Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWALD2R)

• DOT Name: Replication factor C subunit 4 (RFC4)
• Synonyms: Activator 1 37 kDa subunit; A1 37 kDa subunit; Activator 1 subunit 4; Replication factor C 37 kDa subunit; RF-C 37 kDa subunit; RFC37
• Gene Name: RFC4
• Related Disease:
  Adult glioblastoma
  B-cell neoplasm
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Glioblastoma multiforme
  Lung adenocarcinoma
  Lung squamous cell carcinoma
  Hepatocellular carcinoma
  Advanced cancer
  Colorectal carcinoma
• UniProt ID: RFC4_HUMAN
• PDB ID: 6VVO; 7Z6H
• Pfam ID: PF00004 ; PF08542
• Sequence:
  MQAFLKGTSISTKPPLTKDRGVAASAGSSGENKKAKPVPWVEKYRPKCVDEVAFQEEVVA
  VLKKSLEGADLPNLLFYGPPGTGKTSTILAAARELFGPELFRLRVLELNASDERGIQVVR
  EKVKNFAQLTVSGSRSDGKPCPPFKIVILDEADSMTSAAQAALRRTMEKESKTTRFCLIC
  NYVSRIIEPLTSRCSKFRFKPLSDKIQQQRLLDIAKKENVKISDEGIAYLVKVSEGDLRK
  AITFLQSATRLTGGKEITEKVITDIAGVIPAEKIDGVFAACQSGSFDKLEAVVKDLIDEG
  HAATQLVNQLHDVVVENNLSDKQKSIITEKLAEVDKCLADGADEHLQLISLCATVMQQLS
  QNC
• Function: The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins proliferating cell nuclear antigen (PCNA) and activator 1. This subunit may be involved in the elongation of the multiprimed DNA template.
• KEGG Pathway:
  D. replication (hsa03030)
  Base excision repair (hsa03410)
  Nucleotide excision repair (hsa03420)
  Mismatch repair (hsa03430)
• Reactome Pathway:
  Recognition of DNA damage by PCNA-containing replication complex (R-HSA-110314)
  Translesion Synthesis by POLH (R-HSA-110320)
  Polymerase switching on the C-strand of the telomere (R-HSA-174411)
  Activation of ATR in response to replication stress (R-HSA-176187)
  PCNA-Dependent Long Patch Base Excision Repair (R-HSA-5651801)
  Translesion synthesis by POLK (R-HSA-5655862)
  Translesion synthesis by POLI (R-HSA-5656121)
  Termination of translesion DNA synthesis (R-HSA-5656169)
  HDR through Single Strand Annealing (SSA) (R-HSA-5685938)
  HDR through Homologous Recombination (HRR) (R-HSA-5685942)
  Processing of DNA double-strand break ends (R-HSA-5693607)
  Presynaptic phase of homologous DNA pairing and strand exchange (R-HSA-5693616)
  Gap-filling DNA repair synthesis and ligation in GG-NER (R-HSA-5696397)
  Dual Incision in GG-NER (R-HSA-5696400)
  Dual incision in TC-NER (R-HSA-6782135)
  Gap-filling DNA repair synthesis and ligation in TC-NER (R-HSA-6782210)
  Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756)
  Polymerase switching (R-HSA-69091)
  G2/M DNA damage checkpoint (R-HSA-69473)
  Impaired BRCA2 binding to RAD51 (R-HSA-9709570)
  Translesion synthesis by REV1 (R-HSA-110312)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Altered Expression	[1]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[2]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[3]
Cervical cancer	DISFSHPF	Strong	Biomarker	[4]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[4]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[6]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[8]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[9]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[9]

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 Replication factor C subunit 4 (RFC4).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Replication factor C subunit 4 (RFC4).	[18]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Replication factor C subunit 4 (RFC4).	[29]

24 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 Replication factor C subunit 4 (RFC4).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Replication factor C subunit 4 (RFC4).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Replication factor C subunit 4 (RFC4).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Replication factor C subunit 4 (RFC4).	[14]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Replication factor C subunit 4 (RFC4).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Replication factor C subunit 4 (RFC4).	[16]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Replication factor C subunit 4 (RFC4).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Replication factor C subunit 4 (RFC4).	[17]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Replication factor C subunit 4 (RFC4).	[17]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Replication factor C subunit 4 (RFC4).	[19]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Replication factor C subunit 4 (RFC4).	[20]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Replication factor C subunit 4 (RFC4).	[21]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Replication factor C subunit 4 (RFC4).	[22]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Replication factor C subunit 4 (RFC4).	[23]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Replication factor C subunit 4 (RFC4).	[24]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Replication factor C subunit 4 (RFC4).	[25]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Replication factor C subunit 4 (RFC4).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Replication factor C subunit 4 (RFC4).	[27]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Replication factor C subunit 4 (RFC4).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Replication factor C subunit 4 (RFC4).	[30]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Replication factor C subunit 4 (RFC4).	[31]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Replication factor C subunit 4 (RFC4).	[32]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Replication factor C subunit 4 (RFC4).	[33]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Replication factor C subunit 4 (RFC4).	[34]

References

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