IGF1_CANLF
ID IGF1_CANLF Reviewed; 153 AA.
AC P33712;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 2.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Insulin-like growth factor I;
DE Short=IGF-I;
DE AltName: Full=Somatomedin;
DE Flags: Precursor;
GN Name=IGF1; Synonyms=IGFIA;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Synovium;
RA Staten N.R.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 30-151.
RX PubMed=8359700; DOI=10.1016/0378-1119(93)90437-8;
RA Delafontaine P., Lou H., Harrison D.G., Bernstein K.E.;
RT "Sequence of a cDNA encoding dog insulin-like growth factor I.";
RL Gene 130:305-306(1993).
RN [3]
RP POLYMORPHISM.
RX PubMed=17412960; DOI=10.1126/science.1137045;
RA Sutter N.B., Bustamante C.D., Chase K., Gray M.M., Zhao K., Zhu L.,
RA Padhukasahasram B., Karlins E., Davis S., Jones P.G., Quignon P.,
RA Johnson G.S., Parker H.G., Fretwell N., Mosher D.S., Lawler D.F.,
RA Satyaraj E., Nordborg M., Lark K.G., Wayne R.K., Ostrander E.A.;
RT "A single IGF1 allele is a major determinant of small size in dogs.";
RL Science 316:112-115(2007).
CC -!- FUNCTION: The insulin-like growth factors, isolated from plasma, are
CC structurally and functionally related to insulin but have a much higher
CC growth-promoting activity. May be a physiological regulator of [1-14C]-
CC 2-deoxy-D-glucose (2DG) transport and glycogen synthesis in
CC osteoblasts. Stimulates glucose transport in bone-derived osteoblastic
CC (PyMS) cells and is effective at much lower concentrations than
CC insulin, not only regarding glycogen and DNA synthesis but also with
CC regard to enhancing glucose uptake. May play a role in synapse
CC maturation. Ca(2+)-dependent exocytosis of IGF1 is required for sensory
CC perception of smell in the olfactory bulb. Acts as a ligand for IGF1R.
CC Binds to the alpha subunit of IGF1R, leading to the activation of the
CC intrinsic tyrosine kinase activity which autophosphorylates tyrosine
CC residues in the beta subunit thus initiatiating a cascade of down-
CC stream signaling events leading to activation of the PI3K-AKT/PKB and
CC the Ras-MAPK pathways. Binds to integrins ITGAV:ITGB3 and ITGA6:ITGB4.
CC Its binding to integrins and subsequent ternary complex formation with
CC integrins and IGFR1 are essential for IGF1 signaling. Induces the
CC phosphorylation and activation of IGFR1, MAPK3/ERK1, MAPK1/ERK2 and
CC AKT1 (By similarity). {ECO:0000250|UniProtKB:P05017,
CC ECO:0000250|UniProtKB:P05019}.
CC -!- SUBUNIT: Forms a ternary complex with IGFR1 and ITGAV:ITGB3. Forms a
CC ternary complex with IGFR1 and ITGA6:ITGB4.
CC {ECO:0000250|UniProtKB:P05019}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P05017}.
CC -!- POLYMORPHISM: The domestic dog exhibits greater diversity in body size
CC than any other terrestrial vertebrate. A major quantitative trait locus
CC (QTL) on chromosome 15 influences size variation within a single breed.
CC In particular, a single-nucleotide polymorphism haplotype in IGF1
CC (synonymous SNP in exon 3) is common to all small breeds (less than 9
CC kg) and nearly absent from giant breeds (more than 30 kg), suggesting
CC that the same causal sequence variant is a major contributor to body
CC size in all small dogs. {ECO:0000269|PubMed:17412960}.
CC -!- SIMILARITY: Belongs to the insulin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A dog's life - Issue 92 of
CC March 2008;
CC URL="https://web.expasy.org/spotlight/back_issues/092";
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DR EMBL; DN380306; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; L08254; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; PN0622; PN0622.
DR RefSeq; NP_001300784.1; NM_001313855.1.
DR AlphaFoldDB; P33712; -.
DR BMRB; P33712; -.
DR SMR; P33712; -.
DR STRING; 9612.ENSCAFP00000010834; -.
DR PaxDb; P33712; -.
DR Ensembl; ENSCAFT00030017817; ENSCAFP00030015562; ENSCAFG00030009527.
DR Ensembl; ENSCAFT00040031570; ENSCAFP00040027456; ENSCAFG00040017054.
DR Ensembl; ENSCAFT00845016544; ENSCAFP00845012869; ENSCAFG00845009366.
DR GeneID; 610255; -.
DR KEGG; cfa:610255; -.
DR CTD; 3479; -.
DR VEuPathDB; HostDB:ENSCAFG00845009366; -.
DR eggNOG; ENOG502RCAB; Eukaryota.
DR GeneTree; ENSGT00940000159081; -.
DR HOGENOM; CLU_123939_0_0_1; -.
DR InParanoid; P33712; -.
DR OMA; FFYLALC; -.
DR OrthoDB; 1644517at2759; -.
DR Reactome; R-CFA-114608; Platelet degranulation.
DR Reactome; R-CFA-2404192; Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R).
DR Reactome; R-CFA-2428928; IRS-related events triggered by IGF1R.
DR Reactome; R-CFA-2428933; SHC-related events triggered by IGF1R.
DR Reactome; R-CFA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-CFA-422085; Synthesis, secretion, and deacylation of Ghrelin.
DR Proteomes; UP000002254; Chromosome 15.
DR Bgee; ENSCAFG00000007304; Expressed in bone marrow and 47 other tissues.
DR GO; GO:0035867; C:alphav-beta3 integrin-IGF-1-IGF1R complex; ISS:UniProtKB.
DR GO; GO:0070382; C:exocytic vesicle; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005179; F:hormone activity; IBA:GO_Central.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IBA:GO_Central.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0046326; P:positive regulation of glucose import; ISS:UniProtKB.
DR GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IBA:GO_Central.
DR InterPro; IPR022341; IGF-I.
DR InterPro; IPR016179; Insulin-like.
DR InterPro; IPR022350; Insulin-like_growth_factor.
DR InterPro; IPR036438; Insulin-like_sf.
DR InterPro; IPR022353; Insulin_CS.
DR InterPro; IPR022352; Insulin_family.
DR Pfam; PF00049; Insulin; 1.
DR PRINTS; PR02002; INSLNLIKEGF.
DR PRINTS; PR02005; INSLNLIKEGF1.
DR PRINTS; PR00276; INSULINFAMLY.
DR SMART; SM00078; IlGF; 1.
DR SUPFAM; SSF56994; SSF56994; 1.
DR PROSITE; PS00262; INSULIN; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..?
FT /evidence="ECO:0000255"
FT PROPEP ?..48
FT /evidence="ECO:0000250"
FT /id="PRO_0000330685"
FT CHAIN 49..118
FT /note="Insulin-like growth factor I"
FT /id="PRO_0000015650"
FT PROPEP 119..153
FT /note="E peptide"
FT /id="PRO_0000015651"
FT REGION 49..77
FT /note="B"
FT REGION 78..89
FT /note="C"
FT REGION 90..110
FT /note="A"
FT REGION 111..118
FT /note="D"
FT REGION 120..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 121..138
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 54..96
FT /evidence="ECO:0000250"
FT DISULFID 66..109
FT /evidence="ECO:0000250"
FT DISULFID 95..100
FT /evidence="ECO:0000250"
FT CONFLICT 150..153
FT /note="NYRM -> TY (in Ref. 2; L08254)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 153 AA; 16970 MW; 19D16DBF9151C0EF CRC64;
MGKISSLPTQ LFKCCFCDFL KVKMHTVSSS HLFYLALCLL TFPSPATAGP ETLCGAELVD
ALQFVCGDRG FYFNKPTGYG SSSRRAPQTG IVDECCFRSC DLRRLEMYCA PLKPAKSARS
VRAQRHTDMP KAQKEVHLKN ASRGSAGNKN YRM
