Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW8E3SC)

• DOT Name: Fanconi anemia group I protein (FANCI)
• Synonyms: Protein FACI
• Gene Name: FANCI
• Related Disease:
  Fanconi anemia complementation group I
  Hepatocellular carcinoma
  Acute monocytic leukemia
  Acute myelogenous leukaemia
  Breast cancer
  Chromosomal disorder
  Fanconi anemia complementation group C
  Myelodysplastic syndrome
  Pancytopenia
  Triple negative breast cancer
  Fanconi's anemia
  Breast carcinoma
  Fanconi anemia complementation group A
  Fanconi anemia complementation group D2
  Hereditary breast carcinoma
• UniProt ID: FANCI_HUMAN
• PDB ID: 6VAA; 6VAD; 6VAE; 6VAF; 7AY1; 7ZF1; 8A9J; 8A9K
• Pfam ID: PF14679 ; PF14680 ; PF14675 ; PF14674 ; PF14676 ; PF14677 ; PF14678
• Sequence:
  MDQKILSLAAEKTADKLQEFLQTLREGDLTNLLQNQAVKGKVAGALLRAIFKGSPCSEEA
  GTLRRRKIYTCCIQLVESGDLQKEIASEIIGLLMLEAHHFPGPLLVELANEFISAVREGS
  LVNGKSLELLPIILTALATKKENLAYGKGVLSGEECKKQLINTLCSGRWDQQYVIQLTSM
  FKDVPLTAEEVEFVVEKALSMFSKMNLQEIPPLVYQLLVLSSKGSRKSVLEGIIAFFSAL
  DKQHNEEQSGDELLDVVTVPSGELRHVEGTIILHIVFAIKLDYELGRELVKHLKVGQQGD
  SNNNLSPFSIALLLSVTRIQRFQDQVLDLLKTSVVKSFKDLQLLQGSKFLQNLVPHRSYV
  STMILEVVKNSVHSWDHVTQGLVELGFILMDSYGPKKVLDGKTIETSPSLSRMPNQHACK
  LGANILLETFKIHEMIRQEILEQVLNRVVTRASSPISHFLDLLSNIVMYAPLVLQSCSSK
  VTEAFDYLSFLPLQTVQRLLKAVQPLLKVSMSMRDCLILVLRKAMFANQLDARKSAVAGF
  LLLLKNFKVLGSLSSSQCSQSLSVSQVHVDVHSHYNSVANETFCLEIMDSLRRCLSQQAD
  VRLMLYEGFYDVLRRNSQLANSVMQTLLSQLKQFYEPKPDLLPPLKLEACILTQGDKISL
  QEPLDYLLCCIQHCLAWYKNTVIPLQQGEEEEEEEEAFYEDLDDILESITNRMIKSELED
  FELDKSADFSQSTSIGIKNNICAFLVMGVCEVLIEYNFSISSFSKNRFEDILSLFMCYKK
  LSDILNEKAGKAKTKMANKTSDSLLSMKFVSSLLTALFRDSIQSHQESLSVLRSSNEFMR
  YAVNVALQKVQQLKETGHVSGPDGQNPEKIFQNLCDITRVLLWRYTSIPTSVEESGKKEK
  GKSISLLCLEGLQKIFSAVQQFYQPKIQQFLRALDVTDKEGEEREDADVSVTQRTAFQIR
  QFQRSLLNLLSSQEEDFNSKEALLLVTVLTSLSKLLEPSSPQFVQMLSWTSKICKENSRE
  DALFCKSLMNLLFSLHVSYKSPVILLRDLSQDIHGHLGDIDQDVEVEKTNHFAIVNLRTA
  APTVCLLVLSQAEKVLEEVDWLITKLKGQVSQETLSEEASSQATLPNQPVEKAIIMQLGT
  LLTFFHELVQTALPSGSCVDTLLKDLCKMYTTLTALVRYYLQVCQSSGGIPKNMEKLVKL
  SGSHLTPLCYSFISYVQNKSKSLNYTGEKKEKPAAVATAMARVLRETKPIPNLIFAIEQY
  EKFLIHLSKKSKVNLMQHMKLSTSRDFKIKGNILDMVLREDGEDENEEGTASEHGGQNKE
  PAKKKRKK
• Function: Plays an essential role in the repair of DNA double-strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA repair sites. Required for maintenance of chromosomal stability. Specifically binds branched DNA: binds both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). Participates in S phase and G2 phase checkpoint activation upon DNA damage.
• KEGG Pathway: Fanconi anemia pathway (hsa03460)
• Reactome Pathway:
  TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648)
  Fanconi Anemia Pathway (R-HSA-6783310)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Fanconi anemia complementation group I	DISCD3U7	Definitive	Autosomal recessive	[1]
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[5]
Fanconi anemia complementation group C	DISKMU3D	Strong	Biomarker	[6]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[3]
Pancytopenia	DISVKEHV	Strong	Biomarker	[3]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[7]
Fanconi's anemia	DISGW6Q8	Supportive	Autosomal recessive	[8]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[4]
Fanconi anemia complementation group A	DIS8PZLI	Limited	Biomarker	[9]
Fanconi anemia complementation group D2	DISC76W3	Limited	Biomarker	[10]
Hereditary breast carcinoma	DISAEZT5	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Fanconi anemia group I protein (FANCI) affects the response to substance of Fluorouracil.	[41]
Topotecan	DMP6G8T	Approved	Fanconi anemia group I protein (FANCI) affects the response to substance of Topotecan.	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Fanconi anemia group I protein (FANCI).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fanconi anemia group I protein (FANCI).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fanconi anemia group I protein (FANCI).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Fanconi anemia group I protein (FANCI).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Fanconi anemia group I protein (FANCI).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Fanconi anemia group I protein (FANCI).	[17]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Fanconi anemia group I protein (FANCI).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Fanconi anemia group I protein (FANCI).	[19]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Fanconi anemia group I protein (FANCI).	[20]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Fanconi anemia group I protein (FANCI).	[21]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Fanconi anemia group I protein (FANCI).	[22]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Fanconi anemia group I protein (FANCI).	[23]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Fanconi anemia group I protein (FANCI).	[22]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fanconi anemia group I protein (FANCI).	[12]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Fanconi anemia group I protein (FANCI).	[24]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Fanconi anemia group I protein (FANCI).	[25]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Fanconi anemia group I protein (FANCI).	[26]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Fanconi anemia group I protein (FANCI).	[27]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Fanconi anemia group I protein (FANCI).	[28]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Fanconi anemia group I protein (FANCI).	[29]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Fanconi anemia group I protein (FANCI).	[30]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Fanconi anemia group I protein (FANCI).	[31]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Fanconi anemia group I protein (FANCI).	[32]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Fanconi anemia group I protein (FANCI).	[31]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Fanconi anemia group I protein (FANCI).	[18]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Fanconi anemia group I protein (FANCI).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Fanconi anemia group I protein (FANCI).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fanconi anemia group I protein (FANCI).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Fanconi anemia group I protein (FANCI).	[36]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Fanconi anemia group I protein (FANCI).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fanconi anemia group I protein (FANCI).	[39]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Fanconi anemia group I protein (FANCI).	[40]

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 affects the phosphorylation of Fanconi anemia group I protein (FANCI).	[37]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Fanconi anemia group I protein (FANCI).	[37]

References

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