General Information of Target

Target ID LDTP08177
Target Name Dehydrodolichyl diphosphate synthase complex subunit DHDDS (DHDDS)
Gene Name DHDDS
Gene ID 79947
Synonyms
HDS; Dehydrodolichyl diphosphate synthase complex subunit DHDDS; EC 2.5.1.87; Cis-isoprenyltransferase; CIT; Cis-IPTase; Cis-prenyltransferase subunit hCIT; Epididymis tissue protein Li 189m
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSWIKEGELSLWERFCANIIKAGPMPKHIAFIMDGNRRYAKKCQVERQEGHSQGFNKLAE
TLRWCLNLGILEVTVYAFSIENFKRSKSEVDGLMDLARQKFSRLMEEKEKLQKHGVCIRV
LGDLHLLPLDLQELIAQAVQATKNYNKCFLNVCFAYTSRHEISNAVREMAWGVEQGLLDP
SDISESLLDKCLYTNRSPHPDILIRTSGEVRLSDFLLWQTSHSCLVFQPVLWPEYTFWNL
FEAILQFQMNHSVLQKARDMYAEERKRQQLERDQATVTEQLLREGLQASGDAQLRRTRLH
KLSARREERVQGFLQALELKRADWLARLGTASA
Target Bioclass
Enzyme
Family
UPP synthase family
Subcellular location
Endoplasmic reticulum membrane
Function
With NUS1, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery. Both subunits contribute to enzymatic activity, i.e. condensation of multiple copies of isopentenyl pyrophosphate (IPP) to farnesyl pyrophosphate (FPP) to produce dehydrodolichyl diphosphate (Dedol-PP), a precursor of dolichol phosphate which is utilized as a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER). Synthesizes long-chain polyprenols, mostly of C95 and C100 chain length. Regulates the glycosylation and stability of nascent NPC2, thereby promoting trafficking of LDL-derived cholesterol.
Uniprot ID
Q86SQ9
Ensemble ID
ENST00000236342.12
HGNC ID
HGNC:20603

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CCK81 SNV: p.N250I .
FTC133 SNV: p.E60G .
LS180 Deletion: p.V173WfsTer31 .
MOLT4 Insertion: p.V173GfsTer10 .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 6 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C117(2.28)  LDD3333  [1]
BTD
 Probe Info 
C43(0.77)  LDD2092  [2]
IA-alkyne
 Probe Info 
C191(0.00); C16(0.00)  LDD0165  [3]
TFBX
 Probe Info 
C117(0.00); C16(0.00)  LDD0148  [4]
Phosphinate-6
 Probe Info 
N.A.  LDD0018  [5]
AOyne
 Probe Info 
9.10  LDD0443  [6]
PAL-AfBPP Probe
Click To Hide/Show 7 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C134
 Probe Info 
22.63  LDD1816  [7]
C249
 Probe Info 
25.28  LDD1922  [7]
C287
 Probe Info 
10.48  LDD1957  [7]
C288
 Probe Info 
6.87  LDD1958  [7]
C289
 Probe Info 
41.93  LDD1959  [7]
C293
 Probe Info 
27.86  LDD1963  [7]
C296
 Probe Info 
67.65  LDD1966  [7]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0548  1-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-2-nitroethan-1-one MDA-MB-231 C43(0.76)  LDD2142  [2]
 LDCM0519  1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-2-nitroethan-1-one MDA-MB-231 C43(0.96)  LDD2112  [2]
 LDCM0226  AC11 HEK-293T C16(0.92)  LDD1509  [8]
 LDCM0278  AC19 HEK-293T C16(0.81)  LDD1517  [8]
 LDCM0287  AC27 HEK-293T C16(0.89)  LDD1526  [8]
 LDCM0290  AC3 HEK-293T C16(0.93)  LDD1529  [8]
 LDCM0296  AC35 HEK-293T C16(0.95)  LDD1535  [8]
 LDCM0305  AC43 HEK-293T C16(1.11)  LDD1544  [8]
 LDCM0314  AC51 HEK-293T C16(1.02)  LDD1553  [8]
 LDCM0322  AC59 HEK-293T C16(0.97)  LDD1561  [8]
 LDCM0406  CL19 HEK-293T C16(1.01)  LDD1610  [8]
 LDCM0420  CL31 HEK-293T C16(0.98)  LDD1624  [8]
 LDCM0433  CL43 HEK-293T C16(0.87)  LDD1637  [8]
 LDCM0446  CL55 HEK-293T C16(0.96)  LDD1649  [8]
 LDCM0459  CL67 HEK-293T C16(1.06)  LDD1662  [8]
 LDCM0462  CL7 HEK-293T C16(0.87)  LDD1665  [8]
 LDCM0472  CL79 HEK-293T C16(0.98)  LDD1675  [8]
 LDCM0486  CL91 HEK-293T C16(0.97)  LDD1689  [8]
 LDCM0022  KB02 ICC10 C117(1.44)  LDD2379  [1]
 LDCM0023  KB03 ICC10 C117(1.89)  LDD2796  [1]
 LDCM0024  KB05 MOLM-13 C117(2.28)  LDD3333  [1]
 LDCM0499  Nucleophilic fragment 12b MDA-MB-231 C43(0.77)  LDD2092  [2]
 LDCM0500  Nucleophilic fragment 13a MDA-MB-231 C43(1.08)  LDD2093  [2]
 LDCM0501  Nucleophilic fragment 13b MDA-MB-231 C43(0.67)  LDD2094  [2]
 LDCM0503  Nucleophilic fragment 14b MDA-MB-231 C43(0.68)  LDD2096  [2]
 LDCM0505  Nucleophilic fragment 15b MDA-MB-231 C43(1.01)  LDD2098  [2]
 LDCM0516  Nucleophilic fragment 21a MDA-MB-231 C43(0.73)  LDD2109  [2]
 LDCM0523  Nucleophilic fragment 24b MDA-MB-231 C43(1.13)  LDD2116  [2]
 LDCM0526  Nucleophilic fragment 26a MDA-MB-231 C43(0.98)  LDD2119  [2]
 LDCM0530  Nucleophilic fragment 28a MDA-MB-231 C43(0.71)  LDD2123  [2]
 LDCM0534  Nucleophilic fragment 30a MDA-MB-231 C43(0.93)  LDD2127  [2]
 LDCM0543  Nucleophilic fragment 38 MDA-MB-231 C43(1.42)  LDD2136  [2]
 LDCM0550  Nucleophilic fragment 5a MDA-MB-231 C43(1.58)  LDD2144  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Dehydrodolichyl diphosphate synthase complex subunit NUS1 (NUS1) UPP synthase family Q96E22

References

1 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
2 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
3 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
4 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
5 DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling. Angew Chem Int Ed Engl. 2022 Oct 10;61(41):e202205348. doi: 10.1002/anie.202205348. Epub 2022 Aug 22.
Mass spectrometry data entry: PXD033004
6 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.
7 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
8 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402