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2l29
From Proteopedia
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| - | [[Image:2l29.png|left|200px]] | ||
| - | + | ==Complex structure of E4 mutant human IGF2R domain 11 bound to IGF-II== | |
| + | <StructureSection load='2l29' size='340' side='right'caption='[[2l29]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2l29]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L29 FirstGlance]. <br> | ||
| + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2l29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l29 OCA], [https://pdbe.org/2l29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l29 RCSB], [https://www.ebi.ac.uk/pdbsum/2l29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l29 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/IGF2_HUMAN IGF2_HUMAN] Epigenetic changes of DNA hypomethylation in IGF2 are a cause of Silver-Russell syndrome (SRS) [MIM:[https://omim.org/entry/180860 180860]. A clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age.<ref>PMID:19066168</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/IGF2_HUMAN IGF2_HUMAN] The insulin-like growth factors possess growth-promoting activity. In vitro, they are potent mitogens for cultured cells. IGF-II is influenced by placental lactogen and may play a role in fetal development.<ref>PMID:16912056</ref> Preptin undergoes glucose-mediated co-secretion with insulin, and acts as physiological amplifier of glucose-mediated insulin secretion. Exhibits osteogenic properties by increasing osteoblast mitogenic activity through phosphoactivation of MAPK1 and MAPK3.<ref>PMID:16912056</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Placental development and genomic imprinting coevolved with parental conflict over resource distribution to mammalian offspring. The imprinted genes IGF2 and IGF2R code for the growth promoter insulin-like growth factor 2 (IGF2) and its inhibitor, mannose 6-phosphate (M6P)/IGF2 receptor (IGF2R), respectively. M6P/IGF2R of birds and fish do not recognize IGF2. In monotremes, which lack imprinting, IGF2 specifically bound M6P/IGF2R via a hydrophobic CD loop. We show that the DNA coding the CD loop in monotremes functions as an exon splice enhancer (ESE) and that structural evolution of binding site loops (AB, HI, FG) improved therian IGF2 affinity. We propose that ESE evolution led to the fortuitous acquisition of IGF2 binding by M6P/IGF2R that drew IGF2R into parental conflict; subsequent imprinting may then have accelerated affinity maturation. | ||
| - | + | An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution.,Williams C, Hoppe HJ, Rezgui D, Strickland M, Forbes BE, Grutzner F, Frago S, Ellis RZ, Wattana-Amorn P, Prince SN, Zaccheo OJ, Nolan CM, Mungall AJ, Jones EY, Crump MP, Hassan AB Science. 2012 Nov 30;338(6111):1209-13. doi: 10.1126/science.1228633. PMID:23197533<ref>PMID:23197533</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2l29" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
*[[Insulin-like growth factor receptor|Insulin-like growth factor receptor]] | *[[Insulin-like growth factor receptor|Insulin-like growth factor receptor]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Crump | + | [[Category: Large Structures]] |
| - | [[Category: Ellis | + | [[Category: Crump MP]] |
| - | [[Category: Forbes | + | [[Category: Ellis RZ]] |
| - | [[Category: Frago | + | [[Category: Forbes B]] |
| - | [[Category: Hassan | + | [[Category: Frago S]] |
| - | [[Category: Hoppe | + | [[Category: Hassan AB]] |
| - | [[Category: Jones | + | [[Category: Hoppe H]] |
| - | [[Category: Prince | + | [[Category: Jones EY]] |
| - | [[Category: Rezgui | + | [[Category: Prince SN]] |
| - | [[Category: Strickland | + | [[Category: Rezgui D]] |
| - | [[Category: Wattana-Amorn | + | [[Category: Strickland M]] |
| - | [[Category: Williams | + | [[Category: Wattana-Amorn P]] |
| - | [[Category: Zaccheo | + | [[Category: Williams C]] |
| - | + | [[Category: Zaccheo OJ]] | |
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Current revision
Complex structure of E4 mutant human IGF2R domain 11 bound to IGF-II
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Categories: Homo sapiens | Large Structures | Crump MP | Ellis RZ | Forbes B | Frago S | Hassan AB | Hoppe H | Jones EY | Prince SN | Rezgui D | Strickland M | Wattana-Amorn P | Williams C | Zaccheo OJ
