Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQVMF74)

• DOT Name: Structural maintenance of chromosomes protein 1B (SMC1B)
• Synonyms: SMC protein 1B; SMC-1-beta; SMC-1B
• Gene Name: SMC1B
• Related Disease:
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: SMC1B_HUMAN
• Pfam ID: PF06470 ; PF02463
• Sequence:
  MAHLELLLVENFKSWRGRQVIGPFRRFTCIIGPNGSGKSNVMDALSFVMGEKIANLRVKN
  IQELIHGAHIGKPISSSASVKIIYVEESGEEKTFARIIRGGCSEFRFNDNLVSRSVYIAE
  LEKIGIIVKAQNCLVFQGTVESISVKKPKERTQFFEEISTSGELIGEYEEKKRKLQKAEE
  DAQFNFNKKKNIAAERRQAKLEKEEAERYQSLLEELKMNKIQLQLFQLYHNEKKIHLLNT
  KLEHVNRDLSVKRESLSHHENIVKARKKEHGMLTRQLQQTEKELKSVETLLNQKRPQYIK
  AKENTSHHLKKLDVAKKSIKDSEKQCSKQEDDIKALETELADLDAAWRSFEKQIEEEILH
  KKRDIELEASQLDRYKELKEQVRKKVATMTQQLEKLQWEQKTDEERLAFEKRRHGEVQGN
  LKQIKEQIEDHKKRIEKLEEYTKTCMDCLKEKKQQEETLVDEIEKTKSRMSEVNEELNLI
  RSELQNAGIDTHEGKRQQKRAEVLEHLKRLYPDSVFGRLFDLCHPIHKKYQLAVTKVFGR
  FITAIVVASEKVAKDCIRFLKEERAEPETFLALDYLDIKPINERLRELKGCKMVIDVIKT
  QFPQLKKVIQFVCGNGLVCETMEEARHIALSGPERQKTVALDGTLFLKSGVISGGSSDLK
  YKARCWDEKELKNLRDRRSQKIQELKGLMKTLRKETDLKQIQTLIQGTQTRLKYSQNELE
  MIKKKHLVAFYQEQSQLQSELLNIESQCIMLSEGIKERQRRIKEFQEKIDKVEDDIFQHF
  CEEIGVENIREFENKHVKRQQEIDQKRLEFEKQKTRLNVQLEYSRSHLKKKLNKINTLKE
  TIQKGSEDIDHLKKAEENCLQTVNELMAKQQQLKDIRVTQNSSAEKVQTQIEEERKKFLA
  VDREVGKLQKEVVSIQTSLEQKRLEKHNLLLDCKVQDIEIILLSGSLDDIIEVEMGTEAE
  STQATIDIYEKEEAFEIDYSSLKEDLKALQSDQEIEAHLRLLLQQVASQEDILLKTAAPN
  LRALENLKTVRDKFQESTDAFEASRKEARLCRQEFEQVKKRRYDLFTQCFEHVSISIDQI
  YKKLCRNNSAQAFLSPENPEEPYLEGISYNCVAPGKRFMPMDNLSGGEKCVAALALLFAV
  HSFRPAPFFVLDEVDAALDNTNIGKVSSYIKEQTQDQFQMIVISLKEEFYSRADALIGIY
  PEYDDCMFSRVLTLDLSQYPDTEGQESSKRHGESR
• Function: Meiosis-specific component of cohesin complex. Required for the maintenance of meiotic cohesion, but not, or only to a minor extent, for its establishment. Contributes to axial element (AE) formation and the organization of chromatin loops along the AE. Plays a key role in synapsis, recombination and chromosome movements. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The meiosis-specific cohesin complex probably replaces mitosis specific cohesin complex when it dissociates from chromatin during prophase I.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Oocyte meiosis (hsa04114)
• Reactome Pathway: Meiotic synapsis (R-HSA-1221632)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[1]

2 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 Structural maintenance of chromosomes protein 1B (SMC1B).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Structural maintenance of chromosomes protein 1B (SMC1B).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Structural maintenance of chromosomes protein 1B (SMC1B).	[3]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Structural maintenance of chromosomes protein 1B (SMC1B).	[4]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Structural maintenance of chromosomes protein 1B (SMC1B).	[6]

References

• [1] Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy.Nat Genet. 2013 Dec;45(12):1464-9. doi: 10.1038/ng.2799. Epub 2013 Oct 13.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [5] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [6] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.