Details of the Target

General Information of Target

Target ID LDTP05679
Target Name Dihydropyrimidine dehydrogenase [NADP(+)] (DPYD)
Gene Name DPYD
Gene ID 1806
Synonyms
Dihydropyrimidine dehydrogenase [NADP(+)]; DHPDHase; DPD; EC 1.3.1.2; Dihydrothymine dehydrogenase; Dihydrouracil dehydrogenase
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAPVLSKDSADIESILALNPRTQTHATLCSTSAKKLDKKHWKRNPDKNCFNCEKLENNFD
DIKHTTLGERGALREAMRCLKCADAPCQKSCPTNLDIKSFITSIANKNYYGAAKMIFSDN
PLGLTCGMVCPTSDLCVGGCNLYATEEGPINIGGLQQFATEVFKAMSIPQIRNPSLPPPE
KMSEAYSAKIALFGAGPASISCASFLARLGYSDITIFEKQEYVGGLSTSEIPQFRLPYDV
VNFEIELMKDLGVKIICGKSLSVNEMTLSTLKEKGYKAAFIGIGLPEPNKDAIFQGLTQD
QGFYTSKDFLPLVAKGSKAGMCACHSPLPSIRGVVIVLGAGDTAFDCATSALRCGARRVF
IVFRKGFVNIRAVPEEMELAKEEKCEFLPFLSPRKVIVKGGRIVAMQFVRTEQDETGKWN
EDEDQMVHLKADVVISAFGSVLSDPKVKEALSPIKFNRWGLPEVDPETMQTSEAWVFAGG
DVVGLANTTVESVNDGKQASWYIHKYVQSQYGASVSAKPELPLFYTPIDLVDISVEMAGL
KFINPFGLASATPATSTSMIRRAFEAGWGFALTKTFSLDKDIVTNVSPRIIRGTTSGPMY
GPGQSSFLNIELISEKTAAYWCQSVTELKADFPDNIVIASIMCSYNKNDWTELAKKSEDS
GADALELNLSCPHGMGERGMGLACGQDPELVRNICRWVRQAVQIPFFAKLTPNVTDIVSI
ARAAKEGGANGVTATNTVSGLMGLKSDGTPWPAVGIAKRTTYGGVSGTAIRPIALRAVTS
IARALPGFPILATGGIDSAESGLQFLHSGASVLQVCSAIQNQDFTVIEDYCTGLKALLYL
KSIEELQDWDGQSPATVSHQKGKPVPRIAELMDKKLPSFGPYLEQRKKIIAENKIRLKEQ
NVAFSPLKRNCFIPKRPIPTIKDVIGKALQYLGTFGELSNVEQVVAMIDEEMCINCGKCY
MTCNDSGYQAIQFDPETHLPTITDTCTGCTLCLSVCPIVDCIKMVSRTTPYEPKRGVPLS
VNPVC
Target Type
Successful
Target Bioclass
Enzyme
Family
Dihydropyrimidine dehydrogenase family
Subcellular location
Cytoplasm
Function Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine. Also involved the degradation of the chemotherapeutic drug 5-fluorouracil.
TTD ID
T75890
Uniprot ID
Q12882
DrugMap ID
TTZPS91
Ensemble ID
ENST00000306031.5
HGNC ID
HGNC:3012
ChEMBL ID
CHEMBL3172

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
A498 SNV: p.R678K DBIA    Probe Info 
BICR22 SNV: p.I770M .
CAL78 Substitution: p.C29H DBIA    Probe Info 
CASKI SNV: p.S9L DBIA    Probe Info 
COLO792 SNV: p.L95F DBIA    Probe Info 
HCC1954 SNV: p.C671G DBIA    Probe Info 
HCC827 SNV: p.G681C DBIA    Probe Info 
HCT15 SNV: p.V815E; p.P1010H .
HEC1 SNV: p.V490M DBIA    Probe Info 
IGR1 SNV: p.S392F .
IPC298 SNV: p.L806R DBIA    Probe Info 
KMCH1 SNV: p.A810D DBIA    Probe Info 
MDAMB453 SNV: p.D649N DBIA    Probe Info 
MEWO SNV: p.P705S .
NALM6 Deletion: p.F707LfsTer4 DBIA    Probe Info 
NCIH1793 SNV: p.Y960C .
NCIH2170 SNV: p.G224V .
RKO SNV: p.L122P .
RL Substitution: p.A777Y DBIA    Probe Info 
RL952 SNV: p.T934K DBIA    Probe Info 
SKMEL3 Substitution: p.C29H .
SNU5 SNV: p.E415Ter DBIA    Probe Info 
SW620 SNV: p.A818S .
TOV21G Deletion: p.F707LfsTer4 .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 11 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
BTD
 Probe Info  		C49(0.68)  LDD2108  [1]
IPM
 Probe Info  		C91(4.40); C49(4.28); C52(2.50)  LDD1701  [1]
DBIA
 Probe Info  		C322(0.85); C324(0.85)  LDD0078  [2]
4-Iodoacetamidophenylacetylene
 Probe Info  		C385(0.00); C684(0.00); C202(0.00); C91(0.00)  LDD0038  [3]
IA-alkyne
 Probe Info  		C385(0.00); C684(0.00); C202(0.00); C91(0.00)  LDD0036  [3]
Lodoacetamide azide
 Probe Info  		C385(0.00); C684(0.00); C202(0.00); C91(0.00)  LDD0037  [3]
NAIA_4
 Probe Info  		N.A.  LDD2226  [4]
WYneN
 Probe Info  		N.A.  LDD0021  [5]
WYneO
 Probe Info  		N.A.  LDD0022  [5]
TFBX
 Probe Info  		N.A.  LDD0148  [6]
Acrolein
 Probe Info  		N.A.  LDD0217  [7]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0020  ARS-1620 HCC44 C322(0.85); C324(0.85)  LDD0078  [2]
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [7]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C911(6.08); C52(2.51); C49(1.94); C684(1.74)  LDD1702  [1]
 LDCM0022  KB02 42-MG-BA C684(2.30); C671(4.92)  LDD2244  [8]
 LDCM0023  KB03 Jurkat C671(89.09)  LDD0209  [9]
 LDCM0024  KB05 COLO792 C1025(1.64)  LDD3310  [8]
 LDCM0515  Nucleophilic fragment 20b MDA-MB-231 C49(0.68)  LDD2108  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC) . Q9HD26
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Latexin (LXN) Protease inhibitor I47 (latexin) family Q9BS40

The Drug(s) Related To This Target

Approved
Click To Hide/Show 6 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Capecitabine Small molecular drug DB01101
Flavin Adenine Dinucleotide Small molecular drug DB03147
Fluorouracil Small molecular drug D05LEO
Tegafur-uracil Small molecular drug DB09327
Flavin Mononucleotide . DB03247
Gimeracil . DB09257
Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Eniluracil Small molecular drug D09QOR
Phase 1
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Ro-09-4889 . D03GGN
Investigative
Click To Hide/Show 7 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
(5s)-5-iododihydro-2,4(1h,3h)-pyrimidinedione Small molecular drug D0HR8H
(5s)-5-iododihydro-24(1h3h)-pyrimidinedione Small molecular drug DB02303
5-iodouracil Small molecular drug D08EZR
6-carboxymethyluracil Small molecular drug D0O0AI
Flavin-adenine Dinucleotide Small molecular drug D00IMW
Nadph Small molecular drug DB02338
Uracil Small molecular drug D0Y0DG
Discontinued
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Fl-386 Small molecular drug D05YLL

References

1 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
2 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
3 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
4 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
5 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
6 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
7 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.
8 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
9 Covalent Inhibition by a Natural Product-Inspired Latent Electrophile. J Am Chem Soc. 2023 May 24;145(20):11097-11109. doi: 10.1021/jacs.3c00598. Epub 2023 May 15.