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Protein

Insulin-like growth factor II

Gene

IGF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

The insulin-like growth factors possess growth-promoting activity. Major fetal growth hormone in mammals. Plays a key role in regulating fetoplacental development. IGF-II is influenced by placental lactogen. Also involved in tissue differentiation. Positively regulates myogenic transcription factor MYOD1 function by facilitating the recruitment of transcriptional coactivators, thereby controlling muscle terminal differentiation (By similarity). 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 (PubMed:28873464).By similarity1 Publication1 Publication
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. Transcripts from 5 promoters P0, P1, P2, P3 and P4 code for the same protein but are differentially regulated in a developmental stage and tissue specificity.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei48Important for interaction with integrin1 Publication1
Sitei58Important for interaction with integrin1 Publication1
Sitei61Important for interaction with integrin1 Publication1
Sitei62Important for interaction with integrin1 Publication1

GO - Molecular functioni

  • growth factor activity Source: BHF-UCL
  • hormone activity Source: UniProtKB-KW
  • insulin-like growth factor receptor binding Source: AgBase
  • insulin receptor binding Source: BHF-UCL
  • 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-HSA-114608 Platelet degranulation
R-HSA-2404192 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-2428928 IRS-related events triggered by IGF1R
R-HSA-2428933 SHC-related events triggered by IGF1R
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
SignaLinkiP01344
SIGNORiP01344

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-like growth factor II
Short name:
IGF-II
Alternative name(s):
Somatomedin-A
T3M-11-derived growth factor
Cleaved into the following 3 chains:
Gene namesi
Name:IGF2
ORF Names:PP1446
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000167244.18
HGNCiHGNC:5466 IGF2
MIMi147470 gene+phenotype
neXtProtiNX_P01344

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

Involvement in diseasei

Silver-Russell syndrome (SRS)1 Publication
The gene represented in this entry is involved in disease pathogenesis. Most of the cases of Silver-Russell syndrome are caused by the epigenetic changes of DNA hypomethylation at the telomeric imprinting control region (ICR1) on chromosome 11p15, involving the H19 and IGF2 genes.
Disease descriptionA clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age.
See also OMIM:180860
Growth restriction, severe, with distinctive facies (GRDF)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by severe prenatal and postnatal growth restriction, facial dysmorphism, and short stature in the presence of normal or slightly elevated growth hormone levels.
See also OMIM:616489

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi48R → E: Does not affect integrin binding. Defective integrin binding and IGF2 signaling; when associated with E-58; E-61 and E-62. 1 Publication1
Mutagenesisi58R → E: Does not affect integrin binding. Defective integrin binding and IGF2 signaling; when associated with E-48; E-61 and E-62. 1 Publication1
Mutagenesisi61R → E: Does not affect integrin binding. Defective integrin binding and IGF2 signaling; when associated with E-48; E-58 and E-62. 1 Publication1
Mutagenesisi62R → E: Does not affect integrin binding. Defective integrin binding and IGF2 signaling; when associated with E-48; E-58 and E-61. 1 Publication1
Mutagenesisi64R → E: Slight but significant increase in integrin binding. 1 Publication1
Mutagenesisi92R → A: Decreases mature IGF2 levels. 1 Publication1
Mutagenesisi112K → A: No effect in proteolytical processing. 1 Publication1
Mutagenesisi128R → A: Abolishes proteolytical processing. 1 Publication1

Keywords - Diseasei

Dwarfism

Organism-specific databases

DisGeNETi3481
GeneReviewsiIGF2
MalaCardsiIGF2
MIMi147470 gene+phenotype
180860 phenotype
616489 phenotype
OpenTargetsiENSG00000167244
Orphaneti231117 Beckwith-Wiedemann syndrome due to imprinting defect of 11p15
2128 Hemihypertrophy
231144 Silver-Russell syndrome due to 11p15 microduplication
231140 Silver-Russell syndrome due to imprinting defect of 11p15
PharmGKBiPA29699

Chemistry databases

ChEMBLiCHEMBL3712957

Polymorphism and mutation databases

BioMutaiIGF2
DMDMi124255

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 242 PublicationsAdd BLAST24
ChainiPRO_000001571725 – 91Insulin-like growth factor IIAdd BLAST67
ChainiPRO_000001571826 – 91Insulin-like growth factor II Ala-25 DelAdd BLAST66
PropeptideiPRO_000001571992 – 180E peptideAdd BLAST89
PeptideiPRO_000037037693 – 126PreptinAdd BLAST34

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi33 ↔ 711 Publication
Disulfide bondi45 ↔ 841 Publication
Disulfide bondi70 ↔ 751 Publication
Glycosylationi96O-linked (GalNAc...) threonine2 Publications1
Glycosylationi99O-linked (GalNAc...) threonine2 Publications1
Glycosylationi163O-linked (GalNAc...) threonine2 Publications1

Post-translational modificationi

O-glycosylated with core 1 or possibly core 8 glycans. Thr-96 is a minor glycosylation site compared to Thr-99.4 Publications
Proteolytically processed by PCSK4, proIGF2 is cleaved at Arg-128 and Arg-92 to generate big-IGF2 and mature IGF2.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiP01344
PaxDbiP01344
PeptideAtlasiP01344
PRIDEiP01344
ProteomicsDBi12641 [P01344-2]
51375
51376 [P01344-2]

PTM databases

GlyConnecti760
iPTMnetiP01344
PhosphoSitePlusiP01344
UniCarbKBiP01344

Miscellaneous databases

PMAP-CutDBiP01344

Expressioni

Tissue specificityi

Expressed in heart, placenta, lung, liver, muscle, kidney, tongue, limb, eye and pancreas.1 Publication

Developmental stagei

During embryogenesis, detected in liver, lung, skeletal muscle and placenta.1 Publication

Gene expression databases

BgeeiENSG00000167244
CleanExiHS_IGF2
GenevisibleiP01344 HS

Organism-specific databases

HPAiHPA007556
HPA007993

Interactioni

Subunit structurei

Interacts with MYORG; this interaction is required for IGF2 secretion (By similarity). Interacts with integrins ITGAV:ITGB3 and ITGA6:ITGB4; integrin-binding is required for IGF2 signaling (PubMed:28873464).By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi109702, 30 interactors
CORUMiP01344
DIPiDIP-29508N
IntActiP01344, 10 interactors
MINTiP01344
STRINGi9606.ENSP00000391826

Structurei

Secondary structure

1180
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi34 – 44Combined sources11
Turni45 – 48Combined sources4
Beta strandi50 – 52Combined sources3
Helixi55 – 58Combined sources4
Helixi61 – 72Combined sources12
Helixi77 – 82Combined sources6
Beta strandi86 – 88Combined sources3

3D structure databases

ProteinModelPortaliP01344
SMRiP01344
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01344

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
InParanoidiP01344
KOiK13769
OMAiFPRYPVG
OrthoDBiEOG091G0H56
PhylomeDBiP01344
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, 2 hits
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 (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P01344-1) [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
MGIPMGKSML VLLTFLAFAS CCIAAYRPSE TLCGGELVDT LQFVCGDRGF
60 70 80 90 100
YFSRPASRVS RRSRGIVEEC CFRSCDLALL ETYCATPAKS ERDVSTPPTV
110 120 130 140 150
LPDNFPRYPV GKFFQYDTWK QSTQRLRRGL PALLRARRGH VLAKELEAFR
160 170 180
EAKRHRPLIA LPTQDPAHGG APPEMASNRK
Note: Product of 5 different transcripts regulated by 5 different promoters, denominated P0, P1, P2, P3 and P4.1 Publication
Length:180
Mass (Da):20,140
Last modified:July 21, 1986 - v1
Checksum:iC1B0EB1E016BA37A
GO
Isoform 2 (identifier: P01344-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     53-53: S → RLPG

Show »
Length:183
Mass (Da):20,477
Checksum:iA54CD97B56C2B96F
GO
Isoform 3 (identifier: P01344-3) [UniParc]FASTAAdd to basket

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

Note: Gene prediction based on EST data.
Show »
Length:236
Mass (Da):26,331
Checksum:iCF1395E851055BF6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3I → M in AAA52544 (PubMed:3683205).Curated1
Sequence conflicti107 – 110RYPV → EIPL in CAA27249 (PubMed:6382022).Curated4
Sequence conflicti147E → ELE in AAA60088 (PubMed:3476948).Curated1

Mass spectrometryi

Molecular mass is 7469.4 Da from positions 25 - 91. Determined by MALDI. 2 Publications
Molecular mass is 7398.3 Da from positions 26 - 91. Determined by MALDI. 2 Publications

Polymorphismi

Genetic variations in IGF2 are associated with body mass index (BMI). The BMI is a statistical measurement which compares a person's weight and height.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011959120K → N. Corresponds to variant dbSNP:rs14367Ensembl.1
Natural variantiVAR_011960173P → Q. Corresponds to variant dbSNP:rs1050342Ensembl.1
Natural variantiVAR_011961180K → N. Corresponds to variant dbSNP:rs12993Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0456241M → MVSPDPQIIVVAPETELASM QVQRTEDGVTIIQIFWVGRK GELLRRTPVSSAMQTPM in isoform 3. 1 Publication1
Alternative sequenceiVSP_00270853S → RLPG in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03562 Genomic DNA Translation: CAA27249.1
X00910 mRNA Translation: CAA25426.1
J03242 mRNA Translation: AAA52545.1
X03425 Genomic DNA Translation: CAA27155.1
X03426 Genomic DNA Translation: CAA27156.1
X03427 Genomic DNA Translation: CAA27157.1
M17426 mRNA Translation: AAA60088.1
M29645 mRNA Translation: AAA52544.1
M17863 mRNA Translation: AAA52443.1 Sequence problems.
S77035 mRNA Translation: AAB34155.1
DQ104203 mRNA Translation: ABD93451.1
HM481219 mRNA Translation: ADO21454.1
AF217977 mRNA Translation: AAG17220.1
BT007013 mRNA Translation: AAP35659.1
AF517226 Genomic DNA Translation: AAM51825.1
AC132217 Genomic DNA No translation available.
AK126688 mRNA Translation: BAG54360.1
CH471158 Genomic DNA Translation: EAX02485.1
BC000531 mRNA Translation: AAH00531.1
X07868 Genomic DNA Translation: CAA30717.1
X06159 mRNA Translation: CAA29516.1
X06160 Transcribed RNA Translation: CAA29517.1
X06161 mRNA Translation: CAA29518.1
M22373 Genomic DNA Translation: AAA52536.1
CCDSiCCDS44517.1 [P01344-3]
CCDS7728.1 [P01344-1]
PIRiB23614 IGHU2
I67610
S02423
RefSeqiNP_000603.1, NM_000612.5 [P01344-1]
NP_001007140.2, NM_001007139.5 [P01344-1]
NP_001121070.1, NM_001127598.2 [P01344-3]
NP_001278790.1, NM_001291861.2 [P01344-1]
NP_001278791.1, NM_001291862.2 [P01344-1]
UniGeneiHs.272259

Genome annotation databases

EnsembliENST00000381389; ENSP00000370796; ENSG00000167244 [P01344-1]
ENST00000381392; ENSP00000370799; ENSG00000167244 [P01344-2]
ENST00000381395; ENSP00000370802; ENSG00000167244 [P01344-1]
ENST00000381406; ENSP00000370813; ENSG00000167244 [P01344-2]
ENST00000416167; ENSP00000414497; ENSG00000167244 [P01344-1]
ENST00000418738; ENSP00000402047; ENSG00000167244 [P01344-1]
ENST00000434045; ENSP00000391826; ENSG00000167244 [P01344-3]
ENST00000641326; ENSP00000493122; ENSG00000167244 [P01344-1]
GeneIDi3481
KEGGihsa:3481
UCSCiuc001lvf.4 human [P01344-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIGF2_HUMAN
AccessioniPrimary (citable) accession number: P01344
Secondary accession number(s): B3KX48
, B7WP08, C9JAF2, E3UN45, P78449, Q14299, Q1WM26, Q9UC68, Q9UC69
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: July 18, 2018
This is version 227 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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