Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9ZMRK9)

• DOT Name: Structural maintenance of chromosomes protein 1A (SMC1A)
• Synonyms: SMC protein 1A; SMC-1-alpha; SMC-1A; Sb1.8
• Gene Name: SMC1A
• Related Disease:
  Acute myelogenous leukaemia
  Cornelia de Lange syndrome 2
  Holoprosencephaly
  X-linked complex neurodevelopmental disorder
  Absence epilepsy
  Adenoma
  Adult glioblastoma
  Ataxia-telangiectasia
  B-cell lymphoma
  Chronic myelomonocytic leukaemia
  Chronic myelomonocytic leukemia
  Cleft lip
  Cleft palate
  Colorectal carcinoma
  Colorectal neoplasm
  Craniosynostosis
  Developmental and epileptic encephalopathy, 85, with or without midline brain defects
  Dowling-Degos disease
  Epilepsy
  Glioblastoma multiforme
  Glioma
  Hypertrophic cardiomyopathy
  Intellectual disability
  Isolated cleft lip
  Isolated cleft palate
  Metastatic prostate carcinoma
  Movement disorder
  Myeloid leukaemia
  Neoplasm
  Neurodevelopmental disorder
  Nijmegen breakage syndrome
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Retinitis pigmentosa
  Systemic lupus erythematosus
  Trichohepatoenteric syndrome
  Turner syndrome
  Metastatic malignant neoplasm
  Triple negative breast cancer
  Wiedemann-Steiner syndrome
  Atypical Rett syndrome
  Cornelia de Lange syndrome
  Advanced cancer
  Cervical cancer
  Cervical carcinoma
  Hepatocellular carcinoma
  Promyelocytic leukaemia
  Rett syndrome
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: SMC1A_HUMAN
• PDB ID: 6WG3; 6WG4; 6WG6; 6WGE; 7W1M
• Pfam ID: PF06470 ; PF02463
• Sequence:
  MGFLKLIEIENFKSYKGRQIIGPFQRFTAIIGPNGSGKSNLMDAISFVLGEKTSNLRVKT
  LRDLIHGAPVGKPAANRAFVSMVYSEEGAEDRTFARVIVGGSSEYKINNKVVQLHEYSEE
  LEKLGILIKARNFLVFQGAVESIAMKNPKERTALFEEISRSGELAQEYDKRKKEMVKAEE
  DTQFNYHRKKNIAAERKEAKQEKEEADRYQRLKDEVVRAQVQLQLFKLYHNEVEIEKLNK
  ELASKNKEIEKDKKRMDKVEDELKEKKKELGKMMREQQQIEKEIKEKDSELNQKRPQYIK
  AKENTSHKIKKLEAAKKSLQNAQKHYKKRKGDMDELEKEMLSVEKARQEFEERMEEESQS
  QGRDLTLEENQVKKYHRLKEEASKRAATLAQELEKFNRDQKADQDRLDLEERKKVETEAK
  IKQKLREIEENQKRIEKLEEYITTSKQSLEEQKKLEGELTEEVEMAKRRIDEINKELNQV
  MEQLGDARIDRQESSRQQRKAEIMESIKRLYPGSVYGRLIDLCQPTQKKYQIAVTKVLGK
  NMDAIIVDSEKTGRDCIQYIKEQRGEPETFLPLDYLEVKPTDEKLRELKGAKLVIDVIRY
  EPPHIKKALQYACGNALVCDNVEDARRIAFGGHQRHKTVALDGTLFQKSGVISGGASDLK
  AKARRWDEKAVDKLKEKKERLTEELKEQMKAKRKEAELRQVQSQAHGLQMRLKYSQSDLE
  QTKTRHLALNLQEKSKLESELANFGPRINDIKRIIQSREREMKDLKEKMNQVEDEVFEEF
  CREIGVRNIREFEEEKVKRQNEIAKKRLEFENQKTRLGIQLDFEKNQLKEDQDKVHMWEQ
  TVKKDENEIEKLKKEEQRHMKIIDETMAQLQDLKNQHLAKKSEVNDKNHEMEEIRKKLGG
  ANKEMTHLQKEVTAIETKLEQKRSDRHNLLQACKMQDIKLPLSKGTMDDISQEEGSSQGE
  DSVSGSQRISSIYAREALIEIDYGDLCEDLKDAQAEEEIKQEMNTLQQKLNEQQSVLQRI
  AAPNMKAMEKLESVRDKFQETSDEFEAARKRAKKAKQAFEQIKKERFDRFNACFESVATN
  IDEIYKALSRNSSAQAFLGPENPEEPYLDGINYNCVAPGKRFRPMDNLSGGEKTVAALAL
  LFAIHSYKPAPFFVLDEIDAALDNTNIGKVANYIKEQSTCNFQAIVISLKEEFYTKAESL
  IGVYPEQGDCVISKVLTFDLTKYPDANPNPNEQ
• Function: Involved in chromosome cohesion during cell cycle and in DNA repair. Central component of cohesin complex. 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 cohesin complex may also play a role in spindle pole assembly during mitosis. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, or via its phosphorylation by ATR. Works as a downstream effector both in the ATM/NBS1 branch and in the ATR/MSH2 branch of S-phase checkpoint.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Oocyte meiosis (hsa04114)
• Reactome Pathway:
  Separation of Sister Chromatids (R-HSA-2467813)
  Establishment of Sister Chromatid Cohesion (R-HSA-2468052)
  Cohesin Loading onto Chromatin (R-HSA-2470946)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  SUMOylation of DNA damage response and repair proteins (R-HSA-3108214)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Meiotic synapsis (R-HSA-1221632)

Molecular Interaction Atlas (MIA) of This DOT

51 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Cornelia de Lange syndrome 2	DISUCHUA	Definitive	X-linked	[2]
Holoprosencephaly	DISR35EC	Definitive	Altered Expression	[3]
X-linked complex neurodevelopmental disorder	DISI3QE9	Definitive	X-linked	[4]
Absence epilepsy	DISJPOUD	Strong	Genetic Variation	[5]
Adenoma	DIS78ZEV	Strong	Altered Expression	[6]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[7]
Ataxia-telangiectasia	DISP3EVR	Strong	Posttranslational Modification	[8]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[9]
Chronic myelomonocytic leukaemia	DISDN5P7	Strong	Genetic Variation	[10]
Chronic myelomonocytic leukemia	DISIL8UR	Strong	Genetic Variation	[10]
Cleft lip	DISV3XW6	Strong	Genetic Variation	[11]
Cleft palate	DIS6G5TF	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[12]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[13]
Craniosynostosis	DIS6J405	Strong	Genetic Variation	[14]
Developmental and epileptic encephalopathy, 85, with or without midline brain defects	DISHPMHB	Strong	X-linked	[15]
Dowling-Degos disease	DISGTTEP	Strong	Genetic Variation	[15]
Epilepsy	DISBB28L	Strong	Genetic Variation	[16]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[7]
Glioma	DIS5RPEH	Strong	Biomarker	[17]
Hypertrophic cardiomyopathy	DISQG2AI	Strong	Biomarker	[11]
Intellectual disability	DISMBNXP	Strong	Biomarker	[11]
Isolated cleft lip	DIS2O2JV	Strong	Genetic Variation	[11]
Isolated cleft palate	DISV80CD	Strong	Biomarker	[11]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[18]
Movement disorder	DISOJJ2D	Strong	Genetic Variation	[11]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[21]
Nijmegen breakage syndrome	DIS98HVL	Strong	Biomarker	[22]
Prostate cancer	DISF190Y	Strong	Biomarker	[18]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[18]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[18]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[23]
Systemic lupus erythematosus	DISI1SZ7	Strong	Posttranslational Modification	[24]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[25]
Turner syndrome	DIS2035C	Strong	Genetic Variation	[26]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[27]
Triple negative breast cancer	DISAMG6N	moderate	Altered Expression	[28]
Wiedemann-Steiner syndrome	DIS67KX5	moderate	GermlineCausalMutation	[29]
Atypical Rett syndrome	DISWF699	Supportive	Autosomal dominant	[30]
Cornelia de Lange syndrome	DISEQSXO	Supportive	Autosomal dominant	[31]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[18]
Cervical cancer	DISFSHPF	Limited	Altered Expression	[32]
Cervical carcinoma	DIST4S00	Limited	Altered Expression	[32]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[33]
Promyelocytic leukaemia	DISYGG13	Limited	Biomarker	[34]
Rett syndrome	DISGG5UV	Limited	Genetic Variation	[35]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[36]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[41]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[42]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[44]
Marinol	DM70IK5	Approved	Marinol increases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[45]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[46]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[47]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[48]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[49]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[50]
Arecoline	DMFJZK3	Phase 1	Arecoline decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[52]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[54]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[55]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[57]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[58]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[59]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[60]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[61]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Structural maintenance of chromosomes protein 1A (SMC1A).	[62]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the phosphorylation of Structural maintenance of chromosomes protein 1A (SMC1A).	[43]
Bleomycin	DMNER5S	Approved	Bleomycin increases the phosphorylation of Structural maintenance of chromosomes protein 1A (SMC1A).	[43]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the phosphorylation of Structural maintenance of chromosomes protein 1A (SMC1A).	[43]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Structural maintenance of chromosomes protein 1A (SMC1A).	[51]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Structural maintenance of chromosomes protein 1A (SMC1A).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Structural maintenance of chromosomes protein 1A (SMC1A).	[56]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Structural maintenance of chromosomes protein 1A (SMC1A).	[53]

References

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