(88)80959-8

PubMed ID: 1373120

Title: Contiguous localization of the genes encoding human insulin-like growth factor binding proteins 1 (IGBP1) and 3 (IGBP3) on chromosome 7.

PubMed ID: 1373120

DOI: 10.1016/0888-7543(92)90440-4

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 19765076

Title: Identification of the amniotic fluid insulin-like growth factor binding protein-1 phosphorylation sites and propensity to proteolysis of the isoforms.

PubMed ID: 19765076

DOI: 10.1111/j.1742-4658.2009.07318.x

PubMed ID: 2466665

Title: Human insulin-like growth-factor-binding protein. Low-molecular-mass form: protein sequence and cDNA cloning.

PubMed ID: 2466665

DOI: 10.1111/j.1432-1033.1989.tb14641.x

PubMed ID: 2971653

Title: Purification of a 31,000-dalton insulin-like growth factor binding protein from human amniotic fluid. Isolation of two forms with different biologic actions.

PubMed ID: 2971653

DOI: 10.1016/s0021-9258(18)68206-7

PubMed ID: 1718783

Title: Site-directed mutagenesis of the N-terminal region of IGF binding protein 1; analysis of IGF binding capability.

PubMed ID: 1718783

DOI: 10.1016/0014-5793(91)81298-m

PubMed ID: 7678248

Title: Identification of the sites of phosphorylation in insulin-like growth factor binding protein-1. Regulation of its affinity by phosphorylation of serine 101.

PubMed ID: 7678248

DOI: 10.1016/s0021-9258(18)54050-3

PubMed ID: 10329650

Title: The N-terminal disulfide linkages of human insulin-like growth factor-binding protein-6 (hIGFBP-6) and hIGFBP-1 are different as determined by mass spectrometry.

PubMed ID: 10329650

DOI: 10.1074/jbc.274.21.14587

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 26091039

Title: A single kinase generates the majority of the secreted phosphoproteome.

PubMed ID: 26091039

DOI: 10.1016/j.cell.2015.05.028

PubMed ID: 15972819

Title: Structure and properties of the C-terminal domain of insulin-like growth factor-binding protein-1 isolated from human amniotic fluid.

PubMed ID: 15972819

DOI: 10.1074/jbc.m504304200

PubMed ID: 16924115

Title: Structural basis for the inhibition of insulin-like growth factors by insulin-like growth factor-binding proteins.

PubMed ID: 16924115

DOI: 10.1073/pnas.0605652103

Sequence Information:

  • Length: 259
  • Mass: 27904
  • Checksum: 8AA75AF7DC966012
  • Sequence:
    • MSEVPVARVW LVLLLLTVQV GVTAGAPWQC APCSAEKLAL CPPVSASCSE VTRSAGCGCC 
PMCALPLGAA CGVATARCAR GLSCRALPGE QQPLHALTRG QGACVQESDA SAPHAAEAGS 
PESPESTEIT EEELLDNFHL MAPSEEDHSI LWDAISTYDG SKALHVTNIK KWKEPCRIEL 
YRVVESLAKA QETSGEEISK FYLPNCNKNG FYHSRQCETS MDGEAGLCWC VYPWNGKRIP 
GSPEIRGDPN CQIYFNVQN