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Protein

Insulin-like growth factor I

Gene

IGF1

Organism
Homo sapiens (Human)
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 (PubMed:21076856, PubMed:24132240). Ca2+-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb (By similarity). 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 (PubMed:19578119, PubMed:22351760, PubMed:23696648, PubMed:23243309).By similarity6 Publications

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionGrowth factor

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)
R-HSA-422085 Synthesis, secretion, and deacylation of Ghrelin
SABIO-RKiP05019
SignaLinkiP05019
SIGNORiP05019

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-like growth factor I
Short name:
IGF-I
Alternative name(s):
Mechano growth factor
Short name:
MGF
Somatomedin-C
Gene namesi
Name:IGF1
Synonyms:IBP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000017427.15
HGNCiHGNC:5464 IGF1
MIMi147440 gene
neXtProtiNX_P05019

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

Insulin-like growth factor I deficiency (IGF1 deficiency)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation.
See also OMIM:608747

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi84R → E: Dominant-negative mutant, no effect on IGFR1-binding, defective in integrin-binding and the formation of ternary complex with integrins and IGFR1, defective in inducing IGF1 signaling and cell proliferation, and suppresses activation of IGF1R by insulin and tumorigenesis in vivo; when associated with E-85. 4 Publications1
Mutagenesisi85R → E: Dominant-negative mutant, no effect on IGFR1-binding, defective in integrin-binding and the formation of ternary complex with integrins and IGFR1, defective in inducing IGF1 signaling and cell proliferation, and suppresses activation of IGF1R by insulin and tumorigenesis in vivo; when associated with E-84. 4 Publications1

Keywords - Diseasei

Deafness

Organism-specific databases

DisGeNETi3479
MalaCardsiIGF1
MIMi608747 phenotype
OpenTargetsiENSG00000017427
Orphaneti73272 Growth delay due to insulin-like growth factor type 1 deficiency
PharmGKBiPA29697

Protein family/group databases

Allergomei11751 Hom s IGF-1

Chemistry databases

ChEMBLiCHEMBL3217394

Polymorphism and mutation databases

BioMutaiIGF1
DMDMi124263

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
PropeptideiPRO_000001566322 – 48Add BLAST27
ChainiPRO_000001566449 – 118Insulin-like growth factor IAdd BLAST70
PropeptideiPRO_0000015665119 – 195E peptideAdd BLAST77

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi54 ↔ 961 Publication
Disulfide bondi66 ↔ 1091 Publication
Disulfide bondi95 ↔ 1001 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP05019
PeptideAtlasiP05019
PRIDEiP05019
ProteomicsDBi51765
51766 [P05019-2]
51767 [P05019-3]

PTM databases

iPTMnetiP05019
PhosphoSitePlusiP05019

Expressioni

Gene expression databases

BgeeiENSG00000017427 Expressed in 218 organ(s), highest expression level in endometrium
CleanExiHS_IGF1
ExpressionAtlasiP05019 baseline and differential
GenevisibleiP05019 HS

Organism-specific databases

HPAiHPA048946

Interactioni

Subunit structurei

Forms a ternary complex with IGFR1 and ITGAV:ITGB3 (PubMed:19578119). Forms a ternary complex with IGFR1 and ITGA6:ITGB4 (PubMed:22351760, PubMed:23696648).3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109700, 14 interactors
CORUMiP05019
DIPiDIP-41933N
DIP-6021N
IntActiP05019, 11 interactors
MINTiP05019
STRINGi9606.ENSP00000302665

Structurei

Secondary structure

1195
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP05019
SMRiP05019
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05019

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

eggNOGiENOG410IJ2T Eukaryota
ENOG4111MIV LUCA
GeneTreeiENSGT00530000063856
HOGENOMiHOG000233362
HOVERGENiHBG006137
InParanoidiP05019
KOiK05459
OMAiCFQSCDL
OrthoDBiEOG091G0H56
PhylomeDBiP05019
TreeFamiTF332820

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, 1 hit
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 (4+)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P05019-1) [UniParc]FASTAAdd to basket
Also known as: IGF-IB

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 LFKCCFCDFL KVKMHTMSSS HLFYLALCLL TFTSSATAGP
60 70 80 90 100
ETLCGAELVD ALQFVCGDRG FYFNKPTGYG SSSRRAPQTG IVDECCFRSC
110 120 130 140 150
DLRRLEMYCA PLKPAKSARS VRAQRHTDMP KTQKYQPPST NKNTKSQRRK
160 170 180 190
GWPKTHPGGE QKEGTEASLQ IRGKKKEQRR EIGSRNAECR GKKGK
Length:195
Mass (Da):21,841
Last modified:August 13, 1987 - v1
Checksum:iE88A8CFBD1CD1873
GO
Isoform 2 (identifier: P05019-2) [UniParc]FASTAAdd to basket
Also known as: IGF-IA

The sequence of this isoform differs from the canonical sequence as follows:
     135-195: YQPPSTNKNT...NAECRGKKGK → EVHLKNASRGSAGNKNYRM

Show »
Length:153
Mass (Da):17,026
Checksum:iC6ECD92DCA9B37BC
GO
Isoform 3 (identifier: P05019-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: MGKISSLPTQLFKCCFCDFLK → MITPT
     135-195: YQPPSTNKNT...NAECRGKKGK → EVHLKNASRGSAGNKNYRM

Note: Expressed in liver.
Show »
Length:137
Mass (Da):15,177
Checksum:iBFCC0D11E32AB75D
GO
Isoform 4 (identifier: P05019-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     152-195: WPKTHPGGEQKEGTEASLQIRGKKKEQRREIGSRNAECRGKKGK → STFEERK

Note: Gene prediction based on EST data.
Show »
Length:158
Mass (Da):17,762
Checksum:i59DB4A0437679B6A
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q13429Q13429_HUMAN
Insulin-like growth factor I
IGF1 IGF-I
139Annotation score:

Sequence cautioni

The sequence CAA27250 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07582598R → W Found in a patient with primordial dwarfism; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587779350EnsemblClinVar.1
Natural variantiVAR_056113115A → T. Corresponds to variant dbSNP:rs17884626Ensembl.1
Natural variantiVAR_013945187A → D1 PublicationCorresponds to variant dbSNP:rs6213EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0433171 – 21MGKIS…CDFLK → MITPT in isoform 3. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_039637135 – 195YQPPS…GKKGK → EVHLKNASRGSAGNKNYRM in isoform 2 and isoform 3. 5 PublicationsAdd BLAST61
Alternative sequenceiVSP_047399152 – 195WPKTH…GKKGK → STFEERK in isoform 4. CuratedAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X00173 mRNA Translation: CAA24998.1
X03420 Genomic DNA Translation: CAA27152.1
X03421 Genomic DNA Translation: CAA27153.1
X03422 Genomic DNA Translation: CAA27154.1
M27544 mRNA Translation: AAA52787.1
M14155
, M12659, M14153, M14154 Genomic DNA Translation: AAA52537.1
M14156
, M12659, M14153, M14154 Genomic DNA Translation: AAA52538.1
M11568 mRNA Translation: AAA52539.1
M37484 mRNA Translation: AAA52789.1
X57025 mRNA Translation: CAA40342.1
X56773 mRNA Translation: CAA40092.1
X56774 mRNA Translation: CAA40093.1
AY260957 Genomic DNA Translation: AAO74829.1
AC010202 Genomic DNA No translation available.
AC068648 Genomic DNA No translation available.
CH471054 Genomic DNA Translation: EAW97696.1
CH471054 Genomic DNA Translation: EAW97697.1
BC148266 mRNA Translation: AAI48267.1
X03563 Genomic DNA Translation: CAA27250.1 Sequence problems.
CCDSiCCDS44960.1 [P05019-3]
CCDS44961.1 [P05019-4]
CCDS9091.1 [P05019-2]
PIRiA01611 IGHU1B
A92581 IGHU1
RefSeqiNP_000609.1, NM_000618.4 [P05019-2]
NP_001104754.1, NM_001111284.1 [P05019-3]
NP_001104755.1, NM_001111285.2 [P05019-1]
UniGeneiHs.160562

Genome annotation databases

EnsembliENST00000307046; ENSP00000302665; ENSG00000017427 [P05019-1]
ENST00000337514; ENSP00000337612; ENSG00000017427 [P05019-2]
ENST00000392904; ENSP00000376637; ENSG00000017427 [P05019-4]
ENST00000392905; ENSP00000376638; ENSG00000017427 [P05019-4]
ENST00000424202; ENSP00000416811; ENSG00000017427 [P05019-3]
ENST00000644491; ENSP00000494228; ENSG00000017427 [P05019-2]
GeneIDi3479
KEGGihsa:3479
UCSCiuc001tjm.2 human [P05019-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

SHMPD

The Singapore human mutation and polymorphism database

NIEHS-SNPs
Wikipedia

Insulin-like growth factor 1 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X00173 mRNA Translation: CAA24998.1
X03420 Genomic DNA Translation: CAA27152.1
X03421 Genomic DNA Translation: CAA27153.1
X03422 Genomic DNA Translation: CAA27154.1
M27544 mRNA Translation: AAA52787.1
M14155
, M12659, M14153, M14154 Genomic DNA Translation: AAA52537.1
M14156
, M12659, M14153, M14154 Genomic DNA Translation: AAA52538.1
M11568 mRNA Translation: AAA52539.1
M37484 mRNA Translation: AAA52789.1
X57025 mRNA Translation: CAA40342.1
X56773 mRNA Translation: CAA40092.1
X56774 mRNA Translation: CAA40093.1
AY260957 Genomic DNA Translation: AAO74829.1
AC010202 Genomic DNA No translation available.
AC068648 Genomic DNA No translation available.
CH471054 Genomic DNA Translation: EAW97696.1
CH471054 Genomic DNA Translation: EAW97697.1
BC148266 mRNA Translation: AAI48267.1
X03563 Genomic DNA Translation: CAA27250.1 Sequence problems.
CCDSiCCDS44960.1 [P05019-3]
CCDS44961.1 [P05019-4]
CCDS9091.1 [P05019-2]
PIRiA01611 IGHU1B
A92581 IGHU1
RefSeqiNP_000609.1, NM_000618.4 [P05019-2]
NP_001104754.1, NM_001111284.1 [P05019-3]
NP_001104755.1, NM_001111285.2 [P05019-1]
UniGeneiHs.160562

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B9GNMR-A49-118[»]
1BQTNMR-A49-118[»]
1GF1model-A49-118[»]
1GZRX-ray2.00B49-118[»]
1GZYX-ray2.54B49-118[»]
1GZZX-ray2.30B49-118[»]
1H02X-ray2.00B49-118[»]
1H59X-ray2.10A49-118[»]
1IMXX-ray1.82A49-118[»]
1PMXNMR-A49-118[»]
1TGRX-ray1.42A/B49-77[»]
A/B90-110[»]
1WQJX-ray1.60I49-118[»]
2DSPX-ray2.50I49-118[»]
2DSQX-ray2.80C/I49-118[»]
2DSRX-ray2.10I49-118[»]
2GF1NMR-A49-118[»]
3GF1NMR-A49-118[»]
3LRINMR-A49-118[»]
4XSSX-ray3.00B49-118[»]
5U8QX-ray3.27B49-118[»]
ProteinModelPortaliP05019
SMRiP05019
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109700, 14 interactors
CORUMiP05019
DIPiDIP-41933N
DIP-6021N
IntActiP05019, 11 interactors
MINTiP05019
STRINGi9606.ENSP00000302665

Chemistry databases

ChEMBLiCHEMBL3217394

Protein family/group databases

Allergomei11751 Hom s IGF-1

PTM databases

iPTMnetiP05019
PhosphoSitePlusiP05019

Polymorphism and mutation databases

BioMutaiIGF1
DMDMi124263

Proteomic databases

PaxDbiP05019
PeptideAtlasiP05019
PRIDEiP05019
ProteomicsDBi51765
51766 [P05019-2]
51767 [P05019-3]

Protocols and materials databases

DNASUi3479
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000307046; ENSP00000302665; ENSG00000017427 [P05019-1]
ENST00000337514; ENSP00000337612; ENSG00000017427 [P05019-2]
ENST00000392904; ENSP00000376637; ENSG00000017427 [P05019-4]
ENST00000392905; ENSP00000376638; ENSG00000017427 [P05019-4]
ENST00000424202; ENSP00000416811; ENSG00000017427 [P05019-3]
ENST00000644491; ENSP00000494228; ENSG00000017427 [P05019-2]
GeneIDi3479
KEGGihsa:3479
UCSCiuc001tjm.2 human [P05019-1]

Organism-specific databases

CTDi3479
DisGeNETi3479
EuPathDBiHostDB:ENSG00000017427.15
GeneCardsiIGF1
HGNCiHGNC:5464 IGF1
HPAiHPA048946
MalaCardsiIGF1
MIMi147440 gene
608747 phenotype
neXtProtiNX_P05019
OpenTargetsiENSG00000017427
Orphaneti73272 Growth delay due to insulin-like growth factor type 1 deficiency
PharmGKBiPA29697
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJ2T Eukaryota
ENOG4111MIV LUCA
GeneTreeiENSGT00530000063856
HOGENOMiHOG000233362
HOVERGENiHBG006137
InParanoidiP05019
KOiK05459
OMAiCFQSCDL
OrthoDBiEOG091G0H56
PhylomeDBiP05019
TreeFamiTF332820

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)
R-HSA-422085 Synthesis, secretion, and deacylation of Ghrelin
SABIO-RKiP05019
SignaLinkiP05019
SIGNORiP05019

Miscellaneous databases

ChiTaRSiIGF1 human
EvolutionaryTraceiP05019
GeneWikiiInsulin-like_growth_factor_1
GenomeRNAii3479
PROiPR:P05019
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000017427 Expressed in 218 organ(s), highest expression level in endometrium
CleanExiHS_IGF1
ExpressionAtlasiP05019 baseline and differential
GenevisibleiP05019 HS

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, 1 hit
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
ProtoNetiSearch...

Entry informationi

Entry nameiIGF1_HUMAN
AccessioniPrimary (citable) accession number: P05019
Secondary accession number(s): B2RWM7
, E9PD02, P01343, Q14620
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: October 10, 2018
This is version 218 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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