IGF1_SHEEP
ID IGF1_SHEEP Reviewed; 154 AA.
AC P10763;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Insulin-like growth factor I;
DE Short=IGF-I;
DE AltName: Full=Somatomedin;
DE Flags: Precursor;
GN Name=IGF1;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2575490; DOI=10.1089/dna.1.1989.8.649;
RA Wong E.A., Ohlsen S.M., Godfredson J.A., Dean D.M., Wheaton J.E.;
RT "Cloning of ovine insulin-like growth factor-I cDNAs: heterogeneity in the
RT mRNA population.";
RL DNA 8:649-657(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Liver;
RX PubMed=2015053; DOI=10.1677/jme.0.0060017;
RA Dickson M.C., Saunders J.C., Gilmour R.S.;
RT "The ovine insulin-like growth factor-I gene: characterization, expression
RT and identification of a putative promoter.";
RL J. Mol. Endocrinol. 6:17-31(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=8466647; DOI=10.1089/dna.1993.12.243;
RA Ohlsen S.M., Dean D.M., Wong E.A.;
RT "Characterization of multiple transcription initiation sites of the ovine
RT insulin-like growth factor-I gene and expression profiles of three
RT alternatively spliced transcripts.";
RL DNA Cell Biol. 12:243-251(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 55-135.
RC STRAIN=Coopworth; TISSUE=Liver;
RX PubMed=8485157; DOI=10.1016/0167-4781(93)90246-a;
RA Demmer J., Hill D.F., Petersen G.B.;
RT "Characterization of two sheep insulin-like growth factor II cDNAs with
RT different 5'-untranslated regions.";
RL Biochim. Biophys. Acta 1173:79-80(1993).
RN [5]
RP PROTEIN SEQUENCE OF 50-119.
RX PubMed=2537174; DOI=10.1210/endo-124-3-1173;
RA Francis G.L., McNeil K.A., Wallace J.C., Ballard F.J., Owens P.C.;
RT "Sheep insulin-like growth factors I and II: sequences, activities and
RT assays.";
RL Endocrinology 124:1173-1183(1989).
RN [6]
RP PROTEIN SEQUENCE OF 50-79.
RX PubMed=2752053; DOI=10.1016/0167-4838(89)90131-3;
RA Hey A.W., Browne C.A., Simpson R.J., Thorburn G.D.;
RT "Simultaneous isolation of insulin-like growth factors I and II from adult
RT sheep serum.";
RL Biochim. Biophys. Acta 997:27-35(1989).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=B;
CC IsoId=P10763-1; Sequence=Displayed;
CC Name=A;
CC IsoId=P10763-2; Sequence=VSP_002707;
CC Name=C;
CC IsoId=P10763-3; Sequence=VSP_002706;
CC -!- SIMILARITY: Belongs to the insulin family. {ECO:0000305}.
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DR EMBL; M30653; AAA80532.1; -; mRNA.
DR EMBL; M30653; AAA80533.1; -; mRNA.
DR EMBL; M31734; AAA80535.1; -; mRNA.
DR EMBL; M31734; AAA80534.1; -; mRNA.
DR EMBL; M31736; AAA31545.1; -; mRNA.
DR EMBL; M31735; AAA31546.1; -; mRNA.
DR EMBL; M31735; AAA31547.1; -; mRNA.
DR EMBL; X69472; CAA49230.1; -; Genomic_DNA.
DR EMBL; X69473; CAA49230.1; JOINED; Genomic_DNA.
DR EMBL; X69474; CAA49230.1; JOINED; Genomic_DNA.
DR EMBL; X69475; CAA49230.1; JOINED; Genomic_DNA.
DR EMBL; X69472; CAA49231.1; -; Genomic_DNA.
DR EMBL; X69473; CAA49231.1; JOINED; Genomic_DNA.
DR EMBL; X69474; CAA49231.1; JOINED; Genomic_DNA.
DR EMBL; X69475; CAA49231.1; JOINED; Genomic_DNA.
DR EMBL; X69473; CAA49232.1; -; Genomic_DNA.
DR EMBL; X69474; CAA49232.1; JOINED; Genomic_DNA.
DR EMBL; X69475; CAA49232.1; JOINED; Genomic_DNA.
DR EMBL; M89787; AAA31544.1; -; mRNA.
DR PIR; S22877; A33390.
DR RefSeq; NP_001009774.1; NM_001009774.3. [P10763-1]
DR RefSeq; XP_012015041.1; XM_012159651.2. [P10763-3]
DR AlphaFoldDB; P10763; -.
DR BMRB; P10763; -.
DR SMR; P10763; -.
DR STRING; 9940.ENSOARP00000017024; -.
DR PRIDE; P10763; -.
DR Ensembl; ENSOART00020015334; ENSOARP00020012690; ENSOARG00020009650.
DR GeneID; 443318; -.
DR KEGG; oas:443318; -.
DR CTD; 3479; -.
DR eggNOG; ENOG502RCAB; Eukaryota.
DR Proteomes; UP000002356; Unplaced.
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; IEA:InterPro.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005179; F:hormone activity; IEA:InterPro.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; ISS:UniProtKB.
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 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 1: Evidence at protein level;
KW Alternative splicing; Direct protein sequencing; Disulfide bond;
KW Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..?
FT PROPEP ?..49
FT /id="PRO_0000015684"
FT CHAIN 50..119
FT /note="Insulin-like growth factor I"
FT /id="PRO_0000015685"
FT PROPEP 120..154
FT /note="E peptide"
FT /id="PRO_0000015686"
FT REGION 50..78
FT /note="B"
FT REGION 79..90
FT /note="C"
FT REGION 91..111
FT /note="A"
FT REGION 112..119
FT /note="D"
FT REGION 121..154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 122..139
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 140..154
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 55..97
FT /evidence="ECO:0000250"
FT DISULFID 67..110
FT /evidence="ECO:0000250"
FT DISULFID 96..101
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..24
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000305"
FT /id="VSP_002707"
FT VAR_SEQ 1..21
FT /note="MGKISSLPTQLFKCCFCDFLK -> MVTPT (in isoform C)"
FT /evidence="ECO:0000305"
FT /id="VSP_002706"
FT CONFLICT 57
FT /note="A -> V (in Ref. 4; AAA31544)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 154 AA; 17012 MW; E226CE6AF653CF3F CRC64;
MGKISSLPTQ LFKCCFCDFL KQVKMPVTSS SHLFYLALCL LAFSSSATAG PETLCGAELV
DALQFVCGDR GFYFNKPTGY GSSSRRAPQT GIVDECCFRS CDLRRLEMYC APLKAAKSAR
SVRAQRHTDM PKAQKEVHLK NTSRGSAGNK NYRM
