IGF2_BOVIN
ID IGF2_BOVIN Reviewed; 179 AA.
AC P07456; A0A5F2; Q2HJN0;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 4.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Insulin-like growth factor II;
DE Short=IGF-II;
DE AltName: Full=Erythrotropin;
DE Contains:
DE RecName: Full=Insulin-like growth factor II;
DE Contains:
DE RecName: Full=Preptin;
DE Flags: Precursor;
GN Name=IGF2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16120826; DOI=10.1095/biolreprod.105.044727;
RA Curchoe C., Zhang S., Bin Y., Zhang X., Yang L., Feng D., O'Neill M.,
RA Tian X.C.;
RT "Promoter-specific expression of the imprinted IGF2 gene in cattle (Bos
RT taurus).";
RL Biol. Reprod. 73:1275-1281(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Ascending colon;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 25-91.
RX PubMed=3941093; DOI=10.1016/s0021-9258(17)36130-6;
RA Honegger A., Humbel R.E.;
RT "Insulin-like growth factors I and II in fetal and adult bovine serum.
RT Purification, primary structures, and immunological cross-reactivities.";
RL J. Biol. Chem. 261:569-575(1986).
RN [4]
RP SEQUENCE REVISION.
RX PubMed=3390164; DOI=10.1042/bj2510095;
RA Francis G.L., Upton F.M., Ballard F.J., McNeil K.A., Wallace J.C.;
RT "Insulin-like growth factors 1 and 2 in bovine colostrum. Sequences and
RT biological activities compared with those of a potent truncated form.";
RL Biochem. J. 251:95-103(1988).
RN [5]
RP PROTEIN SEQUENCE OF 25-55.
RX PubMed=2302223; DOI=10.1016/0006-291x(90)90844-d;
RA Li Q., Blacher R., Esch F., Congote L.F.;
RT "A heparin-binding erythroid cell stimulating factor from fetal bovine
RT serum has the N-terminal sequence of insulin-like growth factor II.";
RL Biochem. Biophys. Res. Commun. 166:557-561(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 30-179.
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 30-86.
RX PubMed=1280544; DOI=10.1016/0305-0491(92)90423-o;
RA Congote L.F., Mazza L., Palfree R.G.E.;
RT "Nucleotide sequence of the central coding region of bovine
RT erythrotropin/insulin-like growth factor II cDNA from fetal intestine and
RT northern analysis of the major IGF II transcripts at the time of hepatic
RT erythropoiesis.";
RL Comp. Biochem. Physiol. 103B:127-131(1992).
RN [8]
RP GLYCOSYLATION AT THR-106; SER-154 AND THR-163, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=19674964; DOI=10.1074/mcp.m900211-mcp200;
RA Darula Z., Medzihradszky K.F.;
RT "Affinity enrichment and characterization of mucin core-1 type
RT glycopeptides from bovine serum.";
RL Mol. Cell. Proteomics 8:2515-2526(2009).
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY957981; ABD34310.1; -; mRNA.
DR EMBL; BC116039; AAI16040.1; -; mRNA.
DR EMBL; X53553; CAA37620.1; -; mRNA.
DR EMBL; X53867; CAA37861.1; -; mRNA.
DR PIR; S10983; IGBO2.
DR RefSeq; NP_776512.2; NM_174087.3.
DR RefSeq; XP_005227330.1; XM_005227273.1.
DR RefSeq; XP_005227331.1; XM_005227274.3.
DR RefSeq; XP_005227332.1; XM_005227275.3.
DR RefSeq; XP_005227333.1; XM_005227276.1.
DR RefSeq; XP_015316818.1; XM_015461332.1.
DR AlphaFoldDB; P07456; -.
DR SMR; P07456; -.
DR STRING; 9913.ENSBTAP00000017372; -.
DR GlyConnect; 778; 2 O-Linked glycans (3 sites).
DR iPTMnet; P07456; -.
DR PaxDb; P07456; -.
DR PRIDE; P07456; -.
DR Ensembl; ENSBTAT00000017372; ENSBTAP00000017372; ENSBTAG00000013066.
DR Ensembl; ENSBTAT00000084689; ENSBTAP00000073154; ENSBTAG00000013066.
DR GeneID; 281240; -.
DR KEGG; bta:281240; -.
DR CTD; 3481; -.
DR VEuPathDB; HostDB:ENSBTAG00000013066; -.
DR VGNC; VGNC:30078; IGF2.
DR eggNOG; ENOG502S0I0; Eukaryota.
DR GeneTree; ENSGT00940000160745; -.
DR HOGENOM; CLU_092464_1_0_1; -.
DR InParanoid; P07456; -.
DR OMA; PSHAKYS; -.
DR OrthoDB; 1644517at2759; -.
DR TreeFam; TF332820; -.
DR Proteomes; UP000009136; Chromosome 29.
DR Bgee; ENSBTAG00000013066; Expressed in placenta and 104 other tissues.
DR ExpressionAtlas; P07456; baseline.
DR GO; GO:0005615; C:extracellular space; IDA:AgBase.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IBA:GO_Central.
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:0042104; P:positive regulation of activated T cell proliferation; IBA:GO_Central.
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:2000467; P:positive regulation of glycogen (starch) synthase activity; IBA:GO_Central.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IBA:GO_Central.
DR GO; GO:0031056; P:regulation of histone modification; ISS:UniProtKB.
DR GO; GO:0051147; P:regulation of muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0032868; P:response to insulin; IDA:AgBase.
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:2302223,
FT ECO:0000269|PubMed:3941093"
FT CHAIN 25..91
FT /note="Insulin-like growth factor II"
FT /id="PRO_0000015711"
FT PROPEP 92..179
FT /note="E peptide"
FT /id="PRO_0000015712"
FT PEPTIDE 93..126
FT /note="Preptin"
FT /id="PRO_0000370373"
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:0000269|PubMed:19674964"
FT CARBOHYD 154
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:19674964"
FT CARBOHYD 163
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:19674964"
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"
FT CONFLICT 58
FT /note="R -> L (in Ref. 1; ABD34310)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="I -> S (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="T -> I (in Ref. 6; CAA37620)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 179 AA; 19682 MW; DEA16ED2D792EA53 CRC64;
MGITAGKSVL VLLAFLAFAS CCYAAYRPSE TLCGGELVDT LQFVCGDRGF YFSRPSSRIN
RRSRGIVEEC CFRSCDLALL ETYCATPAKS ERDVSASTTV LPDDVTAYPV GKFFQYDIWK
QSTQRLRRGL PAFLRARRGR TLAKELEALR EAKSHRPLIA LPTQDPATHG GASSKASSD
