Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVLYBUS)

DOT Name	Dehydrodolichyl diphosphate synthase complex subunit DHDDS (DHDDS)
Synonyms	EC 2.5.1.87; Cis-isoprenyltransferase; CIT; Cis-IPTase; Cis-prenyltransferase subunit hCIT; Epididymis tissue protein Li 189m
Gene Name	DHDDS
Related Disease	Gastrointestinal mucositis ( ) Glioblastoma multiforme ( ) Liver cirrhosis ( ) Parkinson disease ( ) Retinitis pigmentosa 59 ( ) Triple negative breast cancer ( ) Acute myelogenous leukaemia ( ) Advanced cancer ( ) Attention deficit hyperactivity disorder ( ) Bone osteosarcoma ( ) Breast cancer ( ) Breast carcinoma ( ) Carnitine palmitoyltransferase II deficiency ( ) Clear cell renal carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Colorectal carcinoma ( ) Colorectal neoplasm ( ) Congenital disorder of glycosylation ( ) Dementia ( ) Developmental delay and seizures with or without movement abnormalities ( ) Epithelial ovarian cancer ( ) Fatty liver disease ( ) Lung adenocarcinoma ( ) Lung carcinoma ( ) Neuroblastoma ( ) Non-insulin dependent diabetes ( ) Non-small-cell lung cancer ( ) Osteosarcoma ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Prostate cancer ( ) Prostate carcinoma ( ) Rectal carcinoma ( ) Renal cell carcinoma ( ) Schizophrenia ( ) Small-cell lung cancer ( ) Tourette syndrome ( ) Urinary bladder neoplasm ( ) Autism ( ) Hepatocellular carcinoma ( ) Leukopenia ( ) Medulloblastoma ( ) Retinitis pigmentosa ( ) Undetermined early-onset epileptic encephalopathy ( ) Lung cancer ( ) Adenocarcinoma ( ) Cataract ( ) Pancreatic cancer ( ) Psychotic disorder ( )
UniProt ID	DHDDS_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	6W2L; 6Z1N; 7PAX; 7PAY; 7PB0; 7PB1
EC Number	2.5.1.87
Pfam ID	PF01255
Sequence	MSWIKEGELSLWERFCANIIKAGPMPKHIAFIMDGNRRYAKKCQVERQEGHSQGFNKLAE TLRWCLNLGILEVTVYAFSIENFKRSKSEVDGLMDLARQKFSRLMEEKEKLQKHGVCIRV LGDLHLLPLDLQELIAQAVQATKNYNKCFLNVCFAYTSRHEISNAVREMAWGVEQGLLDP SDISESLLDKCLYTNRSPHPDILIRTSGEVRLSDFLLWQTSHSCLVFQPVLWPEYTFWNL FEAILQFQMNHSVLQKARDMYAEERKRQQLERDQATVTEQLLREGLQASGDAQLRRTRLH KLSARREERVQGFLQALELKRADWLARLGTASA
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.
Tissue Specificity	Expressed at high levels in testis and kidney. Expressed in epididymis (at protein level). Slightly expressed in heart, spleen and thymus.
KEGG Pathway	Terpenoid backbone biosynthesis (hsa00900 )
Reactome Pathway	Defective DHDDS causes RP59 (R-HSA-4755609 ) Synthesis of Dolichyl-phosphate (R-HSA-446199 )
BioCyc Pathway	MetaCyc:HS04165-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Gastrointestinal mucositis	DIS140OB	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[2]
Liver cirrhosis	DIS4G1GX	Definitive	Biomarker	[3]
Parkinson disease	DISQVHKL	Definitive	Biomarker	[4]
Retinitis pigmentosa 59	DIS5C4LU	Definitive	Autosomal recessive	[5]
Triple negative breast cancer	DISAMG6N	Definitive	Biomarker	[6]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[7]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[8]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[9]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[10]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Carnitine palmitoyltransferase II deficiency	DIS3GFD9	Strong	Altered Expression	[11]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[12]
Colon cancer	DISVC52G	Strong	Biomarker	[13]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[14]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[15]
Congenital disorder of glycosylation	DIS400QP	Strong	Biomarker	[16]
Dementia	DISXL1WY	Strong	Biomarker	[17]
Developmental delay and seizures with or without movement abnormalities	DISWBLYL	Strong	Autosomal dominant	[18]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[19]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[20]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[21]
Lung carcinoma	DISTR26C	Strong	Biomarker	[22]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[23]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[24]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[25]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[10]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[19]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[19]
Prostate cancer	DISF190Y	Strong	Biomarker	[26]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[26]
Rectal carcinoma	DIS8FRR7	Strong	Biomarker	[27]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[12]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[28]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[29]
Tourette syndrome	DISX9D54	Strong	Biomarker	[30]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[31]
Autism	DISV4V1Z	moderate	Biomarker	[32]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[33]
Leukopenia	DISJMBMM	moderate	Genetic Variation	[34]
Medulloblastoma	DISZD2ZL	moderate	Biomarker	[35]
Retinitis pigmentosa	DISCGPY8	Supportive	Autosomal dominant	[36]
Undetermined early-onset epileptic encephalopathy	DISISEI2	Supportive	Autosomal dominant	[37]
Lung cancer	DISCM4YA	Disputed	Biomarker	[38]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[39]
Cataract	DISUD7SL	Limited	Biomarker	[40]
Pancreatic cancer	DISJC981	Limited	Biomarker	[41]
Psychotic disorder	DIS4UQOT	Limited	Genetic Variation	[42]
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⏷ Show the Full List of 50 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Dehydrodolichyl diphosphate synthase complex subunit DHDDS (DHDDS).	[43]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Dehydrodolichyl diphosphate synthase complex subunit DHDDS (DHDDS).	[46]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Dehydrodolichyl diphosphate synthase complex subunit DHDDS (DHDDS).	[47]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dehydrodolichyl diphosphate synthase complex subunit DHDDS (DHDDS).	[44]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Dehydrodolichyl diphosphate synthase complex subunit DHDDS (DHDDS).	[45]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Dehydrodolichyl diphosphate synthase complex subunit DHDDS (DHDDS).	[48]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Dehydrodolichyl diphosphate synthase complex subunit DHDDS (DHDDS).	[49]
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