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FLASH GENE

Symbol

IGF1

contributors: mct/npt/pgu/shn - updated : 19-07-2013

HGNC name	insulin-like growth factor 1 (somatomedin C)
HGNC id	5464

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

an extended C terminus

isoforms

Precursor

HOMOLOGY

interspecies	ortholog to Igf1, Mus musculus
	ortholog to igf1, Danio rerio
	ortholog to Igf1, Rattus norvegicus
	ortholog to IGF1, Pan troglodytes

Homologene

FAMILY

insulin family

CATEGORY

signaling hormone

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic,vesicle
text	SYT10 colocalized with IGF1 in somatodendritic vesicles of olfactory bulb neurons

basic FUNCTION	insulin-like growth factor 1, inducer of the phosphatidylinositol 3-kinase survival pathway through activation of AKT1, AKT2
	associated with increased BCL2 expression
	also inducer of calcineurin mediated signaling and activation of GATA2
	inducing myoblast differentiation, in part, by increasing SOCS3 expression
	potent mitogen for both normal and malignant prostate epithelial cells
	important regulator of cell proliferation, differentiation and apoptosis
	role in the polarization of hippocampal neurons
	may have specific roles in axonal growth and myelination
	circulating IGF-I may play a role in the age-related reduction of certain cognitive functions
	IGF-I is a physiological regulator of brain amyloid levels
	can reverse vascular endothelial cells arrested at G0/G1
	IGF1 and epidermal growth factor (EGF) play important roles in the regulation of cell metabolism in response to different internal as well as external stimuli
	may play a role in the function of the endocrine pancreas and in the pathogenesis of the diabetes mellitus
	required for purkinje cells survival in the neonatal cerebellum
	GH1/IGF1 is likely to play an important role in the regulation of tendon and muscle collagen
	GH1/IGF1 axis is the key regulator of somatic growth
	IGF1 and IGFBP2 function coordinately to stimulate AKT1 and osteoblast differentiation

CELLULAR PROCESS	cell life, differentiation
	cell life, proliferation/growth
	cell life, cell death/apoptosis
	cell communication

PHYSIOLOGICAL PROCESS

development

text	regulation, development : muscle, skeletal

PATHWAY

metabolism

organic acid

signaling

signal transduction

a component

majority of circulating IGF1 is bound in a complex with IGF binding protein-3 (IGFBP3), which in turn limits IGF1 bio-availability

INTERACTION

DNA

RNA

small molecule

protein	upregulating K+ channels (Kus/KCNs) via PI3 kinase, PDK1, SGK1
	SOCS3
	GFBP-rP3 (
	IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-5, IGFBP-6, IGFBP-7 (
	fibronectin (FN)
	Transferin (Tf)
	SYT10 is a vesicular Ca2+-sensor for IGF1 containing vesicles that mediates rapid activity-dependent secretion of IGF1
	reciprocal functional interaction between RELA and IGF1 in which the transcription factor modulates both IGF1 synthesis and action in growth plate chondrocytes
	IGF1 system regulates GPER1 expression and function, triggering the activation of a signaling network that leads to the migration and proliferation of cancer cells
	necessary for normal postnatal growth and enhances the expression of local bone IGF1 expression
	IGF1 induced MUC8 and MUC5B expression is regulated by activation of the ERK1 and MAPK14 signaling pathway in human airway epithelial cells
	regulates MSTN expression via CREB1 transcription factor during muscle cell differentiation
	PPARA controls IGF1 signalling through the up-regulation of hepatic IGFBP2 transcription during fasting
	early induction of AMPK in response to IGF1/IGFBP2 followed by suppression is required for osteoblast differentiation
	MEF2D regulates IGF1-induced proliferation and apoptosis in cardiac myxoma (CM) development
	IGFBP2/IGF1 stimulated vimentin binding to PTPRZ1 and this was required for PTPRZ1 polymerization

cell & other

REGULATION

inhibited by

TNF in its neuroprotective role

ASSOCIATED DISORDERS

corresponding disease(s)

IGF1D

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   deletion     homozygous deletion in intrauterine growth retardation and severe short stature

Susceptibility

to type 2 diabetes, myocardial infarction and low birthweight to breast cancer to prostate cancer to adult height variation

Variant & Polymorphism repeat , other	polymorphism 192-bp allele
	variant increasing the risk of breast cancer
	19-CA-repeat homozygous state may be protecting against prostate cancer

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed neurology acquired   IGF-I is a physiological regulator of brain amyloid levels with therapeutic potential neurosensorial visual retina IGF-I seems to protect neural cells following a physiopathological or an experimental increase in intracellular Ca(2+), an observation that may have therapeutic consequences in neurodegenerative diseases such as retinitis pigmentosa tumor     IGF1-MEF2D pathway may be a useful target for treatment of cardiac myxoma

ANIMAL & CELL MODELS

	Newborn mice with IgfI null mutation exhibit a growth deficiency die shortly after birt or can each adulthood (
	mice with severe IGF-1 deficiency display elevated blood pressure and enhanced myocardial contractility (
	profound embryonic and postnatal growth retardation in IGF1 knockout mice
	normoglycemic/normoinsulinemic transgenic mice overexpressing IGF-1 in the retina developed most alterations observed in human diabetic eye disease (
	mice lacking both Insr and Ifg1r developed diabetes in contrast to mild phenotypes observed in single mutants
	IGF1 knockout mice have defects in neurologic development
	IGF1 decreased photoreceptor apoptosis in rd1 mouse retinal explants in parallel with reduced activation of calpain-2 and increased levels of calpastatin and activation of phospho-CREB (