Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT54RLO1)

• DOT Name: Survival motor neuron protein (SMN2)
• Synonyms: Component of gems 1; Gemin-1
• Gene Name: SMN2
• Related Disease:
  Congenital myopathy
  Hyperglycemia
  Non-alcoholic fatty liver disease
  Spinal muscular atrophy
  Spinal muscular atrophy, type 1
  Adult glioblastoma
  Advanced cancer
  Bulbospinal muscular atrophy
  Charcot marie tooth disease
  Clear cell renal carcinoma
  Cone-rod dystrophy 2
  Glioblastoma multiforme
  Glioma
  Hepatitis
  Hepatocellular carcinoma
  IgA nephropathy
  Liver cirrhosis
  Motor neurone disease
  Myopathy
  Neuroblastoma
  Osteoarthritis
  Parkinson disease
  Proliferative vitreoretinopathy
  Pulmonary fibrosis
  Renal fibrosis
  Scapuloperoneal spinal muscular atrophy, autosomal dominant
  Spinal disease
  Spinal muscular atrophy, type II
  Spinal muscular atrophy, type III
  Spinal muscular atrophy, type IV
  Stroke
  Tourette syndrome
  Uterine fibroids
  Breast cancer
  Breast carcinoma
  Diabetic kidney disease
  Triple negative breast cancer
  Autosomal recessive distal spinal muscular atrophy 1
  Distal hereditary motor neuropathy
  Arthrogryposis
  Asthma
  Methicillin-resistant staphylococci infection
  Myocardial infarction
  Respiratory failure
• UniProt ID: SMN_HUMAN
• PDB ID: 1G5V; 1MHN; 2LEH; 4A4E; 4A4G; 4GLI; 4QQ6; 5XJL; 5XJQ; 5XJR; 5XJS; 5XJT; 5XJU; 7W2P; 7W30
• Pfam ID: PF20636 ; PF06003 ; PF20635
• Sequence:
  MAMSSGGSGGGVPEQEDSVLFRRGTGQSDDSDIWDDTALIKAYDKAVASFKHALKNGDIC
  ETSGKPKTTPKRKPAKKNKSQKKNTAASLQQWKVGDKCSAIWSEDGCIYPATIASIDFKR
  ETCVVVYTGYGNREEQNLSDLLSPICEVANNIEQNAQENENESQVSTDESENSRSPGNKS
  DNIKPKSAPWNSFLPPPPPMPGPRLGPGKPGLKFNGPPPPPPPPPPHLLSCWLPPFPSGP
  PIIPPPPPICPDSLDDADALGSMLISWYMSGYHTGYYMGFRQNQKEGRCSHSLN
• Function: The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Within the SMN complex, SMN1 acts as a structural backbone and together with GEMIN2 it gathers the Sm complex subunits. Binding of snRNA inside 5Sm ultimately triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP. Ensures the correct splicing of U12 intron-containing genes that may be important for normal motor and proprioceptive neurons development. Also required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination. May also play a role in the metabolism of small nucleolar ribonucleoprotein (snoRNPs).
• Tissue Specificity: Expressed in a wide variety of tissues. Expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. Also seen at high levels in spinal cord. Present in osteoclasts and mononuclear cells (at protein level).
• Reactome Pathway:
  SARS-CoV-2 modulates host translation machinery (R-HSA-9754678)
  snRNP Assembly (R-HSA-191859)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital myopathy	DISLSK9G	Definitive	Biomarker	[1]
Hyperglycemia	DIS0BZB5	Definitive	Altered Expression	[2]
Non-alcoholic fatty liver disease	DISDG1NL	Definitive	Biomarker	[3]
Spinal muscular atrophy	DISTLKOB	Definitive	Autosomal recessive	[4]
Spinal muscular atrophy, type 1	DISYCWUG	Definitive	Autosomal recessive	[5]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[6]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[7]
Bulbospinal muscular atrophy	DISRL4MG	Strong	Therapeutic	[8]
Charcot marie tooth disease	DIS3BT2L	Strong	Biomarker	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[10]
Cone-rod dystrophy 2	DISX2RWY	Strong	Biomarker	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[6]
Glioma	DIS5RPEH	Strong	Biomarker	[12]
Hepatitis	DISXXX35	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[14]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[15]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[14]
Motor neurone disease	DISUHWUI	Strong	Genetic Variation	[16]
Myopathy	DISOWG27	Strong	Altered Expression	[17]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[6]
Osteoarthritis	DIS05URM	Strong	Biomarker	[18]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[19]
Proliferative vitreoretinopathy	DISZTEK1	Strong	Altered Expression	[20]
Pulmonary fibrosis	DISQKVLA	Strong	Biomarker	[21]
Renal fibrosis	DISMHI3I	Strong	Altered Expression	[22]
Scapuloperoneal spinal muscular atrophy, autosomal dominant	DISCOCGI	Strong	Therapeutic	[8]
Spinal disease	DISQRITY	Strong	Altered Expression	[23]
Spinal muscular atrophy, type II	DIS3GNQ4	Strong	Autosomal recessive	[24]
Spinal muscular atrophy, type III	DISNG3SD	Strong	Autosomal recessive	[24]
Spinal muscular atrophy, type IV	DIS8UDXL	Strong	Autosomal recessive	[24]
Stroke	DISX6UHX	Strong	Altered Expression	[25]
Tourette syndrome	DISX9D54	Strong	Biomarker	[26]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[27]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[28]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[28]
Diabetic kidney disease	DISJMWEY	moderate	Biomarker	[29]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[30]
Autosomal recessive distal spinal muscular atrophy 1	DISA9P1I	Disputed	Biomarker	[31]
Distal hereditary motor neuropathy	DISGS2ID	Disputed	Therapeutic	[8]
Arthrogryposis	DISC81CM	Limited	Genetic Variation	[32]
Asthma	DISW9QNS	Limited	Altered Expression	[33]
Methicillin-resistant staphylococci infection	DIS6DRDZ	Limited	Genetic Variation	[34]
Myocardial infarction	DIS655KI	Limited	Altered Expression	[35]
Respiratory failure	DISVMYJO	Limited	Biomarker	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Camptothecin	DM6CHNJ	Phase 3	Survival motor neuron protein (SMN2) increases the response to substance of Camptothecin.	[51]

17 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 Survival motor neuron protein (SMN2).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Survival motor neuron protein (SMN2).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Survival motor neuron protein (SMN2).	[39]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Survival motor neuron protein (SMN2).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Survival motor neuron protein (SMN2).	[41]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Survival motor neuron protein (SMN2).	[43]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Survival motor neuron protein (SMN2).	[44]
Amikacin	DM5PDRB	Approved	Amikacin increases the expression of Survival motor neuron protein (SMN2).	[37]
Tobramycin	DMUI0CH	Approved	Tobramycin increases the expression of Survival motor neuron protein (SMN2).	[37]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Survival motor neuron protein (SMN2).	[45]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Survival motor neuron protein (SMN2).	[45]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Survival motor neuron protein (SMN2).	[45]
RG7800	DMAGE91	Phase 1/2	RG7800 increases the splicing of Survival motor neuron protein (SMN2).	[46]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Survival motor neuron protein (SMN2).	[49]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Survival motor neuron protein (SMN2).	[37]
G418	DMKTJBU	Investigative	G418 increases the expression of Survival motor neuron protein (SMN2).	[37]
5'-(N-ethyl-N-isopropyl)amiloride	DM3TPMO	Investigative	5'-(N-ethyl-N-isopropyl)amiloride affects the expression of Survival motor neuron protein (SMN2).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Survival motor neuron protein (SMN2).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Survival motor neuron protein (SMN2).	[47]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Survival motor neuron protein (SMN2).	[48]

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