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Insulin-like growth factor I (IGF-I) (Somatomedin)

 IGF1_RAT                Reviewed;         153 AA.
P08025; P08024;
01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
01-FEB-1991, sequence version 3.
23-MAY-2018, entry version 164.
RecName: Full=Insulin-like growth factor I;
Short=IGF-I;
AltName: Full=Somatomedin;
Flags: Precursor;
Name=Igf1; Synonyms=Igf-1;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS IGF-IA AND IGF-IB).
TISSUE=Liver;
PubMed=3034909;
Shimatsu A., Rotwein P.;
"Mosaic evolution of the insulin-like growth factors. Organization,
sequence, and expression of the rat insulin-like growth factor I
gene.";
J. Biol. Chem. 262:7894-7900(1987).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IGF-IA).
TISSUE=Testis;
PubMed=3652906; DOI=10.1089/dna.1987.6.325;
Casella S.J., Smith E.P., van Wyk J.J., Joseph D.R., Hynes M.A.,
Hoyt E.C., Lund P.K.;
"Isolation of rat testis cDNAs encoding an insulin-like growth factor
I precursor.";
DNA 6:325-330(1987).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IGF-IA).
PubMed=3453891; DOI=10.1210/mend-1-3-243;
Roberts C.T. Jr., Lasky S.R., Lowe W.L. Jr., Seaman W.T., LeRoith D.;
"Molecular cloning of rat insulin-like growth factor I complementary
deoxyribonucleic acids: differential messenger ribonucleic acid
processing and regulation by growth hormone in extrahepatic tissues.";
Mol. Endocrinol. 1:243-248(1987).
[4]
NUCLEOTIDE SEQUENCE (ISOFORM IGF-IB).
PubMed=3658684; DOI=10.1093/nar/15.17.7196;
Shimatsu A., Rotwein P.;
"Sequence of two rat insulin-like growth factor I mRNAs differing
within the 5' untranslated region.";
Nucleic Acids Res. 15:7196-7196(1987).
[5]
NUCLEOTIDE SEQUENCE (ISOFORM IGF-IA).
PubMed=1368571; DOI=10.1271/bbb1961.54.1599;
Kato H., Okoshi A., Miura Y., Noguchi T.;
"A new cDNA clone relating to larger molecular species of rat insulin-
like growth factor-I mRNA.";
Agric. Biol. Chem. 54:1599-1601(1990).
[6]
NUCLEOTIDE SEQUENCE OF 46-153 (ISOFORM IGF-IA).
PubMed=3595538; DOI=10.1210/endo-121-2-684;
Murphy L.J., Bell G.I., Duckworth M.L., Friesen H.G.;
"Identification, characterization, and regulation of a rat
complementary deoxyribonucleic acid which encodes insulin-like growth
factor-I.";
Endocrinology 121:684-691(1987).
[7]
PROTEIN SEQUENCE OF 49-118.
PubMed=2538424;
Tamura K., Kobayashi M., Ishii Y., Tamura T., Hashimoto K.,
Nakamura S., Niwa M., Zapf J.;
"Primary structure of rat insulin-like growth factor-I and its
biological activities.";
J. Biol. Chem. 264:5616-5621(1989).
-!- FUNCTION: The insulin-like growth factors, isolated from plasma,
are structurally and functionally related to insulin but have a
much higher growth-promoting activity. May be a physiological
regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and
glycogen synthesis in osteoblasts. Stimulates glucose transport in
bone-derived osteoblastic (PyMS) cells and is effective at much
lower concentrations than insulin, not only regarding glycogen and
DNA synthesis but also with regard to enhancing glucose uptake.
May play a role in synapse maturation. Ca(2+)-dependent exocytosis
of IGF1 is required for sensory perception of smell in the
olfactory bulb. Acts as a ligand for IGF1R. Binds to the alpha
subunit of IGF1R, leading to the activation of the intrinsic
tyrosine kinase activity which autophosphorylates tyrosine
residues in the beta subunit thus initiatiating a cascade of down-
stream signaling events leading to activation of the PI3K-AKT/PKB
and the Ras-MAPK pathways. Binds to integrins ITGAV:ITGB3 and
ITGA6:ITGB4. Its binding to integrins and subsequent ternary
complex formation with integrins and IGFR1 are essential for IGF1
signaling. Induces the phosphorylation and activation of IGFR1,
MAPK3/ERK1, MAPK1/ERK2 and AKT1 (By similarity).
{ECO:0000250|UniProtKB:P05017, ECO:0000250|UniProtKB:P05019}.
-!- SUBUNIT: Forms a ternary complex with IGFR1 and ITGAV:ITGB3. Forms
a ternary complex with IGFR1 and ITGA6:ITGB4.
{ECO:0000250|UniProtKB:P05019}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P05017}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=IGF-IA;
IsoId=P08025-1; Sequence=Displayed;
Name=IGF-IB;
IsoId=P08025-2; Sequence=VSP_012166;
-!- SIMILARITY: Belongs to the insulin family. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=AAA41385.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
Sequence=AAA41386.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
Sequence=AAA41387.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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EMBL; M15651; AAA41215.1; -; Genomic_DNA.
EMBL; M15647; AAA41215.1; JOINED; Genomic_DNA.
EMBL; M15648; AAA41215.1; JOINED; Genomic_DNA.
EMBL; M15649; AAA41215.1; JOINED; Genomic_DNA.
EMBL; M15650; AAA41214.1; -; Genomic_DNA.
EMBL; M15647; AAA41214.1; JOINED; Genomic_DNA.
EMBL; M15648; AAA41214.1; JOINED; Genomic_DNA.
EMBL; M15649; AAA41214.1; JOINED; Genomic_DNA.
EMBL; M17335; AAA41386.1; ALT_INIT; mRNA.
EMBL; M15480; AAA41385.1; ALT_INIT; mRNA.
EMBL; M15481; AAA41387.1; ALT_INIT; mRNA.
EMBL; X06107; CAA29480.1; -; mRNA.
EMBL; X06043; CAA29436.1; -; mRNA.
PIR; A27804; A27804.
PIR; A40912; A40912.
PIR; B27804; B27804.
RefSeq; NP_001075946.2; NM_001082477.2.
RefSeq; NP_001075947.1; NM_001082478.1.
RefSeq; NP_001075948.1; NM_001082479.1. [P08025-1]
RefSeq; XP_006241253.1; XM_006241191.2.
RefSeq; XP_006241254.1; XM_006241192.1.
RefSeq; XP_006241255.1; XM_006241193.3. [P08025-1]
UniGene; Rn.201887; -.
UniGene; Rn.228346; -.
UniGene; Rn.6282; -.
ProteinModelPortal; P08025; -.
SMR; P08025; -.
STRING; 10116.ENSRNOP00000005995; -.
iPTMnet; P08025; -.
PaxDb; P08025; -.
Ensembl; ENSRNOT00000038780; ENSRNOP00000035899; ENSRNOG00000004517. [P08025-1]
GeneID; 24482; -.
KEGG; rno:24482; -.
CTD; 3479; -.
RGD; 2868; Igf1.
eggNOG; ENOG410IJ2T; Eukaryota.
eggNOG; ENOG4111MIV; LUCA.
GeneTree; ENSGT00530000063856; -.
HOGENOM; HOG000233362; -.
HOVERGEN; HBG006137; -.
InParanoid; P08025; -.
KO; K05459; -.
OMA; CFQSCDL; -.
PhylomeDB; P08025; -.
TreeFam; TF332820; -.
Reactome; R-RNO-114608; Platelet degranulation.
Reactome; R-RNO-2404192; Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R).
Reactome; R-RNO-2428928; IRS-related events triggered by IGF1R.
Reactome; R-RNO-2428933; SHC-related events triggered by IGF1R.
Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
Reactome; R-RNO-422085; Synthesis, secretion, and deacylation of Ghrelin.
PRO; PR:P08025; -.
Proteomes; UP000002494; Chromosome 7.
Bgee; ENSRNOG00000004517; -.
ExpressionAtlas; P08025; baseline and differential.
Genevisible; P08025; RN.
GO; GO:0035867; C:alphav-beta3 integrin-IGF-1-IGF1R complex; ISS:UniProtKB.
GO; GO:0005737; C:cytoplasm; IDA:RGD.
GO; GO:0070382; C:exocytic vesicle; ISS:UniProtKB.
GO; GO:0005615; C:extracellular space; IDA:RGD.
GO; GO:0005614; C:interstitial matrix; IDA:RGD.
GO; GO:0043025; C:neuronal cell body; IDA:RGD.
GO; GO:0005886; C:plasma membrane; IDA:RGD.
GO; GO:0031091; C:platelet alpha granule; IDA:RGD.
GO; GO:0008083; F:growth factor activity; TAS:RGD.
GO; GO:0005179; F:hormone activity; IDA:RGD.
GO; GO:0005159; F:insulin-like growth factor receptor binding; IDA:RGD.
GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:BHF-UCL.
GO; GO:0005496; F:steroid binding; IDA:RGD.
GO; GO:0007568; P:aging; IEP:RGD.
GO; GO:0060348; P:bone development; IEP:RGD.
GO; GO:0003230; P:cardiac atrium development; IEP:RGD.
GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
GO; GO:0071257; P:cellular response to electrical stimulus; IEP:RGD.
GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:RGD.
GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
GO; GO:0071316; P:cellular response to nicotine; IEP:RGD.
GO; GO:0071393; P:cellular response to progesterone stimulus; IEP:RGD.
GO; GO:1904017; P:cellular response to Thyroglobulin triiodothyronine; IEP:RGD.
GO; GO:0060363; P:cranial suture morphogenesis; IEP:RGD.
GO; GO:0050974; P:detection of mechanical stimulus involved in sensory perception; IMP:RGD.
GO; GO:0007565; P:female pregnancy; IEP:RGD.
GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IDA:BHF-UCL.
GO; GO:0007613; P:memory; IMP:RGD.
GO; GO:0043066; P:negative regulation of apoptotic process; IDA:RGD.
GO; GO:1904193; P:negative regulation of cholangiocyte apoptotic process; IMP:RGD.
GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:BHF-UCL.
GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IDA:BHF-UCL.
GO; GO:0002683; P:negative regulation of immune system process; IMP:RGD.
GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IMP:RGD.
GO; GO:1901215; P:negative regulation of neuron death; IDA:RGD.
GO; GO:1900142; P:negative regulation of oligodendrocyte apoptotic process; IDA:RGD.
GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IGI:BHF-UCL.
GO; GO:0030307; P:positive regulation of cell growth; IDA:RGD.
GO; GO:0008284; P:positive regulation of cell proliferation; ISS:UniProtKB.
GO; GO:0045600; P:positive regulation of fat cell differentiation; IDA:RGD.
GO; GO:0060252; P:positive regulation of glial cell proliferation; IDA:RGD.
GO; GO:0046326; P:positive regulation of glucose import; ISS:UniProtKB.
GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISS:UniProtKB.
GO; GO:0045669; P:positive regulation of osteoblast differentiation; IDA:RGD.
GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IDA:BHF-UCL.
GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IDA:BHF-UCL.
GO; GO:0090031; P:positive regulation of steroid hormone biosynthetic process; IDA:BHF-UCL.
GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IGI:BHF-UCL.
GO; GO:0051924; P:regulation of calcium ion transport; IDA:RGD.
GO; GO:0042127; P:regulation of cell proliferation; IDA:RGD.
GO; GO:0006417; P:regulation of translation; IMP:RGD.
GO; GO:0014823; P:response to activity; IEP:RGD.
GO; GO:0031000; P:response to caffeine; IEP:RGD.
GO; GO:0070849; P:response to epidermal growth factor; IEP:RGD.
GO; GO:0032355; P:response to estradiol; IEP:RGD.
GO; GO:0045471; P:response to ethanol; IDA:RGD.
GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
GO; GO:0060416; P:response to growth hormone; IEP:RGD.
GO; GO:0001666; P:response to hypoxia; IEP:RGD.
GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
GO; GO:0035094; P:response to nicotine; IEP:RGD.
GO; GO:0007584; P:response to nutrient; IEP:RGD.
GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
GO; GO:0010033; P:response to organic substance; IEP:RGD.
GO; GO:0042594; P:response to starvation; IEP:RGD.
GO; GO:0048545; P:response to steroid hormone; IEP:RGD.
GO; GO:0097066; P:response to thyroid hormone; IEP:RGD.
InterPro; IPR022341; IGF-I.
InterPro; IPR016179; Insulin-like.
InterPro; IPR022350; Insulin-like_growth_factor.
InterPro; IPR036438; Insulin-like_sf.
InterPro; IPR022353; Insulin_CS.
InterPro; IPR022352; Insulin_family.
Pfam; PF00049; Insulin; 2.
PRINTS; PR02002; INSLNLIKEGF.
PRINTS; PR02005; INSLNLIKEGF1.
PRINTS; PR00276; INSULINFAMLY.
SMART; SM00078; IlGF; 1.
SUPFAM; SSF56994; SSF56994; 1.
PROSITE; PS00262; INSULIN; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Direct protein sequencing;
Disulfide bond; Growth factor; Reference proteome; Secreted; Signal.
SIGNAL 1 ? {ECO:0000255}.
PROPEP ? 48 {ECO:0000269|PubMed:2538424}.
/FTId=PRO_0000015681.
CHAIN 49 118 Insulin-like growth factor I.
/FTId=PRO_0000015682.
PROPEP 119 153 E peptide.
/FTId=PRO_0000015683.
REGION 49 77 B.
REGION 78 89 C.
REGION 90 110 A.
REGION 111 118 D.
DISULFID 54 96 {ECO:0000250}.
DISULFID 66 109 {ECO:0000250}.
DISULFID 95 100 {ECO:0000250}.
VAR_SEQ 135 153 EVHLKNTSRGSAGNKTYRM -> SQPLSTHKKRKLQRRRKG
STLEEH (in isoform IGF-IB).
{ECO:0000305}.
/FTId=VSP_012166.
CONFLICT 110 112 APL -> VRC (in Ref. 3; AAA41385/
AAA41387). {ECO:0000305}.
SEQUENCE 153 AA; 17079 MW; 966F3C0FA4EB3DE7 CRC64;
MGKISSLPTQ LFKICLCDFL KIKIHIMSSS HLFYLALCLL TFTSSATAGP ETLCGAELVD
ALQFVCGPRG FYFNKPTGYG SSIRRAPQTG IVDECCFRSC DLRRLEMYCA PLKPTKSARS
IRAQRHTDMP KTQKEVHLKN TSRGSAGNKT YRM


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