IGF2_NEOVI
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 03-AUG-2022, entry version 89.
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; Mustelidae; Mustelinae;
OC 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 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: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 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
