ID   IGF2_NEOVI              Reviewed;         129 AA.
AC   P41694;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   24-JAN-2024, entry version 93.
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; Fragment;
GN   Name=IGF2;
OS   Neovison vison (American mink) (Mustela vison).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Caniformia; Musteloidea; Mustelidae;
OC   Mustelinae; Neogale.
OX   NCBI_TaxID=452646;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RX   PubMed=7686523; DOI=10.1006/gcen.1993.1079;
RA   Ekstroem T.J., Baecklin B.M., Lindqvist Y., Engstroem W.;
RT   "Insulin-like growth factor II in the mink (Mustela vison): determination
RT   of a cDNA nucleotide sequence and developmental regulation of its
RT   expression.";
RL   Gen. Comp. Endocrinol. 90:243-250(1993).
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-129
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; S63459; AAB27392.2; -; mRNA.
DR   AlphaFoldDB; P41694; -.
DR   BMRB; P41694; -.
DR   SMR; P41694; -.
DR   Proteomes; UP000694425; Unplaced.
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:UniProtKB-KW.
DR   GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR   GO; GO:0001892; P:embryonic placenta development; ISS:UniProtKB.
DR   GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
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: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; 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; PF00049; Insulin; 2.
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   2: Evidence at transcript level;
KW   Carbohydrate metabolism; Cleavage on pair of basic residues;
KW   Disulfide bond; Glucose metabolism; Growth factor; Hormone; Mitogen;
KW   Osteogenesis; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000250"
FT   CHAIN           25..92
FT                   /note="Insulin-like growth factor II"
FT                   /id="PRO_0000015722"
FT   PROPEP          93..>129
FT                   /note="E peptide"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000015723"
FT   PEPTIDE         94..127
FT                   /note="Preptin"
FT                   /id="PRO_0000370378"
FT   REGION          25..52
FT                   /note="B"
FT   REGION          53..65
FT                   /note="C"
FT   REGION          66..86
FT                   /note="A"
FT   REGION          87..92
FT                   /note="D"
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   DISULFID        33..72
FT                   /evidence="ECO:0000250"
FT   DISULFID        45..85
FT                   /evidence="ECO:0000250"
FT   DISULFID        71..76
FT                   /evidence="ECO:0000250"
FT   NON_TER         129
SQ   SEQUENCE   129 AA;  14437 MW;  FD06661DAFB473D0 CRC64;
     MGVPMGKSLL APLTFLALAS CCFAAYRPSE TLCGGELVDT LQFVCGDRGF YFSRPASRVS
     RRSSRGIVEE CCFRSCDLAL LETYCATPAK SERDVSTPPT VLPDNFPRYP VGKFFQYDTW
     KQSAQRLRR
//