Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEJE6AG)

• DOT Name: Structural maintenance of chromosomes protein 4 (SMC4)
• Synonyms: SMC protein 4; SMC-4; Chromosome-associated polypeptide C; hCAP-C; XCAP-C homolog
• Gene Name: SMC4
• Related Disease:
  T-cell acute lymphoblastic leukaemia
  Acute myelogenous leukaemia
  Acute undifferentiated leukemia
  Colorectal carcinoma
  Glioma
  Hepatocellular carcinoma
  Herpes simplex infection
  leukaemia
  Leukemia
  Liver cancer
  Neoplasm
  Breast cancer
  Breast carcinoma
  Prostate cancer
  Prostate carcinoma
  Lymphoma
  Lymphoma, non-Hodgkin, familial
  Non-hodgkin lymphoma
  Pleural empyema
  Advanced cancer
• UniProt ID: SMC4_HUMAN
• PDB ID: 4U4P
• Pfam ID: PF06470 ; PF02463
• Sequence:
  MPRKGTQPSTARRREEGPPPPSPDGASSDAEPEPPSGRTESPATAAETASEELDNRSLEE
  ILNSIPPPPPPAMTNEAGAPRLMITHIVNQNFKSYAGEKILGPFHKRFSCIIGPNGSGKS
  NVIDSMLFVFGYRAQKIRSKKLSVLIHNSDEHKDIQSCTVEVHFQKIIDKEGDDYEVIPN
  SNFYVSRTACRDNTSVYHISGKKKTFKDVGNLLRSHGIDLDHNRFLILQGEVEQIAMMKP
  KGQTEHDEGMLEYLEDIIGCGRLNEPIKVLCRRVEILNEHRGEKLNRVKMVEKEKDALEG
  EKNIAIEFLTLENEIFRKKNHVCQYYIYELQKRIAEMETQKEKIHEDTKEINEKSNILSN
  EMKAKNKDVKDTEKKLNKITKFIEENKEKFTQLDLEDVQVREKLKHATSKAKKLEKQLQK
  DKEKVEEFKSIPAKSNNIINETTTRNNALEKEKEKEEKKLKEVMDSLKQETQGLQKEKES
  REKELMGFSKSVNEARSKMDVAQSELDIYLSRHNTAVSQLTKAKEALIAASETLKERKAA
  IRDIEGKLPQTEQELKEKEKELQKLTQEETNFKSLVHDLFQKVEEAKSSLAMNRSRGKVL
  DAIIQEKKSGRIPGIYGRLGDLGAIDEKYDVAISSCCHALDYIVVDSIDIAQECVNFLKR
  QNIGVATFIGLDKMAVWAKKMTEIQTPENTPRLFDLVKVKDEKIRQAFYFALRDTLVADN
  LDQATRVAYQKDRRWRVVTLQGQIIEQSGTMTGGGSKVMKGRMGSSLVIEISEEEVNKME
  SQLQNDSKKAMQIQEQKVQLEERVVKLRHSEREMRNTLEKFTASIQRLIEQEEYLNVQVK
  ELEANVLATAPDKKKQKLLEENVSAFKTEYDAVAEKAGKVEAEVKRLHNTIVEINNHKLK
  AQQDKLDKINKQLDECASAITKAQVAIKTADRNLQKAQDSVLRTEKEIKDTEKEVDDLTA
  ELKSLEDKAAEVVKNTNAAEESLPEIQKEHRNLLQELKVIQENEHALQKDALSIKLKLEQ
  IDGHIAEHNSKIKYWHKEISKISLHPIEDNPIEEISVLSPEDLEAIKNPDSITNQIALLE
  ARCHEMKPNLGAIAEYKKKEELYLQRVAELDKITYERDSFRQAYEDLRKQRLNEFMAGFY
  IITNKLKENYQMLTLGGDAELELVDSLDPFSEGIMFSVRPPKKSWKKIFNLSGGEKTLSS
  LALVFALHHYKPTPLYFMDEIDAALDFKNVSIVAFYIYEQTKNAQFIIISLRNNMFEISD
  RLIGIYKTYNITKSVAVNPKEIASKGLC
• Function: Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases.
• Tissue Specificity: Widely expressed. Higher expression in testis, colon, thymus.
• Reactome Pathway:
  Condensation of Prometaphase Chromosomes (R-HSA-2514853)
  Condensation of Prophase Chromosomes (R-HSA-2299718)

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[2]
Acute undifferentiated leukemia	DISJ4SSG	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[5]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[6]
leukaemia	DISS7D1V	Strong	Biomarker	[2]
Leukemia	DISNAKFL	Strong	Biomarker	[2]
Liver cancer	DISDE4BI	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	moderate	Biomarker	[9]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[9]
Prostate cancer	DISF190Y	moderate	Biomarker	[9]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[9]
Lymphoma	DISN6V4S	Disputed	Genetic Variation	[10]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Disputed	Biomarker	[10]
Non-hodgkin lymphoma	DISS2Y8A	Disputed	Biomarker	[10]
Pleural empyema	DIS9L97J	Disputed	Biomarker	[10]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[3]

2 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 Structural maintenance of chromosomes protein 4 (SMC4).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Structural maintenance of chromosomes protein 4 (SMC4).	[34]

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 Structural maintenance of chromosomes protein 4 (SMC4).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[15]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[16]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[17]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[18]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[19]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[20]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[21]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[21]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[22]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[23]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[20]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[24]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[25]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[26]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[27]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[28]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[29]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[30]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[13]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[17]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[31]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[32]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[35]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[36]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[37]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Structural maintenance of chromosomes protein 4 (SMC4).	[38]

References

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