ID   IGF2_PIG                Reviewed;         181 AA.
AC   P23695;
DT   01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 2.
DT   24-JAN-2024, entry version 136.
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   Sus scrofa (Pig).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX   NCBI_TaxID=9823;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2243790; DOI=10.1093/nar/18.21.6430;
RA   Catchpole I.R., Engstroem W.;
RT   "Nucleotide sequence of a porcine insulin-like growth factor II cDNA.";
RL   Nucleic Acids Res. 18:6430-6430(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Large white;
RX   PubMed=12140686; DOI=10.1007/s00335-001-3059-x;
RA   Amarger V., Nguyen M., Van Laere A.-S., Braunschweig M., Nezer C.,
RA   Georges M., Andersson L.;
RT   "Comparative sequence analysis of the INS-IGF2-H19 gene cluster in pigs.";
RL   Mamm. Genome 13:388-398(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=European wild boar, Hampshire, Japanese wild boar, Landrace,
RC   Large white, Meishan, and Pietrain;
RX   PubMed=14574411; DOI=10.1038/nature02064;
RA   Van Laere A.-S., Nguyen M., Braunschweig M., Nezer C., Collette C.,
RA   Moreau L., Archibald A.L., Haley C., Buys N., Tally M., Andersson G.,
RA   Georges M., Andersson L.;
RT   "A regulatory mutation in IGF2 causes a major QTL effect on muscle growth
RT   in the pig.";
RL   Nature 425:832-836(2003).
RN   [4]
RP   PROTEIN SEQUENCE OF 25-91.
RX   PubMed=2809477; DOI=10.1677/joe.0.1220681;
RA   Francis G.L., Owens P.C., McNeil K.A., Wallace J.C., Ballard F.J.;
RT   "Purification, amino acid sequences and assay cross-reactivities of porcine
RT   insulin-like growth factor-I and -II.";
RL   J. Endocrinol. 122:681-687(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 a 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; X56094; CAA39574.1; -; mRNA.
DR   EMBL; AY044828; AAL69551.1; -; Genomic_DNA.
DR   EMBL; AY242098; AAQ00953.1; -; Genomic_DNA.
DR   EMBL; AY242099; AAQ00955.1; -; Genomic_DNA.
DR   EMBL; AY242100; AAQ00958.1; -; Genomic_DNA.
DR   EMBL; AY242101; AAQ00961.1; -; Genomic_DNA.
DR   EMBL; AY242102; AAQ00964.1; -; Genomic_DNA.
DR   EMBL; AY242103; AAQ00967.1; -; Genomic_DNA.
DR   EMBL; AY242104; AAQ00970.1; -; Genomic_DNA.
DR   EMBL; AY242105; AAQ00973.1; -; Genomic_DNA.
DR   EMBL; AY242106; AAQ00976.1; -; Genomic_DNA.
DR   EMBL; AY242107; AAQ00979.1; -; Genomic_DNA.
DR   EMBL; AY242108; AAQ00982.1; -; Genomic_DNA.
DR   EMBL; AY242109; AAQ00984.1; -; Genomic_DNA.
DR   EMBL; AY242110; AAQ00986.1; -; Genomic_DNA.
DR   EMBL; AY242111; AAQ00988.1; -; Genomic_DNA.
DR   EMBL; AY242112; AAQ00991.1; -; Genomic_DNA.
DR   PIR; S12614; B60738.
DR   RefSeq; NP_999048.1; NM_213883.2.
DR   AlphaFoldDB; P23695; -.
DR   BMRB; P23695; -.
DR   SMR; P23695; -.
DR   STRING; 9823.ENSSSCP00000056721; -.
DR   GlyCosmos; P23695; 1 site, No reported glycans.
DR   PeptideAtlas; P23695; -.
DR   Ensembl; ENSSSCT00015005337.1; ENSSSCP00015002091.1; ENSSSCG00015004041.1.
DR   Ensembl; ENSSSCT00030103755.1; ENSSSCP00030047984.1; ENSSSCG00030074012.1.
DR   Ensembl; ENSSSCT00030103768.1; ENSSSCP00030047991.1; ENSSSCG00030074012.1.
DR   Ensembl; ENSSSCT00030103773.1; ENSSSCP00030047995.1; ENSSSCG00030074012.1.
DR   Ensembl; ENSSSCT00030103785.1; ENSSSCP00030048005.1; ENSSSCG00030074012.1.
DR   Ensembl; ENSSSCT00030103817.1; ENSSSCP00030048019.1; ENSSSCG00030074012.1.
DR   Ensembl; ENSSSCT00035026239.1; ENSSSCP00035009979.1; ENSSSCG00035020195.1.
DR   Ensembl; ENSSSCT00040023119.1; ENSSSCP00040009714.1; ENSSSCG00040017113.1.
DR   Ensembl; ENSSSCT00055031766.1; ENSSSCP00055025286.1; ENSSSCG00055016061.1.
DR   Ensembl; ENSSSCT00070030062.1; ENSSSCP00070025075.1; ENSSSCG00070015301.1.
DR   Ensembl; ENSSSCT00070030070.1; ENSSSCP00070025080.1; ENSSSCG00070015301.1.
DR   Ensembl; ENSSSCT00070030084.1; ENSSSCP00070025091.1; ENSSSCG00070015301.1.
DR   Ensembl; ENSSSCT00070030095.1; ENSSSCP00070025100.1; ENSSSCG00070015301.1.
DR   Ensembl; ENSSSCT00070030111.1; ENSSSCP00070025114.1; ENSSSCG00070015301.1.
DR   GeneID; 396916; -.
DR   KEGG; ssc:396916; -.
DR   CTD; 3481; -.
DR   InParanoid; P23695; -.
DR   OMA; IFVEACA; -.
DR   OrthoDB; 5402912at2759; -.
DR   Reactome; R-SSC-114608; Platelet degranulation.
DR   Reactome; R-SSC-2404192; Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R).
DR   Reactome; R-SSC-2428928; IRS-related events triggered by IGF1R.
DR   Reactome; R-SSC-2428933; SHC-related events triggered by IGF1R.
DR   Reactome; R-SSC-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR   Proteomes; UP000008227; Unplaced.
DR   Proteomes; UP000314985; Unassembled WGS sequence.
DR   Proteomes; UP000694570; Unplaced.
DR   Proteomes; UP000694571; Unplaced.
DR   Proteomes; UP000694720; Unplaced.
DR   Proteomes; UP000694722; Unplaced.
DR   Proteomes; UP000694723; Unplaced.
DR   Proteomes; UP000694724; Unplaced.
DR   Proteomes; UP000694725; Unplaced.
DR   Proteomes; UP000694726; Unplaced.
DR   Proteomes; UP000694727; Unplaced.
DR   Proteomes; UP000694728; Unplaced.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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: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:0051147; P:regulation of muscle cell differentiation; ISS:UniProtKB.
DR   CDD; cd04368; IlGF; 1.
DR   Gene3D; 1.10.100.10; Insulin-like; 1.
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   PANTHER; PTHR46886; INSULIN-LIKE GROWTH FACTOR II; 1.
DR   PANTHER; PTHR46886:SF1; INSULIN-LIKE GROWTH FACTOR II; 1.
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; Insulin-like; 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:0000250"
FT   CHAIN           25..91
FT                   /note="Insulin-like growth factor II"
FT                   /id="PRO_0000015727"
FT   PROPEP          92..181
FT                   /note="E peptide"
FT                   /id="PRO_0000015728"
FT   PEPTIDE         93..126
FT                   /note="Preptin"
FT                   /id="PRO_0000370379"
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          151..181
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        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"
SQ   SEQUENCE   181 AA;  20313 MW;  1816B935299B44E1 CRC64;
     MGIPMRKPLL VLLVFLALAS CCYAAYRPSE TLCGGELVDT LQFVCGDRGF YFSRPASRVN
     RRSRGIVEEC CFRSCDLALL ETYCATPAKS ERDVSTPPTV LPDNFPRYPV GKFFRYDTWK
     QSAQRLRRGL PALLRARRGR TLAKELEAVR EAKRHRPLTA RPTRDPAAHG GASPEASGHR
     K
//