3bce - Revision history

OCA at 09:28, 21 February 2024

2024-02-21T09:28:27Z

←Older revision		Revision as of 09:28, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='3bce' size='340' side='right'caption='[[3bce]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='3bce' size='340' side='right'caption='[[3bce]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3bce]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BCE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3bce]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BCE FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>~~, ~~<scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.5Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max-height: 3em;~~'>~~[[3bbt\|3bbt]], [[3bbw\|3bbw]]~~</~~div~~><~~/td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
-	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>[[Gene\|Gene~~:~~]]</b></td><td class="sblockDat">ERBB4, HER4~~ (~~[https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]~~)~~</td~~></tr>	+
-	<~~tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[https://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1]~~ </~~span~~></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=3bce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bce OCA], [https://pdbe.org/3bce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bce RCSB], [https://www.ebi.ac.uk/pdbsum/3bce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bce ProSAT]</span></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=3bce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bce OCA], [https://pdbe.org/3bce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bce RCSB], [https://www.ebi.ac.uk/pdbsum/3bce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bce ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/ERBB4_HUMAN ERBB4_HUMAN]] Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.<ref>PMID:8383326</ref> <ref>PMID:9334263</ref> <ref>PMID:8617750</ref> <ref>PMID:9135143</ref> <ref>PMID:9168115</ref> <ref>PMID:10358079</ref> <ref>PMID:10353604</ref> <ref>PMID:10348342</ref> <ref>PMID:10722704</ref> <ref>PMID:10867024</ref> <ref>PMID:11178955</ref> <ref>PMID:11390655</ref> <ref>PMID:12807903</ref> <ref>PMID:15534001</ref> <ref>PMID:15746097</ref> <ref>PMID:16778220</ref> <ref>PMID:16251361</ref> <ref>PMID:16837552</ref> <ref>PMID:17120616</ref> <ref>PMID:17638867</ref> <ref>PMID:17486069</ref> <ref>PMID:19098003</ref> <ref>PMID:20858735</ref> <ref>PMID:21811097</ref>	+	[https://www.uniprot.org/uniprot/ERBB4_HUMAN ERBB4_HUMAN] Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.<ref>PMID:8383326</ref> <ref>PMID:9334263</ref> <ref>PMID:8617750</ref> <ref>PMID:9135143</ref> <ref>PMID:9168115</ref> <ref>PMID:10358079</ref> <ref>PMID:10353604</ref> <ref>PMID:10348342</ref> <ref>PMID:10722704</ref> <ref>PMID:10867024</ref> <ref>PMID:11178955</ref> <ref>PMID:11390655</ref> <ref>PMID:12807903</ref> <ref>PMID:15534001</ref> <ref>PMID:15746097</ref> <ref>PMID:16778220</ref> <ref>PMID:16251361</ref> <ref>PMID:16837552</ref> <ref>PMID:17120616</ref> <ref>PMID:17638867</ref> <ref>PMID:17486069</ref> <ref>PMID:19098003</ref> <ref>PMID:20858735</ref> <ref>PMID:21811097</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 22:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bce ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bce ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	HER4/ErbB4 is a ubiquitously expressed member of the EGF/ErbB family of receptor tyrosine kinases that is essential for normal development of the heart, nervous system, and mammary gland. We report here crystal structures of the ErbB4 kinase domain in active and lapatinib-inhibited forms. Active ErbB4 kinase adopts an asymmetric dimer conformation essentially identical to that observed to be important for activation of the EGF receptor/ErbB1 kinase. Mutagenesis studies of intact ErbB4 in Ba/F3 cells confirm the importance of this asymmetric dimer for activation of intact ErbB4. Lapatinib binds to an inactive form of the ErbB4 kinase in a mode equivalent to its interaction with the EGF receptor. All ErbB4 residues contacted by lapatinib are conserved in the EGF receptor and HER2/ErbB2, which lapatinib also targets. These results demonstrate that key elements of kinase activation and inhibition are conserved among ErbB family members.
-
-	Mechanism of activation and inhibition of the HER4/ErbB4 kinase.,Qiu C, Tarrant MK, Choi SH, Sathyamurthy A, Bose R, Banjade S, Pal A, Bornmann WG, Lemmon MA, Cole PA, Leahy DJ Structure. 2008 Mar;16(3):460-7. PMID:18334220<ref>PMID:18334220</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 3bce" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Qiu C]]
-	[[Category: Qiu, C]]	+
-	~~[[Category: Active conformation]]~~	+
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Receptor]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transmembrane]]~~	+
-	~~[[Category: Tyrosine-protein kinase~~]]	+

OCA at 11:31, 5 January 2022

2022-01-05T11:31:07Z

←Older revision		Revision as of 11:31, 5 January 2022
Line 1:		Line 1:

	==Crystal structure of the ErbB4 kinase==		==Crystal structure of the ErbB4 kinase==
-	<StructureSection load='3bce' size='340' side='right' caption='[[3bce]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='3bce' size='340' side='right'caption='[[3bce]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3bce]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BCE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3BCE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3bce]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BCE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3bbt\|3bbt]], [[3bbw\|3bbw]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3bbt\|3bbt]], [[3bbw\|3bbw]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERBB4, HER4 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERBB4, HER4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></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=3bce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bce OCA], [~~http~~://pdbe.org/3bce PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3bce RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3bce PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3bce ProSAT]</span></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=3bce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bce OCA], [https://pdbe.org/3bce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bce RCSB], [https://www.ebi.ac.uk/pdbsum/3bce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bce ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/ERBB4_HUMAN ERBB4_HUMAN]] Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.<ref>PMID:8383326</ref> <ref>PMID:9334263</ref> <ref>PMID:8617750</ref> <ref>PMID:9135143</ref> <ref>PMID:9168115</ref> <ref>PMID:10358079</ref> <ref>PMID:10353604</ref> <ref>PMID:10348342</ref> <ref>PMID:10722704</ref> <ref>PMID:10867024</ref> <ref>PMID:11178955</ref> <ref>PMID:11390655</ref> <ref>PMID:12807903</ref> <ref>PMID:15534001</ref> <ref>PMID:15746097</ref> <ref>PMID:16778220</ref> <ref>PMID:16251361</ref> <ref>PMID:16837552</ref> <ref>PMID:17120616</ref> <ref>PMID:17638867</ref> <ref>PMID:17486069</ref> <ref>PMID:19098003</ref> <ref>PMID:20858735</ref> <ref>PMID:21811097</ref>	+	[[https://www.uniprot.org/uniprot/ERBB4_HUMAN ERBB4_HUMAN]] Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.<ref>PMID:8383326</ref> <ref>PMID:9334263</ref> <ref>PMID:8617750</ref> <ref>PMID:9135143</ref> <ref>PMID:9168115</ref> <ref>PMID:10358079</ref> <ref>PMID:10353604</ref> <ref>PMID:10348342</ref> <ref>PMID:10722704</ref> <ref>PMID:10867024</ref> <ref>PMID:11178955</ref> <ref>PMID:11390655</ref> <ref>PMID:12807903</ref> <ref>PMID:15534001</ref> <ref>PMID:15746097</ref> <ref>PMID:16778220</ref> <ref>PMID:16251361</ref> <ref>PMID:16837552</ref> <ref>PMID:17120616</ref> <ref>PMID:17638867</ref> <ref>PMID:17486069</ref> <ref>PMID:19098003</ref> <ref>PMID:20858735</ref> <ref>PMID:21811097</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bc/3bce_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bc/3bce_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 36:		Line 36:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Qiu, C]]		[[Category: Qiu, C]]

OCA at 07:59, 25 October 2017

2017-10-25T07:59:50Z

←Older revision		Revision as of 07:59, 25 October 2017
Line 1:		Line 1:
		+
	==Crystal structure of the ErbB4 kinase==		==Crystal structure of the ErbB4 kinase==
	<StructureSection load='3bce' size='340' side='right' caption='[[3bce]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='3bce' size='340' side='right' caption='[[3bce]], [[Resolution\|resolution]] 2.50Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERBB4, HER4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERBB4, HER4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></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=3bce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bce OCA], [http://pdbe.org/3bce PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bce RCSB], [http://www.ebi.ac.uk/pdbsum/3bce PDBsum]</span></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=3bce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bce OCA], [http://pdbe.org/3bce PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bce RCSB], [http://www.ebi.ac.uk/pdbsum/3bce PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3bce ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 19:15, 7 February 2016

2016-02-07T19:15:52Z

←Older revision		Revision as of 19:15, 7 February 2016
Line 2:		Line 2:
	<StructureSection load='3bce' size='340' side='right' caption='[[3bce]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='3bce' size='340' side='right' caption='[[3bce]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3bce]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BCE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BCE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3bce]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BCE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BCE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3bbt\|3bbt]], [[3bbw\|3bbw]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3bbt\|3bbt]], [[3bbw\|3bbw]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERBB4, HER4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERBB4, HER4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></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=3bce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bce OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bce RCSB], [http://www.ebi.ac.uk/pdbsum/3bce PDBsum]</span></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=3bce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bce OCA], [http://pdbe.org/3bce PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3bce RCSB], [http://www.ebi.ac.uk/pdbsum/3bce PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bce ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 29:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3bce" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Qiu, C]]		[[Category: Qiu, C]]

OCA at 17:39, 24 December 2014

2014-12-24T17:39:45Z

←Older revision		Revision as of 17:39, 24 December 2014
Line 9:		Line 9:
	<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=3bce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bce OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bce RCSB], [http://www.ebi.ac.uk/pdbsum/3bce PDBsum]</span></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=3bce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bce OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bce RCSB], [http://www.ebi.ac.uk/pdbsum/3bce PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ERBB4_HUMAN ERBB4_HUMAN]] Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.<ref>PMID:8383326</ref> <ref>PMID:9334263</ref> <ref>PMID:8617750</ref> <ref>PMID:9135143</ref> <ref>PMID:9168115</ref> <ref>PMID:10358079</ref> <ref>PMID:10353604</ref> <ref>PMID:10348342</ref> <ref>PMID:10722704</ref> <ref>PMID:10867024</ref> <ref>PMID:11178955</ref> <ref>PMID:11390655</ref> <ref>PMID:12807903</ref> <ref>PMID:15534001</ref> <ref>PMID:15746097</ref> <ref>PMID:16778220</ref> <ref>PMID:16251361</ref> <ref>PMID:16837552</ref> <ref>PMID:17120616</ref> <ref>PMID:17638867</ref> <ref>PMID:17486069</ref> <ref>PMID:19098003</ref> <ref>PMID:20858735</ref> <ref>PMID:21811097</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 33:		Line 35:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: Qiu, C.]]	+	[[Category: Qiu, C]]
	[[Category: Active conformation]]		[[Category: Active conformation]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]

OCA at 06:06, 10 October 2014

2014-10-10T06:06:17Z

←Older revision		Revision as of 06:06, 10 October 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3bce~~\| ~~PDB~~=3bce \| ~~SCENE~~= }}	+	==Crystal structure of the ErbB4 kinase==
-	===~~Crystal~~ structure of the ~~ErbB4 kinase~~===	+	<StructureSection load='3bce' size='340' side='right' caption='[[3bce]], [[Resolution\|resolution]] 2.50Å' scene=''>
-	~~{{ABSTRACT_PUBMED_18334220}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3bce]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BCE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BCE FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3bbt\|3bbt]], [[3bbw\|3bbw]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERBB4, HER4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></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=3bce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bce OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bce RCSB], [http://www.ebi.ac.uk/pdbsum/3bce PDBsum]</span></td></tr>
		+	</table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bc/3bce_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	HER4/ErbB4 is a ubiquitously expressed member of the EGF/ErbB family of receptor tyrosine kinases that is essential for normal development of the heart, nervous system, and mammary gland. We report here crystal structures of the ErbB4 kinase domain in active and lapatinib-inhibited forms. Active ErbB4 kinase adopts an asymmetric dimer conformation essentially identical to that observed to be important for activation of the EGF receptor/ErbB1 kinase. Mutagenesis studies of intact ErbB4 in Ba/F3 cells confirm the importance of this asymmetric dimer for activation of intact ErbB4. Lapatinib binds to an inactive form of the ErbB4 kinase in a mode equivalent to its interaction with the EGF receptor. All ErbB4 residues contacted by lapatinib are conserved in the EGF receptor and HER2/ErbB2, which lapatinib also targets. These results demonstrate that key elements of kinase activation and inhibition are conserved among ErbB family members.

-	~~==Function==~~	+	Mechanism of activation and inhibition of the HER4/ErbB4 kinase.,Qiu C, Tarrant MK, Choi SH, Sathyamurthy A, Bose R, Banjade S, Pal A, Bornmann WG, Lemmon MA, Cole PA, Leahy DJ Structure. 2008 Mar;16(3):460-7. PMID:18334220<ref>PMID:18334220</ref>
-	[[http://www.uniprot.org/uniprot/ERBB4_HUMAN ERBB4_HUMAN]] Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of ~~the heart, the central nervous system~~ and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the ~~embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance~~. ~~Required for mammary gland differentiation~~, ~~induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1~~, ~~NRG2~~, ~~NRG3 and NRG4 and the EGF family members BTC~~, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A ~~CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1~~, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, ~~and hence do not phosphorylate PIK3R1~~, ~~do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-~~A ~~CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus~~, ~~promote nuclear import of STAT5A~~, ~~activation of STAT5A~~, ~~mammary epithelium differentiation~~, ~~cell proliferation and activation of gene expression~~. ~~The ERBB4 soluble intracellular domains~~ (~~4ICD~~) ~~colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation~~. ~~The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.<ref>~~PMID:8383326</ref> <ref>PMID:9334263</ref> <ref>PMID:8617750</ref> <ref>PMID:9135143</ref> <ref>PMID:9168115</ref> <ref>PMID:10358079</ref> <ref>PMID:10353604</ref> <ref>PMID:10348342</ref> <ref>PMID:10722704</ref> <ref>PMID:10867024</ref> <ref>PMID:11178955</ref> <ref>PMID:11390655</ref> <ref>PMID:12807903</ref> <ref>PMID:15534001</ref> <ref>PMID:15746097</ref> <ref>PMID:16778220</ref> <ref>PMID:16251361</ref> <ref>PMID:16837552</ref> <ref>PMID:17120616</ref> <ref>PMID:17638867</ref> <ref>PMID:17486069</ref> <ref>PMID:19098003</ref> <ref>PMID:20858735</ref> <ref>PMID:~~21811097~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[3bce]] is~~ a ~~3 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3BCE OCA].~~	+	</div>
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:018334220</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]

OCA at 07:22, 30 June 2013

2013-06-30T07:22:00Z

←Older revision		Revision as of 07:22, 30 June 2013
Line 1:		Line 1:
-	[[Image:3bce.png\|left\|200px]]
-
	{{STRUCTURE_3bce\| PDB=3bce \| SCENE= }}		{{STRUCTURE_3bce\| PDB=3bce \| SCENE= }}
-
	===Crystal structure of the ErbB4 kinase===		===Crystal structure of the ErbB4 kinase===
		+	{{ABSTRACT_PUBMED_18334220}}

-	~~{{ABSTRACT_PUBMED_18334220}}~~	+	==Function==
		+	[[http://www.uniprot.org/uniprot/ERBB4_HUMAN ERBB4_HUMAN]] Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mammary gland, gene transcription, cell proliferation, differentiation, migration and apoptosis. Required for normal cardiac muscle differentiation during embryonic development, and for postnatal cardiomyocyte proliferation. Required for normal development of the embryonic central nervous system, especially for normal neural crest cell migration and normal axon guidance. Required for mammary gland differentiation, induction of milk proteins and lactation. Acts as cell-surface receptor for the neuregulins NRG1, NRG2, NRG3 and NRG4 and the EGF family members BTC, EREG and HBEGF. Ligand binding triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Ligand specificity and signaling is modulated by alternative splicing, proteolytic processing, and by the formation of heterodimers with other ERBB family members, thereby creating multiple combinations of intracellular phosphotyrosines that trigger ligand- and context-specific cellular responses. Mediates phosphorylation of SHC1 and activation of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Isoform JM-A CYT-1 and isoform JM-B CYT-1 phosphorylate PIK3R1, leading to the activation of phosphatidylinositol 3-kinase and AKT1 and protect cells against apoptosis. Isoform JM-A CYT-1 and isoform JM-B CYT-1 mediate reorganization of the actin cytoskeleton and promote cell migration in response to NRG1. Isoform JM-A CYT-2 and isoform JM-B CYT-2 lack the phosphotyrosine that mediates interaction with PIK3R1, and hence do not phosphorylate PIK3R1, do not protect cells against apoptosis, and do not promote reorganization of the actin cytoskeleton and cell migration. Proteolytic processing of isoform JM-A CYT-1 and isoform JM-A CYT-2 gives rise to the corresponding soluble intracellular domains (4ICD) that translocate to the nucleus, promote nuclear import of STAT5A, activation of STAT5A, mammary epithelium differentiation, cell proliferation and activation of gene expression. The ERBB4 soluble intracellular domains (4ICD) colocalize with STAT5A at the CSN2 promoter to regulate transcription of milk proteins during lactation. The ERBB4 soluble intracellular domains can also translocate to mitochondria and promote apoptosis.<ref>PMID:8383326</ref> <ref>PMID:9334263</ref> <ref>PMID:8617750</ref> <ref>PMID:9135143</ref> <ref>PMID:9168115</ref> <ref>PMID:10358079</ref> <ref>PMID:10353604</ref> <ref>PMID:10348342</ref> <ref>PMID:10722704</ref> <ref>PMID:10867024</ref> <ref>PMID:11178955</ref> <ref>PMID:11390655</ref> <ref>PMID:12807903</ref> <ref>PMID:15534001</ref> <ref>PMID:15746097</ref> <ref>PMID:16778220</ref> <ref>PMID:16251361</ref> <ref>PMID:16837552</ref> <ref>PMID:17120616</ref> <ref>PMID:17638867</ref> <ref>PMID:17486069</ref> <ref>PMID:19098003</ref> <ref>PMID:20858735</ref> <ref>PMID:21811097</ref>

	==About this Structure==		==About this Structure==
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	==Reference==		==Reference==
-	<ref group="xtra">PMID:018334220</ref><references group="xtra"/>	+	<ref group="xtra">PMID:018334220</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]

OCA: Protected "3bce" [edit=sysop:move=sysop]

2013-01-07T18:13:32Z

Protected "3bce" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:13, 7 January 2013

OCA at 18:13, 7 January 2013

2013-01-07T18:13:27Z

←Older revision		Revision as of 18:13, 7 January 2013
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-	{{Seed}}
	[[Image:3bce.png\|left\|200px]]		[[Image:3bce.png\|left\|200px]]

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	{{STRUCTURE_3bce\| PDB=3bce \| SCENE= }}		{{STRUCTURE_3bce\| PDB=3bce \| SCENE= }}

	===Crystal structure of the ErbB4 kinase===		===Crystal structure of the ErbB4 kinase===

-
-	<!--
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	{{ABSTRACT_PUBMED_18334220}}		{{ABSTRACT_PUBMED_18334220}}

	==About this Structure==		==About this Structure==
-	~~3BCE~~ is a 3 ~~chains~~ structure ~~of sequences~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BCE OCA].	+	[[3bce]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BCE OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~18334220~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:018334220</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Qiu, C.]]		[[Category: Qiu, C.]]
	[[Category: Active conformation]]		[[Category: Active conformation]]
-	[[Category: Alternative splicing]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Glycoprotein]]		[[Category: Glycoprotein]]
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	[[Category: Transmembrane]]		[[Category: Transmembrane]]
	[[Category: Tyrosine-protein kinase]]		[[Category: Tyrosine-protein kinase]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 15:57:21 2009''

OCA at 13:57, 16 February 2009

2009-02-16T13:57:21Z

←Older revision		Revision as of 13:57, 16 February 2009
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	==About this Structure==		==About this Structure==
-	3BCE is a ~~[[Single protein]]~~ structure of ~~sequence~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BCE OCA].	+	3BCE is a 3 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BCE OCA].

	==Reference==		==Reference==
-	Mechanism of Activation and Inhibition of the HER4/ErbB4 Kinase., Qiu C, Tarrant MK, Choi SH, Sathyamurthy A, Bose R, Banjade S, Pal A, Bornmann WG, Lemmon MA, Cole PA, Leahy DJ, Structure. 2008 Mar;16(3):460-7. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/18334220 18334220]~~	+	<ref group="xtra">PMID:18334220</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: Single protein]]
	[[Category: Qiu, C.]]		[[Category: Qiu, C.]]
	[[Category: Active conformation]]		[[Category: Active conformation]]
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	[[Category: Tyrosine-protein kinase]]		[[Category: Tyrosine-protein kinase]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun Jul 27 18~~:59:~~44 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 15:57:21 2009''