4hrm - Revision history

OCA at 14:10, 8 November 2023

2023-11-08T14:10:20Z

←Older revision		Revision as of 14:10, 8 November 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4hrm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HRM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HRM FirstGlance]. <br>		<table><tr><td colspan='2'>[[4hrm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HRM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HRM 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=4hrm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hrm OCA], [https://pdbe.org/4hrm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hrm RCSB], [https://www.ebi.ac.uk/pdbsum/4hrm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hrm ProSAT]</span></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]] 3.2Å</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=4hrm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hrm OCA], [https://pdbe.org/4hrm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hrm RCSB], [https://www.ebi.ac.uk/pdbsum/4hrm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hrm ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==

OCA at 08:08, 9 November 2022

2022-11-09T08:08:10Z

←Older revision		Revision as of 08:08, 9 November 2022
Line 1:		Line 1:

	==Structural Basis for Eliciting a Cytotoxic Effect in HER2-Overexpressing Cancer Cells via Binding to the Extracellular Domain of HER2==		==Structural Basis for Eliciting a Cytotoxic Effect in HER2-Overexpressing Cancer Cells via Binding to the Extracellular Domain of HER2==
-	<StructureSection load='4hrm' size='340' side='right' caption='[[4hrm]], [[Resolution\|resolution]] 3.20Å' scene=''>	+	<StructureSection load='4hrm' size='340' side='right'caption='[[4hrm]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4hrm]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~] and [~~http~~://en.wikipedia.org/wiki/~~Synthetic_construct_sequences~~ Synthetic construct ~~sequences~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HRM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4HRM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4hrm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HRM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HRM FirstGlance]. <br>
-	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hrl\|4hrl]], [[4hrn\|4hrn]], [[1n8z\|1n8z]], [[1s78\|1s78]], [[3h3b\|3h3b]], [[3mzw\|3mzw]]</td></tr>	+	</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=4hrm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hrm OCA], [https://pdbe.org/4hrm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hrm RCSB], [https://www.ebi.ac.uk/pdbsum/4hrm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hrm ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERBB2, HER2, MLN19, NEU, NGL ([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='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=4hrm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hrm OCA], [~~http~~://pdbe.org/4hrm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4hrm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4hrm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4hrm ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/ERBB2_HUMAN ERBB2_HUMAN]] Defects in ERBB2 are a cause of hereditary diffuse gastric cancer (HDGC) [MIM:[~~http~~://omim.org/entry/137215 137215]]. A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Defects in ERBB2 are involved in the development of glioma (GLM) [MIM:[~~http~~://omim.org/entry/137800 137800]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Defects in ERBB2 are a cause of susceptibility to ovarian cancer (OC) [MIM:[~~http~~://omim.org/entry/167000 167000]]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Defects in ERBB2 may be a cause of lung cancer (LNCR) [MIM:[~~http~~://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in ERBB2 are a cause of gastric cancer (GASC) [MIM:[~~http~~://omim.org/entry/613659 613659]]. A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. Note=Chromosomal aberrations involving ERBB2 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with CDK12, leading to CDK12-ERBB2 fusion leading to truncated CDK12 protein not in-frame with ERBB2.	+	[https://www.uniprot.org/uniprot/ERBB2_HUMAN ERBB2_HUMAN] Defects in ERBB2 are a cause of hereditary diffuse gastric cancer (HDGC) [MIM:[https://omim.org/entry/137215 137215]. A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Defects in ERBB2 are involved in the development of glioma (GLM) [MIM:[https://omim.org/entry/137800 137800]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Defects in ERBB2 are a cause of susceptibility to ovarian cancer (OC) [MIM:[https://omim.org/entry/167000 167000]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Defects in ERBB2 may be a cause of lung cancer (LNCR) [MIM:[https://omim.org/entry/211980 211980]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in ERBB2 are a cause of gastric cancer (GASC) [MIM:[https://omim.org/entry/613659 613659]. A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. Note=Chromosomal aberrations involving ERBB2 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with CDK12, leading to CDK12-ERBB2 fusion leading to truncated CDK12 protein not in-frame with ERBB2.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ERBB2_HUMAN ERBB2_HUMAN]] Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.<ref>PMID:10358079</ref> <ref>PMID:15380516</ref> <ref>PMID:16794579</ref> <ref>PMID:19372587</ref> <ref>PMID:20937854</ref> <ref>PMID:21555369</ref> In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.<ref>PMID:10358079</ref> <ref>PMID:15380516</ref> <ref>PMID:16794579</ref> <ref>PMID:19372587</ref> <ref>PMID:20937854</ref> <ref>PMID:21555369</ref>	+	[https://www.uniprot.org/uniprot/ERBB2_HUMAN ERBB2_HUMAN] Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.<ref>PMID:10358079</ref> <ref>PMID:15380516</ref> <ref>PMID:16794579</ref> <ref>PMID:19372587</ref> <ref>PMID:20937854</ref> <ref>PMID:21555369</ref> In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.<ref>PMID:10358079</ref> <ref>PMID:15380516</ref> <ref>PMID:16794579</ref> <ref>PMID:19372587</ref> <ref>PMID:20937854</ref> <ref>PMID:21555369</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Receptor protein-tyrosine kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Synthetic construct ~~sequences~~]]	+	[[Category: Synthetic construct]]
-	[[Category: Jost, C]]	+	[[Category: Jost C]]
-	[[Category: Plueckthun, A]]	+	[[Category: Plueckthun A]]
-	[[Category: Schilling, J]]	+	[[Category: Schilling J]]
-	~~[[Category: Transferase-de novo protein complex~~]]	+

OCA at 09:17, 5 August 2016

2016-08-05T09:17:42Z

←Older revision		Revision as of 09:17, 5 August 2016
Line 1:		Line 1:
-	{{STRUCTURE_4hrm\| PDB=4hrm \| SCENE= }}
-	===Structural Basis for Eliciting a Cytotoxic Effect in HER2-Overexpressing Cancer Cells via Binding to the Extracellular Domain of HER2===
-	{{ABSTRACT_PUBMED_24095059}}

-	==Disease==	+	==Structural Basis for Eliciting a Cytotoxic Effect in HER2-Overexpressing Cancer Cells via Binding to the Extracellular Domain of HER2==
		+	<StructureSection load='4hrm' size='340' side='right' caption='[[4hrm]], [[Resolution\|resolution]] 3.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4hrm]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HRM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HRM FirstGlance]. <br>
		+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4hrl\|4hrl]], [[4hrn\|4hrn]], [[1n8z\|1n8z]], [[1s78\|1s78]], [[3h3b\|3h3b]], [[3mzw\|3mzw]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERBB2, HER2, MLN19, NEU, NGL ([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='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=4hrm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hrm OCA], [http://pdbe.org/4hrm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hrm RCSB], [http://www.ebi.ac.uk/pdbsum/4hrm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hrm ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/ERBB2_HUMAN ERBB2_HUMAN]] Defects in ERBB2 are a cause of hereditary diffuse gastric cancer (HDGC) [MIM:[http://omim.org/entry/137215 137215]]. A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Defects in ERBB2 are involved in the development of glioma (GLM) [MIM:[http://omim.org/entry/137800 137800]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Defects in ERBB2 are a cause of susceptibility to ovarian cancer (OC) [MIM:[http://omim.org/entry/167000 167000]]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Defects in ERBB2 may be a cause of lung cancer (LNCR) [MIM:[http://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in ERBB2 are a cause of gastric cancer (GASC) [MIM:[http://omim.org/entry/613659 613659]]. A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. Note=Chromosomal aberrations involving ERBB2 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with CDK12, leading to CDK12-ERBB2 fusion leading to truncated CDK12 protein not in-frame with ERBB2.		[[http://www.uniprot.org/uniprot/ERBB2_HUMAN ERBB2_HUMAN]] Defects in ERBB2 are a cause of hereditary diffuse gastric cancer (HDGC) [MIM:[http://omim.org/entry/137215 137215]]. A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Defects in ERBB2 are involved in the development of glioma (GLM) [MIM:[http://omim.org/entry/137800 137800]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Defects in ERBB2 are a cause of susceptibility to ovarian cancer (OC) [MIM:[http://omim.org/entry/167000 167000]]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Defects in ERBB2 may be a cause of lung cancer (LNCR) [MIM:[http://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in ERBB2 are a cause of gastric cancer (GASC) [MIM:[http://omim.org/entry/613659 613659]]. A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. Note=Chromosomal aberrations involving ERBB2 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with CDK12, leading to CDK12-ERBB2 fusion leading to truncated CDK12 protein not in-frame with ERBB2.
-		+	== Function ==
-	==Function==	+
	[[http://www.uniprot.org/uniprot/ERBB2_HUMAN ERBB2_HUMAN]] Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.<ref>PMID:10358079</ref> <ref>PMID:15380516</ref> <ref>PMID:16794579</ref> <ref>PMID:19372587</ref> <ref>PMID:20937854</ref> <ref>PMID:21555369</ref> In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.<ref>PMID:10358079</ref> <ref>PMID:15380516</ref> <ref>PMID:16794579</ref> <ref>PMID:19372587</ref> <ref>PMID:20937854</ref> <ref>PMID:21555369</ref>		[[http://www.uniprot.org/uniprot/ERBB2_HUMAN ERBB2_HUMAN]] Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.<ref>PMID:10358079</ref> <ref>PMID:15380516</ref> <ref>PMID:16794579</ref> <ref>PMID:19372587</ref> <ref>PMID:20937854</ref> <ref>PMID:21555369</ref> In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.<ref>PMID:10358079</ref> <ref>PMID:15380516</ref> <ref>PMID:16794579</ref> <ref>PMID:19372587</ref> <ref>PMID:20937854</ref> <ref>PMID:21555369</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human epidermal growth factor receptor-2 (HER2) is a receptor tyrosine kinase directly linked to the growth of malignancies from various origins and a validated target for monoclonal antibodies and kinase inhibitors. Utilizing a new approach with designed ankyrin repeat proteins (DARPins) as alternative binders, we show that binding of two DARPins connected by a short linker, one targeting extracellular subdomain I and the other subdomain IV, causes much stronger cytotoxic effects on the HER2-addicted breast cancer cell line BT474, surpassing the therapeutic antibody trastuzumab. We determined crystal structures of these DARPins in complex with the respective subdomains. Detailed models of the full-length receptor, constrained by its rigid domain structures and its membrane anchoring, explain how the bispecific DARPins connect two membrane-bound HER2 molecules, distorting them such that they cannot form signaling-competent dimers with any EGFR family member, preventing any kinase dimerization, and thus leading to a complete loss of signaling.

-	~~==About this Structure==~~	+	Structural Basis for Eliciting a Cytotoxic Effect in HER2-Overexpressing Cancer Cells via Binding to the Extracellular Domain of HER2.,Jost C, Schilling J, Tamaskovic R, Schwill M, Honegger A, Pluckthun A Structure. 2013 Oct 2. pii: S0969-2126(13)00341-9. doi:, 10.1016/j.str.2013.08.020. PMID:24095059<ref>PMID:24095059</ref>
-	~~[[4hrm]] is~~ a ~~4 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens] and [http~~:~~//en~~.~~wikipedia~~.~~org~~/~~wiki/Synthetic_construct Synthetic construct]~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann~~.ac.il/~~oca-bin/ocashort?id=4HRM OCA].~~	+

-	~~==Reference==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	<~~ref group~~="~~xtra~~"~~>PMID~~:~~024095059~~</~~ref~~><references ~~group="xtra"~~/><~~references~~/>	+	</div>
-	[[Category: ~~Homo sapiens~~]]	+	<div class="pdbe-citations 4hrm" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: Synthetic construct]]	+	[[Category: Synthetic construct sequences]]
-	[[Category: Jost, C.]]	+	[[Category: Jost, C]]
-	[[Category: Plueckthun, A.]]	+	[[Category: Plueckthun, A]]
-	[[Category: Schilling, J.]]	+	[[Category: Schilling, J]]
	[[Category: Transferase-de novo protein complex]]		[[Category: Transferase-de novo protein complex]]

OCA at 08:13, 30 October 2013

2013-10-30T08:13:06Z

←Older revision		Revision as of 08:13, 30 October 2013
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	{{STRUCTURE_4hrm\| PDB=4hrm \| SCENE= }}		{{STRUCTURE_4hrm\| PDB=4hrm \| SCENE= }}
-	===Structural Basis for ~~driving~~ HER2-~~addicted cancer cells into apoptosis~~===	+	===Structural Basis for Eliciting a Cytotoxic Effect in HER2-Overexpressing Cancer Cells via Binding to the Extracellular Domain of HER2===
	{{ABSTRACT_PUBMED_24095059}}		{{ABSTRACT_PUBMED_24095059}}

OCA at 08:00, 16 October 2013

2013-10-16T08:00:42Z

←Older revision		Revision as of 08:00, 16 October 2013
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-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4hrm\| PDB=4hrm \| SCENE= }}
		+	===Structural Basis for driving HER2-addicted cancer cells into apoptosis===
		+	{{ABSTRACT_PUBMED_24095059}}

-	~~The~~ entry ~~4hrm~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/ERBB2_HUMAN ERBB2_HUMAN]] Defects in ERBB2 are a cause of hereditary diffuse gastric cancer (HDGC) [MIM:[http://omim.org/entry/137215 137215]]. A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Defects in ERBB2 are involved in the development of glioma (GLM) [MIM:[http://omim.org/entry/137800 137800]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Defects in ERBB2 are a cause of susceptibility to ovarian cancer (OC) [MIM:[http://omim.org/entry/167000 167000]]. Ovarian cancer common malignancy originating from ovarian tissue. Although many histologic types of ovarian neoplasms have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Defects in ERBB2 may be a cause of lung cancer (LNCR) [MIM:[http://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in ERBB2 are a cause of gastric cancer (GASC) [MIM:[http://omim.org/entry/613659 613659]]. A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. Note=Chromosomal aberrations involving ERBB2 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with CDK12, leading to CDK12-ERBB2 fusion leading to truncated CDK12 protein not in-frame with ERBB2.

-	~~Authors~~: ~~Jost~~, C., ~~Schilling~~, J., ~~Plueckthun~~, A.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/ERBB2_HUMAN ERBB2_HUMAN]] Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.<ref>PMID:10358079</ref> <ref>PMID:15380516</ref> <ref>PMID:16794579</ref> <ref>PMID:19372587</ref> <ref>PMID:20937854</ref> <ref>PMID:21555369</ref> In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.<ref>PMID:10358079</ref> <ref>PMID:15380516</ref> <ref>PMID:16794579</ref> <ref>PMID:19372587</ref> <ref>PMID:20937854</ref> <ref>PMID:21555369</ref>

-	~~Description~~: ~~Structural Basis for driving HER2~~-~~addicted cancer cells into apoptosis~~	+	==About this Structure==
		+	[[4hrm]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HRM OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:024095059</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Synthetic construct]]
		+	[[Category: Jost, C.]]
		+	[[Category: Plueckthun, A.]]
		+	[[Category: Schilling, J.]]
		+	[[Category: Transferase-de novo protein complex]]

OCA at 07:10, 8 May 2013

2013-05-08T07:10:26Z

←Older revision		Revision as of 07:10, 8 May 2013
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	The entry 4hrm is ON HOLD until Paper Publication		The entry 4hrm is ON HOLD until Paper Publication

-	Authors: Jost, C., Schilling, J.	+	Authors: Jost, C., Schilling, J., Plueckthun, A.

	Description: Structural Basis for driving HER2-addicted cancer cells into apoptosis		Description: Structural Basis for driving HER2-addicted cancer cells into apoptosis

OCA at 20:44, 12 December 2012

2012-12-12T20:44:39Z

←Older revision		Revision as of 20:44, 12 December 2012
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Jost, C., Schilling, J.		Authors: Jost, C., Schilling, J.

	Description: Structural Basis for driving HER2-addicted cancer cells into apoptosis		Description: Structural Basis for driving HER2-addicted cancer cells into apoptosis

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

2012-11-08T13:25:31Z

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

←Older revision

Revision as of 13:25, 8 November 2012

OCA: New page: '''Unreleased structure''' The entry 4hrm is ON HOLD Authors: Jost, C., Schilling, J. Description: Structural Basis for driving HER2-addicted cancer cells into apoptosis

2012-11-08T13:25:30Z

New page: '''Unreleased structure''' The entry 4hrm is ON HOLD Authors: Jost, C., Schilling, J. Description: Structural Basis for driving HER2-addicted cancer cells into apoptosis

New page

'''Unreleased structure'''

The entry 4hrm is ON HOLD

Authors: Jost, C., Schilling, J.

Description: Structural Basis for driving HER2-addicted cancer cells into apoptosis