Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJFVU43)

• DOT Name: Cyclin-F (CCNF)
• Synonyms: F-box only protein 1
• Gene Name: CCNF
• Related Disease:
  Hepatocellular carcinoma
  Breast cancer
  Breast carcinoma
  Frontotemporal dementia
  Frontotemporal dementia and/or amyotrophic lateral sclerosis 5
  Glioma
  Pick disease
  Polycystic kidney disease
  Polycystic kidney disease 1
  Advanced cancer
  Amyotrophic lateral sclerosis
  Cutaneous melanoma
  Melanoma
• UniProt ID: CCNF_HUMAN
• Pfam ID: PF02984 ; PF00134 ; PF12937
• Sequence:
  MGSGGVVHCRCAKCFCYPTKRRIRRRPRNLTILSLPEDVLFHILKWLSVEDILAVRAVHS
  QLKDLVDNHASVWACASFQELWPSPGNLKLFERAAEKGNFEAAVKLGIAYLYNEGLSVSD
  EARAEVNGLKASRFFSLAERLNVGAAPFIWLFIRPPWSVSGSCCKAVVHESLRAECQLQR
  THKASILHCLGRVLSLFEDEEKQQQAHDLFEEAAHQGCLTSSYLLWESDRRTDVSDPGRC
  LHSFRKLRDYAAKGCWEAQLSLAKACANANQLGLEVRASSEIVCQLFQASQAVSKQQVFS
  VQKGLNDTMRYILIDWLVEVATMKDFTSLCLHLTVECVDRYLRRRLVPRYRLQLLGIACM
  VICTRFISKEILTIREAVWLTDNTYKYEDLVRMMGEIVSALEGKIRVPTVVDYKEVLLTL
  VPVELRTQHLCSFLCELSLLHTSLSAYAPARLAAAALLLARLTHGQTQPWTTQLWDLTGF
  SYEDLIPCVLSLHKKCFHDDAPKDYRQVSLTAVKQRFEDKRYGEISQEEVLSYSQLCAAL
  GVTQDSPDPPTFLSTGEIHAFLSSPSGRRTKRKRENSLQEDRGSFVTTPTAELSSQEETL
  LGSFLDWSLDCCSGYEGDQESEGEKEGDVTAPSGILDVTVVYLNPEQHCCQESSDEEACP
  EDKGPQDPQALALDTQIPATPGPKPLVRTSREPGKDVTTSGYSSVSTASPTSSVDGGLGA
  LPQPTSVLSLDSDSHTQPCHHQARKSCLQCRPPSPPESSVPQQQVKRINLCIHSEEEDMN
  LGLVRL
• Function: Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. The SCF(CCNF) E3 ubiquitin-protein ligase complex is an integral component of the ubiquitin proteasome system (UPS) and links proteasome degradation to the cell cycle. Mediates the substrate recognition and the proteasomal degradation of various target proteins involved in the regulation of cell cycle progression and in the maintenance of genome stability. Mediates the ubiquitination and proteasomal degradation of CP110 during G2 phase, thereby acting as an inhibitor of centrosome reduplication. In G2, mediates the ubiquitination and subsequent degradation of ribonucleotide reductase RRM2, thereby maintaining a balanced pool of dNTPs and genome integrity. In G2, mediates the ubiquitination and proteasomal degradation of CDC6, thereby suppressing DNA re-replication and preventing genome instability. Involved in the ubiquitination and degradation of the substrate adapter CDH1 of the anaphase-promoting complex (APC/C), thereby acting as an antagonist of APC/C in regulating G1 progression and S phase entry. May play a role in the G2 cell cycle checkpoint control after DNA damage, possibly by promoting the ubiquitination of MYBL2/BMYB.
• Tissue Specificity: Widely expressed, with expression detected in the heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Frontotemporal dementia	DISKYHXL	Strong	Genetic Variation	[3]
Frontotemporal dementia and/or amyotrophic lateral sclerosis 5	DISM2TT8	Strong	Autosomal dominant	[4]
Glioma	DIS5RPEH	Strong	Altered Expression	[5]
Pick disease	DISP6X50	Strong	Genetic Variation	[6]
Polycystic kidney disease	DISWS3UY	Strong	Genetic Variation	[7]
Polycystic kidney disease 1	DIS9FB3R	Strong	Genetic Variation	[7]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[5]
Amyotrophic lateral sclerosis	DISF7HVM	Supportive	Autosomal dominant	[4]
Cutaneous melanoma	DIS3MMH9	Limited	Biomarker	[8]
Melanoma	DIS1RRCY	Limited	Altered Expression	[8]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Cyclin-F (CCNF) affects the response to substance of Fluorouracil.	[36]
Topotecan	DMP6G8T	Approved	Cyclin-F (CCNF) affects the response to substance of Topotecan.	[37]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cyclin-F (CCNF).	[9]

29 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 Cyclin-F (CCNF).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cyclin-F (CCNF).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cyclin-F (CCNF).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cyclin-F (CCNF).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cyclin-F (CCNF).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cyclin-F (CCNF).	[15]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cyclin-F (CCNF).	[16]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cyclin-F (CCNF).	[17]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cyclin-F (CCNF).	[18]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cyclin-F (CCNF).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cyclin-F (CCNF).	[19]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Cyclin-F (CCNF).	[20]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Cyclin-F (CCNF).	[21]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Cyclin-F (CCNF).	[22]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Cyclin-F (CCNF).	[23]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Cyclin-F (CCNF).	[24]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Cyclin-F (CCNF).	[19]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Cyclin-F (CCNF).	[25]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Cyclin-F (CCNF).	[11]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Cyclin-F (CCNF).	[26]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine decreases the expression of Cyclin-F (CCNF).	[27]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Cyclin-F (CCNF).	[28]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Cyclin-F (CCNF).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cyclin-F (CCNF).	[30]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cyclin-F (CCNF).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cyclin-F (CCNF).	[32]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cyclin-F (CCNF).	[33]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Cyclin-F (CCNF).	[34]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Cyclin-F (CCNF).	[35]

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