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Protein

Insulin-like growth factor I

Gene

Igf1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Ca2+-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).By similarity

GO - Molecular functioni

  • growth factor activity Source: RGD
  • hormone activity Source: RGD
  • insulin-like growth factor receptor binding Source: RGD
  • protein serine/threonine kinase activator activity Source: BHF-UCL
  • steroid binding Source: RGD

GO - Biological processi

  • aging Source: RGD
  • cellular response to electrical stimulus Source: RGD
  • cellular response to estradiol stimulus Source: RGD
  • cellular response to insulin stimulus Source: RGD
  • detection of mechanical stimulus involved in sensory perception Source: RGD
  • female pregnancy Source: RGD
  • insulin-like growth factor receptor signaling pathway Source: BHF-UCL
  • memory Source: RGD
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cholangiocyte apoptotic process Source: RGD
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
  • negative regulation of extrinsic apoptotic signaling pathway Source: BHF-UCL
  • negative regulation of neuron death Source: RGD
  • negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
  • positive regulation of cell growth Source: RGD
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of fat cell differentiation Source: RGD
  • positive regulation of glucose import Source: UniProtKB
  • positive regulation of glycogen biosynthetic process Source: UniProtKB
  • positive regulation of osteoblast differentiation Source: RGD
  • positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: BHF-UCL
  • positive regulation of protein serine/threonine kinase activity Source: BHF-UCL
  • positive regulation of steroid hormone biosynthetic process Source: BHF-UCL
  • regulation of calcium ion transport Source: RGD
  • regulation of cell proliferation Source: RGD
  • regulation of translation Source: RGD
  • response to activity Source: RGD
  • response to caffeine Source: RGD
  • response to glucocorticoid Source: RGD
  • response to hypoxia Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to mechanical stimulus Source: RGD
  • response to nicotine Source: RGD
  • response to nutrient Source: RGD
  • response to nutrient levels Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to organic substance Source: RGD
  • response to steroid hormone Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Enzyme and pathway databases

ReactomeiR-RNO-114608. Platelet degranulation.
R-RNO-2404192. Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R).
R-RNO-2428928. IRS-related events triggered by IGF1R.
R-RNO-2428933. SHC-related events triggered by IGF1R.
R-RNO-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-RNO-422085. Synthesis, secretion, and deacylation of Ghrelin.

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-like growth factor I
Short name:
IGF-I
Alternative name(s):
Somatomedin
Gene namesi
Name:Igf1
Synonyms:Igf-1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi2868. Igf1.

Subcellular locationi

  • Secreted By similarity

GO - Cellular componenti

  • alphav-beta3 integrin-IGF-1-IGF1R complex Source: UniProtKB
  • cytoplasm Source: RGD
  • exocytic vesicle Source: UniProtKB
  • extracellular space Source: RGD
  • interstitial matrix Source: RGD
  • neuronal cell body Source: RGD
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Propeptidei? – 481 PublicationPRO_0000015681
Signal peptidei1 – ?Sequence analysis
Chaini49 – 11870Insulin-like growth factor IPRO_0000015682Add
BLAST
Propeptidei119 – 15335E peptidePRO_0000015683Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi54 ↔ 96By similarity
Disulfide bondi66 ↔ 109By similarity
Disulfide bondi95 ↔ 100By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP08025.

PTM databases

iPTMnetiP08025.

Expressioni

Gene expression databases

ExpressionAtlasiP08025. baseline and differential.
GenevisibleiP08025. RN.

Interactioni

Subunit structurei

Forms a ternary complex with IGFR1 and ITGAV:ITGB3. Forms a ternary complex with IGFR1 and ITGA6:ITGB4.By similarity

GO - Molecular functioni

  • growth factor activity Source: RGD
  • hormone activity Source: RGD
  • insulin-like growth factor receptor binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000005995.

Structurei

3D structure databases

ProteinModelPortaliP08025.
SMRiP08025. Positions 49-118.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni49 – 7729BAdd
BLAST
Regioni78 – 8912CAdd
BLAST
Regioni90 – 11021AAdd
BLAST
Regioni111 – 1188D

Sequence similaritiesi

Belongs to the insulin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IJ2T. Eukaryota.
ENOG4111MIV. LUCA.
GeneTreeiENSGT00530000063856.
HOGENOMiHOG000233362.
HOVERGENiHBG006137.
InParanoidiP08025.
KOiK05459.
OrthoDBiEOG7TF7CG.
PhylomeDBiP08025.
TreeFamiTF332820.

Family and domain databases

Gene3Di1.10.100.10. 1 hit.
InterProiIPR022341. IGF-I.
IPR016179. Insulin-like.
IPR022350. Insulin-like_growth_factor.
IPR022353. Insulin_CS.
IPR022352. Insulin_family.
[Graphical view]
PfamiPF00049. Insulin. 2 hits.
[Graphical view]
PRINTSiPR02002. INSLNLIKEGF.
PR02005. INSLNLIKEGF1.
PR00276. INSULINFAMLY.
SMARTiSM00078. IlGF. 1 hit.
[Graphical view]
SUPFAMiSSF56994. SSF56994. 1 hit.
PROSITEiPS00262. INSULIN. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform IGF-IA (identifier: P08025-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGKISSLPTQ LFKICLCDFL KIKIHIMSSS HLFYLALCLL TFTSSATAGP
60 70 80 90 100
ETLCGAELVD ALQFVCGPRG FYFNKPTGYG SSIRRAPQTG IVDECCFRSC
110 120 130 140 150
DLRRLEMYCA PLKPTKSARS IRAQRHTDMP KTQKEVHLKN TSRGSAGNKT

YRM
Length:153
Mass (Da):17,079
Last modified:February 1, 1991 - v3
Checksum:i966F3C0FA4EB3DE7
GO
Isoform IGF-IB (identifier: P08025-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     135-153: EVHLKNTSRGSAGNKTYRM → SQPLSTHKKRKLQRRRKGSTLEEH

Show »
Length:158
Mass (Da):17,831
Checksum:i27ECE1968BA152D3
GO

Sequence cautioni

The sequence AAA41385.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAA41386.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAA41387.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti110 – 1123APL → VRC in AAA41385 (PubMed:3453891).Curated
Sequence conflicti110 – 1123APL → VRC in AAA41387 (PubMed:3453891).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei135 – 15319EVHLK…KTYRM → SQPLSTHKKRKLQRRRKGST LEEH in isoform IGF-IB. CuratedVSP_012166Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M15651
, M15647, M15648, M15649 Genomic DNA. Translation: AAA41215.1.
M15650
, M15647, M15648, M15649 Genomic DNA. Translation: AAA41214.1.
M17335 mRNA. Translation: AAA41386.1. Different initiation.
M15480 mRNA. Translation: AAA41385.1. Different initiation.
M15481 mRNA. Translation: AAA41387.1. Different initiation.
X06107 mRNA. Translation: CAA29480.1.
X06043 mRNA. Translation: CAA29436.1.
PIRiA27804.
A40912.
B27804.
RefSeqiNP_001075946.2. NM_001082477.2.
NP_001075947.1. NM_001082478.1.
NP_001075948.1. NM_001082479.1. [P08025-1]
XP_006241253.1. XM_006241191.2.
XP_006241254.1. XM_006241192.1.
XP_006241255.1. XM_006241193.2. [P08025-1]
UniGeneiRn.201887.
Rn.228346.
Rn.6282.

Genome annotation databases

EnsembliENSRNOT00000038780; ENSRNOP00000035899; ENSRNOG00000004517. [P08025-1]
GeneIDi24482.
KEGGirno:24482.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M15651
, M15647, M15648, M15649 Genomic DNA. Translation: AAA41215.1.
M15650
, M15647, M15648, M15649 Genomic DNA. Translation: AAA41214.1.
M17335 mRNA. Translation: AAA41386.1. Different initiation.
M15480 mRNA. Translation: AAA41385.1. Different initiation.
M15481 mRNA. Translation: AAA41387.1. Different initiation.
X06107 mRNA. Translation: CAA29480.1.
X06043 mRNA. Translation: CAA29436.1.
PIRiA27804.
A40912.
B27804.
RefSeqiNP_001075946.2. NM_001082477.2.
NP_001075947.1. NM_001082478.1.
NP_001075948.1. NM_001082479.1. [P08025-1]
XP_006241253.1. XM_006241191.2.
XP_006241254.1. XM_006241192.1.
XP_006241255.1. XM_006241193.2. [P08025-1]
UniGeneiRn.201887.
Rn.228346.
Rn.6282.

3D structure databases

ProteinModelPortaliP08025.
SMRiP08025. Positions 49-118.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000005995.

PTM databases

iPTMnetiP08025.

Proteomic databases

PaxDbiP08025.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000038780; ENSRNOP00000035899; ENSRNOG00000004517. [P08025-1]
GeneIDi24482.
KEGGirno:24482.

Organism-specific databases

CTDi3479.
RGDi2868. Igf1.

Phylogenomic databases

eggNOGiENOG410IJ2T. Eukaryota.
ENOG4111MIV. LUCA.
GeneTreeiENSGT00530000063856.
HOGENOMiHOG000233362.
HOVERGENiHBG006137.
InParanoidiP08025.
KOiK05459.
OrthoDBiEOG7TF7CG.
PhylomeDBiP08025.
TreeFamiTF332820.

Enzyme and pathway databases

ReactomeiR-RNO-114608. Platelet degranulation.
R-RNO-2404192. Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R).
R-RNO-2428928. IRS-related events triggered by IGF1R.
R-RNO-2428933. SHC-related events triggered by IGF1R.
R-RNO-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-RNO-422085. Synthesis, secretion, and deacylation of Ghrelin.

Miscellaneous databases

PROiP08025.

Gene expression databases

ExpressionAtlasiP08025. baseline and differential.
GenevisibleiP08025. RN.

Family and domain databases

Gene3Di1.10.100.10. 1 hit.
InterProiIPR022341. IGF-I.
IPR016179. Insulin-like.
IPR022350. Insulin-like_growth_factor.
IPR022353. Insulin_CS.
IPR022352. Insulin_family.
[Graphical view]
PfamiPF00049. Insulin. 2 hits.
[Graphical view]
PRINTSiPR02002. INSLNLIKEGF.
PR02005. INSLNLIKEGF1.
PR00276. INSULINFAMLY.
SMARTiSM00078. IlGF. 1 hit.
[Graphical view]
SUPFAMiSSF56994. SSF56994. 1 hit.
PROSITEiPS00262. INSULIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Mosaic evolution of the insulin-like growth factors. Organization, sequence, and expression of the rat insulin-like growth factor I gene."
    Shimatsu A., Rotwein P.
    J. Biol. Chem. 262:7894-7900(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS IGF-IA AND IGF-IB).
    Tissue: Liver.
  2. "Isolation of rat testis cDNAs encoding an insulin-like growth factor I precursor."
    Casella S.J., Smith E.P., van Wyk J.J., Joseph D.R., Hynes M.A., Hoyt E.C., Lund P.K.
    DNA 6:325-330(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IGF-IA).
    Tissue: Testis.
  3. "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."
    Roberts C.T. Jr., Lasky S.R., Lowe W.L. Jr., Seaman W.T., LeRoith D.
    Mol. Endocrinol. 1:243-248(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IGF-IA).
  4. "Sequence of two rat insulin-like growth factor I mRNAs differing within the 5' untranslated region."
    Shimatsu A., Rotwein P.
    Nucleic Acids Res. 15:7196-7196(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE (ISOFORM IGF-IB).
  5. "A new cDNA clone relating to larger molecular species of rat insulin-like growth factor-I mRNA."
    Kato H., Okoshi A., Miura Y., Noguchi T.
    Agric. Biol. Chem. 54:1599-1601(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE (ISOFORM IGF-IA).
  6. "Identification, characterization, and regulation of a rat complementary deoxyribonucleic acid which encodes insulin-like growth factor-I."
    Murphy L.J., Bell G.I., Duckworth M.L., Friesen H.G.
    Endocrinology 121:684-691(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE OF 46-153 (ISOFORM IGF-IA).
  7. "Primary structure of rat insulin-like growth factor-I and its biological activities."
    Tamura K., Kobayashi M., Ishii Y., Tamura T., Hashimoto K., Nakamura S., Niwa M., Zapf J.
    J. Biol. Chem. 264:5616-5621(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 49-118.

Entry informationi

Entry nameiIGF1_RAT
AccessioniPrimary (citable) accession number: P08025
Secondary accession number(s): P08024
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: February 1, 1991
Last modified: July 6, 2016
This is version 149 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.