D4 — HyTdb

Basic Information

EDLIIKGISV

KGSGS

POITARDBP — TAR DNA-binding protein 43（TDP-43）

Degradation Pathway

Reference10.1016/j.bioorg.2018.11.042

Published2018.11.30

Remarks

Chemical Identifiers

SMILES[H]OC[C@H](NC(CNC([C@H](CCCCNC([C@@]12C[C@H](C[C@H](C2)C3)C[C@H]3C1)=O)NC([C@@]45C[C@@H](CC(C5)C6)CC6C4)=O)=O)=O)C(NCC(N[C@@H](CO[H])C(N[C@@H](CCC(O)=O)C(N[C@@H](CC(O)=O)C(N[C@H](C(N[C@@](C(N[C@@](C(N[C@@H](CCCCN[H])C(NCC(N[C@@](C(N[C@@H](CO[H])C(N[C@@H](C(C)C)C(N[C@@H](CS[H])C(N[C@@H](CCC/N=C(N)\N[H])C(N[C@@H](CCCCN[H])C(N[C@@H](CCCCN[H])C(N[C@@H](CCC/N=C(N)\N[H])C(N[C@@H](CCC/N=C(N)\N[H])C(N[C@@H](CCC(N[H])=O)C(N[C@@H](CCC/N=C(N)\N[H])C(N[C@@H](CCC/N=C(N)\N[H])C(N[C@@H](CCC/N=C(N)\N[H])C(O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)([H])[C@H](CC)C)=O)=O)=O)([H])[C@H](CC)C)=O)([H])[C@H](CC)C)=O)CC(C)C)=O)=O)=O)=O)=O

Molecular FormulaC143H252N48O36S

InChIInChI=1S/C143H252N48O36S/c1-11-75(8)109(188-105(198)68-168-112(203)84(28-14-18-42-144)181-131(222)110(76(9)12-2)191-132(223)111(77(10)13-3)190-125(216)96(52-73(4)5)183-124(215)97(59-107(201)202)184-123(214)94(39-41-106(199)200)180-126(217)99(70-193)171-104(197)67-169-114(205)98(69-192)170-103(196)66-167-113(204)85(187-135(227)143-63-81-56-82(64-143)58-83(57-81)65-143)31-17-21-45-160-134(226)142-60-78-53-79(61-142)55-80(54-78)62-142)130(221)185-100(71-194)127(218)189-108(74(6)7)129(220)186-101(72-228)128(219)178-91(35-25-49-164-139(154)155)119(210)173-86(29-15-19-43-145)115(206)172-87(30-16-20-44-146)116(207)174-88(32-22-46-161-136(148)149)117(208)175-90(34-24-48-163-138(152)153)120(211)179-93(38-40-102(147)195)122(213)177-89(33-23-47-162-137(150)151)118(209)176-92(36-26-50-165-140(156)157)121(212)182-95(133(224)225)37-27-51-166-141(158)159/h73-101,108-111,192-194,228H,11-72,144-146H2,1-10H3,(H2,147,195)(H,160,226)(H,167,204)(H,168,203)(H,169,205)(H,170,196)(H,171,197)(H,172,206)(H,173,210)(H,174,207)(H,175,208)(H,176,209)(H,177,213)(H,178,219)(H,179,211)(H,180,217)(H,181,222)(H,182,212)(H,183,215)(H,184,214)(H,185,221)(H,186,220)(H,187,227)(H,188,198)(H,189,218)(H,190,216)(H,191,223)(H,199,200)(H,201,202)(H,224,225)(H4,148,149,161)(H4,150,151,162)(H4,152,153,163)(H4,154,155,164)(H4,156,157,165)(H4,158,159,166)/t75-,76-,77-,78-,79+,80-,81-,82?,83?,84-,85-,86-,87-,88-,89-,90-,91-,92-,93-,94-,95-,96-,97-,98-,99-,100-,101-,108-,109-,110-,111-,142-,143+/m0/s1

InChI KeyUDSUDAIRVFOHLD-QAWXQNRESA-N

IUPAC Name/

PubChem CID/

Basic Properties

TPSAComputing…

RingsComputing…

FSP3Computing…

Heavy Atom CountComputing…

Lipinski RO5

RO5 ViolationComputing…

MWComputing…

ClogPComputing…

HBDComputing…

HBAComputing…

RBComputing…

Hydrophobic Tag Properties

Tag Structure

Tag TypeAdamantane

Tag SMILES

Tag ClogP5.022

HydrophobicityHigh(ClopP>5)

Mechanism of Action

POI (Protein of Interest)

POI NameTAR DNA-binding protein 43（TDP-43）

GeneTARDBP

UniProt IDQ13148

Amino Acid Sequence

MSEYIRVTEDENDEPIEIPSEDDGTVLLSTVTAQFPGACGLRYRNPVSQCMRGVRLVEGILHAPDAGWGNLVYVVNYPKDNKRKMDETDASSAVKVKRAVQKTSDLIVLGLPWKTTEQDLKEYFSTFGEVLMVQVKKDLKTGHSKGFGFVRFTEYETQVKVMSQRHMIDGRWCDCKLPNSKQSQDEPLRSRKVFVGRCTEDMTEDELREFFSQYGDVMDVFIPKPFRAFAFVTFADDQIAQSLCGEDLIIKGISVHISNAEPKHNSNRQLERSGRFGGNPGGFGNQGGFGNSRGGGAGLGNNQGSNMGGGMNFGAFSINPAMMAAAQAALQSSWGMMGMLASQQNQSGPSGNNQNQGNMQREPNQAFGSGNNSYSGSNSGAAIGWGSASNAGSGSGFNGGFGSSMDSKSSGWGM

3D Structure (/structures/AF-Q13148-F1-model_v6.cif)

Loading /structures/AF-Q13148-F1-model_v6.cif …

Function

RNA-binding protein that is involved in various steps of RNA biogenesis and processing. Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs. In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases. Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts. Also regulates mRNA stability by recruiting CNOT7/CAF1 deadenylase on mRNA 3'UTR leading to poly(A) tail deadenylation and thus shortening. In response to oxidative insult, associates with stalled ribosomes localized to stress granules (SGs) and contributes to cell survival. Also participates in the normal skeletal muscle formation and regeneration, forming cytoplasmic myo-granules and binding mRNAs that encode sarcomeric proteins. Plays a role in the maintenance of the circadian clock periodicity via stabilization of the CRY1 and CRY2 proteins in a FBXL3-dependent manner. Negatively regulates the expression of CDK6. Regulates the expression of HDAC6, ATG7 and VCP in a PPIA/CYPA-dependent manner.

Degradation Pathway

Activity Data

Disease Information

Disease	ICD-11	Source
Amyotrophic lateral sclerosis	8B60.0	Gene-Disease Association
Frontotemporal dementia with motor neuron disease	6D83	Gene-Disease Association
Dementia	6D8Z	Gene-Disease Association
Amyotrophic lateral sclerosis	8B60.0	Gene-Disease Association
Alzheimer's Disease	8A20	Gene-Disease Association