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Protein

Insulin-like growth factor I

Gene

Igf1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

  • growth factor activity Source: UniProtKB-KW
  • 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 amyloid-beta 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
  • negative regulation of vascular associated 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 gene expression 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 by RNA polymerase II 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 STAT protein Source: MGI
  • positive regulation of vascular smooth muscle cell proliferation 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

Keywordsi

Molecular functionGrowth 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:96432 Igf1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

  • growth factor activity Source: UniProtKB-KW
  • 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

MINTiP05017

Structurei

3D structure databases

ProteinModelPortaliP05017
SMRiP05017
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

InterProiView protein in InterPro
IPR022341 IGF-I
IPR016179 Insulin-like
IPR022350 Insulin-like_growth_factor
IPR036438 Insulin-like_sf
IPR022353 Insulin_CS
IPR022352 Insulin_family
PfamiView protein in Pfam
PF00049 Insulin, 2 hits
PRINTSiPR02002 INSLNLIKEGF
PR02005 INSLNLIKEGF1
PR00276 INSULINFAMLY
SMARTiView protein in SMART
SM00078 IlGF, 1 hit
SUPFAMiSSF56994 SSF56994, 1 hit
PROSITEiView protein in PROSITE
PS00262 INSULIN, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiIGF1_MOUSE
AccessioniPrimary (citable) accession number: P05017
Secondary accession number(s): P05018, Q6LDP4, Q8C4U6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: December 7, 2004
Last modified: May 23, 2018
This is version 181 of the entry and version 2 of the sequence. See 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

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