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Protein

Insulin-like growth factor II

Gene

Igf2

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 possess growth-promoting activity (Probable). Major fetal growth hormone in mammals. Plays a key role in regulating fetoplacental development (Probable) (PubMed:2330056, PubMed:12087403). IGF-II is influenced by placental lactogen (Probable). Also involved in tissue differentiation (Probable). Positively regulates myogenic transcription factor MYOD1 function by facilitating the recruitment of transcriptional coactivators, thereby controlling muscle terminal differentiation (PubMed:16901893). In adults, involved in glucose metabolism in adipose tissue, skeletal muscle and liver (Probable).2 Publications3 Publications
Preptin undergoes glucose-mediated co-secretion with insulin, and acts as physiological amplifier of glucose-mediated insulin secretion. Exhibits osteogenic properties by increasing osteoblast mitogenic activity through phosphoactivation of MAPK1 and MAPK3.1 Publication

Miscellaneous

The IGF2 locus is imprinted. Paternal inherited gene is expressed, while the maternal inherited gene is imprinted, hence silenced (PubMed:1997210). It is differentially regulated in the placenta and fetus, transcribed from 3 promoters P1, P2 and P3 in both fetus and placenta and additionally from a fourth placental-specific promoter, P0 (Probable).1 Publication1 Publication

GO - Molecular functioni

  • growth factor activity Source: MGI
  • hormone activity Source: UniProtKB-KW
  • insulin-like growth factor receptor binding Source: MGI
  • insulin receptor binding Source: MGI
  • protein serine/threonine kinase activator activity Source: BHF-UCL
  • receptor ligand activity Source: BHF-UCL

GO - Biological processi

  • animal organ morphogenesis Source: MGI
  • embryonic placenta development Source: UniProtKB
  • embryonic placenta morphogenesis Source: UniProtKB
  • exocrine pancreas development Source: MGI
  • glucose metabolic process Source: UniProtKB-KW
  • insulin receptor signaling pathway via phosphatidylinositol 3-kinase Source: BHF-UCL
  • in utero embryonic development Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • osteoblast differentiation Source: BHF-UCL
  • positive regulation of activated T cell proliferation Source: MGI
  • positive regulation of catalytic activity Source: BHF-UCL
  • positive regulation of cell division Source: UniProtKB-KW
  • positive regulation of glycogen (starch) synthase activity Source: BHF-UCL
  • positive regulation of glycogen biosynthetic process Source: BHF-UCL
  • positive regulation of insulin receptor signaling pathway Source: BHF-UCL
  • positive regulation of MAPK cascade Source: MGI
  • positive regulation of mitotic nuclear division Source: MGI
  • positive regulation of multicellular organism growth Source: MGI
  • positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
  • positive regulation of protein kinase B signaling Source: MGI
  • positive regulation of protein phosphorylation Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • regulation of histone modification Source: UniProtKB
  • regulation of muscle cell differentiation Source: UniProtKB
  • striated muscle cell differentiation Source: MGI

Keywordsi

Molecular functionGrowth factor, Hormone, Mitogen
Biological processCarbohydrate metabolism, Glucose metabolism, Osteogenesis

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).

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-like growth factor II
Alternative name(s):
IGF-II
Multiplication-stimulating polypeptide
Cleaved into the following 2 chains:
Gene namesi
Name:Igf2
Synonyms:Igf-2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:96434. Igf2.

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

Pathology & Biotechi

Disruption phenotypei

Heterozygous animals are smaller than their wild type littermates but appear normal, reach sexual maturity and are fertile (PubMed:2330056). Transmission of this mutation through the male germline results in heterozygous progeny that are growth deficient. In contrast, when the disrupted gene is transmitted maternally, the heterozygous offspring are phenotypically normal. Homozygous mutants are indistinguishable in appearance from growth-deficient heterozygous siblings (PubMed:1997210). Mutant animals for transcript P0 specifically show a reduced growth of the placenta followed by fetal growth restriction, passive permeability for nutrients of the placenta is decreased (PubMed:12087403).3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Add BLAST24
ChainiPRO_000001572025 – 91Insulin-like growth factor IIAdd BLAST67
PropeptideiPRO_000001572192 – 180E peptideAdd BLAST89
PeptideiPRO_000037037793 – 126PreptinAdd BLAST34

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi33 ↔ 71By similarity
Disulfide bondi45 ↔ 84By similarity
Disulfide bondi70 ↔ 75By similarity

Post-translational modificationi

Proteolytically processed by PCSK4, proIGF2 is cleaved at Arg-128 and Arg-92 to generate big-IGF2 and mature IGF2.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond

Proteomic databases

MaxQBiP09535.
PaxDbiP09535.
PeptideAtlasiP09535.
PRIDEiP09535.

PTM databases

iPTMnetiP09535.
PhosphoSitePlusiP09535.

Expressioni

Developmental stagei

At E8, E9.5 and E16.5, transcripts from parental allele are detected in embryonic and extraembryonic tissues (PubMed:28522536, PubMed:1997210). At E16.5, transcripts from parental and maternal alleles are detected only in the choroid plexus and the leptomeninges (PubMed:1997210). Low levels of expression during myoblast proliferation. Levels rise rapidly during myoblast differentiation and then decrease.2 Publications

Gene expression databases

BgeeiENSMUSG00000048583.
CleanExiMM_IGF2.
ExpressionAtlasiP09535. baseline and differential.
GenevisibleiP09535. MM.

Interactioni

Subunit structurei

Interacts with MYORG; this interaction is required for IGF2 secretion.1 Publication

GO - Molecular functioni

  • growth factor activity Source: MGI
  • hormone activity Source: UniProtKB-KW
  • insulin-like growth factor receptor binding Source: MGI
  • insulin receptor binding Source: MGI
  • receptor ligand activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi200549. 2 interactors.
STRINGi10090.ENSMUSP00000114076.

Structurei

3D structure databases

ProteinModelPortaliP09535.
SMRiP09535.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni25 – 52BAdd BLAST28
Regioni53 – 64CAdd BLAST12
Regioni65 – 85AAdd BLAST21
Regioni86 – 91D6

Sequence similaritiesi

Belongs to the insulin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IY3P. Eukaryota.
ENOG4111KP2. LUCA.
GeneTreeiENSGT00530000063856.
HOGENOMiHOG000233362.
HOVERGENiHBG006137.
InParanoidiP09535.
KOiK13769.
OMAiFPRYPVG.
OrthoDBiEOG091G0H56.
PhylomeDBiP09535.
TreeFamiTF332820.

Family and domain databases

Gene3Di1.10.100.10. 1 hit.
InterProiView protein in InterPro
IPR022334. IGF2.
IPR013576. IGF2_C.
IPR016179. Insulin-like.
IPR022350. Insulin-like_growth_factor.
IPR036438. Insulin-like_sf.
IPR022353. Insulin_CS.
IPR022352. Insulin_family.
PfamiView protein in Pfam
PF08365. IGF2_C. 1 hit.
PF00049. Insulin. 1 hit.
PRINTSiPR02002. INSLNLIKEGF.
PR02006. INSLNLIKEGF2.
PR00276. INSULINFAMLY.
ProDomiView protein in ProDom or Entries sharing at least one domain
PD005188. IGF2_C. 1 hit.
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 promoter usage. AlignAdd to basket

Isoform 1 (identifier: P09535-1) [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
MGIPVGKSML VLLISLAFAL CCIAAYGPGE TLCGGELVDT LQFVCSDRGF
60 70 80 90 100
YFSRPSSRAN RRSRGIVEEC CFRSCDLALL ETYCATPAKS ERDVSTSQAV
110 120 130 140 150
LPDDFPRYPV GKFFQYDTWR QSAGRLRRGL PALLRARRGR MLAKELKEFR
160 170 180
EAKRHRPLIV LPPKDPAHGG ASSEMSSNHQ
Note: Product of 4 different transcripts regulated by 4 different promoters, denominated P0, P1, P2 and P3.1 Publication
Length:180
Mass (Da):20,030
Last modified:July 1, 1989 - v1
Checksum:i01730F8856EE6D7B
GO
Isoform 2 (identifier: P09535-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MGGSVAGFQVPM

Show »
Length:191
Mass (Da):21,061
Checksum:iECF67B35396A7821
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0591131M → MGGSVAGFQVPM in isoform 2. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14951 mRNA. Translation: AAA37683.1.
M36332, M36331 Genomic DNA. Translation: AAA37926.1.
U71085 Genomic DNA. Translation: AAC53516.1.
M24633 Genomic DNA. Translation: AAA37923.1.
X71921 Genomic DNA. Translation: CAA50737.1.
X71922 Genomic DNA. Translation: CAA50738.1.
AC013548 Genomic DNA. No translation available.
BC053489 mRNA. Translation: AAH53489.1.
CCDSiCCDS52458.1. [P09535-1]
PIRiA24913.
RefSeqiNP_001116208.1. NM_001122736.2.
NP_001116209.1. NM_001122737.2.
NP_001302417.1. NM_001315488.1.
NP_001302418.1. NM_001315489.1.
NP_034644.2. NM_010514.3.
XP_006508550.1. XM_006508487.1.
UniGeneiMm.3862.

Genome annotation databases

EnsembliENSMUST00000000033; ENSMUSP00000000033; ENSMUSG00000048583. [P09535-1]
ENSMUST00000097936; ENSMUSP00000095549; ENSMUSG00000048583. [P09535-1]
ENSMUST00000105935; ENSMUSP00000101555; ENSMUSG00000048583. [P09535-1]
ENSMUST00000105936; ENSMUSP00000101556; ENSMUSG00000048583. [P09535-1]
ENSMUST00000121128; ENSMUSP00000114076; ENSMUSG00000048583. [P09535-2]
GeneIDi16002.
KEGGimmu:16002.
UCSCiuc009kod.2. mouse. [P09535-1]

Keywords - Coding sequence diversityi

Alternative promoter usage

Similar proteinsi

Entry informationi

Entry nameiIGF2_MOUSE
AccessioniPrimary (citable) accession number: P09535
Secondary accession number(s): E9QLW5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: November 22, 2017
This is version 150 of the entry and version 1 of the sequence. See 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families