Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJ9N6BD)

• DOT Name: Replication factor C subunit 2 (RFC2)
• Synonyms: Activator 1 40 kDa subunit; A1 40 kDa subunit; Activator 1 subunit 2; Replication factor C 40 kDa subunit; RF-C 40 kDa subunit; RFC40
• Gene Name: RFC2
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Bone osteosarcoma
  Breast cancer
  Colon cancer
  Colon carcinoma
  Depression
  Esophageal squamous cell carcinoma
  Obesity
  Osteosarcoma
  Psoriatic arthritis
  Age-related macular degeneration
  Choriocarcinoma
  Nasopharyngeal carcinoma
  Neoplasm
  Squamous cell carcinoma
  Type-1/2 diabetes
  Non-insulin dependent diabetes
  Asthma
  Breast carcinoma
  Neuroblastoma
• UniProt ID: RFC2_HUMAN
• PDB ID: 6VVO; 7Z6H
• Pfam ID: PF00004 ; PF08542
• Sequence:
  MEVEAVCGGAGEVEAQDSDPAPAFSKAPGSAGHYELPWVEKYRPVKLNEIVGNEDTVSRL
  EVFAREGNVPNIIIAGPPGTGKTTSILCLARALLGPALKDAMLELNASNDRGIDVVRNKI
  KMFAQQKVTLPKGRHKIIILDEADSMTDGAQQALRRTMEIYSKTTRFALACNASDKIIEP
  IQSRCAVLRYTKLTDAQILTRLMNVIEKERVPYTDDGLEAIIFTAQGDMRQALNNLQSTF
  SGFGFINSENVFKVCDEPHPLLVKEMIQHCVNANIDEAYKILAHLWHLGYSPEDIIGNIF
  RVCKTFQMAEYLKLEFIKEIGYTHMKIAEGVNSLLQMAGLLARLCQKTMAPVAS
• 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 binds ATP.
• 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

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Definitive	Genetic Variation	[1]
Atherosclerosis	DISMN9J3	Definitive	Genetic Variation	[1]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Colon cancer	DISVC52G	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[4]
Depression	DIS3XJ69	Strong	Biomarker	[5]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[6]
Obesity	DIS47Y1K	Strong	Altered Expression	[7]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[2]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[8]
Age-related macular degeneration	DIS0XS2C	moderate	Biomarker	[9]
Choriocarcinoma	DISDBVNL	moderate	Altered Expression	[10]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Biomarker	[11]
Neoplasm	DISZKGEW	moderate	Altered Expression	[12]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[12]
Type-1/2 diabetes	DISIUHAP	moderate	Altered Expression	[13]
Non-insulin dependent diabetes	DISK1O5Z	Disputed	Biomarker	[13]
Asthma	DISW9QNS	Limited	Biomarker	[14]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[3]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Replication factor C subunit 2 (RFC2) affects the response to substance of Fluorouracil.	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Replication factor C subunit 2 (RFC2).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Replication factor C subunit 2 (RFC2).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Replication factor C subunit 2 (RFC2).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Replication factor C subunit 2 (RFC2).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Replication factor C subunit 2 (RFC2).	[20]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Replication factor C subunit 2 (RFC2).	[21]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Replication factor C subunit 2 (RFC2).	[22]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Replication factor C subunit 2 (RFC2).	[23]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Replication factor C subunit 2 (RFC2).	[24]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Replication factor C subunit 2 (RFC2).	[25]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Replication factor C subunit 2 (RFC2).	[26]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Replication factor C subunit 2 (RFC2).	[26]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Replication factor C subunit 2 (RFC2).	[27]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Replication factor C subunit 2 (RFC2).	[28]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Replication factor C subunit 2 (RFC2).	[29]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Replication factor C subunit 2 (RFC2).	[30]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Replication factor C subunit 2 (RFC2).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Replication factor C subunit 2 (RFC2).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Replication factor C subunit 2 (RFC2).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Replication factor C subunit 2 (RFC2).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Replication factor C subunit 2 (RFC2).	[36]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Replication factor C subunit 2 (RFC2).	[37]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Replication factor C subunit 2 (RFC2).	[22]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Replication factor C subunit 2 (RFC2).	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Replication factor C subunit 2 (RFC2).	[35]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Replication factor C subunit 2 (RFC2).	[35]

References

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