Details of Drug Off-Target (DOT)

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

• DOT Name: Structural maintenance of chromosomes protein 3 (SMC3)
• Synonyms: SMC protein 3; SMC-3; Basement membrane-associated chondroitin proteoglycan; Bamacan; Chondroitin sulfate proteoglycan 6; Chromosome-associated polypeptide; hCAP
• Gene Name: SMC3
• Related Disease:
  Cornelia de Lange syndrome
  Cornelia de Lange syndrome 3
  Lung cancer
  Lung carcinoma
  Neurodevelopmental disorder
  Roberts-SC phocomelia syndrome
  Acute myelogenous leukaemia
  Adenocarcinoma
  Adult lymphoma
  Advanced cancer
  Allergic asthma
  Bone cancer
  Bone osteosarcoma
  Burkitt lymphoma
  Carcinoma
  Castration-resistant prostate carcinoma
  Colon carcinoma
  Colorectal neoplasm
  Early-onset anterior polar cataract
  Fetal growth restriction
  Intestinal neoplasm
  Isolated congenital microcephaly
  Lymphoma
  Myeloid leukaemia
  Pediatric lymphoma
  Pneumonia
  Pneumonitis
  Prostate cancer
  Prostate carcinoma
  Retinitis pigmentosa
  Trichohepatoenteric syndrome
  Turner syndrome
  Gingivitis
  Intellectual disability
  Neoplasm
  Wiedemann-Steiner syndrome
  Hepatocellular carcinoma
  Prune belly syndrome
• UniProt ID: SMC3_HUMAN
• PDB ID: 6WG3; 6WG4; 6WG6; 6WGE; 7W1M
• Pfam ID: PF06470 ; PF02463
• Sequence:
  MYIKQVIIQGFRSYRDQTIVDPFSSKHNVIVGRNGSGKSNFFYAIQFVLSDEFSHLRPEQ
  RLALLHEGTGPRVISAFVEIIFDNSDNRLPIDKEEVSLRRVIGAKKDQYFLDKKMVTKND
  VMNLLESAGFSRSNPYYIVKQGKINQMATAPDSQRLKLLREVAGTRVYDERKEESISLMK
  ETEGKREKINELLKYIEERLHTLEEEKEELAQYQKWDKMRRALEYTIYNQELNETRAKLD
  ELSAKRETSGEKSRQLRDAQQDARDKMEDIERQVRELKTKISAMKEEKEQLSAERQEQIK
  QRTKLELKAKDLQDELAGNSEQRKRLLKERQKLLEKIEEKQKELAETEPKFNSVKEKEER
  GIARLAQATQERTDLYAKQGRGSQFTSKEERDKWIKKELKSLDQAINDKKRQIAAIHKDL
  EDTEANKEKNLEQYNKLDQDLNEVKARVEELDRKYYEVKNKKDELQSERNYLWREENAEQ
  QALAAKREDLEKKQQLLRAATGKAILNGIDSINKVLDHFRRKGINQHVQNGYHGIVMNNF
  ECEPAFYTCVEVTAGNRLFYHIVDSDEVSTKILMEFNKMNLPGEVTFLPLNKLDVRDTAY
  PETNDAIPMISKLRYNPRFDKAFKHVFGKTLICRSMEVSTQLARAFTMDCITLEGDQVSH
  RGALTGGYYDTRKSRLELQKDVRKAEEELGELEAKLNENLRRNIERINNEIDQLMNQMQQ
  IETQQRKFKASRDSILSEMKMLKEKRQQSEKTFMPKQRSLQSLEASLHAMESTRESLKAE
  LGTDLLSQLSLEDQKRVDALNDEIRQLQQENRQLLNERIKLEGIITRVETYLNENLRKRL
  DQVEQELNELRETEGGTVLTATTSELEAINKRVKDTMARSEDLDNSIDKTEAGIKELQKS
  MERWKNMEKEHMDAINHDTKELEKMTNRQGMLLKKKEECMKKIRELGSLPQEAFEKYQTL
  SLKQLFRKLEQCNTELKKYSHVNKKALDQFVNFSEQKEKLIKRQEELDRGYKSIMELMNV
  LELRKYEAIQLTFKQVSKNFSEVFQKLVPGGKATLVMKKGDVEGSQSQDEGEGSGESERG
  SGSQSSVPSVDQFTGVGIRVSFTGKQGEMREMQQLSGGQKSLVALALIFAIQKCDPAPFY
  LFDEIDQALDAQHRKAVSDMIMELAVHAQFITTTFRPELLESADKFYGVKFRNKVSHIDV
  ITAEMAKDFVEDDTTHG
• Function: Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form 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. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex also plays an important role in spindle pole assembly during mitosis and in chromosomes movement.
• 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

38 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cornelia de Lange syndrome	DISEQSXO	Definitive	Autosomal dominant	[1]
Cornelia de Lange syndrome 3	DIS69WC6	Definitive	Autosomal dominant	[2]
Lung cancer	DISCM4YA	Definitive	Biomarker	[3]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[3]
Neurodevelopmental disorder	DIS372XH	Definitive	Biomarker	[4]
Roberts-SC phocomelia syndrome	DIS4JXZ4	Definitive	Biomarker	[5]
Acute myelogenous leukaemia	DISCSPTN	Strong	Genetic Variation	[6]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[7]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[8]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[6]
Allergic asthma	DISHF0H3	Strong	Biomarker	[9]
Bone cancer	DIS38NA0	Strong	Biomarker	[10]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[10]
Burkitt lymphoma	DIS9D5XU	Strong	Altered Expression	[11]
Carcinoma	DISH9F1N	Strong	Altered Expression	[7]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[12]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[13]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[14]
Early-onset anterior polar cataract	DISTOPIY	Strong	Biomarker	[15]
Fetal growth restriction	DIS5WEJ5	Strong	Biomarker	[16]
Intestinal neoplasm	DISK0GUH	Strong	Biomarker	[17]
Isolated congenital microcephaly	DISUXHZ6	Strong	Biomarker	[16]
Lymphoma	DISN6V4S	Strong	Biomarker	[8]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[18]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[8]
Pneumonia	DIS8EF3M	Strong	Genetic Variation	[15]
Pneumonitis	DIS88E0K	Strong	Biomarker	[15]
Prostate cancer	DISF190Y	Strong	Biomarker	[12]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[12]
Retinitis pigmentosa	DISCGPY8	Strong	Genetic Variation	[19]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[20]
Turner syndrome	DIS2035C	Strong	Genetic Variation	[21]
Gingivitis	DISC8RMX	moderate	Altered Expression	[22]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[2]
Neoplasm	DISZKGEW	moderate	Genetic Variation	[23]
Wiedemann-Steiner syndrome	DIS67KX5	moderate	Genetic Variation	[24]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[25]
Prune belly syndrome	DISBIBMN	Limited	Biomarker	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Afimoxifene	DMFORDT	Phase 2	Structural maintenance of chromosomes protein 3 (SMC3) affects the response to substance of Afimoxifene.	[46]

17 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 Structural maintenance of chromosomes protein 3 (SMC3).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[29]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[30]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[31]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[32]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[33]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[34]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[35]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[36]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[40]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[42]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[43]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[44]
Taurine	DMVW7N3	Investigative	Taurine increases the expression of Structural maintenance of chromosomes protein 3 (SMC3).	[45]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 affects the sumoylation of Structural maintenance of chromosomes protein 3 (SMC3).	[39]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Structural maintenance of chromosomes protein 3 (SMC3).	[41]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Structural maintenance of chromosomes protein 3 (SMC3).	[41]

References

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