Details of the Target

General Information of Target

Target ID LDTP05190
Target Name Mothers against decapentaplegic homolog 3 (SMAD3)
Gene Name SMAD3
Gene ID 4088
Synonyms
MADH3; Mothers against decapentaplegic homolog 3; MAD homolog 3; Mad3; Mothers against DPP homolog 3; hMAD-3; JV15-2; SMAD family member 3; SMAD 3; Smad3; hSMAD3
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSSILPFTPPIVKRLLGWKKGEQNGQEEKWCEKAVKSLVKKLKKTGQLDELEKAITTQNV
NTKCITIPRSLDGRLQVSHRKGLPHVIYCRLWRWPDLHSHHELRAMELCEFAFNMKKDEV
CVNPYHYQRVETPVLPPVLVPRHTEIPAEFPPLDDYSHSIPENTNFPAGIEPQSNIPETP
PPGYLSEDGETSDHQMNHSMDAGSPNLSPNPMSPAHNNLDLQPVTYCEPAFWCSISYYEL
NQRVGETFHASQPSMTVDGFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYIG
GEVFAECLSDSAIFVQSPNCNQRYGWHPATVCKIPPGCNLKIFNNQEFAALLAQSVNQGF
EAVYQLTRMCTIRMSFVKGWGAEYRRQTVTSTPCWIELHLNGPLQWLDKVLTQMGSPSIR
CSSVS
Target Type
Successful
Target Bioclass
Transcription factor
Family
Dwarfin/SMAD family
Subcellular location
Cytoplasm
Function
Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.
TTD ID
T35445
Uniprot ID
P84022
DrugMap ID
TTHQZV7
Ensemble ID
ENST00000327367.9
HGNC ID
HGNC:6769
ChEMBL ID
CHEMBL1293258

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HT115 SNV: p.E239K .
JURKAT SNV: p.A250V .
KASUMI2 SNV: p.R80P DBIA    Probe Info 
MCF7 SNV: p.V134F .
SNU1 Deletion: p.V424GfsTer52 DBIA    Probe Info 

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 13 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info  		15.00  LDD0402  [1]
TH211
 Probe Info  		Y324(6.49)  LDD0257  [2]
STPyne
 Probe Info  		K33(5.56); K36(4.34); K378(1.73); K81(2.68)  LDD0277  [3]
DBIA
 Probe Info  		C374(2.84)  LDD3311  [4]
AHL-Pu-1
 Probe Info  		C121(6.51)  LDD0168  [5]
HHS-475
 Probe Info  		Y324(0.99)  LDD0264  [6]
HHS-465
 Probe Info  		Y324(4.17)  LDD2237  [7]
ATP probe
 Probe Info  		N.A.  LDD0199  [8]
IA-alkyne
 Probe Info  		C332(0.00); C89(0.00); C121(0.00); C270(0.00)  LDD0162  [9]
IPM
 Probe Info  		N.A.  LDD0005  [10]
Methacrolein
 Probe Info  		N.A.  LDD0218  [11]
AOyne
 Probe Info  		15.00  LDD0443  [12]
NAIA_5
 Probe Info  		N.A.  LDD2223  [13]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0025  4SU-RNA HEK-293T C121(6.51)  LDD0168  [5]
 LDCM0026  4SU-RNA+native RNA HEK-293T C121(2.05)  LDD0169  [5]
 LDCM0156  Aniline NCI-H1299 12.01  LDD0403  [1]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C64(1.12)  LDD1702  [14]
 LDCM0116  HHS-0101 DM93 Y324(0.99)  LDD0264  [6]
 LDCM0117  HHS-0201 DM93 Y324(0.70)  LDD0265  [6]
 LDCM0118  HHS-0301 DM93 Y324(0.74)  LDD0266  [6]
 LDCM0119  HHS-0401 DM93 Y324(0.74)  LDD0267  [6]
 LDCM0120  HHS-0701 DM93 Y324(1.85)  LDD0268  [6]
 LDCM0022  KB02 22RV1 C77(1.34)  LDD2243  [4]
 LDCM0023  KB03 MDA-MB-231 C64(1.02)  LDD1701  [14]
 LDCM0024  KB05 G361 C374(2.84)  LDD3311  [4]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 14 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Histone-lysine N-methyltransferase SETD2 (SETD2) Histone-lysine methyltransferase family Q9BYW2
Probable ATP-dependent RNA helicase DDX5 (DDX5) DEAD box helicase family P17844
Ubiquitin carboxyl-terminal hydrolase 7 (USP7) Peptidase C19 family Q93009
Proteasome subunit beta type-1 (PSMB1) Peptidase T1B family P20618
Phosphoenolpyruvate carboxykinase [GTP], mitochondrial (PCK2) Phosphoenolpyruvate carboxykinase [GTP] family Q16822
cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) AGC Ser/Thr protein kinase family P17612
Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMK2A) CAMK Ser/Thr protein kinase family Q9UQM7
Uncharacterized serine/threonine-protein kinase SBK3 (SBK3) Ser/Thr protein kinase family P0C264
Myotubularin-related protein 4 (MTMR4) Protein-tyrosine phosphatase family Q9NYA4
E3 ubiquitin-protein ligase RNF31 (RNF31) RBR family Q96EP0
Endoribonuclease ZC3H12A (ZC3H12A) ZC3H12 family Q5D1E8
E3 ubiquitin-protein ligase SMURF2 (SMURF2) . Q9HAU4
NEDD4-like E3 ubiquitin-protein ligase WWP1 (WWP1) . Q9H0M0
NEDD4-like E3 ubiquitin-protein ligase WWP2 (WWP2) . O00308
Transporter and channel
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Amyloid-beta precursor protein (APP) APP family P05067
Importin-8 (IPO8) Importin beta family O15397
Junctophilin-3 (JPH3) Junctophilin family Q8WXH2
Transcription factor
Click To Hide/Show 14 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Mothers against decapentaplegic homolog 2 (SMAD2) Dwarfin/SMAD family Q15796
Mothers against decapentaplegic homolog 3 (SMAD3) Dwarfin/SMAD family P84022
Mothers against decapentaplegic homolog 4 (SMAD4) Dwarfin/SMAD family Q13485
Friend leukemia integration 1 transcription factor (FLI1) ETS family Q01543
Zinc finger protein GLI2 (GLI2) GLI C2H2-type zinc-finger protein family P10070
Zinc finger protein 774 (ZNF774) Krueppel C2H2-type zinc-finger protein family Q6NX45
Cone-rod homeobox protein (CRX) Paired homeobox family O43186
Homeobox protein TGIF1 (TGIF1) TALE/TGIF homeobox family Q15583
TSC22 domain family protein 4 (TSC22D4) TSC-22/Dip/Bun family Q9Y3Q8
Forkhead box protein H1 (FOXH1) . O75593
Forkhead box protein O3 (FOXO3) . O43524
Golgin-45 (BLZF1) . Q9H2G9
Homeobox protein MOX-2 (MEOX2) . P50222
Hypoxia-inducible factor 1-alpha (HIF1A) . Q16665
Other
Click To Hide/Show 16 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Chordin (CHRD) Chordin family Q9H2X0
CUB and sushi domain-containing protein 1 (CSMD1) CSMD family Q96PZ7
Dedicator of cytokinesis protein 9 (DOCK9) DOCK family Q9BZ29
Protein FAM90A1 (FAM90A1) FAM90 family Q86YD7
Cleavage and polyadenylation specificity factor subunit 7 (CPSF7) RRM CPSF6/7 family Q8N684
Ski oncogene (SKI) SKI family P12755
SNW domain-containing protein 1 (SNW1) SNW family Q13573
Tektin-4 (TEKT4) Tektin family Q8WW24
TLE family member 5 (TLE5) WD repeat Groucho/TLE family Q08117
Coiled-coil domain-containing protein 33 (CCDC33) . Q8N5R6
Disabled homolog 2 (DAB2) . P98082
Myeloid differentiation primary response protein MyD88 (MYD88) . Q99836
Polyhomeotic-like protein 2 (PHC2) . Q8IXK0
Protein phosphatase 1 regulatory subunit 12C (PPP1R12C) . Q9BZL4
Sequestosome-1 (SQSTM1) . Q13501
Zinc finger FYVE domain-containing protein 9 (ZFYVE9) . O95405

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Fluorescein Small molecular drug D06TJJ
Preclinical
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Sis-3 Small molecular drug DF90DS
Investigative
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Ellagic Acid Small molecular drug D0A1CM
Gnf-pf-2272 Small molecular drug D0P0CM

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
2 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
3 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
4 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
5 Chemoproteomic capture of RNA binding activity in living cells. Nat Commun. 2023 Oct 7;14(1):6282. doi: 10.1038/s41467-023-41844-z.
Mass spectrometry data entry: PXD044625
6 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.
7 Global targeting of functional tyrosines using sulfur-triazole exchange chemistry. Nat Chem Biol. 2020 Feb;16(2):150-159. doi: 10.1038/s41589-019-0404-5. Epub 2019 Nov 25.
8 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
9 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
10 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
11 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
12 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
13 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
14 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761