| Insulin-like growth factor 2 (somatomedin A) |
PDB rendering based on 1igl. |
| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
|
1IGL, 2L29, 2V5P, 3E4Z, 3KR3
|
|
|
| Identifiers |
| Symbols |
IGF2; C11orf43; IGF-II; PP9974 |
| External IDs |
OMIM: 147470 MGI: 96434 HomoloGene: 510 GeneCards: IGF2 Gene |
| Gene Ontology |
| Molecular function |
• insulin receptor binding
• insulin-like growth factor receptor binding
• hormone activity
• protein binding
• growth factor activity
• receptor activator activity
• protein serine/threonine kinase activator activity
|
| Cellular component |
• extracellular region
• extracellular space
|
| Biological process |
• skeletal system development
• ossification
• positive regulation of protein phosphorylation
• glucose metabolic process
• regulation of gene expression by genetic imprinting
• regulation of transcription, DNA-dependent
• multicellular organismal development
• positive regulation of cell proliferation
• insulin receptor signaling pathway
• insulin receptor signaling pathway via phosphatidylinositol 3-kinase cascade
• positive regulation of activated T cell proliferation
• positive regulation of catalytic activity
• positive regulation of MAPK cascade
• positive regulation of glycogen biosynthetic process
• positive regulation of mitosis
• positive regulation of insulin receptor signaling pathway
• positive regulation of peptidyl-tyrosine phosphorylation
• positive regulation of cell division
• positive regulation of protein kinase B signaling cascade
• positive regulation of protein serine/threonine kinase activity
• positive regulation of receptor activity
• positive regulation of glycogen (starch) synthase activity
|
| Sources: Amigo / QuickGO |
|
| RNA expression pattern |
|
|
|
| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
|
| Entrez |
3481 |
16002 |
|
| Ensembl |
ENSG00000167244 |
ENSMUSG00000048583 |
|
| UniProt |
P01344 |
P09535 |
|
| RefSeq (mRNA) |
NM_000612.4 |
NM_001122736.1 |
|
| RefSeq (protein) |
NP_000603.1 |
NP_001116208.1 |
|
| Location (UCSC) |
Chr 11:
2.15 – 2.18 Mb |
Chr 7:
142.65 – 142.67 Mb |
|
| PubMed search |
[2] |
[3] |
|
|
|
| Insulin-like growth factor II E-peptide |
| Identifiers |
| Symbol |
IGF2_C |
| Pfam |
PF08365 |
| InterPro |
IPR013576 |
| Available protein structures: |
| Pfam |
structures |
| PDB |
RCSB PDB; PDBe |
| PDBsum |
structure summary |
|
Insulin-like growth factor 2 (IGF-2) is one of three protein hormones that share structural similarity to insulin. The MeSH definition reads: "A well-characterized neutral peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on somatotropin. It is believed to be a major fetal growth factor in contrast to Insulin-like growth factor 1, which is a major growth factor in adults".[1]
|
Contents
- 1 Gene structure
- 2 Function
- 3 Diseases
- 4 Interactions
- 5 See also
- 6 References
- 7 External links
- 8 Further reading
|
Gene structure
In humans, the IGF2 gene is located on chromosome 11p15.5, a region which contains numerous imprinted genes. In mice this homologous region is found at distal chromosome 7. In both organisms, Igf2 is imprinted, with expression resulting favourably from the paternally inherited allele. However, in the human brain a loss of imprinting occurs resulting in both IGF2 and H19 being transcribed from both parental alleles.[2]
The protein CTCF is involved in repressing expression of the gene, by binding to the H19 imprinting control region (ICR) along with Differentially-methylated Region-1 (DMR1) and Matrix Attachment Region -3 (MAR3). These three DNA sequences bind to CTCF in a way that limits downstream enhancer access to the Igf2 region. The mechanism in which CTCF binds to these regions is currently unknown, but could include either a direct DNA-CTCF interaction or it could possibly be mediated by other proteins. In mammals (mice, humans, pigs), only the allele for insulin-like growth factor-2 (IGF2) inherited from one's father is active; that inherited from the mother is not — a phenomenon called imprinting.The mechanism: the mother's allele has an insulator between the IGF2 promoter and enhancer. So does the father's allele, but in his case, the insulator has been methylated. CTCF can no longer bind to the insulator, and so the enhancer is now free to turn on the father's IGF2 promoter.
Function
The major role of IGF-2 is as a growth promoting hormone during gestation.
IGF-2 exerts its effects by binding to the IGF-1 receptor. IGF2 may also bind to the IGF-2 receptor (also called the cation-independent mannose 6-phosphate receptor), which acts as a signalling antagonist; that is, to prevent IGF2 responses.
In the process of Folliculogenesis, IGF-2 is created by Theca cells to act in an autocrine manner on the theca cells themselves, and in a paracrine manner on Granulosa cells in the ovary. IGF2 promotes granulosa cell proliferation during the follicular phase of the menstrual cycle, acting alongside Follicle Stimulating Hormone (FSH). After ovulation has occurred, IGF-2 promotes progesterone secretion during the luteal phase of the menstrual cycle together with Luteinizing Hormone (LH). Thus, IGF2 acts as a Co-hormone together with both FSH and LH.
A study at the Mount Sinai School of Medicine found that IGF-2 may be linked to memory.[3] The study found that it may play a key role in memory and could potentially be used to treat Alzheimer's Disease.[4][5] A study at the European Neuroscience Institute-Goettingen (Germany) found that fear extinction-induced IGF2/IGFBP7 signalling promotes the survival of 17–19-day-old newborn hippocampal neurons. This suggests that therapeutic strategies that enhance IGF2 signalling and adult neurogenesis might be suitable to treat diseases linked to excessive fear memory such as PTSD.[6]
Diseases
It is sometimes produced in excess in islet cell tumours, causing hypoglycemia. Doege-Potter syndrome is a paraneoplastic syndrome[7] in which hypoglycemia is associated with the presence of one or more non-islet fibrous tumors in the pleural cavity. Loss of imprinting of IGF2 is a common feature in tumours seen in Beckwith-Wiedemann syndrome. As IGF2 promotes development of fetal pancreatic beta cells, it is believed to be related to some forms of diabetes mellitus.
Interactions
Insulin-like growth factor 2 has been shown to interact with IGFBP3[8][9][10][11] and Transferrin.[8]
See also
- Insulin-like growth factor 2 receptor
- Insulin-like growth factor II IRES
References
- ^ http://www.ncbi.nlm.nih.gov/mesh/68007335
- ^ [1]
- ^ http://www.nature.com/nature/journal/v469/n7331/full/nature09667.html
- ^ "Brain chemical could treat Alzheimer's". The Times Of India. http://timesofindia.indiatimes.com/life-style/health-fitness/health/Brain-chemical-could-treat-Alzheimers/articleshow/7371086.cms.
- ^ MacRae, Fiona (27 January 2011). "Scientists find key chemical that could boost memory and end the misery of Alzheimer's". Daily Mail (London). http://www.dailymail.co.uk/health/article-1350791/Alzheimers-Scientists-key-chemical-IGF-II-boost-memory.html.
- ^ http://www.nature.com/emboj/journal/vaop/ncurrent/full/emboj2011293a.html
- ^ Balduyck B, Lauwers P, Govaert K, Hendriks J, De Maeseneer M, Van Schil P (July 2006). "Solitary fibrous tumor of the pleura with associated hypoglycemia: Doege-Potter syndrome: a case report". J Thorac Oncol 1 (6): 588–90. doi:10.1097/01243894-200607000-00016. PMID 17409923.
- ^ a b Storch, S; Kübler B, Höning S, Ackmann M, Zapf J, Blum W, Braulke T (Dec. 2001). "Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3". FEBS Lett. (Netherlands) 509 (3): 395–8. doi:10.1016/S0014-5793(01)03204-5. ISSN 0014-5793. PMID 11749962.
- ^ Buckway, C K; Wilson E M, Ahlsén M, Bang P, Oh Y, Rosenfeld R G (Oct. 2001). "Mutation of three critical amino acids of the N-terminal domain of IGF-binding protein-3 essential for high affinity IGF binding". J. Clin. Endocrinol. Metab. (United States) 86 (10): 4943–50. doi:10.1210/jc.86.10.4943. ISSN 0021-972X. PMID 11600567.
- ^ Twigg, S M; Baxter R C (Mar. 1998). "Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit". J. Biol. Chem. (UNITED STATES) 273 (11): 6074–9. doi:10.1074/jbc.273.11.6074. ISSN 0021-9258. PMID 9497324.
- ^ Firth, S M; Ganeshprasad U, Baxter R C (Jan. 1998). "Structural determinants of ligand and cell surface binding of insulin-like growth factor-binding protein-3". J. Biol. Chem. (UNITED STATES) 273 (5): 2631–8. doi:10.1074/jbc.273.5.2631. ISSN 0021-9258. PMID 9446566.
External links
- Insulin-Like+Growth+Factor+II at the US National Library of Medicine Medical Subject Headings (MeSH)
Further reading
- O'Dell SD, Day IN (1998). "Insulin-like growth factor II (IGF-II).". Int. J. Biochem. Cell Biol. 30 (7): 767–71. doi:10.1016/S1357-2725(98)00048-X. PMID 9722981.
- Butler AA, Yakar S, Gewolb IH, et al. (1999). "Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology.". Comp. Biochem. Physiol. B, Biochem. Mol. Biol. 121 (1): 19–26. doi:10.1016/S0305-0491(98)10106-2. PMID 9972281.
- Kalli KR, Conover CA (2004). "The insulin-like growth factor/insulin system in epithelial ovarian cancer.". Front. Biosci. 8: d714–22. doi:10.2741/1034. PMID 12700030.
- Wood AW, Duan C, Bern HA (2005). "Insulin-like growth factor signaling in fish.". Int. Rev. Cytol. 243: 215–85. doi:10.1016/S0074-7696(05)43004-1. PMID 15797461.
- Fowden AL, Sibley C, Reik W, Constancia M (2006). "Imprinted genes, placental development and fetal growth.". Horm. Res. 65 Suppl 3 (3): 50–8. doi:10.1159/000091506. PMID 16612114.
|
PDB gallery
|
|
|
|
|
1igl: SOLUTION STRUCTURE OF HUMAN INSULIN-LIKE GROWTH FACTOR II RELATIONSHIP TO RECEPTOR AND BINDING PROTEIN INTERACTIONS
|
|
|
|
|
Growth factors
|
|
| Fibroblast |
FGF receptor ligands: FGF1/FGF2/FGF5 · FGF3/FGF4/FGF6 · KGF (FGF7/FGF10/FGF22) · FGF8/FGF17/FGF18 · FGF9/FGF16/FGF20
FGF homologous factors: FGF11 · FGF12 · FGF13 · FGF14
hormone-like: FGF19 · FGF21 · FGF23
|
|
| EGF-like domain |
TGF-α · EGF · HB-EGF
|
|
| TGFβ pathway |
TGF-β (TGF-β1, TGF-β2, TGF-β3)
|
|
| Insulin-like |
IGF-1 · IGF-2
|
|
| Platelet-derived |
PDGFA · PDGFB · PDGFC · PDGFD
|
|
| Vascular endothelial |
VEGF-A · VEGF-B · VEGF-C · VEGF-D · PGF
|
|
| Other |
Nerve · Hepatocyte
|
|
|
B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
|
|
|
Endocrine system: hormones (Peptide hormones · Steroid hormones)
|
|
Endocrine
glands |
|
Hypothalamic-
pituitary
|
|
Hypothalamus
|
GnRH · TRH · Dopamine · CRH · GHRH/Somatostatin · Melanin concentrating hormone
|
|
|
Posterior pituitary
|
Vasopressin · Oxytocin
|
|
|
Anterior pituitary
|
α (FSH FSHB, LH LHB, TSH TSHB, CGA) · Prolactin · POMC (CLIP, ACTH, MSH, Endorphins, Lipotropin) · GH
|
|
|
|
Adrenal axis
|
Adrenal cortex: aldosterone · cortisol · DHEA
Adrenal medulla: epinephrine · norepinephrine
|
|
|
Thyroid axis
|
Thyroid: thyroid hormone (T3 and T4) · calcitonin
Parathyroid: PTH
|
|
|
Gonadal axis
|
Testis: testosterone · AMH · inhibin
Ovary: estradiol · progesterone · activin and inhibin · relaxin (pregnancy)
Placenta: hCG · HPL · estrogen · progesterone
|
|
|
Islet-Acinar
Axis
|
Pancreas: glucagon · insulin · amylin · somatostatin · pancreatic polypeptide
|
|
|
Pineal gland
|
Pineal gland: melatonin
|
|
|
Non-end.
glands |
Thymus: Thymosin (Thymosin α1, Thymosin beta) · Thymopoietin · Thymulin
Digestive system: Stomach: gastrin · ghrelin · Duodenum: CCK · Incretins (GIP, GLP-1) · secretin · motilin · VIP · Ileum: enteroglucagon · peptide YY · Liver/other: Insulin-like growth factor (IGF-1, IGF-2)
Adipose tissue: leptin · adiponectin · resistin
Skeleton: Osteocalcin
Kidney: JGA (renin) · peritubular cells (EPO) · calcitriol · prostaglandin
Heart: Natriuretic peptide (ANP, BNP)
|
|
|
|
|
noco (d)/cong/tumr, sysi/epon
|
proc, drug (A10/H1/H2/H3/H5)
|
|
|
|
