Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3L5PK3)

• DOT Name: Replication factor C subunit 1 (RFC1)
• Synonyms: Activator 1 140 kDa subunit; A1 140 kDa subunit; Activator 1 large subunit; Activator 1 subunit 1; DNA-binding protein PO-GA; Replication factor C 140 kDa subunit; RF-C 140 kDa subunit; RFC140; Replication factor C large subunit
• Gene Name: RFC1
• Related Disease:
  Esophageal cancer
  Gastric cancer
  Hyperglycemia
  Non-small-cell lung cancer
  Stomach cancer
  Adult lymphoma
  Alcohol dependence
  Alzheimer disease
  Atherosclerosis
  Attention deficit hyperactivity disorder
  Autism
  Autism spectrum disorder
  B-cell lymphoma
  Bladder cancer
  Carcinoma
  Cerebellar ataxia
  Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome
  Charcot-Marie-Tooth disease type 3
  Colon cancer
  Colonic neoplasm
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Hereditary motor and sensory neuropathy
  High blood pressure
  leukaemia
  Leukemia
  Liver cancer
  Lymphoma
  Myocardial infarction
  Nephropathy
  Neuroblastoma
  Non-insulin dependent diabetes
  Pediatric lymphoma
  Retinoblastoma
  Rheumatoid arthritis
  Stroke
  Urinary bladder cancer
  Urinary bladder neoplasm
  Acute lymphocytic leukaemia
  Cardiovascular disease
  Obsolete cerebellar ataxia, neuropathy, and vestibular areflexia syndrome
  Parkinson disease
  Systemic lupus erythematosus
  Bone osteosarcoma
  Advanced cancer
  Carcinoma of liver and intrahepatic biliary tract
  Osteosarcoma
• UniProt ID: RFC1_HUMAN
• PDB ID: 2EBU; 2K6G; 2K7F; 6VVO
• Pfam ID: PF00004 ; PF00533 ; PF08519
• Sequence:
  MDIRKFFGVIPSGKKLVSETVKKNEKTKSDEETLKAKKGIKEIKVNSSRKEDDFKQKQPS
  KKKRIIYDSDSESEETLQVKNAKKPPEKLPVSSKPGKISRQDPVTYISETDEEDDFMCKK
  AASKSKENGRSTNSHLGTSNMKKNEENTKTKNKPLSPIKLTPTSVLDYFGTGSVQRSNKK
  MVASKRKELSQNTDESGLNDEAIAKQLQLDEDAELERQLHEDEEFARTLAMLDEEPKTKK
  ARKDTEAGETFSSVQANLSKAEKHKYPHKVKTAQVSDERKSYSPRKQSKYESSKESQQHS
  KSSADKIGEVSSPKASSKLAIMKRKEESSYKEIEPVASKRKENAIKLKGETKTPKKTKSS
  PAKKESVSPEDSEKKRTNYQAYRSYLNREGPKALGSKEIPKGAENCLEGLIFVITGVLES
  IERDEAKSLIERYGGKVTGNVSKKTNYLVMGRDSGQSKSDKAAALGTKIIDEDGLLNLIR
  TMPGKKSKYEIAVETEMKKESKLERTPQKNVQGKRKISPSKKESESKKSRPTSKRDSLAK
  TIKKETDVFWKSLDFKEQVAEETSGDSKARNLADDSSENKVENLLWVDKYKPTSLKTIIG
  QQGDQSCANKLLRWLRNWQKSSSEDKKHAAKFGKFSGKDDGSSFKAALLSGPPGVGKTTT
  ASLVCQELGYSYVELNASDTRSKSSLKAIVAESLNNTSIKGFYSNGAASSVSTKHALIMD
  EVDGMAGNEDRGGIQELIGLIKHTKIPIICMCNDRNHPKIRSLVHYCFDLRFQRPRVEQI
  KGAMMSIAFKEGLKIPPPAMNEIILGANQDIRQVLHNLSMWCARSKALTYDQAKADSHRA
  KKDIKMGPFDVARKVFAAGEETAHMSLVDKSDLFFHDYSIAPLFVQENYIHVKPVAAGGD
  MKKHLMLLSRAADSICDGDLVDSQIRSKQNWSLLPAQAIYASVLPGELMRGYMTQFPTFP
  SWLGKHSSTGKHDRIVQDLALHMSLRTYSSKRTVNMDYLSLLRDALVQPLTSQGVDGVQD
  VVALMDTYYLMKEDFENIMEISSWGGKPSPFSKLDPKVKAAFTRAYNKEAHLTPYSLQAI
  KASRHSTSPSLDSEYNEELNEDDSQSDEKDQDAIETDAMIKKKTKSSKPSKPEKDKEPRK
  GKGKSSKK
• Function: The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins PCNA and activator 1. This subunit binds to the primer-template junction. Binds the PO-B transcription element as well as other GA rich DNA sequences. Could play a role in DNA transcription regulation as well as DNA replication and/or repair. Can bind single- or double-stranded DNA; Interacts with C-terminus of PCNA. 5' phosphate residue is required for binding of the N-terminal DNA-binding domain to duplex DNA, suggesting a role in recognition of non-primer template DNA structures during replication and/or repair.
• Tissue Specificity: Wide tissue distribution. Undetectable in placental tissue.
• 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)
  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 Homologous Recombination (HRR) (R-HSA-5685942)
  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)
  Polymerase switching (R-HSA-69091)
  Translesion synthesis by REV1 (R-HSA-110312)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal cancer	DISGB2VN	Definitive	Genetic Variation	[1]
Gastric cancer	DISXGOUK	Definitive	Genetic Variation	[1]
Hyperglycemia	DIS0BZB5	Definitive	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Altered Expression	[3]
Stomach cancer	DISKIJSX	Definitive	Genetic Variation	[1]
Adult lymphoma	DISK8IZR	Strong	Genetic Variation	[4]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[5]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[6]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[8]
Autism	DISV4V1Z	Strong	Genetic Variation	[9]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[10]
B-cell lymphoma	DISIH1YQ	Strong	Posttranslational Modification	[11]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[12]
Carcinoma	DISH9F1N	Strong	Biomarker	[12]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[13]
Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome	DISKVS6J	Strong	Autosomal recessive	[14]
Charcot-Marie-Tooth disease type 3	DIS6DQK1	Strong	Biomarker	[15]
Colon cancer	DISVC52G	Strong	Biomarker	[16]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[16]
Head and neck carcinoma	DISOU1DS	Strong	Genetic Variation	[17]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[18]
Hereditary motor and sensory neuropathy	DISR0X2K	Strong	Biomarker	[15]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[19]
leukaemia	DISS7D1V	Strong	Biomarker	[20]
Leukemia	DISNAKFL	Strong	Biomarker	[20]
Liver cancer	DISDE4BI	Strong	Genetic Variation	[21]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[4]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[22]
Nephropathy	DISXWP4P	Strong	Biomarker	[23]
Neuroblastoma	DISVZBI4	Strong	Genetic Variation	[24]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[25]
Pediatric lymphoma	DIS51BK2	Strong	Genetic Variation	[4]
Retinoblastoma	DISVPNPB	Strong	Genetic Variation	[26]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[27]
Stroke	DISX6UHX	Strong	Genetic Variation	[22]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[12]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[12]
Acute lymphocytic leukaemia	DISPX75S	moderate	Genetic Variation	[28]
Cardiovascular disease	DIS2IQDX	moderate	Genetic Variation	[29]
Obsolete cerebellar ataxia, neuropathy, and vestibular areflexia syndrome	DIS0ZI75	Moderate	Autosomal recessive	[30]
Parkinson disease	DISQVHKL	moderate	Genetic Variation	[31]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[31]
Bone osteosarcoma	DIST1004	Disputed	Biomarker	[32]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[33]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[34]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[35]

12 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 Replication factor C subunit 1 (RFC1).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Replication factor C subunit 1 (RFC1).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Replication factor C subunit 1 (RFC1).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Replication factor C subunit 1 (RFC1).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Replication factor C subunit 1 (RFC1).	[40]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Replication factor C subunit 1 (RFC1).	[43]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Replication factor C subunit 1 (RFC1).	[44]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Replication factor C subunit 1 (RFC1).	[40]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Replication factor C subunit 1 (RFC1).	[40]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Replication factor C subunit 1 (RFC1).	[40]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Replication factor C subunit 1 (RFC1).	[40]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Replication factor C subunit 1 (RFC1).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Replication factor C subunit 1 (RFC1).	[41]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Replication factor C subunit 1 (RFC1).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Replication factor C subunit 1 (RFC1).	[45]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Replication factor C subunit 1 (RFC1).	[46]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Replication factor C subunit 1 (RFC1).	[42]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Replication factor C subunit 1 (RFC1).	[42]

References

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