Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8JYKNH)

• DOT Name: Spermine synthase (SMS)
• Synonyms: SPMSY; EC 2.5.1.22; Spermidine aminopropyltransferase
• Gene Name: SMS
• Related Disease:
  Advanced cancer
  Androgen insensitivity syndrome
  Epilepsy
  Lung cancer
  Lung carcinoma
  Osteoporosis
  Syndromic X-linked intellectual disability Snyder type
  Anxiety
  Anxiety disorder
  Arteriosclerosis
  Atherosclerosis
  Atrial septal defect
  Attention deficit hyperactivity disorder
  Autism spectrum disorder
  Beckwith-Wiedemann syndrome
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Colorectal carcinoma
  Depression
  Mood disorder
  Neuroblastoma
  Post-traumatic stress disorder
  Primitive neuroectodermal tumor
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
  Silver-Russell syndrome
  Systemic lupus erythematosus
  Tuberculosis
  X-linked intellectual disability
  High blood pressure
  Influenza
  Intellectual disability
  Metastatic malignant neoplasm
  Rheumatoid arthritis
  Acromegaly
  Coxopodopatellar syndrome
  Melanoma
  Mental disorder
  Non-small-cell lung cancer
  Type-1/2 diabetes
• UniProt ID: SPSY_HUMAN
• PDB ID: 3C6K; 3C6M
• EC Number: 2.5.1.22
• Pfam ID: PF17284 ; PF01564 ; PF17950
• Sequence:
  MAAARHSTLDFMLGAKADGETILKGLQSIFQEQGMAESVHTWQDHGYLATYTNKNGSFAN
  LRIYPHGLVLLDLQSYDGDAQGKEEIDSILNKVEERMKELSQDSTGRVKRLPPIVRGGAI
  DRYWPTADGRLVEYDIDEVVYDEDSPYQNIKILHSKQFGNILILSGDVNLAESDLAYTRA
  IMGSGKEDYTGKDVLILGGGDGGILCEIVKLKPKMVTMVEIDQMVIDGCKKYMRKTCGDV
  LDNLKGDCYQVLIEDCIPVLKRYAKEGREFDYVINDLTAVPISTSPEEDSTWEFLRLILD
  LSMKVLKQDGKYFTQGNCVNLTEALSLYEEQLGRLYCPVEFSKEIVCVPSYLELWVFYTV
  WKKAKP
• Function: Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM).
• KEGG Pathway:
  Cysteine and methionine metabolism (hsa00270)
  Arginine and proline metabolism (hsa00330)
  Glutathione metabolism (hsa00480)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Metabolism of polyamines (R-HSA-351202)
• BioCyc Pathway: MetaCyc:HS02362-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Androgen insensitivity syndrome	DISUZBBO	Definitive	Biomarker	[2]
Epilepsy	DISBB28L	Definitive	Biomarker	[3]
Lung cancer	DISCM4YA	Definitive	Biomarker	[4]
Lung carcinoma	DISTR26C	Definitive	Biomarker	[4]
Osteoporosis	DISF2JE0	Definitive	Genetic Variation	[5]
Syndromic X-linked intellectual disability Snyder type	DISN836E	Definitive	X-linked	[6]
Anxiety	DISIJDBA	Strong	Biomarker	[7]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[7]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[8]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[8]
Atrial septal defect	DISJT76B	Strong	Biomarker	[7]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Biomarker	[9]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[7]
Beckwith-Wiedemann syndrome	DISH15GR	Strong	Biomarker	[10]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[11]
Breast cancer	DIS7DPX1	Strong	Biomarker	[12]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[12]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[13]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[14]
Depression	DIS3XJ69	Strong	Biomarker	[7]
Mood disorder	DISLVMWO	Strong	Biomarker	[15]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[12]
Post-traumatic stress disorder	DISHL1EY	Strong	Biomarker	[16]
Primitive neuroectodermal tumor	DISFHXHA	Strong	Biomarker	[17]
Prostate cancer	DISF190Y	Strong	Biomarker	[18]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[18]
Schizophrenia	DISSRV2N	Strong	Biomarker	[19]
Silver-Russell syndrome	DISSVJ1D	Strong	Genetic Variation	[20]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[21]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[22]
X-linked intellectual disability	DISYJBY3	Strong	Genetic Variation	[23]
High blood pressure	DISY2OHH	moderate	Biomarker	[24]
Influenza	DIS3PNU3	moderate	Biomarker	[25]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[26]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[27]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[28]
Acromegaly	DISCC73U	Limited	Biomarker	[29]
Coxopodopatellar syndrome	DISMJAT7	Limited	Biomarker	[30]
Melanoma	DIS1RRCY	Limited	Biomarker	[31]
Mental disorder	DIS3J5R8	Limited	Biomarker	[32]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Biomarker	[33]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Spermine synthase (SMS).	[35]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Spermine synthase (SMS).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Spermine synthase (SMS).	[37]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Spermine synthase (SMS).	[38]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Spermine synthase (SMS).	[39]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Spermine synthase (SMS).	[40]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Spermine synthase (SMS).	[38]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Spermine synthase (SMS).	[38]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Spermine synthase (SMS).	[38]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Spermine synthase (SMS).	[38]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Spermine synthase (SMS).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Spermine synthase (SMS).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Spermine synthase (SMS).	[44]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Spermine synthase (SMS).	[45]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Spermine synthase (SMS).	[46]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Spermine synthase (SMS).	[47]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Spermine synthase (SMS).	[42]

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