4crp - Revision history

OCA at 10:08, 14 June 2023

OCA — Wed, 14 Jun 2023 10:08:38 GMT

←Older revision		Revision as of 10:08, 14 June 2023
Line 7:		Line 7:
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/NTRK1_HUMAN NTRK1_HUMAN]] Defects in NTRK1 are a cause of congenital insensitivity to pain with anhidrosis (CIPA) [MIM:[https://omim.org/entry/256800 256800]]. CIPA is characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II.<ref>PMID:8696348</ref> <ref>PMID:10090906</ref> <ref>PMID:10330344</ref> <ref>PMID:10233776</ref> <ref>PMID:10861667</ref> <ref>PMID:10982191</ref> <ref>PMID:10567924</ref> <ref>PMID:11310631</ref> <ref>PMID:11159935</ref> <ref>PMID:22302274</ref> Defects in NTRK1 are a cause of thyroid papillary carcinoma (TPC) [MIM:[https://omim.org/entry/188550 188550]]. TPC is 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=Chromosomal aberrations involving NTRK1 are found in thyroid papillary carcinomas. Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1; a rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1; an intrachromosomal rearrangement that links the protein kinase domain of NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the C-terminus of the NTRK1 protein.	+	[https://www.uniprot.org/uniprot/NTRK1_HUMAN NTRK1_HUMAN] Defects in NTRK1 are a cause of congenital insensitivity to pain with anhidrosis (CIPA) [MIM:[https://omim.org/entry/256800 256800]. CIPA is characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II.<ref>PMID:8696348</ref> <ref>PMID:10090906</ref> <ref>PMID:10330344</ref> <ref>PMID:10233776</ref> <ref>PMID:10861667</ref> <ref>PMID:10982191</ref> <ref>PMID:10567924</ref> <ref>PMID:11310631</ref> <ref>PMID:11159935</ref> <ref>PMID:22302274</ref> Defects in NTRK1 are a cause of thyroid papillary carcinoma (TPC) [MIM:[https://omim.org/entry/188550 188550]. TPC is 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=Chromosomal aberrations involving NTRK1 are found in thyroid papillary carcinomas. Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1; a rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1; an intrachromosomal rearrangement that links the protein kinase domain of NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the C-terminus of the NTRK1 protein.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/NTRK1_HUMAN NTRK1_HUMAN]] Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival. Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors.<ref>PMID:1850821</ref> <ref>PMID:1849459</ref> <ref>PMID:8325889</ref> <ref>PMID:8155326</ref> <ref>PMID:11244088</ref> <ref>PMID:15488758</ref> Isoform TrkA-III is resistant to NGF, constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed.<ref>PMID:1850821</ref> <ref>PMID:1849459</ref> <ref>PMID:8325889</ref> <ref>PMID:8155326</ref> <ref>PMID:11244088</ref> <ref>PMID:15488758</ref>	+	[https://www.uniprot.org/uniprot/NTRK1_HUMAN NTRK1_HUMAN] Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival. Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors.<ref>PMID:1850821</ref> <ref>PMID:1849459</ref> <ref>PMID:8325889</ref> <ref>PMID:8155326</ref> <ref>PMID:11244088</ref> <ref>PMID:15488758</ref> Isoform TrkA-III is resistant to NGF, constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed.<ref>PMID:1850821</ref> <ref>PMID:1849459</ref> <ref>PMID:8325889</ref> <ref>PMID:8155326</ref> <ref>PMID:11244088</ref> <ref>PMID:15488758</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 07:29, 14 September 2022

OCA — Wed, 14 Sep 2022 07:29:38 GMT

←Older revision		Revision as of 07:29, 14 September 2022
Line 1:		Line 1:

	==Solution structure of a TrkAIg2 domain construct for use in drug discovery==		==Solution structure of a TrkAIg2 domain construct for use in drug discovery==
-	<StructureSection load='4crp' size='340' side='right'caption='[[4crp~~]], [[NMR_Ensembles_of_Models \| 25 NMR models~~]]' scene=''>	+	<StructureSection load='4crp' size='340' side='right'caption='[[4crp]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4crp]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CRP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4CRP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4crp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CRP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CRP FirstGlance]. <br>
-	</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>	+	</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=4crp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4crp OCA], [https://pdbe.org/4crp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4crp RCSB], [https://www.ebi.ac.uk/pdbsum/4crp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4crp ProSAT]</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=4crp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4crp OCA], [~~http~~://pdbe.org/4crp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4crp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4crp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4crp ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/NTRK1_HUMAN NTRK1_HUMAN]] Defects in NTRK1 are a cause of congenital insensitivity to pain with anhidrosis (CIPA) [MIM:[~~http~~://omim.org/entry/256800 256800]]. CIPA is characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II.<ref>PMID:8696348</ref> <ref>PMID:10090906</ref> <ref>PMID:10330344</ref> <ref>PMID:10233776</ref> <ref>PMID:10861667</ref> <ref>PMID:10982191</ref> <ref>PMID:10567924</ref> <ref>PMID:11310631</ref> <ref>PMID:11159935</ref> <ref>PMID:22302274</ref> Defects in NTRK1 are a cause of thyroid papillary carcinoma (TPC) [MIM:[~~http~~://omim.org/entry/188550 188550]]. TPC is 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=Chromosomal aberrations involving NTRK1 are found in thyroid papillary carcinomas. Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1; a rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1; an intrachromosomal rearrangement that links the protein kinase domain of NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the C-terminus of the NTRK1 protein.	+	[[https://www.uniprot.org/uniprot/NTRK1_HUMAN NTRK1_HUMAN]] Defects in NTRK1 are a cause of congenital insensitivity to pain with anhidrosis (CIPA) [MIM:[https://omim.org/entry/256800 256800]]. CIPA is characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II.<ref>PMID:8696348</ref> <ref>PMID:10090906</ref> <ref>PMID:10330344</ref> <ref>PMID:10233776</ref> <ref>PMID:10861667</ref> <ref>PMID:10982191</ref> <ref>PMID:10567924</ref> <ref>PMID:11310631</ref> <ref>PMID:11159935</ref> <ref>PMID:22302274</ref> Defects in NTRK1 are a cause of thyroid papillary carcinoma (TPC) [MIM:[https://omim.org/entry/188550 188550]]. TPC is 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=Chromosomal aberrations involving NTRK1 are found in thyroid papillary carcinomas. Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1; a rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1; an intrachromosomal rearrangement that links the protein kinase domain of NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the C-terminus of the NTRK1 protein.
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/NTRK1_HUMAN NTRK1_HUMAN]] Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival. Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors.<ref>PMID:1850821</ref> <ref>PMID:1849459</ref> <ref>PMID:8325889</ref> <ref>PMID:8155326</ref> <ref>PMID:11244088</ref> <ref>PMID:15488758</ref> Isoform TrkA-III is resistant to NGF, constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed.<ref>PMID:1850821</ref> <ref>PMID:1849459</ref> <ref>PMID:8325889</ref> <ref>PMID:8155326</ref> <ref>PMID:11244088</ref> <ref>PMID:15488758</ref>	+	[[https://www.uniprot.org/uniprot/NTRK1_HUMAN NTRK1_HUMAN]] Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival. Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors.<ref>PMID:1850821</ref> <ref>PMID:1849459</ref> <ref>PMID:8325889</ref> <ref>PMID:8155326</ref> <ref>PMID:11244088</ref> <ref>PMID:15488758</ref> Isoform TrkA-III is resistant to NGF, constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed.<ref>PMID:1850821</ref> <ref>PMID:1849459</ref> <ref>PMID:8325889</ref> <ref>PMID:8155326</ref> <ref>PMID:11244088</ref> <ref>PMID:15488758</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 22:
	==See Also==		==See Also==
	*[[High affinity nerve growth factor receptor\|High affinity nerve growth factor receptor]]		*[[High affinity nerve growth factor receptor\|High affinity nerve growth factor receptor]]
		+	*[[Tyrosine kinase receptor\|Tyrosine kinase receptor]]
	== 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: Allen-Birt SJ]]
-	[[Category: Allen-Birt~~, S J~~]]	+	[[Category: Crump MP]]
-	[[Category: Crump~~, M P~~]]	+	[[Category: Fahey M]]
-	[[Category: Fahey, M]]	+	[[Category: Sessions RB]]
-	[[Category: Sessions~~, R B~~]]	+	[[Category: Shoemark DK]]
-	[[Category: Shoemark~~, D K~~]]	+	[[Category: Williams C]]
-	[[Category: Williams, C]]	+
-	~~[[Category: Alzheimer]]~~	+
-	~~[[Category: Nmr construct]]~~	+
-	~~[[Category: Pain]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Trkaig2~~]]	+

OCA at 09:48, 20 March 2019

OCA — Wed, 20 Mar 2019 09:48:24 GMT

←Older revision		Revision as of 09:48, 20 March 2019
Line 1:		Line 1:

	==Solution structure of a TrkAIg2 domain construct for use in drug discovery==		==Solution structure of a TrkAIg2 domain construct for use in drug discovery==
-	<StructureSection load='4crp' size='340' side='right' caption='[[4crp]], [[NMR_Ensembles_of_Models \| 25 NMR models]]' scene=''>	+	<StructureSection load='4crp' size='340' side='right'caption='[[4crp]], [[NMR_Ensembles_of_Models \| 25 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4crp]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CRP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CRP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4crp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CRP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CRP FirstGlance]. <br>
	</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>		</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=4crp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4crp OCA], [http://pdbe.org/4crp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4crp RCSB], [http://www.ebi.ac.uk/pdbsum/4crp 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=4crp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4crp OCA], [http://pdbe.org/4crp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4crp RCSB], [http://www.ebi.ac.uk/pdbsum/4crp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4crp ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4crp" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4crp" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[High affinity nerve growth factor receptor\|High affinity nerve growth factor receptor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Allen-Birt, S J]]		[[Category: Allen-Birt, S J]]

OCA at 19:30, 10 May 2016

OCA — Tue, 10 May 2016 19:30:05 GMT

←Older revision		Revision as of 19:30, 10 May 2016
Line 1:		Line 1:
		+
	==Solution structure of a TrkAIg2 domain construct for use in drug discovery==		==Solution structure of a TrkAIg2 domain construct for use in drug discovery==
	<StructureSection load='4crp' size='340' side='right' caption='[[4crp]], [[NMR_Ensembles_of_Models \| 25 NMR models]]' scene=''>		<StructureSection load='4crp' size='340' side='right' caption='[[4crp]], [[NMR_Ensembles_of_Models \| 25 NMR models]]' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[4crp]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CRP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CRP FirstGlance]. <br>		<table><tr><td colspan='2'>[[4crp]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CRP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CRP FirstGlance]. <br>
	</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>		</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=4crp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4crp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4crp RCSB], [http://www.ebi.ac.uk/pdbsum/4crp 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=4crp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4crp OCA], [http://pdbe.org/4crp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4crp RCSB], [http://www.ebi.ac.uk/pdbsum/4crp PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 18:		Line 19:
	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 4crp" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:30, 14 January 2015

OCA — Wed, 14 Jan 2015 13:30:31 GMT

←Older revision		Revision as of 13:30, 14 January 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Solution structure of a TrkAIg2 domain construct for use in drug discovery==
		+	<StructureSection load='4crp' size='340' side='right' caption='[[4crp]], [[NMR_Ensembles_of_Models \| 25 NMR models]]' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4crp]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CRP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CRP FirstGlance]. <br>
		+	</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=4crp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4crp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4crp RCSB], [http://www.ebi.ac.uk/pdbsum/4crp PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/NTRK1_HUMAN NTRK1_HUMAN]] Defects in NTRK1 are a cause of congenital insensitivity to pain with anhidrosis (CIPA) [MIM:[http://omim.org/entry/256800 256800]]. CIPA is characterized by a congenital insensitivity to pain, anhidrosis (absence of sweating), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. This rare autosomal recessive disorder is also known as congenital sensory neuropathy with anhidrosis or hereditary sensory and autonomic neuropathy type IV or familial dysautonomia type II.<ref>PMID:8696348</ref> <ref>PMID:10090906</ref> <ref>PMID:10330344</ref> <ref>PMID:10233776</ref> <ref>PMID:10861667</ref> <ref>PMID:10982191</ref> <ref>PMID:10567924</ref> <ref>PMID:11310631</ref> <ref>PMID:11159935</ref> <ref>PMID:22302274</ref> Defects in NTRK1 are a cause of thyroid papillary carcinoma (TPC) [MIM:[http://omim.org/entry/188550 188550]]. TPC is 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=Chromosomal aberrations involving NTRK1 are found in thyroid papillary carcinomas. Translocation t(1;3)(q21;q11) with TFG generates the TRKT3 (TRK-T3) transcript by fusing TFG to the 3'-end of NTRK1; a rearrangement with TPM3 generates the TRK transcript by fusing TPM3 to the 3'-end of NTRK1; an intrachromosomal rearrangement that links the protein kinase domain of NTRK1 to the 5'-end of the TPR gene forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the C-terminus of the NTRK1 protein.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NTRK1_HUMAN NTRK1_HUMAN]] Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 but has no effect on neuron survival. Upon dimeric NGF ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades driving cell survival and differentiation. Through SHC1 and FRS2 activates a GRB2-Ras-MAPK cascade that regulates cell differentiation and survival. Through PLCG1 controls NF-Kappa-B activation and the transcription of genes involved in cell survival. Through SHC1 and SH2B1 controls a Ras-PI3 kinase-AKT1 signaling cascade that is also regulating survival. In absence of ligand and activation, may promote cell death, making the survival of neurons dependent on trophic factors.<ref>PMID:1850821</ref> <ref>PMID:1849459</ref> <ref>PMID:8325889</ref> <ref>PMID:8155326</ref> <ref>PMID:11244088</ref> <ref>PMID:15488758</ref> Isoform TrkA-III is resistant to NGF, constitutively activates AKT1 and NF-kappa-B and is unable to activate the Ras-MAPK signaling cascade. Antagonizes the anti-proliferative NGF-NTRK1 signaling that promotes neuronal precursors differentiation. Isoform TrkA-III promotes angiogenesis and has oncogenic activity when overexpressed.<ref>PMID:1850821</ref> <ref>PMID:1849459</ref> <ref>PMID:8325889</ref> <ref>PMID:8155326</ref> <ref>PMID:11244088</ref> <ref>PMID:15488758</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The tyrosine kinase A (TrkA) receptor is a validated therapeutic intervention point for a wide range of conditions. TrkA activation by nerve growth factor (NGF) binding the second extracellular immunoglobulin (TrkAIg2) domain triggers intracellular signaling cascades. In the periphery, this promotes the pain phenotype and, in the brain, cell survival or differentiation. Reproducible structural information and detailed validation of protein-ligand interactions aid drug discovery. However, the isolated TrkAIg2 domain crystallizes as a beta-strand-swapped dimer in the absence of NGF, occluding the binding surface. Here we report the design and structural validation by nuclear magnetic resonance spectroscopy of the first stable, biologically active construct of the TrkAIg2 domain for binding site confirmation. Our structure closely mimics the wild-type fold of TrkAIg2 in complex with NGF ( 1WWW .pdb), and the 1H-15N correlation spectra confirm that both NGF and a competing small molecule interact at the known binding interface in solution.

-	~~The entry 4crp is ON HOLD until Paper Publication~~	+	Design and Nuclear Magnetic Resonance (NMR) Structure Determination of the Second Extracellular Immunoglobulin Tyrosine Kinase A (TrkAIg2) Domain Construct for Binding Site Elucidation in Drug Discovery.,Shoemark DK, Williams C, Fahey MS, Watson JJ, Tyler SJ, Scoltock SJ, Ellis RZ, Wickenden E, Burton AJ, Hemmings JL, Bailey CD, Dawbarn D, Jane DE, Willis CL, Sessions RB, Allen SJ, Crump MP J Med Chem. 2014 Dec 22. PMID:25454499<ref>PMID:25454499</ref>

-	~~Authors: Shoemark~~, D.K.~~, Fahey, M., Williams, C~~.~~, Sessions, R.B., Crump, M.P.,~~ Allen-Birt, S.J.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Solution structure of a TrkAIg2 domain construct for use in drug discovery~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
-	[[Category: ~~Crump~~, ~~M.P~~]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Allen-Birt, S J]]
		+	[[Category: Crump, M P]]
		+	[[Category: Fahey, M]]
		+	[[Category: Sessions, R B]]
		+	[[Category: Shoemark, D K]]
	[[Category: Williams, C]]		[[Category: Williams, C]]
-	[[Category: ~~Shoemark, D.K~~]]	+	[[Category: Alzheimer]]
-	[[Category: ~~Fahey, M~~]]	+	[[Category: Nmr construct]]
-	[[Category: ~~Allen-Birt, S.J~~]]	+	[[Category: Pain]]
-	[[Category: ~~Sessions, R.B~~]]	+	[[Category: Transferase]]
		+	[[Category: Trkaig2]]

OCA at 13:30, 24 December 2014

OCA — Wed, 24 Dec 2014 13:30:01 GMT

←Older revision		Revision as of 13:30, 24 December 2014
Line 6:		Line 6:

	Description: Solution structure of a TrkAIg2 domain construct for use in drug discovery		Description: Solution structure of a TrkAIg2 domain construct for use in drug discovery
		+	[[Category: Unreleased Structures]]
		+	[[Category: Crump, M.P]]
		+	[[Category: Williams, C]]
		+	[[Category: Shoemark, D.K]]
		+	[[Category: Fahey, M]]
		+	[[Category: Allen-Birt, S.J]]
		+	[[Category: Sessions, R.B]]

OCA at 08:26, 26 March 2014

OCA — Wed, 26 Mar 2014 08:26:40 GMT

←Older revision		Revision as of 08:26, 26 March 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Shoemark, D.K., Fahey, M., Williams, C., Sessions, R.B., Crump, M.P., Allen-Birt, S.J.		Authors: Shoemark, D.K., Fahey, M., Williams, C., Sessions, R.B., Crump, M.P., Allen-Birt, S.J.

	Description: Solution structure of a TrkAIg2 domain construct for use in drug discovery		Description: Solution structure of a TrkAIg2 domain construct for use in drug discovery

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

OCA — Wed, 12 Mar 2014 11:48:25 GMT

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

←Older revision

Revision as of 11:48, 12 March 2014

OCA: New page: '''Unreleased structure''' The entry 4crp is ON HOLD Authors: Shoemark, D.K., Fahey, M., Williams, C., Sessions, R.B., Crump, M.P., Allen-Birt, S.J. Description: Solution structure of ...

OCA — Wed, 12 Mar 2014 11:48:24 GMT

New page: '''Unreleased structure''' The entry 4crp is ON HOLD Authors: Shoemark, D.K., Fahey, M., Williams, C., Sessions, R.B., Crump, M.P., Allen-Birt, S.J. Description: Solution structure of ...

New page

'''Unreleased structure'''

The entry 4crp is ON HOLD

Authors: Shoemark, D.K., Fahey, M., Williams, C., Sessions, R.B., Crump, M.P., Allen-Birt, S.J.

Description: Solution structure of a TrkAIg2 domain construct for use in drug discovery