Details of Drug Off-Target (DOT)

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

• DOT Name: SH3 and multiple ankyrin repeat domains protein 2 (SHANK2)
• Synonyms: Shank2; Cortactin-binding protein 1; CortBP1; Proline-rich synapse-associated protein 1
• Gene Name: SHANK2
• Related Disease:
  Complex neurodevelopmental disorder
  Alzheimer disease
  Amyloidosis
  Atrial septal defect
  Autism, susceptibility to, 17
  Bipolar depression
  Bipolar disorder
  Bronchopulmonary dysplasia
  Esophageal squamous cell carcinoma
  Glioma
  Intellectual disability
  Language disorder
  Major depressive disorder
  Mental disorder
  Neurodevelopmental disorder
  Pervasive developmental disorder
  Squamous cell carcinoma
  Acute myelogenous leukaemia
  Autism
  Schizophrenia
  Nervous system disease
• UniProt ID: SHAN2_HUMAN
• PDB ID: 8ATJ; 8B10
• Pfam ID: PF12796 ; PF16511 ; PF17820 ; PF00536 ; PF07653
• Sequence:
  MPRSPTSSEDEMAQSFSDYSVGSESDSSKEETIYDTIRATAEKPGGARTEESQGNTLVIR
  VVIHDLQQTKCIRFNPDATVWVAKQRILCTLTQSLKDVLNYGLFQPASNGRDGKFLDEER
  LLREYPQPVGEGVPSLEFRYKKRVYKQASLDEKQLAKLHTKTNLKKCMDHIQHRLVEKIT
  KMLDRGLDPNFHDPETGETPLTLAAQLDDSVEVIKALKNGGAHLDFRAKDGMTALHKAAR
  ARNQVALKTLLELGASPDYKDSYGLTPLYHTAIVGGDPYCCELLLHEHATVCCKDENGWH
  EIHQACRYGHVQHLEHLLFYGADMSAQNASGNTALHICALYNQDSCARVLLFRGGNKELK
  NYNSQTPFQVAIIAGNFELAEYIKNHKETDIVPFREAPAYSNRRRRPPNTLAAPRVLLRS
  NSDNNLNASAPDWAVCSTATSHRSLSPQLLQQMPSKPEGAAKTIGSYVPGPRSRSPSLNR
  LGGAGEDGKRPQPLWHVGSPFALGANKDSLSAFEYPGPKRKLYSAVPGRLFVAVKPYQPQ
  VDGEIPLHRGDRVKVLSIGEGGFWEGSARGHIGWFPAECVEEVQCKPRDSQAETRADRSK
  KLFRHYTVGSYDSFDTSSDCIIEEKTVVLQKKDNEGFGFVLRGAKADTPIEEFTPTPAFP
  ALQYLESVDEGGVAWQAGLRTGDFLIEVNNENVVKVGHRQVVNMIRQGGNHLVLKVVTVT
  RNLDPDDTARKKAPPPPKRAPTTALTLRSKSMTSELEELVDKASVRKKKDKPEEIVPASK
  PSRAAENMAVEPRVATIKQRPSSRCFPAGSDMNSVYERQGIAVMTPTVPGSPKAPFLGIP
  RGTMRRQKSIDSRIFLSGITEEERQFLAPPMLKFTRSLSMPDTSEDIPPPPQSVPPSPPP
  PSPTTYNCPKSPTPRVYGTIKPAFNQNSAAKVSPATRSDTVATMMREKGMYFRRELDRYS
  LDSEDLYSRNAGPQANFRNKRGQMPENPYSEVGKIASKAVYVPAKPARRKGMLVKQSNVE
  DSPEKTCSIPIPTIIVKEPSTSSSGKSSQGSSMEIDPQAPEPPSQLRPDESLTVSSPFAA
  AIAGAVRDREKRLEARRNSPAFLSTDLGDEDVGLGPPAPRTRPSMFPEEGDFADEDSAEQ
  LSSPMPSATPREPENHFVGGAEASAPGEAGRPLNSTSKAQGPESSPAVPSASSGTAGPGN
  YVHPLTGRLLDPSSPLALALSARDRAMKESQQGPKGEAPKADLNKPLYIDTKMRPSLDAG
  FPTVTRQNTRGPLRRQETENKYETDLGRDRKGDDKKNMLIDIMDTSQQKSAGLLMVHTVD
  ATKLDNALQEEDEKAEVEMKPDSSPSEVPEGVSETEGALQISAAPEPTTVPGRTIVAVGS
  MEEAVILPFRIPPPPLASVDLDEDFIFTEPLPPPLEFANSFDIPDDRAASVPALSDLVKQ
  KKSDTPQSPSLNSSQPTNSADSKKPASLSNCLPASFLPPPESFDAVADSGIEEVDSRSSS
  DHHLETTSTISTVSSISTLSSEGGENVDTCTVYADGQAFMVDKPPVPPKPKMKPIIHKSN
  ALYQDALVEEDVDSFVIPPPAPPPPPGSAQPGMAKVLQPRTSKLWGDVTEIKSPILSGPK
  ANVISELNSILQQMNREKLAKPGEGLDSPMGAKSASLAPRSPEIMSTISGTRSTTVTFTV
  RPGTSQPITLQSRPPDYESRTSGTRRAPSPVVSPTEMNKETLPAPLSAATASPSPALSDV
  FSLPSQPPSGDLFGLNPAGRSRSPSPSILQQPISNKPFTTKPVHLWTKPDVADWLESLNL
  GEHKEAFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQLLDR
• Function: Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors, and the actin-based cytoskeleton. May play a role in the structural and functional organization of the dendritic spine and synaptic junction.
• Tissue Specificity: Isoform 3 is present in epithelial colonic cells (at protein level).
• KEGG Pathway: Glutamatergic sy.pse (hsa04724)
• Reactome Pathway: Neurexins and neuroligins (R-HSA-6794361)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex neurodevelopmental disorder	DISB9AFI	Definitive	Autosomal dominant	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Amyloidosis	DISHTAI2	Strong	Altered Expression	[3]
Atrial septal defect	DISJT76B	Strong	Biomarker	[4]
Autism, susceptibility to, 17	DISCTW39	Strong	Autosomal dominant	[5]
Bipolar depression	DISA75FU	Strong	Biomarker	[6]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[6]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Genetic Variation	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[8]
Glioma	DIS5RPEH	Strong	Genetic Variation	[9]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[10]
Language disorder	DISTLKP7	Strong	Genetic Variation	[11]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[12]
Mental disorder	DIS3J5R8	Strong	Biomarker	[13]
Neurodevelopmental disorder	DIS372XH	Strong	Genetic Variation	[10]
Pervasive developmental disorder	DIS51975	Strong	Genetic Variation	[14]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[15]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[16]
Autism	DISV4V1Z	moderate	Genetic Variation	[2]
Schizophrenia	DISSRV2N	moderate	Biomarker	[10]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[18]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[34]

26 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 SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[19]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[20]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[23]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[24]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[26]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[27]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[28]
Selenium	DM25CGV	Approved	Selenium decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[29]
Menadione	DMSJDTY	Approved	Menadione affects the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[26]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[30]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[31]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[24]
Imipramine	DM2NUH3	Approved	Imipramine decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[24]
Gabapentin	DM6T924	Approved	Gabapentin decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[24]
Sulfadiazine	DMTW3R8	Approved	Sulfadiazine decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[24]
Urethane	DM7NSI0	Phase 4	Urethane affects the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[32]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[29]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[35]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[24]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[24]
2-Methylamino-succinic acid(NMDA)	DMKP6BM	Investigative	2-Methylamino-succinic acid(NMDA) decreases the expression of SH3 and multiple ankyrin repeat domains protein 2 (SHANK2).	[24]

References

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