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Protein

Insulin-like growth factor II

Gene

Igf2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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). Acts as a ligand for integrin which is required for IGF2 signaling (By similarity).By similarity2 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei48Important for interaction with integrinBy similarity1
Sitei58Important for interaction with integrinBy similarity1
Sitei61Important for interaction with integrinBy similarity1
Sitei62Important for interaction with integrinBy similarity1

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
  • integrin binding Source: UniProtKB
  • protein serine/threonine kinase activator activity Source: BHF-UCL
  • receptor ligand activity Source: BHF-UCL

GO - Biological processi

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 Expressed in 338 organ(s), highest expression level in tracheobronchial tree
CleanExiMM_IGF2
ExpressionAtlasiP09535 baseline and differential
GenevisibleiP09535 MM

Interactioni

Subunit structurei

Interacts with MYORG; this interaction is required for IGF2 secretion (PubMed:19706595). Interacts with integrins ITGAV:ITGB3 and ITGA6:ITGB4; integrin-binding is required for IGF2 signaling (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200549, 3 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
OMAiWQRKAAQ
OrthoDBiEOG091G0H56
PhylomeDBiP09535
TreeFamiTF332820

Family and domain databases

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D3Z4N4D3Z4N4_MOUSE
Insulin-like growth factor II
Igf2
103Annotation score:
J3QJZ9J3QJZ9_MOUSE
Insulin-like growth factor II
Igf2
121Annotation score:

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
CCDSiCCDS22033.2 [P09535-2]
CCDS52458.1 [P09535-1]
PIRiA24913
RefSeqiNP_001116208.1, NM_001122736.2 [P09535-1]
NP_001116209.1, NM_001122737.2 [P09535-1]
NP_001302417.1, NM_001315488.1 [P09535-1]
NP_001302418.1, NM_001315489.1 [P09535-1]
NP_034644.2, NM_010514.3 [P09535-2]
XP_006508550.1, XM_006508487.1 [P09535-1]
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

Cross-referencesi

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
CCDSiCCDS22033.2 [P09535-2]
CCDS52458.1 [P09535-1]
PIRiA24913
RefSeqiNP_001116208.1, NM_001122736.2 [P09535-1]
NP_001116209.1, NM_001122737.2 [P09535-1]
NP_001302417.1, NM_001315488.1 [P09535-1]
NP_001302418.1, NM_001315489.1 [P09535-1]
NP_034644.2, NM_010514.3 [P09535-2]
XP_006508550.1, XM_006508487.1 [P09535-1]
UniGeneiMm.3862

3D structure databases

ProteinModelPortaliP09535
SMRiP09535
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200549, 3 interactors
STRINGi10090.ENSMUSP00000114076

PTM databases

iPTMnetiP09535
PhosphoSitePlusiP09535

Proteomic databases

MaxQBiP09535
PaxDbiP09535
PeptideAtlasiP09535
PRIDEiP09535

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi3481
MGIiMGI:96434 Igf2

Phylogenomic databases

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

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)

Miscellaneous databases

ChiTaRSiIgf2 mouse
PROiPR:P09535
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000048583 Expressed in 338 organ(s), highest expression level in tracheobronchial tree
CleanExiMM_IGF2
ExpressionAtlasiP09535 baseline and differential
GenevisibleiP09535 MM

Family and domain databases

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
ProtoNetiSearch...

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 7, 2018
This is version 157 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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