Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Igf1. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Igf1
  • participates in the following biological processes:
    • chondroitin sulfate proteoglycan biosynthetic process ^[7]
    • inner ear development ^[11]
    • insulin-like growth factor receptor signaling pathway ^[4]
    • multicellular organism growth ^[10]
    • negative regulation of apoptotic process ^{[19, 21]}
    • negative regulation of release of cytochrome c from mitochondria ^[21]
    • positive regulation of cerebellar granule cell precursor proliferation ^[26]
    • positive regulation of protein kinase B signaling cascade ^[15]
    • positive regulation of transcription from RNA polymerase II promoter ^{[7, 25]}
    • prostate gland growth ^[8]
    • regulation of establishment or maintenance of cell polarity ^[1]
    • regulation of protein phosphorylation ^[5]
  • is located in the following cellular components:
    • extracellular space ^{[2, 9, 23]}
• The gene product of Igf1 has been shown to bind to the gene products of Igfbp1, Igfbp2, Igfbp3, Igfbp4, Igfbp5. ^{[3, 13]} Researchers have inferred, based on physical interactions, that the gene product of Igf1
  • performs the following molecular functions:
    • insulin-like growth factor receptor binding ^[13]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Igf1
  • participates in the following biological processes:
    • blood vessel remodeling ^[14]
    • branching morphogenesis of a tube ^[17]
    • cell development ^[20]
    • exocrine pancreas development ^[6]
    • glial cell differentiation ^[24]
    • lung alveolus development ^[14]
    • lung lobe morphogenesis ^[14]
    • lung vasculature development ^[14]
    • mammary gland development ^[17]
    • negative regulation of androgen receptor signaling pathway ^[22]
    • negative regulation of cell proliferation ^[14]
    • nervous system development ^[24]
    • positive regulation of myoblast proliferation ^[12]
    • positive regulation of transcription from RNA polymerase II promoter ^[14]
    • prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis ^[18]
    • prostate gland epithelium morphogenesis ^[8]
    • prostate gland growth ^[22]
    • prostate gland stromal morphogenesis ^[8]
    • Type I pneumocyte differentiation ^[14]
    • Type II pneumocyte differentiation ^[14]
• Researchers have inferred, based on genetic interactions, that the gene product of Igf1
  • participates in the following biological processes:
    • blood vessel remodeling based on interactions with Lif ^[14]
    • lung alveolus development based on interactions with Lif ^[14]
    • lung development based on interactions with Lif ^[14]
    • lung lobe morphogenesis based on interactions with Lif ^[14]
    • lung vasculature development based on interactions with Lif ^[14]
    • negative regulation of cell proliferation based on interactions with Lif ^[14]
    • negative regulation of ERK1 and ERK2 cascade based on interactions with Lif ^[14]
    • positive regulation of cell proliferation based on interactions with Irs2, Phip ^[16]
    • positive regulation of transcription from RNA polymerase II promoter based on interactions with Lif ^[14]
    • regulation of protein metabolic process based on interactions with Ghrhr ^[2]
    • water homeostasis based on interactions with Ghrhr ^[2]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Igf1:
  • participates in the following biological processes:
    • bone mineralization involved in bone maturation
    • insulin-like growth factor receptor signaling pathway
    • memory
    • muscle hypertrophy
    • myoblast differentiation
    • myoblast proliferation
    • myotube cell development
    • negative regulation of apoptotic process
    • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
    • negative regulation of smooth muscle cell apoptotic process
    • phosphatidylinositol-mediated signaling
    • positive regulation of activated T cell proliferation
    • positive regulation of calcineurin-NFAT signaling cascade
    • positive regulation of cardiac muscle hypertrophy
    • positive regulation of cell growth
    • positive regulation of cell proliferation
    • positive regulation of DNA binding
    • positive regulation of DNA replication
    • positive regulation of epithelial cell proliferation
    • positive regulation of fat cell differentiation
    • positive regulation of fibroblast proliferation
    • positive regulation of glucose import
    • positive regulation of glycogen biosynthetic process
    • positive regulation of glycolysis
    • positive regulation of insulin-like growth factor receptor signaling pathway
    • positive regulation of MAPK cascade
    • positive regulation of mitosis
    • positive regulation of osteoblast differentiation
    • positive regulation of peptidyl-tyrosine phosphorylation
    • positive regulation of phosphatidylinositol 3-kinase cascade
    • positive regulation of protein import into nucleus, translocation
    • positive regulation of protein serine/threonine kinase activity
    • positive regulation of Ras protein signal transduction
    • positive regulation of smooth muscle cell migration
    • positive regulation of smooth muscle cell proliferation
    • positive regulation of steroid hormone biosynthetic process
    • positive regulation of transcription from RNA polymerase II promoter
    • positive regulation of transcription, DNA-dependent
    • positive regulation of tyrosine phosphorylation of Stat5 protein
    • proteoglycan biosynthetic process
    • regulation of calcium ion transport
    • regulation of cell proliferation
    • regulation of intracellular steroid hormone receptor signaling pathway
    • regulation of translation
    • satellite cell maintenance involved in skeletal muscle regeneration
  • performs the following molecular functions:
    • hormone activity
    • insulin receptor binding
    • insulin-like growth factor receptor binding
    • integrin binding
    • protein serine/threonine kinase activator activity
    • steroid binding
  • is located in the following cellular components:
    • extracellular space
    • interstitial matrix

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Summary text based on GO annotations supported by structural data

• Igf1 encodes a protein or proteins that contain the following InterPro domains: Insulin family, Insulin, conserved site, Insulin-like, Insulin-like growth factor, Insulin-like growth factor I, indicating that the gene product:
  • performs the following molecular functions:
    • growth factor activity
  • is located in the following cellular components:
    • extracellular region

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Igf1 indicates that it:
  • performs the following molecular functions:
    • growth factor activity
  • is located in the following cellular components:
    • extracellular region

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References

1. Begue-Kirn C et al. (1994) Comparative analysis of TGF beta s, BMPs, IGF1, msxs, fibronectin, osteonectin and bone sialoprotein gene expression during normal and in vitro-induced odontoblast differentiation. Int J Dev Biol, 38:405-20. (PubMed:7848824)
2. Donahue LR et al. (1993) Regulation of metabolic water and protein compartments by insulin-like growth factor-I and testosterone in growth hormone-deficient lit/lit mice. J Endocrinol, 139:431-9. (PubMed:7510770)
3. Donahue LR et al. (1993) Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4. J Endocrinol, 136:91-104. (PubMed:7679139)
4. Font de Mora J et al. (2003) Ras-GRF1 signaling is required for normal beta-cell development and glucose homeostasis. EMBO J, 22:3039-49. (PubMed:12805218)
5. Giovannone B et al. (2009) GIGYF2 gene disruption in mice results in neurodegeneration and altered insulin-like growth factor signaling. Hum Mol Genet, 18:4629-39. (PubMed:19744960)
6. Kido Y et al. (2002) Effects of Mutations in the Insulin-like Growth Factor Signaling System on Embryonic Pancreas Development and beta -Cell Compensation to Insulin Resistance. J Biol Chem, 277:36740-7. (PubMed:12101187)
7. Kim JS et al. (2007) Cytokine-like 1 (CYTL1) Regulates the Chondrogenesis of Mesenchymal Cells. J Biol Chem, 282:29359-67. (PubMed:17644814)
8. Kleinberg DL et al. (2007) Insulin-like growth factor (IGF)-I controls prostate fibromuscular development: IGF-I inhibition prevents both fibromuscular and glandular development in eugonadal mice. Endocrinology, 148:1080-8. (PubMed:17138659)
9. Lee NK et al. (2007) Endocrine regulation of energy metabolism by the skeleton. Cell, 130:456-69. (PubMed:17693256)
10. Li Y et al. (2003) PERK eIF2alpha kinase regulates neonatal growth by controlling the expression of circulating insulin-like growth factor-I derived from the liver. Endocrinology, 144:3505-13. (PubMed:12865332)
11. Lu CC et al. (2011) Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly. J Neurosci, 31:10903-18. (PubMed:21795542)
12. Matheny RW Jr et al. (2011) Loss of IGF-IEa or IGF-IEb impairs myogenic differentiation. Endocrinology, 152:1923-34. (PubMed:21406500)
13. McCusker RH et al. (2003) Zinc partitions insulin-like growth factors (IGFs) from soluble IGF binding protein (IGFBP)-5 to the cell surface receptors of BC3H-1 muscle cells. J Cell Physiol, 197:388-99. (PubMed:14566968)
14. Moreno-Barriuso N et al. (2006) Alterations in alveolar epithelium differentiation and vasculogenesis in lungs of LIF/IGF-I double deficient embryos Dev Dyn, 235:2040-50. (PubMed:16691571)
15. Mukherjee A et al. (2009) Akt promotes BMP2-mediated osteoblast differentiation and bone development. J Cell Sci, 122:716-26. (PubMed:19208758)
16. Podcheko A et al. (2007) Identification of a WD40 repeat-containing isoform of PHIP as a novel regulator of beta-cell growth and survival. Mol Cell Biol, 27:6484-96. (PubMed:17636024)
17. Richards RG et al. (2004) Mammary gland branching morphogenesis is diminished in mice with a deficiency of insulin-like growth factor-I (IGF-I), but not in mice with a liver-specific deletion of IGF-I. Endocrinology, 145:3106-10. (PubMed:15059953)
18. Ruan W et al. (1999) Evidence that insulin-like growth factor I and growth hormone are required for prostate gland development. Endocrinology, 140:1984-9. (PubMed:10218945)
19. Schubert M et al. (2003) Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation. J Neurosci, 23:7084-92. (PubMed:12904469)
20. Stefaneanu L et al. (1999) Somatotroph and lactotroph changes in the adenohypophyses of mice with disrupted insulin-like growth factor I gene. Endocrinology, 140:3881-9. (PubMed:10465256)
21. Sun X et al. (2008) Akt activation prevents Apop-1-induced death of cells. Biochem Biophys Res Commun, 377:1097-101. (PubMed:18977203)
22. Svensson J et al. (2008) Liver-derived IGF1 enhances the androgenic response in prostate. J Endocrinol, 199:489-97. (PubMed:18827067)
23. Teglund S et al. (1998) Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell, 93:841-50. (PubMed:9630227)
24. Vicario-Abejon C et al. (2003) Locally born olfactory bulb stem cells proliferate in response to insulin-related factors and require endogenous insulin-like growth factor-I for differentiation into neurons and glia. J Neurosci, 23:895-906. (PubMed:12574418)
25. Vinals F et al. (2004) Myogenin protein stability is decreased by BMP-2 through a mechanism implicating Id1. J Biol Chem, 279:45766-72. (PubMed:15322112)
26. Wechsler-Reya RJ et al. (1999) Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog [see comments] Neuron, 22:103-14. (PubMed:10027293)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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