IGF2_SHEEP
ID IGF2_SHEEP Reviewed; 179 AA.
AC P10764;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Insulin-like growth factor II;
DE Short=IGF-II;
DE Contains:
DE RecName: Full=Insulin-like growth factor II;
DE Contains:
DE RecName: Full=Preptin;
DE Flags: Precursor;
GN Name=IGF2;
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=2762134; DOI=10.1093/nar/17.13.5392;
RA O'Mahoney J.V., Adams T.E.;
RT "Nucleotide sequence of an ovine insulin-like growth factor-II cDNA.";
RL Nucleic Acids Res. 17:5392-5392(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=2388846; DOI=10.1093/nar/18.15.4614;
RA Brown W.M., Dziegielewska K.M., Foreman R.C., Saunders N.R.;
RT "The nucleotide and deduced amino acid sequences of insulin-like growth
RT factor II cDNAs from adult bovine and fetal sheep liver.";
RL Nucleic Acids Res. 18:4614-4614(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Liver;
RA Ohlsen S.M., Wong E.A.;
RL Submitted (SEP-1990) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PROTEIN SEQUENCE OF 25-91.
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 25-58.
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 possess growth-promoting
CC activity (By similarity). Major fetal growth hormone in mammals. Plays
CC a key role in regulating fetoplacental development. IGF2 is influenced
CC by placental lactogen. Also involved in tissue differentiation. In
CC adults, involved in glucose metabolism in adipose tissue, skeletal
CC muscle and liver. Acts as a ligand for integrin which is required for
CC IGF2 signaling. Positively regulates myogenic transcription factor
CC MYOD1 function by facilitating the recruitment of transcriptional
CC coactivators, thereby controlling muscle terminal differentiation (By
CC similarity). Inhibits myoblast differentiation and modulates metabolism
CC via increasing the mitochondrial respiration rate (By similarity).
CC {ECO:0000250|UniProtKB:P01344, ECO:0000250|UniProtKB:P09535}.
CC -!- FUNCTION: Preptin undergoes glucose-mediated co-secretion with insulin,
CC and acts as physiological amplifier of glucose-mediated insulin
CC secretion. Exhibits osteogenic properties by increasing osteoblast
CC mitogenic activity through phosphoactivation of MAPK1 and MAPK3.
CC {ECO:0000250|UniProtKB:P01344, ECO:0000250|UniProtKB:P09535}.
CC -!- SUBUNIT: Interacts with MYORG; this interaction is required for IGF2
CC secretion. Interacts with integrins ITGAV:ITGB3 and ITGA6:ITGB4;
CC integrin-binding is required for IGF2 signaling.
CC {ECO:0000250|UniProtKB:P01344, ECO:0000250|UniProtKB:P09535}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P01344,
CC ECO:0000250|UniProtKB:P09535}.
CC -!- PTM: Proteolytically processed by PCSK4, proIGF2 is cleaved at Arg-128
CC and Arg-92 to generate big-IGF2 and mature IGF2.
CC {ECO:0000250|UniProtKB:P01344}.
CC -!- MISCELLANEOUS: The IGF2 locus is imprinted. Paternal inherited gene is
CC expressed, while the maternal inherited gene is imprinted, hence
CC silenced. {ECO:0000250|UniProtKB:P09535}.
CC -!- SIMILARITY: Belongs to the insulin family. {ECO:0000305}.
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DR EMBL; U00668; AAB60626.1; -; Genomic_DNA.
DR EMBL; U00666; AAB60626.1; JOINED; Genomic_DNA.
DR EMBL; U00667; AAB60626.1; JOINED; Genomic_DNA.
DR EMBL; X15248; CAA33324.1; -; mRNA.
DR EMBL; X53554; CAA37621.1; -; mRNA.
DR EMBL; M89788; AAA31548.1; -; mRNA.
DR EMBL; M89789; AAA31549.1; -; mRNA.
DR EMBL; X55638; CAA39163.1; -; mRNA.
DR PIR; S04858; S04858.
DR RefSeq; NP_001009311.1; NM_001009311.1.
DR RefSeq; XP_014958377.1; XM_015102891.1.
DR AlphaFoldDB; P10764; -.
DR STRING; 9940.ENSOARP00000003830; -.
DR PRIDE; P10764; -.
DR Ensembl; ENSOART00020011909; ENSOARP00020009805; ENSOARG00020007754.
DR GeneID; 443325; -.
DR KEGG; oas:443325; -.
DR CTD; 3481; -.
DR eggNOG; ENOG502S0I0; Eukaryota.
DR OrthoDB; 1644517at2759; -.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0005615; C:extracellular space; IDA:AgBase.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR GO; GO:0001892; P:embryonic placenta development; ISS:UniProtKB.
DR GO; GO:0060669; P:embryonic placenta morphogenesis; ISS:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0001701; P:in utero embryonic development; ISS:UniProtKB.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW.
DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0031056; P:regulation of histone modification; ISS:UniProtKB.
DR GO; GO:0051147; P:regulation of muscle cell differentiation; ISS:UniProtKB.
DR InterPro; IPR022334; IGF2.
DR InterPro; IPR013576; IGF2_C.
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; PF08365; IGF2_C; 1.
DR Pfam; PF00049; Insulin; 1.
DR PRINTS; PR02002; INSLNLIKEGF.
DR PRINTS; PR02006; INSLNLIKEGF2.
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 Carbohydrate metabolism; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Glucose metabolism;
KW Glycoprotein; Growth factor; Hormone; Mitogen; Osteogenesis;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:2537174,
FT ECO:0000269|PubMed:2752053"
FT CHAIN 25..91
FT /note="Insulin-like growth factor II"
FT /id="PRO_0000015731"
FT PROPEP 92..179
FT /note="E peptide"
FT /id="PRO_0000015732"
FT PEPTIDE 93..126
FT /note="Preptin"
FT /id="PRO_0000370381"
FT REGION 25..52
FT /note="B"
FT REGION 53..64
FT /note="C"
FT REGION 65..85
FT /note="A"
FT REGION 86..91
FT /note="D"
FT REGION 160..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 48
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000250|UniProtKB:P01344"
FT SITE 58
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000250|UniProtKB:P01344"
FT SITE 61
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000250|UniProtKB:P01344"
FT SITE 62
FT /note="Important for interaction with integrin"
FT /evidence="ECO:0000250|UniProtKB:P01344"
FT CARBOHYD 106
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P07456"
FT CARBOHYD 154
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000250|UniProtKB:P07456"
FT CARBOHYD 163
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P07456"
FT DISULFID 33..71
FT /evidence="ECO:0000250"
FT DISULFID 45..84
FT /evidence="ECO:0000250"
FT DISULFID 70..75
FT /evidence="ECO:0000250"
FT CONFLICT 46..47
FT /note="GD -> DG (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 179 AA; 19616 MW; 7B369AE57F2E4378 CRC64;
MGITAGKSML ALLAFLAFAS CCYAAYRPSE TLCGGELVDT LQFVCGDRGF YFSRPSSRIN
RRSRGIVEEC CFRSCDLALL ETYCAAPAKS ERDVSASTTV LPDDFTAYPV GKFFQSDTWK
QSTQRLRRGL PAFLRARRGR TLAKELEALR EAKSHRPLIA LPTQDPATHG GASSEASSD