OCA at 09:19, 26 February 2020

OCA — Wed, 26 Feb 2020 09:19:31 GMT

←Older revision		Revision as of 09:19, 26 February 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6pma is ~~ON HOLD until Paper Publication~~	+	==TRK-A IN COMPLEX WITH LIGAND==
-		+	<StructureSection load='6pma' size='340' side='right'caption='[[6pma]], [[Resolution\|resolution]] 2.53Å' scene=''>
-	~~Authors~~: ~~Subramanian~~, G., ~~Brown~~, D.G.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6pma]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PMA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PMA FirstGlance]. <br>
-	~~Description~~: TRK-~~A IN COMPLEX WITH LIGAND~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OQS:N-[2-chloro-5-(trifluoromethyl)phenyl]-2-[1-(4-methoxyphenyl)-4-oxo-1,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-yl]acetamide'>OQS</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-	[[Category: Brown, D.G]]	+	<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=6pma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pma OCA], [http://pdbe.org/6pma PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pma RCSB], [http://www.ebi.ac.uk/pdbsum/6pma PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pma ProSAT]</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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Brown, D G]]
	[[Category: Subramanian, G]]		[[Category: Subramanian, G]]
		+	[[Category: Transferase]]
		+	[[Category: Trk-a kinase domain]]

OCA at 13:44, 28 August 2019

OCA — Wed, 28 Aug 2019 13:44:08 GMT

←Older revision		Revision as of 13:44, 28 August 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6pma is ON HOLD	+	The entry 6pma is ON HOLD until Paper Publication

	Authors: Subramanian, G., Brown, D.G.		Authors: Subramanian, G., Brown, D.G.

OCA: Protected "6pma" [edit=sysop:move=sysop]

OCA — Wed, 10 Jul 2019 04:15:42 GMT

Protected "6pma" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:15, 10 July 2019

OCA: New page: '''Unreleased structure''' The entry 6pma is ON HOLD Authors: Subramanian, G., Brown, D.G. Description: TRK-A IN COMPLEX WITH LIGAND Category: Unreleased Structures [[Category: Bro...

OCA — Wed, 10 Jul 2019 04:15:40 GMT

New page: '''Unreleased structure''' The entry 6pma is ON HOLD Authors: Subramanian, G., Brown, D.G. Description: TRK-A IN COMPLEX WITH LIGAND Category: Unreleased Structures [[Category: Bro...

New page

'''Unreleased structure'''

The entry 6pma is ON HOLD

Authors: Subramanian, G., Brown, D.G.

Description: TRK-A IN COMPLEX WITH LIGAND
[[Category: Unreleased Structures]]
[[Category: Brown, D.G]]
[[Category: Subramanian, G]]

6pma - Revision history

OCA at 09:19, 26 February 2020

OCA at 13:44, 28 August 2019

OCA: Protected "6pma" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6pma is ON HOLD Authors: Subramanian, G., Brown, D.G. Description: TRK-A IN COMPLEX WITH LIGAND Category: Unreleased Structures [[Category: Bro...