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Protein

Insulin-like growth factor I

Gene

Igf1

Organism
Mus musculus (Mouse)
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 (By similarity). Ca2+-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb (PubMed:21496647). 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 similarity1 Publication

GO - Molecular functioni

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

GO - Biological processi

  • activation of MAPK activity Source: MGI
  • activation of protein kinase B activity Source: MGI
  • blood vessel remodeling Source: MGI
  • bone mineralization involved in bone maturation Source: MGI
  • branching morphogenesis of an epithelial tube Source: MGI
  • cell activation Source: MGI
  • cell development Source: MGI
  • cell proliferation Source: MGI
  • cellular response to glucose stimulus Source: MGI
  • cellular response to insulin-like growth factor stimulus Source: MGI
  • chondroitin sulfate proteoglycan biosynthetic process Source: MGI
  • circadian rhythm Source: UniProtKB
  • ERK1 and ERK2 cascade Source: MGI
  • exocrine pancreas development Source: MGI
  • extrinsic apoptotic signaling pathway in absence of ligand Source: MGI
  • glial cell differentiation Source: MGI
  • inner ear development Source: MGI
  • insulin-like growth factor receptor signaling pathway Source: MGI
  • lung alveolus development Source: MGI
  • lung development Source: MGI
  • lung lobe morphogenesis Source: MGI
  • lung vasculature development Source: MGI
  • mammary gland development Source: MGI
  • multicellular organism growth Source: MGI
  • muscle hypertrophy Source: MGI
  • myoblast differentiation Source: MGI
  • myoblast proliferation Source: MGI
  • myotube cell development Source: MGI
  • negative regulation of androgen receptor signaling pathway Source: MGI
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of ERK1 and ERK2 cascade Source: MGI
  • negative regulation of extrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of gene expression Source: BHF-UCL
  • negative regulation of oocyte development Source: MGI
  • negative regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
  • negative regulation of smooth muscle cell apoptotic process Source: MGI
  • nervous system development Source: MGI
  • osteoblast differentiation Source: BHF-UCL
  • phosphatidylinositol 3-kinase signaling Source: MGI
  • phosphatidylinositol-mediated signaling Source: MGI
  • positive regulation of activated T cell proliferation Source: MGI
  • positive regulation of calcineurin-NFAT signaling cascade Source: MGI
  • positive regulation of cardiac muscle hypertrophy Source: MGI
  • positive regulation of cell growth involved in cardiac muscle cell development Source: MGI
  • positive regulation of cell migration Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of cerebellar granule cell precursor proliferation Source: MGI
  • positive regulation of DNA binding Source: MGI
  • positive regulation of DNA replication Source: MGI
  • positive regulation of epithelial cell proliferation Source: MGI
  • positive regulation of fibroblast proliferation Source: MGI
  • positive regulation of glucose import Source: UniProtKB
  • positive regulation of glycogen biosynthetic process Source: UniProtKB
  • positive regulation of glycolytic process Source: MGI
  • positive regulation of glycoprotein biosynthetic process Source: MGI
  • positive regulation of insulin-like growth factor receptor signaling pathway Source: MGI
  • positive regulation of MAPK cascade Source: MGI
  • positive regulation of mitotic nuclear division Source: MGI
  • positive regulation of myoblast proliferation Source: MGI
  • positive regulation of osteoblast differentiation Source: MGI
  • positive regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: MGI
  • positive regulation of protein import into nucleus, translocation Source: MGI
  • positive regulation of protein kinase B signaling Source: MGI
  • positive regulation of protein secretion Source: MGI
  • positive regulation of Ras protein signal transduction Source: MGI
  • positive regulation of smooth muscle cell migration Source: MGI
  • positive regulation of smooth muscle cell proliferation Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of transcription regulatory region DNA binding Source: MGI
  • positive regulation of trophectodermal cell proliferation Source: MGI
  • positive regulation of tyrosine phosphorylation of Stat5 protein Source: MGI
  • prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis Source: MGI
  • prostate gland epithelium morphogenesis Source: MGI
  • prostate gland growth Source: MGI
  • prostate gland stromal morphogenesis Source: MGI
  • protein kinase B signaling Source: MGI
  • protein stabilization Source: MGI
  • proteoglycan biosynthetic process Source: MGI
  • regulation of establishment or maintenance of cell polarity Source: MGI
  • regulation of gene expression Source: MGI
  • regulation of nitric oxide biosynthetic process Source: MGI
  • regulation of protein metabolic process Source: MGI
  • regulation of protein phosphorylation Source: MGI
  • response to heat Source: MGI
  • sensory perception of smell Source: UniProtKB
  • skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration Source: MGI
  • Type II pneumocyte differentiation Source: MGI
  • Type I pneumocyte differentiation Source: MGI
  • water homeostasis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Growth factor

Enzyme and pathway databases

ReactomeiR-MMU-114608. Platelet degranulation.
R-MMU-2404192. Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R).
R-MMU-2428928. IRS-related events triggered by IGF1R.
R-MMU-2428933. SHC-related events triggered by IGF1R.
R-MMU-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
R-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:96432. Igf1.

Subcellular locationi

  • Secreted 1 Publication

GO - Cellular componenti

  • alphav-beta3 integrin-IGF-1-IGF1R complex Source: UniProtKB
  • exocytic vesicle Source: UniProtKB
  • extracellular space Source: MGI
  • insulin-like growth factor ternary complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_0000015666? – 48By similarity
Signal peptidei1 – ?Sequence analysis
ChainiPRO_000001566749 – 118Insulin-like growth factor IAdd BLAST70
PropeptideiPRO_0000015668119 – 153E peptideAdd BLAST35

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi54 ↔ 96By similarity
Disulfide bondi66 ↔ 109By similarity
Disulfide bondi95 ↔ 100By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PeptideAtlasiP05017.
PRIDEiP05017.

PTM databases

iPTMnetiP05017.
PhosphoSitePlusiP05017.

Expressioni

Inductioni

Expression in the bone oscillates in a circadian manner and its expression is negatively regulated by CCRN4L/NOC.1 Publication

Gene expression databases

BgeeiENSMUSG00000020053.
CleanExiMM_IGF1.
ExpressionAtlasiP05017. baseline and differential.
GenevisibleiP05017. MM.

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

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

Protein-protein interaction databases

MINTiMINT-266530.

Structurei

3D structure databases

ProteinModelPortaliP05017.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni49 – 77BAdd BLAST29
Regioni78 – 89CAdd BLAST12
Regioni90 – 110AAdd BLAST21
Regioni111 – 118D8

Sequence similaritiesi

Belongs to the insulin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

GeneTreeiENSGT00530000063856.
HOGENOMiHOG000233362.
HOVERGENiHBG006137.
InParanoidiP05017.
KOiK05459.

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: P05017-1) [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 TFTSSTTAGP
60 70 80 90 100
ETLCGAELVD ALQFVCGPRG FYFNKPTGYG SSIRRAPQTG IVDECCFRSC
110 120 130 140 150
DLRRLEMYCA PLKPTKAARS IRAQRHTDMP KTQKEVHLKN TSRGSAGNKT

YRM
Length:153
Mass (Da):17,093
Last modified:December 7, 2004 - v2
Checksum:i967596AEAC0CA387
GO
Isoform IGF-IB (identifier: P05017-2) [UniParc]FASTAAdd to basket

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

Show »
Length:157
Mass (Da):17,623
Checksum:i153C6311A323ACA4
GO

Sequence cautioni

The sequence AAH12409 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012165135 – 153EVHLK…KTYRM → SPSLSTNKKTKLQRRRKGST FEE in isoform IGF-IB. 2 PublicationsAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK081019 mRNA. Translation: BAC38117.1.
BC012409 mRNA. Translation: AAH12409.1. Different initiation.
X04480 mRNA. Translation: CAA28168.1.
X04482 mRNA. Translation: CAA28170.1.
M28139 Genomic DNA. Translation: AAA74553.1.
M14983 Genomic DNA. Translation: AAA37925.1.
CCDSiCCDS48661.1. [P05017-1]
PIRiA25540.
RefSeqiNP_001104745.1. NM_001111275.2. [P05017-1]
NP_001300939.1. NM_001314010.1. [P05017-1]
NP_034642.2. NM_010512.5.
UniGeneiMm.268521.

Genome annotation databases

EnsembliENSMUST00000095360; ENSMUSP00000093005; ENSMUSG00000020053. [P05017-1]
ENSMUST00000122386; ENSMUSP00000113905; ENSMUSG00000020053. [P05017-1]
GeneIDi16000.
KEGGimmu:16000.
UCSCiuc007gqw.2. mouse. [P05017-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK081019 mRNA. Translation: BAC38117.1.
BC012409 mRNA. Translation: AAH12409.1. Different initiation.
X04480 mRNA. Translation: CAA28168.1.
X04482 mRNA. Translation: CAA28170.1.
M28139 Genomic DNA. Translation: AAA74553.1.
M14983 Genomic DNA. Translation: AAA37925.1.
CCDSiCCDS48661.1. [P05017-1]
PIRiA25540.
RefSeqiNP_001104745.1. NM_001111275.2. [P05017-1]
NP_001300939.1. NM_001314010.1. [P05017-1]
NP_034642.2. NM_010512.5.
UniGeneiMm.268521.

3D structure databases

ProteinModelPortaliP05017.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-266530.

PTM databases

iPTMnetiP05017.
PhosphoSitePlusiP05017.

Proteomic databases

PeptideAtlasiP05017.
PRIDEiP05017.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000095360; ENSMUSP00000093005; ENSMUSG00000020053. [P05017-1]
ENSMUST00000122386; ENSMUSP00000113905; ENSMUSG00000020053. [P05017-1]
GeneIDi16000.
KEGGimmu:16000.
UCSCiuc007gqw.2. mouse. [P05017-1]

Organism-specific databases

CTDi3479.
MGIiMGI:96432. Igf1.

Phylogenomic databases

GeneTreeiENSGT00530000063856.
HOGENOMiHOG000233362.
HOVERGENiHBG006137.
InParanoidiP05017.
KOiK05459.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiIgf1. mouse.
PROiP05017.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020053.
CleanExiMM_IGF1.
ExpressionAtlasiP05017. baseline and differential.
GenevisibleiP05017. MM.

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...

Entry informationi

Entry nameiIGF1_MOUSE
AccessioniPrimary (citable) accession number: P05017
Secondary accession number(s): P05018, Q6LDP4, Q8C4U6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: December 7, 2004
Last modified: November 30, 2016
This is version 170 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.