UniProt functional annotation for P05019



	UniProt functional annotation for P05019

UniProt code: P05019.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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). Ca(2+)-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). {ECO:0000250|UniProtKB:P05017, ECO:0000269|PubMed:19578119, ECO:0000269|PubMed:21076856, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:23243309, ECO:0000269|PubMed:23696648, ECO:0000269|PubMed:24132240}.

Subunit: Forms a ternary complex with IGFR1 and ITGAV:ITGB3 (PubMed:19578119). Forms a ternary complex with IGFR1 and ITGA6:ITGB4 (PubMed:22351760, PubMed:23696648). Interacts with SH2D3C isoform 2 (PubMed:20881139). {ECO:0000269|PubMed:19578119, ECO:0000269|PubMed:20881139, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:23696648}.

Subcellular location: Secreted {ECO:0000250|UniProtKB:P05017}.

Disease: Insulin-like growth factor I deficiency (IGF1 deficiency) [MIM:608747]: Autosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation. {ECO:0000269|PubMed:8857020}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 3]: Expressed in liver. {ECO:0000305}.

Similarity: Belongs to the insulin family. {ECO:0000305}.

Sequence caution: Sequence=CAA27250.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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). Ca(2+)-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). {ECO:0000250\|UniProtKB:P05017, ECO:0000269\|PubMed:19578119, ECO:0000269\|PubMed:21076856, ECO:0000269\|PubMed:22351760, ECO:0000269\|PubMed:23243309, ECO:0000269\|PubMed:23696648, ECO:0000269\|PubMed:24132240}.


Subunit:		Forms a ternary complex with IGFR1 and ITGAV:ITGB3 (PubMed:19578119). Forms a ternary complex with IGFR1 and ITGA6:ITGB4 (PubMed:22351760, PubMed:23696648). Interacts with SH2D3C isoform 2 (PubMed:20881139). {ECO:0000269\|PubMed:19578119, ECO:0000269\|PubMed:20881139, ECO:0000269\|PubMed:22351760, ECO:0000269\|PubMed:23696648}.
Subcellular location:		Secreted {ECO:0000250\|UniProtKB:P05017}.
Disease:		Insulin-like growth factor I deficiency (IGF1 deficiency) [MIM:608747]: Autosomal recessive disorder characterized by growth retardation, sensorineural deafness and mental retardation. {ECO:0000269\|PubMed:8857020}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 3]: Expressed in liver. {ECO:0000305}.
Similarity:		Belongs to the insulin family. {ECO:0000305}.
Sequence caution:		Sequence=CAA27250.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};