Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNGJDS8)

• DOT Name: Shugoshin 2 (SGO2)
• Synonyms: Shugoshin-2; Shugoshin-like 2; Tripin
• Gene Name: SGO2
• Related Disease: Perrault syndrome
• UniProt ID: SGO2_HUMAN
• Sequence:
  MECPVMETGSLFTSGIKRHLKDKRISKTTKLNVSLASKIKTKILNNSSIFKISLKHNNRA
  LAQALSREKENSRRITTEKMLLQKEVEKLNFENTFLRLKLNNLNKKLIDIEALMNNNLIT
  AIEMSSLSEFHQSSFLLSASKKKRISKQCKLMRLPFARVPLTSNDDEDEDKEKMQCDNNI
  KSKTLPDIPSSGSTTQPLSTQDNSEVLFLKENNQNVYGLDDSEHISSIVDVPPRESHSHS
  DQSSKTSLMSEMRNAQSIGRRWEKPSPSNVTERKKRGSSWESNNLSADTPCATVLDKQHI
  SSPELNCNNEINGHTNETNTEMQRNKQDLPGLSSESAREPNAECMNQIEDNDDFQLQKTV
  YDADMDLTASEVSKIVTVSTGIKKKSNKKTNEHGMKTFRKVKDSSSEKKRERSKRQFKNS
  SDVDIGEKIENRTERSDVLDGKRGAEDPGFIFNNEQLAQMNEQLAQVNELKKMTLQTGFE
  QGDRENVLCNKKEKRITNEQEETYSLSQSSGKFHQESKFDKGQNSLTCNKSKASRQTFVI
  HKLEKDNLLPNQKDKVTIYENLDVTNEFHTANLSTKDNGNLCDYGTHNILDLKKYVTDIQ
  PSEQNESNINKLRKKVNRKTEIISGMNHMYEDNDKDVVHGLKKGNFFFKTQEDKEPISEN
  IEVSKELQIPALSTRDNENQCDYRTQNVLGLQKQITNMYPVQQNESKVNKKLRQKVNRKT
  EIISEVNHLDNDKSIEYTVKSHSLFLTQKDKEIIPGNLEDPSEFETPALSTKDSGNLYDS
  EIQNVLGVKHGHDMQPACQNDSKIGKKPRLNVCQKSEIIPETNQIYENDNKGVHDLEKDN
  FFSLTPKDKETISENLQVTNEFQTVDLLIKDNGNLCDYDTQNILELKKYVTDRKSAEQNE
  SKINKLRNKVNWKTEIISEMNQIYEDNDKDAHVQESYTKDLDFKVNKSKQKLECQDIINK
  HYMEVNSNEKESCDQILDSYKVVKKRKKESSCKAKNILTKAKNKLASQLTESSQTSISLE
  SDLKHITSEADSDPGNPVELCKTQKQSTTTLNKKDLPFVEEIKEGECQVKKVNKMTSKSK
  KRKTSIDPSPESHEVMERILDSVQGKSTVSEQADKENNLENEKMVKNKPDFYTKAFRSLS
  EIHSPNIQDSSFDSVREGLVPLSVSSGKNVIIKENFALECSPAFQVSDDEHEKMNKMKFK
  VNRRTQKSGIGDRPLQDLSNTSFVSNNTAESENKSEDLSSERTSRRRRCTPFYFKEPSLR
  DKMRR
• Function: Cooperates with PPP2CA to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I. Has a crucial role in protecting REC8 at centromeres from cleavage by separase. During meiosis, protects centromeric cohesion complexes until metaphase II/anaphase II transition, preventing premature release of meiosis-specific REC8 cohesin complexes from anaphase I centromeres. Is thus essential for an accurate gametogenesis. May act by targeting PPP2CA to centromeres, thus leading to cohesin dephosphorylation. Essential for recruiting KIF2C to the inner centromere and for correcting defective kinetochore attachments. Involved in centromeric enrichment of AUKRB in prometaphase.
• Reactome Pathway:
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Mitotic Prometaphase (R-HSA-68877)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Perrault syndrome	DISG2YOV	moderate	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Shugoshin 2 (SGO2).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Shugoshin 2 (SGO2).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Shugoshin 2 (SGO2).	[25]

30 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 Shugoshin 2 (SGO2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Shugoshin 2 (SGO2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Shugoshin 2 (SGO2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Shugoshin 2 (SGO2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Shugoshin 2 (SGO2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Shugoshin 2 (SGO2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Shugoshin 2 (SGO2).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Shugoshin 2 (SGO2).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Shugoshin 2 (SGO2).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Shugoshin 2 (SGO2).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Shugoshin 2 (SGO2).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Shugoshin 2 (SGO2).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Shugoshin 2 (SGO2).	[15]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Shugoshin 2 (SGO2).	[16]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Shugoshin 2 (SGO2).	[17]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Shugoshin 2 (SGO2).	[18]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Shugoshin 2 (SGO2).	[19]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Shugoshin 2 (SGO2).	[20]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Shugoshin 2 (SGO2).	[21]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Shugoshin 2 (SGO2).	[22]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Shugoshin 2 (SGO2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Shugoshin 2 (SGO2).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Shugoshin 2 (SGO2).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Shugoshin 2 (SGO2).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Shugoshin 2 (SGO2).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Shugoshin 2 (SGO2).	[27]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Shugoshin 2 (SGO2).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Shugoshin 2 (SGO2).	[28]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Shugoshin 2 (SGO2).	[29]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Shugoshin 2 (SGO2).	[30]

References

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