4zxb - Revision history

OCA at 07:45, 18 May 2023

OCA — Thu, 18 May 2023 07:45:25 GMT

←Older revision		Revision as of 07:45, 18 May 2023
Line 3:		Line 3:
	<StructureSection load='4zxb' size='340' side='right'caption='[[4zxb]], [[Resolution\|resolution]] 3.30Å' scene=''>		<StructureSection load='4zxb' size='340' side='right'caption='[[4zxb]], [[Resolution\|resolution]] 3.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zxb]] is a 5 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~] and [~~http~~://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2dtg 2dtg] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3loh 3loh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZXB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ZXB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zxb]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2dtg 2dtg] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3loh 3loh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZXB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZXB FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2dtg\|2dtg]], [[3loh\|3loh]]</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=4zxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zxb OCA], [https://pdbe.org/4zxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zxb RCSB], [https://www.ebi.ac.uk/pdbsum/4zxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zxb ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Igh-1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Igkc, Igk-C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4zxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zxb OCA], [~~http~~://pdbe.org/4zxb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4zxb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4zxb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4zxb ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Disease ==
-	[[http://www.uniprot.org/uniprot/INSR_HUMAN INSR_HUMAN]] Defects in INSR are the cause of Rabson-Mendenhall syndrome (RMS) [MIM:[http://omim.org/entry/262190 262190]]; also known as Mendenhall syndrome. RMS is a severe insulin resistance syndrome characterized by insulin-resistant diabetes mellitus with pineal hyperplasia and somatic abnormalities. Typical features include coarse, senile-appearing facies, dental and skin abnormalities, abdominal distension, and phallic enlargement. Inheritance is autosomal recessive.<ref>PMID:2121734</ref> <ref>PMID:2365819</ref> <ref>PMID:8314008</ref> <ref>PMID:10443650</ref> <ref>PMID:12023989</ref> <ref>PMID:17201797</ref> Defects in INSR are the cause of leprechaunism (LEPRCH) [MIM:[http://omim.org/entry/246200 246200]]; also known as Donohue syndrome. Leprechaunism represents the most severe form of insulin resistance syndrome, characterized by intrauterine and postnatal growth retardation and death in early infancy. Inheritance is autosomal recessive.<ref>PMID:2365819</ref> <ref>PMID:12023989</ref> <ref>PMID:2834824</ref> <ref>PMID:2479553</ref> <ref>PMID:1607067</ref> <ref>PMID:1730625</ref> <ref>PMID:8326490</ref> <ref>PMID:8419945</ref> <ref>PMID:8188715</ref> <ref>PMID:7815442</ref> <ref>PMID:7538143</ref> <ref>PMID:8636294</ref> <ref>PMID:9299395</ref> <ref>PMID:9249867</ref> <ref>PMID:9703342</ref> <ref>PMID:12538626</ref> <ref>PMID:12970295</ref> Defects in INSR may be associated with noninsulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]; also known as diabetes mellitus type 2.<ref>PMID:1607076</ref> <ref>PMID:1470163</ref> <ref>PMID:7657032</ref> Defects in INSR are the cause of familial hyperinsulinemic hypoglycemia type 5 (HHF5) [MIM:[http://omim.org/entry/609968 609968]]. Familial hyperinsulinemic hypoglycemia [MIM:[http://omim.org/entry/256450 256450]], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels.<ref>PMID:15161766</ref> Defects in INSR are the cause of insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:[http://omim.org/entry/610549 610549]]. This syndrome is characterized by the association of severe insulin resistance (manifested by marked hyperinsulinemia and a failure to respond to exogenous insulin) with the skin lesion acanthosis nigricans and ovarian hyperandrogenism in adolescent female subjects. Women frequently present with hirsutism, acne, amenorrhea or oligomenorrhea, and virilization. This syndrome is different from the type B that has been demonstrated to be secondary to the presence of circulating autoantibodies against the insulin receptor.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~INSR_HUMAN INSR_HUMAN~~]] Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.<ref>PMID:8257688</ref> <ref>PMID:8452530</ref> <ref>PMID:8276809</ref> <ref>PMID:9428692</ref> <ref>PMID:10207053</ref> <ref>PMID:12138094</ref> <ref>PMID:16314505</ref> <ref>PMID:16831875</ref>	+	[https://www.uniprot.org/uniprot/U5LP42_MOUSE U5LP42_MOUSE]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 22:
	*[[Antibody 3D structures\|Antibody 3D structures]]		*[[Antibody 3D structures\|Antibody 3D structures]]
	*[[Insulin receptor 3D structures\|Insulin receptor 3D structures]]		*[[Insulin receptor 3D structures\|Insulin receptor 3D structures]]
		+	*[[3D structures of non-human antibody\|3D structures of non-human antibody]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Croll, T]]	+	[[Category: Croll T]]
-	[[Category: Lawrence~~, M C~~]]	+	[[Category: Lawrence MC]]
-	[[Category: Margetts~~, M B~~]]	+	[[Category: Margetts MB]]
-	[[Category: Smith~~, B J~~]]	+	[[Category: Smith BJ]]
-	[[Category: Ward~~, C W~~]]	+	[[Category: Ward CW]]
-	[[Category: Weiss~~, M A~~]]	+	[[Category: Weiss MA]]
-	[[Category: Whittaker, J]]	+	[[Category: Whittaker J]]
-	~~[[Category: Hormone receptor-immune system complex]]~~	+
-	~~[[Category: Receptor tyrosine kinase extracellular domain antibody fragment~~]]	+

OCA at 07:55, 8 January 2020

OCA — Wed, 08 Jan 2020 07:55:26 GMT

←Older revision		Revision as of 07:55, 8 January 2020
Line 25:		Line 25:
	==See Also==		==See Also==
	*[[Antibody 3D structures\|Antibody 3D structures]]		*[[Antibody 3D structures\|Antibody 3D structures]]
-	*[[Insulin receptor\|Insulin receptor]]	+	*[[Insulin receptor 3D structures\|Insulin receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:01, 26 June 2019

OCA — Wed, 26 Jun 2019 08:01:37 GMT

←Older revision		Revision as of 08:01, 26 June 2019
Line 1:		Line 1:

	==Structure of the human insulin receptor ectodomain, IRDeltabeta construct, in complex with four Fab molecules==		==Structure of the human insulin receptor ectodomain, IRDeltabeta construct, in complex with four Fab molecules==
-	<StructureSection load='4zxb' size='340' side='right' caption='[[4zxb]], [[Resolution\|resolution]] 3.30Å' scene=''>	+	<StructureSection load='4zxb' size='340' side='right'caption='[[4zxb]], [[Resolution\|resolution]] 3.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zxb]] is a 5 chain structure. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2dtg 2dtg] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3loh 3loh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZXB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZXB FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zxb]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2dtg 2dtg] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3loh 3loh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZXB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZXB FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2dtg\|2dtg]], [[3loh\|3loh]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2dtg\|2dtg]], [[3loh\|3loh]]</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zxb OCA], [http://pdbe.org/4zxb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zxb RCSB], [http://www.ebi.ac.uk/pdbsum/4zxb PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Igh-1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Igkc, Igk-C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zxb OCA], [http://pdbe.org/4zxb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zxb RCSB], [http://www.ebi.ac.uk/pdbsum/4zxb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zxb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 4zxb" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4zxb" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	*[[Insulin receptor\|Insulin receptor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Croll, T]]		[[Category: Croll, T]]
	[[Category: Lawrence, M C]]		[[Category: Lawrence, M C]]

OCA at 18:02, 26 February 2016

OCA — Fri, 26 Feb 2016 18:02:12 GMT

←Older revision		Revision as of 18:02, 26 February 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 4zxb is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure of the human insulin receptor ectodomain, IRDeltabeta construct, in complex with four Fab molecules==
		+	<StructureSection load='4zxb' size='340' side='right' caption='[[4zxb]], [[Resolution\|resolution]] 3.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4zxb]] is a 5 chain structure. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2dtg 2dtg] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3loh 3loh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZXB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZXB FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2dtg\|2dtg]], [[3loh\|3loh]]</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zxb OCA], [http://pdbe.org/4zxb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zxb RCSB], [http://www.ebi.ac.uk/pdbsum/4zxb PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/INSR_HUMAN INSR_HUMAN]] Defects in INSR are the cause of Rabson-Mendenhall syndrome (RMS) [MIM:[http://omim.org/entry/262190 262190]]; also known as Mendenhall syndrome. RMS is a severe insulin resistance syndrome characterized by insulin-resistant diabetes mellitus with pineal hyperplasia and somatic abnormalities. Typical features include coarse, senile-appearing facies, dental and skin abnormalities, abdominal distension, and phallic enlargement. Inheritance is autosomal recessive.<ref>PMID:2121734</ref> <ref>PMID:2365819</ref> <ref>PMID:8314008</ref> <ref>PMID:10443650</ref> <ref>PMID:12023989</ref> <ref>PMID:17201797</ref> Defects in INSR are the cause of leprechaunism (LEPRCH) [MIM:[http://omim.org/entry/246200 246200]]; also known as Donohue syndrome. Leprechaunism represents the most severe form of insulin resistance syndrome, characterized by intrauterine and postnatal growth retardation and death in early infancy. Inheritance is autosomal recessive.<ref>PMID:2365819</ref> <ref>PMID:12023989</ref> <ref>PMID:2834824</ref> <ref>PMID:2479553</ref> <ref>PMID:1607067</ref> <ref>PMID:1730625</ref> <ref>PMID:8326490</ref> <ref>PMID:8419945</ref> <ref>PMID:8188715</ref> <ref>PMID:7815442</ref> <ref>PMID:7538143</ref> <ref>PMID:8636294</ref> <ref>PMID:9299395</ref> <ref>PMID:9249867</ref> <ref>PMID:9703342</ref> <ref>PMID:12538626</ref> <ref>PMID:12970295</ref> Defects in INSR may be associated with noninsulin-dependent diabetes mellitus (NIDDM) [MIM:[http://omim.org/entry/125853 125853]]; also known as diabetes mellitus type 2.<ref>PMID:1607076</ref> <ref>PMID:1470163</ref> <ref>PMID:7657032</ref> Defects in INSR are the cause of familial hyperinsulinemic hypoglycemia type 5 (HHF5) [MIM:[http://omim.org/entry/609968 609968]]. Familial hyperinsulinemic hypoglycemia [MIM:[http://omim.org/entry/256450 256450]], also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels.<ref>PMID:15161766</ref> Defects in INSR are the cause of insulin-resistant diabetes mellitus with acanthosis nigricans type A (IRAN type A) [MIM:[http://omim.org/entry/610549 610549]]. This syndrome is characterized by the association of severe insulin resistance (manifested by marked hyperinsulinemia and a failure to respond to exogenous insulin) with the skin lesion acanthosis nigricans and ovarian hyperandrogenism in adolescent female subjects. Women frequently present with hirsutism, acne, amenorrhea or oligomenorrhea, and virilization. This syndrome is different from the type B that has been demonstrated to be secondary to the presence of circulating autoantibodies against the insulin receptor.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/INSR_HUMAN INSR_HUMAN]] Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.<ref>PMID:8257688</ref> <ref>PMID:8452530</ref> <ref>PMID:8276809</ref> <ref>PMID:9428692</ref> <ref>PMID:10207053</ref> <ref>PMID:12138094</ref> <ref>PMID:16314505</ref> <ref>PMID:16831875</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. However, only a low-resolution (3.8 A) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. Here, we revise this structure using new diffraction data to 3.3 A resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding.

-	~~Authors~~: Croll~~, T.~~, Smith~~, B.J.~~, Margetts~~, M.B.~~, Whittaker, J., Weiss~~, M.A.~~, Ward, C.W., ~~Lawrence, M~~.C.	+	Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain.,Croll TI, Smith BJ, Margetts MB, Whittaker J, Weiss MA, Ward CW, Lawrence MC Structure. 2016 Jan 27. pii: S0969-2126(16)00007-1. doi:, 10.1016/j.str.2015.12.014. PMID:26853939<ref>PMID:26853939</ref>

-	~~Description:~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Whittaker, J]]~~	+	<div class="pdbe-citations 4zxb" style="background-color:#fffaf0;"></div>
-	~~[[Category: Margetts, M.B]]~~	+	== References ==
-	~~[[Category: Lawrence, M.C]]~~	+	<references/>
-	~~[[Category: Weiss, M.A]]~~	+	__TOC__
-	~~[[Category: Ward, C.W]]~~	+	</StructureSection>
	[[Category: Croll, T]]		[[Category: Croll, T]]
-	[[Category: Smith, B.J]]	+	[[Category: Lawrence, M C]]
		+	[[Category: Margetts, M B]]
		+	[[Category: Smith, B J]]
		+	[[Category: Ward, C W]]
		+	[[Category: Weiss, M A]]
		+	[[Category: Whittaker, J]]
		+	[[Category: Hormone receptor-immune system complex]]
		+	[[Category: Receptor tyrosine kinase extracellular domain antibody fragment]]

OCA at 13:53, 30 December 2015

OCA — Wed, 30 Dec 2015 13:53:04 GMT

←Older revision		Revision as of 13:53, 30 December 2015
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4zxb is ON HOLD	+	The entry 4zxb is ON HOLD until Paper Publication

	Authors: Croll, T., Smith, B.J., Margetts, M.B., Whittaker, J., Weiss, M.A., Ward, C.W., Lawrence, M.C.		Authors: Croll, T., Smith, B.J., Margetts, M.B., Whittaker, J., Weiss, M.A., Ward, C.W., Lawrence, M.C.

OCA at 08:12, 23 December 2015

OCA — Wed, 23 Dec 2015 08:12:44 GMT

←Older revision		Revision as of 08:12, 23 December 2015
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4zxb is ON HOLD ~~until sometime in the future~~	+	The entry 4zxb is ON HOLD

	Authors: Croll, T., Smith, B.J., Margetts, M.B., Whittaker, J., Weiss, M.A., Ward, C.W., Lawrence, M.C.		Authors: Croll, T., Smith, B.J., Margetts, M.B., Whittaker, J., Weiss, M.A., Ward, C.W., Lawrence, M.C.

OCA at 12:06, 2 December 2015

OCA — Wed, 02 Dec 2015 12:06:02 GMT

←Older revision		Revision as of 12:06, 2 December 2015
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4zxb is ON HOLD	+	The entry 4zxb is ON HOLD until sometime in the future

	Authors: Croll, T., Smith, B.J., Margetts, M.B., Whittaker, J., Weiss, M.A., Ward, C.W., Lawrence, M.C.		Authors: Croll, T., Smith, B.J., Margetts, M.B., Whittaker, J., Weiss, M.A., Ward, C.W., Lawrence, M.C.

OCA at 00:14, 1 December 2015

OCA — Tue, 01 Dec 2015 00:14:39 GMT

←Older revision		Revision as of 00:14, 1 December 2015
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	[[Category: Whittaker, J]]		[[Category: Whittaker, J]]
	[[Category: Margetts, M.B]]		[[Category: Margetts, M.B]]
-	[[Category: Weiss, M.A]]
	[[Category: Lawrence, M.C]]		[[Category: Lawrence, M.C]]
		+	[[Category: Weiss, M.A]]
	[[Category: Ward, C.W]]		[[Category: Ward, C.W]]
	[[Category: Croll, T]]		[[Category: Croll, T]]
	[[Category: Smith, B.J]]		[[Category: Smith, B.J]]

OCA: Protected "4zxb" [edit=sysop:move=sysop]

OCA — Wed, 27 May 2015 14:51:34 GMT

Protected "4zxb" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:51, 27 May 2015

OCA: New page: '''Unreleased structure''' The entry 4zxb is ON HOLD Authors: Croll, T., Smith, B.J., Margetts, M.B., Whittaker, J., Weiss, M.A., Ward, C.W., Lawrence, M.C. Description: [[Category: U...

OCA — Wed, 27 May 2015 14:51:33 GMT

New page: '''Unreleased structure''' The entry 4zxb is ON HOLD Authors: Croll, T., Smith, B.J., Margetts, M.B., Whittaker, J., Weiss, M.A., Ward, C.W., Lawrence, M.C. Description: [[Category: U...

New page

'''Unreleased structure'''

The entry 4zxb is ON HOLD

Authors: Croll, T., Smith, B.J., Margetts, M.B., Whittaker, J., Weiss, M.A., Ward, C.W., Lawrence, M.C.

Description:
[[Category: Unreleased Structures]]
[[Category: Whittaker, J]]
[[Category: Margetts, M.B]]
[[Category: Weiss, M.A]]
[[Category: Lawrence, M.C]]
[[Category: Ward, C.W]]
[[Category: Croll, T]]
[[Category: Smith, B.J]]