Details of Drug Off-Target (DOT)

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

• DOT Name: Separin (ESPL1)
• Synonyms: EC 3.4.22.49; Caspase-like protein ESPL1; Extra spindle poles-like 1 protein; Separase
• Gene Name: ESPL1
• Related Disease:
  Asthma
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Non-small-cell lung cancer
  Acute megakaryoblastic leukemia
  Acute myelogenous leukaemia
  Adult glioblastoma
  B-cell neoplasm
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Childhood acute megakaryoblastic leukemia
  Chromosomal disorder
  Gastric adenocarcinoma
  Glioblastoma multiforme
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Malignant soft tissue neoplasm
  Myelodysplastic syndrome
  Neoplasm
  Osteosarcoma
  Prostate neoplasm
  Sarcoma
  T-cell lymphoma
  Advanced cancer
  Carcinoma
  Pituitary tumor
  Sexually transmitted infection
  Transitional cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: ESPL1_HUMAN
• PDB ID: 7NJ0; 7NJ1
• EC Number: 3.4.22.49
• Pfam ID: PF03568
• Sequence:
  MRSFKRVNFGTLLSSQKEAEELLPALKEFLSNPPAGFPSSRSDAERRQACDAILRACNQQ
  LTAKLACPRHLGSLLELAELACDGYLVSTPQRPPLYLERILFVLLRNAAAQGSPEATLRL
  AQPLHACLVQCSREAAPQDYEAVARGSFSLLWKGAEALLERRAAFAARLKALSFLVLLED
  ESTPCEVPHFASPTACRAVAAHQLFDASGHGLNEADADFLDDLLSRHVIRALVGERGSSS
  GLLSPQRALCLLELTLEHCRRFCWSRHHDKAISAVEKAHSYLRNTNLAPSLQLCQLGVKL
  LQVGEEGPQAVAKLLIKASAVLSKSMEAPSPPLRALYESCQFFLSGLERGTKRRYRLDAI
  LSLFAFLGGYCSLLQQLRDDGVYGGSSKQQQSFLQMYFQGLHLYTVVVYDFAQGCQIVDL
  ADLTQLVDSCKSTVVWMLEALEGLSGQELTDHMGMTASYTSNLAYSFYSHKLYAEACAIS
  EPLCQHLGLVKPGTYPEVPPEKLHRCFRLQVESLKKLGKQAQGCKMVILWLAALQPCSPE
  HMAEPVTFWVRVKMDAARAGDKELQLKTLRDSLSGWDPETLALLLREELQAYKAVRADTG
  QERFNIICDLLELSPEETPAGAWARATHLVELAQVLCYHDFTQQTNCSALDAIREALQLL
  DSVRPEAQARDQLLDDKAQALLWLYICTLEAKMQEGIERDRRAQAPGNLEEFEVNDLNYE
  DKLQEDRFLYSNIAFNLAADAAQSKCLDQALALWKELLTKGQAPAVRCLQQTAASLQILA
  ALYQLVAKPMQALEVLLLLRIVSERLKDHSKAAGSSCHITQLLLTLGCPSYAQLHLEEAA
  SSLKHLDQTTDTYLLLSLTCDLLRSQLYWTHQKVTKGVSLLLSVLRDPALQKSSKAWYLL
  RVQVLQLVAAYLSLPSNNLSHSLWEQLCAQGWQTPEIALIDSHKLLRSIILLLMGSDILS
  TQKAAVETSFLDYGENLVQKWQVLSEVLSCSEKLVCHLGRLGSVSEAKAFCLEALKLTTK
  LQIPRQCALFLVLKGELELARNDIDLCQSDLQQVLFLLESCTEFGGVTQHLDSVKKVHLQ
  KGKQQAQVPCPPQLPEEELFLRGPALELVATVAKEPGPIAPSTNSSPVLKTKPQPIPNFL
  SHSPTCDCSLCASPVLTAVCLRWVLVTAGVRLAMGHQAQGLDLLQVVLKGCPEAAERLTQ
  ALQASLNHKTPPSLVPSLLDEILAQAYTLLALEGLNQPSNESLQKVLQSGLKFVAARIPH
  LEPWRASLLLIWALTKLGGLSCCTTQLFASSWGWQPPLIKSVPGSEPSKTQGQKRSGRGR
  QKLASAPLRLNNTSQKGLEGRGLPCTPKPPDRIRQAGPHVPFTVFEEVCPTESKPEVPQA
  PRVQQRVQTRLKVNFSDDSDLEDPVSAEAWLAEEPKRRGTASRGRGRARKGLSLKTDAVV
  APGSAPGNPGLNGRSRRAKKVASRHCEERRPQRASDQARPGPEIMRTIPEEELTDNWRKM
  SFEILRGSDGEDSASGGKTPAPGPEAASGEWELLRLDSSKKKLPSPCPDKESDKDLGPRL
  RLPSAPVATGLSTLDSICDSLSVAFRGISHCPPSGLYAHLCRFLALCLGHRDPYATAFLV
  TESVSITCRHQLLTHLHRQLSKAQKHRGSLEIADQLQGLSLQEMPGDVPLARIQRLFSFR
  ALESGHFPQPEKESFQERLALIPSGVTVCVLALATLQPGTVGNTLLLTRLEKDSPPVSVQ
  IPTGQNKLHLRSVLNEFDAIQKAQKENSSCTDKREWWTGRLALDHRMEVLIASLEKSVLG
  CWKGLLLPSSEEPGPAQEASRLQELLQDCGWKYPDRTLLKIMLSGAGALTPQDIQALAYG
  LCPTQPERAQELLNEAVGRLQGLTVPSNSHLVLVLDKDLQKLPWESMPSLQALPVTRLPS
  FRFLLSYSIIKEYGASPVLSQGVDPRSTFYVLNPHNNLSSTEEQFRANFSSEAGWRGVVG
  EVPRPEQVQEALTKHDLYIYAGHGAGARFLDGQAVLRLSCRAVALLFGCSSAALAVRGNL
  EGAGIVLKYIMAGCPLFLGNLWDVTDRDIDRYTEALLQGWLGAGPGAPLLYYVNQARQAP
  RLKYLIGAAPIAYGLPVSLR
• Function: Caspase-like protease, which plays a central role in the chromosome segregation by cleaving the SCC1/RAD21 subunit of the cohesin complex at the onset of anaphase. During most of the cell cycle, it is inactivated by different mechanisms.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Oocyte meiosis (hsa04114)
  Human T-cell leukemia virus 1 infection (hsa05166)
• Reactome Pathway: Separation of Sister Chromatids (R-HSA-2467813)
• BioCyc Pathway: MetaCyc:ENSG00000135476-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	Definitive	Biomarker	[2]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[2]
Lung neoplasm	DISVARNB	Definitive	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Altered Expression	[2]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[3]
B-cell neoplasm	DISVY326	Strong	Biomarker	[5]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Biomarker	[6]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[7]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[8]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[8]
Childhood acute megakaryoblastic leukemia	DIS5VZDR	Strong	Biomarker	[3]
Chromosomal disorder	DISM5BB5	Strong	Altered Expression	[4]
Gastric adenocarcinoma	DISWWLTC	Strong	Altered Expression	[9]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[3]
leukaemia	DISS7D1V	Strong	Altered Expression	[10]
Leukemia	DISNAKFL	Strong	Altered Expression	[10]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[11]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[5]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[12]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[7]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[7]
Sarcoma	DISZDG3U	Strong	Biomarker	[5]
T-cell lymphoma	DISSXRTQ	Strong	Altered Expression	[5]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[13]
Carcinoma	DISH9F1N	Limited	Biomarker	[8]
Pituitary tumor	DISN67JD	Limited	Altered Expression	[14]
Sexually transmitted infection	DISIVIAL	Limited	Genetic Variation	[15]
Transitional cell carcinoma	DISWVVDR	Limited	Biomarker	[16]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[16]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Separin (ESPL1) affects the response to substance of Fluorouracil.	[38]

3 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 Separin (ESPL1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Separin (ESPL1).	[29]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Separin (ESPL1).	[33]

19 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 Separin (ESPL1).	[18]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Separin (ESPL1).	[19]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Separin (ESPL1).	[20]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Separin (ESPL1).	[21]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Separin (ESPL1).	[22]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Separin (ESPL1).	[22]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Separin (ESPL1).	[23]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Separin (ESPL1).	[24]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Separin (ESPL1).	[25]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Separin (ESPL1).	[26]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Separin (ESPL1).	[27]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Separin (ESPL1).	[28]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Separin (ESPL1).	[30]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Separin (ESPL1).	[31]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Separin (ESPL1).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Separin (ESPL1).	[34]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Separin (ESPL1).	[35]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Separin (ESPL1).	[36]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Separin (ESPL1).	[37]

References

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