UniProtKB - P01344 (IGF2_HUMAN)
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Protein
Insulin-like growth factor II
Gene
IGF2
Organism
Homo sapiens (Human)
Status
Functioni
The insulin-like growth factors possess growth-promoting activity. In vitro, they are potent mitogens for cultured cells. IGF-II is influenced by placental lactogen and may play a role in fetal development.
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.
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
- protein serine/threonine kinase activator activity Source: BHF-UCL
- receptor activator activity Source: BHF-UCL
GO - Biological processi
- cellular protein metabolic process Source: Reactome
- glucose metabolic process Source: UniProtKB-KW
- insulin receptor signaling pathway Source: ProtInc
- insulin receptor signaling pathway via phosphatidylinositol 3-kinase Source: BHF-UCL
- multicellular organism development Source: ProtInc
- ossification Source: UniProtKB-KW
- platelet degranulation Source: Reactome
- positive regulation of activated T cell proliferation Source: BHF-UCL
- positive regulation of catalytic activity Source: BHF-UCL
- positive regulation of cell division Source: UniProtKB-KW
- positive regulation of cell proliferation Source: BHF-UCL
- 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: BHF-UCL
- positive regulation of mitotic nuclear division Source: BHF-UCL
- positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
- positive regulation of protein kinase B signaling Source: BHF-UCL
- positive regulation of protein phosphorylation Source: BHF-UCL
- regulation of gene expression by genetic imprinting Source: ProtInc
- regulation of transcription, DNA-templated Source: BHF-UCL
- skeletal system development Source: ProtInc
Keywordsi
| Molecular function | Growth factor, Hormone, Mitogen |
| Biological process | Carbohydrate metabolism, Glucose metabolism, Osteogenesis |
Enzyme and pathway databases
| Reactomei | R-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). |
| SignaLinki | P01344. |
| SIGNORi | P01344. |
Names & Taxonomyi
| Protein namesi | Recommended name: Insulin-like growth factor IIShort 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 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:5466. IGF2. |
Subcellular locationi
- Secreted 1 Publication
GO - Cellular componenti
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
- extracellular space Source: InterPro
- plasma membrane Source: Reactome
- platelet alpha granule lumen Source: Reactome
Keywords - Cellular componenti
SecretedPathology & 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:180860Growth 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:616489Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 92 | R → A: Decreases mature IGF2 levels. 1 Publication | 1 | |
| Mutagenesisi | 112 | K → A: No effect in proteolytical processing. 1 Publication | 1 | |
| Mutagenesisi | 128 | R → A: Abolishes proteolytical processing. 1 Publication | 1 |
Keywords - Diseasei
DwarfismOrganism-specific databases
| DisGeNETi | 3481. |
| MalaCardsi | IGF2. |
| MIMi | 147470. gene+phenotype. 180860. phenotype. 616489. phenotype. |
| OpenTargetsi | ENSG00000167244. |
| Orphaneti | 231117. 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. |
| PharmGKBi | PA29699. |
Polymorphism and mutation databases
| BioMutai | IGF2. |
| DMDMi | 124255. |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Signal peptidei | 1 – 24 | 2 PublicationsAdd BLAST | 24 | |
| ChainiPRO_0000015717 | 25 – 91 | Insulin-like growth factor IIAdd BLAST | 67 | |
| ChainiPRO_0000015718 | 26 – 91 | Insulin-like growth factor II Ala-25 DelAdd BLAST | 66 | |
| PropeptideiPRO_0000015719 | 92 – 180 | E peptideAdd BLAST | 89 | |
| PeptideiPRO_0000370376 | 93 – 126 | PreptinAdd BLAST | 34 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Disulfide bondi | 33 ↔ 71 | 1 Publication | ||
| Disulfide bondi | 45 ↔ 84 | 1 Publication | ||
| Disulfide bondi | 70 ↔ 75 | 1 Publication | ||
| Glycosylationi | 96 | O-linked (GalNAc...) threonine2 Publications | 1 | |
| Glycosylationi | 99 | O-linked (GalNAc...) threonine2 Publications | 1 | |
| Glycosylationi | 163 | O-linked (GalNAc...) threonine2 Publications | 1 |
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, GlycoproteinProteomic databases
| MaxQBi | P01344. |
| PaxDbi | P01344. |
| PeptideAtlasi | P01344. |
| PRIDEi | P01344. |
PTM databases
| iPTMneti | P01344. |
| PhosphoSitePlusi | P01344. |
| UniCarbKBi | P01344. |
Miscellaneous databases
| PMAP-CutDBi | P01344. |
Expressioni
Gene expression databases
| Bgeei | ENSG00000167244. |
| CleanExi | HS_IGF2. |
| Genevisiblei | P01344. HS. |
Organism-specific databases
| HPAi | HPA007556. HPA007993. |
Interactioni
Binary interactionsi
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
Protein-protein interaction databases
| BioGridi | 109702. 15 interactors. |
| DIPi | DIP-29508N. |
| IntActi | P01344. 7 interactors. |
| MINTi | MINT-6380943. |
| STRINGi | 9606.ENSP00000391826. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Helixi | 34 – 44 | Combined sources | 11 | |
| Turni | 45 – 48 | Combined sources | 4 | |
| Beta strandi | 50 – 52 | Combined sources | 3 | |
| Helixi | 55 – 58 | Combined sources | 4 | |
| Helixi | 61 – 72 | Combined sources | 12 | |
| Helixi | 77 – 82 | Combined sources | 6 | |
| Beta strandi | 86 – 88 | Combined sources | 3 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1GF2 | model | - | A | 25-91 | [»] | |
| 1IGL | NMR | - | A | 25-91 | [»] | |
| 2L29 | NMR | - | B | 25-91 | [»] | |
| 2V5P | X-ray | 4.10 | C/D | 25-91 | [»] | |
| 3E4Z | X-ray | 2.28 | C/D | 25-91 | [»] | |
| 3KR3 | X-ray | 2.20 | D | 25-91 | [»] | |
| 5L3L | NMR | - | A | 25-91 | [»] | |
| 5L3M | NMR | - | A | 25-91 | [»] | |
| 5L3N | NMR | - | A | 25-91 | [»] | |
| ProteinModelPortali | P01344. | |||||
| SMRi | P01344. | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Miscellaneous databases
| EvolutionaryTracei | P01344. |
Family & Domainsi
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 25 – 52 | BAdd BLAST | 28 | |
| Regioni | 53 – 64 | CAdd BLAST | 12 | |
| Regioni | 65 – 85 | AAdd BLAST | 21 | |
| Regioni | 86 – 91 | D | 6 |
Sequence similaritiesi
Belongs to the insulin family.Curated
Keywords - Domaini
SignalPhylogenomic databases
| eggNOGi | ENOG410IY3P. Eukaryota. ENOG4111KP2. LUCA. |
| GeneTreei | ENSGT00530000063856. |
| HOGENOMi | HOG000233362. |
| HOVERGENi | HBG006137. |
| InParanoidi | P01344. |
| KOi | K13769. |
| OMAi | FPRYPVG. |
| OrthoDBi | EOG091G0H56. |
| PhylomeDBi | P01344. |
| TreeFami | TF332820. |
Family and domain databases
| Gene3Di | 1.10.100.10. 1 hit. |
| InterProi | View protein in InterPro IPR022334. IGF2. IPR013576. IGF2_C. IPR016179. Insulin-like. IPR022350. Insulin-like_growth_factor. IPR022353. Insulin_CS. IPR022352. Insulin_family. |
| Pfami | View protein in Pfam PF08365. IGF2_C. 1 hit. PF00049. Insulin. 2 hits. |
| PRINTSi | PR02002. INSLNLIKEGF. PR02006. INSLNLIKEGF2. PR00276. INSULINFAMLY. |
| ProDomi | View protein in ProDom or Entries sharing at least one domain PD005188. IGF2_C. 1 hit. |
| SMARTi | View protein in SMART SM00078. IlGF. 1 hit. |
| SUPFAMi | SSF56994. SSF56994. 1 hit. |
| PROSITEi | View 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.
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
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 3 | I → M in AAA52544 (PubMed:3683205).Curated | 1 | |
| Sequence conflicti | 107 – 110 | RYPV → EIPL in CAA27249 (PubMed:6382022).Curated | 4 | |
| Sequence conflicti | 147 | E → ELE in AAA60088 (PubMed:3476948).Curated | 1 |
Mass spectrometryi
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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_011959 | 120 | K → N. Corresponds to variant dbSNP:rs14367Ensembl. | 1 | |
| Natural variantiVAR_011960 | 173 | P → Q. Corresponds to variant dbSNP:rs1050342Ensembl. | 1 | |
| Natural variantiVAR_011961 | 180 | K → N. Corresponds to variant dbSNP:rs12993Ensembl. | 1 |
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_045624 | 1 | M → MVSPDPQIIVVAPETELASM QVQRTEDGVTIIQIFWVGRK GELLRRTPVSSAMQTPM in isoform 3. 1 Publication | 1 | |
| Alternative sequenceiVSP_002708 | 53 | S → RLPG in isoform 2. 2 Publications | 1 |
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. |
| CCDSi | CCDS44517.1. [P01344-3] CCDS7728.1. [P01344-1] |
| PIRi | B23614. IGHU2. I67610. S02423. |
| RefSeqi | NP_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] |
| UniGenei | Hs.272259. |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar 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. |
Entry informationi
| Entry namei | IGF2_HUMAN | |
| Accessioni | P01344Primary (citable) accession number: P01344 Secondary accession number(s): B3KX48 Q9UC69 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
| Last sequence update: | July 21, 1986 | |
| Last modified: | June 7, 2017 | |
| This is version 216 of the entry and version 1 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
| Disclaimer | Any 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 proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families
