Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYEWBF7)

• DOT Name: Elongator complex protein 1 (ELP1)
• Synonyms: ELP1; IkappaB kinase complex-associated protein; IKK complex-associated protein; p150
• Gene Name: ELP1
• Related Disease:
  Autonomic neuropathy
  Dysautonomia
  Multiple sclerosis
  Primary dysautonomia
  Allergic asthma
  Amyotrophic lateral sclerosis
  Becker muscular dystrophy
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cervical carcinoma
  Childhood epilepsy with centrotemporal spikes
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Duchenne muscular dystrophy
  Dyschromatosis symmetrica hereditaria
  Epithelial ovarian cancer
  Frontotemporal dementia
  Gastric cancer
  Hereditary sensory and autonomic neuropathy
  Hirschsprung disease
  Lung cancer
  Lung carcinoma
  Male infertility
  Melanoma
  Metastatic malignant neoplasm
  Mood disorder
  Neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Peripheral neuropathy
  rubella
  Stomach cancer
  Warburg micro syndrome 1
  Advanced cancer
  Asthma
  Prostate cancer
  Prostate carcinoma
  Riley-Day syndrome
  Medulloblastoma
  Neuroblastoma
  Parkinsonian disorder
  Type-1/2 diabetes
• UniProt ID: ELP1_HUMAN
• PDB ID: 5CQR
• Pfam ID: PF04762
• Sequence:
  MRNLKLFRTLEFRDIQGPGNPQCFSLRTEQGTVLIGSEHGLIEVDPVSREVKNEVSLVAE
  GFLPEDGSGRIVGVQDLLDQESVCVATASGDVILCSLSTQQLECVGSVASGISVMSWSPD
  QELVLLATGQQTLIMMTKDFEPILEQQIHQDDFGESKFITVGWGRKETQFHGSEGRQAAF
  QMQMHESALPWDDHRPQVTWRGDGQFFAVSVVCPETGARKVRVWNREFALQSTSEPVAGL
  GPALAWKPSGSLIASTQDKPNQQDIVFFEKNGLLHGHFTLPFLKDEVKVNDLLWNADSSV
  LAVWLEDLQREESSIPKTCVQLWTVGNYHWYLKQSLSFSTCGKSKIVSLMWDPVTPYRLH
  VLCQGWHYLAYDWHWTTDRSVGDNSSDLSNVAVIDGNRVLVTVFRQTVVPPPMCTYQLLF
  PHPVNQVTFLAHPQKSNDLAVLDASNQISVYKCGDCPSADPTVKLGAVGGSGFKVCLRTP
  HLEKRYKIQFENNEDQDVNPLKLGLLTWIEEDVFLAVSHSEFSPRSVIHHLTAASSEMDE
  EHGQLNVSSSAAVDGVIISLCCNSKTKSVVLQLADGQIFKYLWESPSLAIKPWKNSGGFP
  VRFPYPCTQTELAMIGEEECVLGLTDRCRFFINDIEVASNITSFAVYDEFLLLTTHSHTC
  QCFCLRDASFKTLQAGLSSNHVSHGEVLRKVERGSRIVTVVPQDTKLVLQMPRGNLEVVH
  HRALVLAQIRKWLDKLMFKEAFECMRKLRINLNLIYDHNPKVFLGNVETFIKQIDSVNHI
  NLFFTELKEEDVTKTMYPAPVTSSVYLSRDPDGNKIDLVCDAMRAVMESINPHKYCLSIL
  TSHVKKTTPELEIVLQKVHELQGNAPSDPDAVSAEEALKYLLHLVDVNELYDHSLGTYDF
  DLVLMVAEKSQKDPKEYLPFLNTLKKMETNYQRFTIDKYLKRYEKAIGHLSKCGPEYFPE
  CLNLIKDKNLYNEALKLYSPSSQQYQDISIAYGEHLMQEHMYEPAGLMFARCGAHEKALS
  AFLTCGNWKQALCVAAQLNFTKDQLVGLGRTLAGKLVEQRKHIDAAMVLEECAQDYEEAV
  LLLLEGAAWEEALRLVYKYNRLDIIETNVKPSILEAQKNYMAFLDSQTATFSRHKKRLLV
  VRELKEQAQQAGLDDEVPHGQESDLFSETSSVVSGSEMSGKYSHSNSRISARSSKNRRKA
  ERKKHSLKEGSPLEDLALLEALSEVVQNTENLKDEVYHILKVLFLFEFDEQGRELQKAFE
  DTLQLMERSLPEIWTLTYQQNSATPVLGPNSTANSIMASYQQQKTSVPVLDAELFIPPKI
  NRRTQWKLSLLD
• Function: Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs. Regulates the migration and branching of projection neurons in the developing cerebral cortex, through a process depending on alpha-tubulin acetylation. ELP1 binds to tRNA, mediating interaction of the elongator complex with tRNA. May act as a scaffold protein that assembles active IKK-MAP3K14 complexes (IKKA, IKKB and MAP3K14/NIK).
• Reactome Pathway: HATs acetylate histones (R-HSA-3214847)
• BioCyc Pathway: MetaCyc:ENSG00000070061-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autonomic neuropathy	DISI3WJ0	Definitive	Genetic Variation	[1]
Dysautonomia	DISF4MT6	Definitive	Altered Expression	[2]
Multiple sclerosis	DISB2WZI	Definitive	Biomarker	[3]
Primary dysautonomia	DIS6ONR0	Definitive	Autosomal recessive	[4]
Allergic asthma	DISHF0H3	Strong	Genetic Variation	[5]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Genetic Variation	[6]
Becker muscular dystrophy	DIS5IYHL	Strong	Genetic Variation	[7]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Altered Expression	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[9]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[10]
Childhood epilepsy with centrotemporal spikes	DISKT2L5	Strong	Genetic Variation	[6]
Dilated cardiomyopathy	DISX608J	Strong	Biomarker	[11]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[11]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[12]
Dyschromatosis symmetrica hereditaria	DIS9HI9T	Strong	Biomarker	[13]
Epithelial ovarian cancer	DIS56MH2	Strong	Posttranslational Modification	[14]
Frontotemporal dementia	DISKYHXL	Strong	Genetic Variation	[3]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[10]
Hereditary sensory and autonomic neuropathy	DIS2VOAM	Strong	Genetic Variation	[6]
Hirschsprung disease	DISUUSM1	Strong	Genetic Variation	[15]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[16]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[16]
Male infertility	DISY3YZZ	Strong	Biomarker	[17]
Melanoma	DIS1RRCY	Strong	Biomarker	[18]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[10]
Mood disorder	DISLVMWO	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[16]
Ovarian cancer	DISZJHAP	Strong	Posttranslational Modification	[14]
Peripheral neuropathy	DIS7KN5G	Strong	Genetic Variation	[21]
rubella	DISXUI9P	Strong	Biomarker	[22]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[10]
Warburg micro syndrome 1	DIS90EI2	Strong	Biomarker	[23]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[24]
Asthma	DISW9QNS	moderate	Biomarker	[25]
Prostate cancer	DISF190Y	moderate	Genetic Variation	[26]
Prostate carcinoma	DISMJPLE	moderate	Genetic Variation	[26]
Riley-Day syndrome	DISJZHNP	Supportive	Autosomal recessive	[27]
Medulloblastoma	DISZD2ZL	Limited	Autosomal dominant	[28]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[29]
Parkinsonian disorder	DISHGY45	Limited	Biomarker	[30]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[31]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Melphalan	DMOLNHF	Approved	Elongator complex protein 1 (ELP1) increases the Injury ADR of Melphalan.	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Elongator complex protein 1 (ELP1).	[32]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Elongator complex protein 1 (ELP1).	[43]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Elongator complex protein 1 (ELP1).	[43]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Elongator complex protein 1 (ELP1).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Elongator complex protein 1 (ELP1).	[34]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Elongator complex protein 1 (ELP1).	[35]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Elongator complex protein 1 (ELP1).	[36]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Elongator complex protein 1 (ELP1).	[37]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Elongator complex protein 1 (ELP1).	[38]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial decreases the expression of Elongator complex protein 1 (ELP1).	[39]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium decreases the expression of Elongator complex protein 1 (ELP1).	[39]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Elongator complex protein 1 (ELP1).	[40]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Elongator complex protein 1 (ELP1).	[41]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Elongator complex protein 1 (ELP1).	[42]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Elongator complex protein 1 (ELP1).	[44]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Elongator complex protein 1 (ELP1).	[45]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Elongator complex protein 1 (ELP1).	[46]

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