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| <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>
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| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| ==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]] |