7run - Revision history

OCA at 13:59, 6 November 2024

2024-11-06T13:59:12Z

← Older revision		Revision as of 13:59, 6 November 2024
Line 3:		Line 3:
	<StructureSection load='7run' size='340' side='right'caption='[[7run]], [[Resolution\|resolution]] 3.51Å' scene=''>		<StructureSection load='7run' size='340' side='right'caption='[[7run]], [[Resolution\|resolution]] 3.51Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>~~[[7run]] is a 2 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=7RUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RUN FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RUN FirstGlance]. <br>
	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 3.51Å</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]] 3.51Å</td></tr>
	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7QU:1-(4-{(1s,3s)-3-[4-amino-5-(3-amino-4-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclobutyl}piperazin-1-yl)ethan-1-one'>7QU</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7QU:1-(4-{(1s,3s)-3-[4-amino-5-(3-amino-4-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclobutyl}piperazin-1-yl)ethan-1-one'>7QU</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=7run FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7run OCA], [https://pdbe.org/7run PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7run RCSB], [https://www.ebi.ac.uk/pdbsum/7run PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7run 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=7run FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7run OCA], [https://pdbe.org/7run PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7run RCSB], [https://www.ebi.ac.uk/pdbsum/7run PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7run ProSAT]</span></td></tr>
	</table>		</table>
	~~== Disease ==~~
	[https://www.uniprot.org/uniprot/RET_HUMAN RET_HUMAN] Unilateral renal dysplasia;Familial medullary thyroid carcinoma;Multiple endocrine neoplasia type 2B;Multiple endocrine neoplasia type 2A;Hirschsprung disease;Bilateral renal agenesis;Bilateral renal dysplasia;Ondine syndrome;Papillary or follicular thyroid carcinoma. Colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The disease may be caused by mutations affecting the gene represented in this entry. Hirschsprung disease 1 (HSCR1) [MIM:[https://omim.org/entry/142623 142623]: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:7704557</ref> <ref>PMID:7881414</ref> <ref>PMID:8114938</ref> <ref>PMID:8114939</ref> <ref>PMID:7633441</ref> <ref>PMID:7581377</ref> <ref>PMID:8595427</ref> <ref>PMID:9043870</ref> <ref>PMID:9090527</ref> <ref>PMID:9259198</ref> <ref>PMID:9094028</ref> <ref>PMID:9384613</ref> <ref>PMID:10090908</ref> <ref>PMID:10484767</ref> <ref>PMID:10618407</ref> <ref>PMID:22174939</ref> Medullary thyroid carcinoma (MTC) [MIM:[https://omim.org/entry/155240 155240]: Rare tumor derived from the C cells of the thyroid. Three hereditary forms are known, that are transmitted in an autosomal dominant fashion: (a) multiple neoplasia type 2A (MEN2A), (b) multiple neoplasia type IIB (MEN2B) and (c) familial MTC (FMTC), which occurs in 25-30% of MTC cases and where MTC is the only clinical manifestation. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:7881414</ref> <ref>PMID:9259198</ref> <ref>PMID:7849720</ref> <ref>PMID:7874109</ref> <ref>PMID:8625130</ref> <ref>PMID:7845675</ref> <ref>PMID:7784092</ref> <ref>PMID:8557249</ref> <ref>PMID:8807338</ref> <ref>PMID:9398735</ref> <ref>PMID:9223675</ref> <ref>PMID:9677065</ref> <ref>PMID:9452077</ref> <ref>PMID:9506724</ref> <ref>PMID:9621513</ref> <ref>PMID:10323403</ref> <ref>PMID:10826520</ref> <ref>PMID:11692159</ref> Multiple neoplasia 2B (MEN2B) [MIM:[https://omim.org/entry/162300 162300]: Uncommon inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with marfanoid habitus, mucosal neuromas, skeletal and ophtalmic abnormalities, and ganglioneuromas of the intestine tract. Then the disease progresses rapidly with the development of metastatic MTC and a pheochromocytome in 50% of cases. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:8625130</ref> <ref>PMID:8807338</ref> <ref>PMID:9223675</ref> <ref>PMID:7911697</ref> <ref>PMID:7906866</ref> <ref>PMID:7906417</ref> <ref>PMID:8595427</ref> <ref>PMID:9360560</ref> <ref>PMID:9294615</ref> Pheochromocytoma (PCC) [MIM:[https://omim.org/entry/171300 171300]: A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Multiple neoplasia 2A (MEN2A) [MIM:[https://omim.org/entry/171400 171400]: The most frequent form of medullary thyroid cancer (MTC). It is an inherited cancer syndrome characterized by MTC, phaeochromocytoma and/or hyperparathyroidism. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:7881414</ref> <ref>PMID:9384613</ref> <ref>PMID:7874109</ref> <ref>PMID:8625130</ref> <ref>PMID:8807338</ref> <ref>PMID:9223675</ref> <ref>PMID:9621513</ref> <ref>PMID:8103403</ref> <ref>PMID:8099202</ref> <ref>PMID:7915165</ref> <ref>PMID:7860065</ref> <ref>PMID:8626834</ref> <ref>PMID:9097963</ref> <ref>PMID:9452064</ref> <ref>PMID:10522989</ref> Thyroid papillary carcinoma (TPC) [MIM:[https://omim.org/entry/188550 188550]: A common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving RET have been found in thyroid papillary carcinomas. Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene; inversion inv(10)(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene; translocation t(10;14)(q11;q32) with GOLGA5 generates the RET/GOLGA5 (PTC5) oncogene; translocation t(8;10)(p21.3;q11.2) with PCM1 generates the PCM1/RET fusion; translocation t(6;10)(p21.3;q11.2) with RFP generates the Delta RFP/RET oncogene; translocation t(1;10)(p13;q11) with TRIM33 generates the TRIM33/RET (PTC7) oncogene; translocation t(7;10)(q32;q11) with TRIM24/TIF1 generates the TRIM24/RET (PTC6) oncogene. The PTC5 oncogene has been found in 2 cases of PACT in children exposed to radioactive fallout after Chernobyl. A chromosomal aberration involving TRIM27/RFP is found in thyroid papillary carcinomas. Translocation t(6;10)(p21.3;q11.2) with RET. The translocation generates TRIM27/RET and delta TRIM27/RET oncogenes. Renal adysplasia (RADYS) [MIM:[https://omim.org/entry/191830 191830]: Renal agenesis refers to the absence of one (unilateral) or both (bilateral) kidneys at birth. Bilateral renal agenesis belongs to a group of perinatally lethal renal diseases, including severe bilateral renal dysplasia, unilateral renal agenesis with contralateral dysplasia and severe obstructive uropathy. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:18252215</ref> Congenital central hypoventilation syndrome (CCHS) [MIM:[https://omim.org/entry/209880 209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:9497256</ref> <ref>PMID:12086152</ref> <ref>PMID:14566559</ref>
	~~== Function ==~~
	[https://www.uniprot.org/uniprot/RET_HUMAN RET_HUMAN] Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration.<ref>PMID:20064382</ref> <ref>PMID:20616503</ref> <ref>PMID:20702524</ref> <ref>PMID:21357690</ref> <ref>PMID:21454698</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 19:

	==See Also==		==See Also==
	*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]		*[[Tyrosine kinase receptor 3D structures\|Tyrosine kinase receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Homo sapiens]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Lee CC]]		[[Category: Lee CC]]
	[[Category: Spraggon G]]		[[Category: Spraggon G]]

OCA at 16:39, 18 October 2023

2023-10-18T16:39:09Z

← Older revision		Revision as of 16:39, 18 October 2023
Line 1:		Line 1:

	==Crystal structure of phosphorylated RET tyrosine kinase domain complexed with a pyrrolo[2,3-d]pyrimidine inhibitor.==		==Crystal structure of phosphorylated RET tyrosine kinase domain complexed with a pyrrolo[2,3-d]pyrimidine inhibitor.==
	<StructureSection load='7run' size='340' side='right'caption='[[7run]]' scene=''>		<StructureSection load='7run' size='340' side='right'caption='[[7run]], [[Resolution\|resolution]] 3.51Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RUN FirstGlance]. <br>		<table><tr><td colspan='2'>[[7run]] is a 2 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=7RUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RUN 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=7run FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7run OCA], [https://pdbe.org/7run PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7run RCSB], [https://www.ebi.ac.uk/pdbsum/7run PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7run 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]] 3.51Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7QU:1-(4-{(1s,3s)-3-[4-amino-5-(3-amino-4-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]cyclobutyl}piperazin-1-yl)ethan-1-one'>7QU</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=7run FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7run OCA], [https://pdbe.org/7run PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7run RCSB], [https://www.ebi.ac.uk/pdbsum/7run PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7run ProSAT]</span></td></tr>
	</table>		</table>
			== Disease ==
			[https://www.uniprot.org/uniprot/RET_HUMAN RET_HUMAN] Unilateral renal dysplasia;Familial medullary thyroid carcinoma;Multiple endocrine neoplasia type 2B;Multiple endocrine neoplasia type 2A;Hirschsprung disease;Bilateral renal agenesis;Bilateral renal dysplasia;Ondine syndrome;Papillary or follicular thyroid carcinoma. Colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The disease may be caused by mutations affecting the gene represented in this entry. Hirschsprung disease 1 (HSCR1) [MIM:[https://omim.org/entry/142623 142623]: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:7704557</ref> <ref>PMID:7881414</ref> <ref>PMID:8114938</ref> <ref>PMID:8114939</ref> <ref>PMID:7633441</ref> <ref>PMID:7581377</ref> <ref>PMID:8595427</ref> <ref>PMID:9043870</ref> <ref>PMID:9090527</ref> <ref>PMID:9259198</ref> <ref>PMID:9094028</ref> <ref>PMID:9384613</ref> <ref>PMID:10090908</ref> <ref>PMID:10484767</ref> <ref>PMID:10618407</ref> <ref>PMID:22174939</ref> Medullary thyroid carcinoma (MTC) [MIM:[https://omim.org/entry/155240 155240]: Rare tumor derived from the C cells of the thyroid. Three hereditary forms are known, that are transmitted in an autosomal dominant fashion: (a) multiple neoplasia type 2A (MEN2A), (b) multiple neoplasia type IIB (MEN2B) and (c) familial MTC (FMTC), which occurs in 25-30% of MTC cases and where MTC is the only clinical manifestation. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:7881414</ref> <ref>PMID:9259198</ref> <ref>PMID:7849720</ref> <ref>PMID:7874109</ref> <ref>PMID:8625130</ref> <ref>PMID:7845675</ref> <ref>PMID:7784092</ref> <ref>PMID:8557249</ref> <ref>PMID:8807338</ref> <ref>PMID:9398735</ref> <ref>PMID:9223675</ref> <ref>PMID:9677065</ref> <ref>PMID:9452077</ref> <ref>PMID:9506724</ref> <ref>PMID:9621513</ref> <ref>PMID:10323403</ref> <ref>PMID:10826520</ref> <ref>PMID:11692159</ref> Multiple neoplasia 2B (MEN2B) [MIM:[https://omim.org/entry/162300 162300]: Uncommon inherited cancer syndrome characterized by predisposition to MTC and phaeochromocytoma which is associated with marfanoid habitus, mucosal neuromas, skeletal and ophtalmic abnormalities, and ganglioneuromas of the intestine tract. Then the disease progresses rapidly with the development of metastatic MTC and a pheochromocytome in 50% of cases. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:8625130</ref> <ref>PMID:8807338</ref> <ref>PMID:9223675</ref> <ref>PMID:7911697</ref> <ref>PMID:7906866</ref> <ref>PMID:7906417</ref> <ref>PMID:8595427</ref> <ref>PMID:9360560</ref> <ref>PMID:9294615</ref> Pheochromocytoma (PCC) [MIM:[https://omim.org/entry/171300 171300]: A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Multiple neoplasia 2A (MEN2A) [MIM:[https://omim.org/entry/171400 171400]: The most frequent form of medullary thyroid cancer (MTC). It is an inherited cancer syndrome characterized by MTC, phaeochromocytoma and/or hyperparathyroidism. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:7881414</ref> <ref>PMID:9384613</ref> <ref>PMID:7874109</ref> <ref>PMID:8625130</ref> <ref>PMID:8807338</ref> <ref>PMID:9223675</ref> <ref>PMID:9621513</ref> <ref>PMID:8103403</ref> <ref>PMID:8099202</ref> <ref>PMID:7915165</ref> <ref>PMID:7860065</ref> <ref>PMID:8626834</ref> <ref>PMID:9097963</ref> <ref>PMID:9452064</ref> <ref>PMID:10522989</ref> Thyroid papillary carcinoma (TPC) [MIM:[https://omim.org/entry/188550 188550]: A common tumor of the thyroid that typically arises as an irregular, solid or cystic mass from otherwise normal thyroid tissue. Papillary carcinomas are malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. Note=The gene represented in this entry is involved in disease pathogenesis. Chromosomal aberrations involving RET have been found in thyroid papillary carcinomas. Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene; inversion inv(10)(q11.2;q11.2) generates the RET/NCOA4 (PTC3) oncogene; translocation t(10;14)(q11;q32) with GOLGA5 generates the RET/GOLGA5 (PTC5) oncogene; translocation t(8;10)(p21.3;q11.2) with PCM1 generates the PCM1/RET fusion; translocation t(6;10)(p21.3;q11.2) with RFP generates the Delta RFP/RET oncogene; translocation t(1;10)(p13;q11) with TRIM33 generates the TRIM33/RET (PTC7) oncogene; translocation t(7;10)(q32;q11) with TRIM24/TIF1 generates the TRIM24/RET (PTC6) oncogene. The PTC5 oncogene has been found in 2 cases of PACT in children exposed to radioactive fallout after Chernobyl. A chromosomal aberration involving TRIM27/RFP is found in thyroid papillary carcinomas. Translocation t(6;10)(p21.3;q11.2) with RET. The translocation generates TRIM27/RET and delta TRIM27/RET oncogenes. Renal adysplasia (RADYS) [MIM:[https://omim.org/entry/191830 191830]: Renal agenesis refers to the absence of one (unilateral) or both (bilateral) kidneys at birth. Bilateral renal agenesis belongs to a group of perinatally lethal renal diseases, including severe bilateral renal dysplasia, unilateral renal agenesis with contralateral dysplasia and severe obstructive uropathy. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:18252215</ref> Congenital central hypoventilation syndrome (CCHS) [MIM:[https://omim.org/entry/209880 209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:9497256</ref> <ref>PMID:12086152</ref> <ref>PMID:14566559</ref>
			== Function ==
			[https://www.uniprot.org/uniprot/RET_HUMAN RET_HUMAN] Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands. Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration.<ref>PMID:20064382</ref> <ref>PMID:20616503</ref> <ref>PMID:20702524</ref> <ref>PMID:21357690</ref> <ref>PMID:21454698</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The selective inhibition of RET kinase as a treatment for relevant cancer types including lung adenocarcinoma has garnered considerable interest in recent years and prompted a variety of efforts toward the discovery of small-molecule therapeutics. Hits uncovered via the analysis of archival kinase data ultimately led to the identification of a promising pyrrolo[2,3-d]pyrimidine scaffold. The optimization of this pyrrolo[2,3-d]pyrimidine core resulted in compound 1, which demonstrated potent in vitro RET kinase inhibition and robust in vivo efficacy in RET-driven tumor xenografts upon multiday dosing in mice. The administration of 1 was well-tolerated at established efficacious doses (10 and 30 mg/kg, po, qd), and plasma exposure levels indicated a minimal risk of KDR or hERG inhibition in vivo, as evaluated by Miles assay and free plasma concentrations, respectively.

			Antitarget Selectivity and Tolerability of Novel Pyrrolo[2,3-d]pyrimidine RET Inhibitors.,Mathison CJN, Yang Y, Nelson J, Huang Z, Jiang J, Chianelli D, Rucker PV, Roland J, Xie YF, Epple R, Bursulaya B, Lee C, Gao MY, Shaffer J, Briones S, Sarkisova Y, Galkin A, Li L, Li N, Li C, Hua S, Kasibhatla S, Kinyamu-Akunda J, Kikkawa R, Molteni V, Tellew JE ACS Med Chem Lett. 2021 Nov 6;12(12):1912-1919. doi:, 10.1021/acsmedchemlett.1c00450. eCollection 2021 Dec 9. PMID:34917254<ref>PMID:34917254</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7run" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Lee CC]]		[[Category: Lee CC]]
	[[Category: Spraggon G]]		[[Category: Spraggon G]]

OCA at 07:31, 19 January 2022

2022-01-19T07:31:11Z

← Older revision		Revision as of 07:31, 19 January 2022
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 7run is ~~ON HOLD until Paper Publication~~		==Crystal structure of phosphorylated RET tyrosine kinase domain complexed with a pyrrolo[2,3-d]pyrimidine inhibitor.==
			<StructureSection load='7run' size='340' side='right'caption='[[7run]]' scene=''>
	~~Authors~~:		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RUN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RUN FirstGlance]. <br>
	~~Description~~:		</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=7run FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7run OCA], [https://pdbe.org/7run PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7run RCSB], [https://www.ebi.ac.uk/pdbsum/7run PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7run ProSAT]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Lee CC]]
			[[Category: Spraggon G]]

OCA at 05:35, 22 September 2021

2021-09-22T05:35:27Z

← Older revision		Revision as of 05:35, 22 September 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7run is ON HOLD		The entry 7run is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7run" [edit=sysop:move=sysop]

2021-08-25T05:18:54Z

Protected "7run" [edit=sysop:move=sysop]

← Older revision	Revision as of 05:18, 25 August 2021
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7run is ON HOLD Authors: Description: Category: Unreleased Structures

2021-08-25T05:18:53Z

New page: '''Unreleased structure''' The entry 7run is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7run is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]