Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0XHHWP)

• DOT Name: Elongin-C (ELOC)
• Synonyms: EloC; Elongin 15 kDa subunit; RNA polymerase II transcription factor SIII subunit C; SIII p15; Transcription elongation factor B polypeptide 1
• Gene Name: ELOC
• Related Disease:
  Asthma
  Acute myelogenous leukaemia
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Brugada syndrome
  Carcinoma
  Clear cell renal carcinoma
  Neoplasm
  Papillary renal cell carcinoma
  Polycythemia
  Prostate neoplasm
  Ventricular tachycardia
  Von hippel-lindau disease
  Eating disorder
  Kidney cancer
  Renal carcinoma
  Advanced cancer
  Cutaneous mastocytosis
  Leiomyomatosis
  Neuroblastoma
  Prostate cancer
  Prostate carcinoma
  Renal cell carcinoma
  Tuberous sclerosis
• UniProt ID: ELOC_HUMAN
• PDB ID: 1LM8 ; 1LQB ; 1VCB ; 2C9W ; 2IZV ; 2MA9 ; 3DCG ; 3ZKJ ; 3ZNG ; 3ZRC ; 3ZRF ; 3ZTC ; 3ZTD ; 3ZUN ; 4AJY ; 4AWJ ; 4B95 ; 4B9K ; 4BKS ; 4BKT ; 4N9F ; 4W9C ; 4W9D ; 4W9E ; 4W9F ; 4W9G ; 4W9H ; 4W9I ; 4W9J ; 4W9K ; 4W9L ; 4WQO ; 5BO4 ; 5LLI ; 5N4W ; 5NVV ; 5NVW ; 5NVX ; 5NVY ; 5NVZ ; 5NW0 ; 5NW1 ; 5NW2 ; 5T35 ; 6BVB ; 6C5X ; 6FMI ; 6FMJ ; 6FMK ; 6GFX ; 6GFY ; 6GFZ ; 6GMN ; 6GMQ ; 6GMR ; 6GMX ; 6HAX ; 6HAY ; 6HR2 ; 6I4X ; 6I5J ; 6I5N ; 6I7R ; 6P59 ; 6R7F ; 6R7H ; 6R7N ; 6SIS ; 6V9H ; 6ZHC ; 7CJB ; 7JTO ; 7JTP ; 7KHH ; 7M6T ; 7PI4 ; 7PLO ; 7Q2J ; 7S4E ; 7UPN ; 7Z6L ; 7Z76 ; 7Z77 ; 7ZLM ; 7ZLN ; 7ZLO ; 7ZLP ; 7ZLR ; 7ZLS ; 7ZNT ; 8BB2 ; 8BB3 ; 8BB4 ; 8BB5 ; 8BDI ; 8BDJ ; 8BDL ; 8BDM ; 8BDN ; 8BDO ; 8BDS ; 8BDT ; 8BDX ; 8BEB ; 8C13 ; 8CQE ; 8CQK ; 8CQL ; 8CX0 ; 8CX1 ; 8CX2 ; 8EBN ; 8EI3 ; 8EWV ; 8FVI ; 8FVJ ; 8G1P ; 8G1Q ; 8JAL ; 8JAQ ; 8JAR ; 8JAS ; 8JAU ; 8JAV ; 8OEV ; 8OEW ; 8OF0 ; 8P0F ; 8PC2 ; 8QU8 ; 8QVU ; 8QW6 ; 8QW7
• Pfam ID: PF03931
• Sequence:
  MDGEEKTYGGCEGPDAMYVKLISSDGHEFIVKREHALTSGTIKAMLSGPGQFAENETNEV
  NFREIPSHVLSKVCMYFTYKVRYTNSSTEIPEFPIAPEIALELLMAANFLDC
• Function: SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex). In embryonic stem cells, the elongin BC complex is recruited by EPOP to Polycomb group (PcG) target genes in order generate genomic region that display both active and repressive chromatin properties, an important feature of pluripotent stem cells; Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. This includes the von Hippel-Lindau ubiquitination complex CBC(VHL). By binding to BC-box motifs it seems to link target recruitment subunits, like VHL and members of the SOCS box family, to Cullin/RBX1 modules that activate E2 ubiquitination enzymes. As part of a multisubunit ubiquitin ligase complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A. A number of ECS complexes (containing either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase.
• Tissue Specificity: Overexpressed in prostate cancer cell line PC-3 and breast cancer cell line SK-BR-3.
• KEGG Pathway:
  HIF-1 sig.ling pathway (hsa04066)
  Ubiquitin mediated proteolysis (hsa04120)
  Human immunodeficiency virus 1 infection (hsa05170)
  Pathways in cancer (hsa05200)
  Re.l cell carcinoma (hsa05211)
• Reactome Pathway:
  Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha (R-HSA-1234176)
  Formation of HIV elongation complex in the absence of HIV Tat (R-HSA-167152)
  Formation of HIV-1 elongation complex containing HIV-1 Tat (R-HSA-167200)
  Pausing and recovery of Tat-mediated HIV elongation (R-HSA-167238)
  Tat-mediated HIV elongation arrest and recovery (R-HSA-167243)
  Tat-mediated elongation of the HIV-1 transcript (R-HSA-167246)
  HIV elongation arrest and recovery (R-HSA-167287)
  Pausing and recovery of HIV elongation (R-HSA-167290)
  Vif-mediated degradation of APOBEC3G (R-HSA-180585)
  RNA Polymerase II Pre-transcription Events (R-HSA-674695)
  TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648)
  RNA Polymerase II Transcription Elongation (R-HSA-75955)
  Neddylation (R-HSA-8951664)
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  Inactivation of CSF3 (G-CSF) signaling (R-HSA-9705462)
  Antigen processing (R-HSA-983168)
  Formation of RNA Pol II elongation complex (R-HSA-112382)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Brugada syndrome	DISSGN0E	Strong	Biomarker	[5]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Papillary renal cell carcinoma	DIS25HBV	Strong	Genetic Variation	[9]
Polycythemia	DIS8B6VW	Strong	Biomarker	[10]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[11]
Ventricular tachycardia	DISIBXJ3	Strong	Biomarker	[5]
Von hippel-lindau disease	DIS6ZFQQ	Strong	Biomarker	[10]
Eating disorder	DISVGXN0	moderate	Biomarker	[12]
Kidney cancer	DISBIPKM	moderate	Genetic Variation	[13]
Renal carcinoma	DISER9XT	moderate	Genetic Variation	[13]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[14]
Cutaneous mastocytosis	DISLBZEF	Limited	Biomarker	[8]
Leiomyomatosis	DISNOOME	Limited	Genetic Variation	[15]
Neuroblastoma	DISVZBI4	Limited	Genetic Variation	[15]
Prostate cancer	DISF190Y	Limited	Biomarker	[16]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[16]
Renal cell carcinoma	DISQZ2X8	Limited	Genetic Variation	[7]
Tuberous sclerosis	DISEMUGZ	Limited	Genetic Variation	[17]

2 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 Elongin-C (ELOC).	[18]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Elongin-C (ELOC).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Elongin-C (ELOC).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Elongin-C (ELOC).	[20]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Elongin-C (ELOC).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Elongin-C (ELOC).	[22]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Elongin-C (ELOC).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Elongin-C (ELOC).	[25]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Elongin-C (ELOC).	[26]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Elongin-C (ELOC).	[27]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Elongin-C (ELOC).	[28]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Elongin-C (ELOC).	[29]

References

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• [17] "Renal Cell Carcinoma With Leiomyomatous Stroma" Harbor Somatic Mutations of TSC1, TSC2, MTOR, and/or ELOC (TCEB1): Clinicopathologic and Molecular Characterization of 18 Sporadic Tumors Supports a Distinct Entity.Am J Surg Pathol. 2020 May;44(5):571-581. doi: 10.1097/PAS.0000000000001422.
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