Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTE02XC)

• DOT Name: Synaptojanin-1 (SYNJ1)
• Synonyms: EC 3.1.3.36; Synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1
• Gene Name: SYNJ1
• Related Disease:
  Epilepsy
  Infantile spasm
  Adult glioblastoma
  Autosomal recessive juvenile Parkinson disease 2
  Bronchopulmonary dysplasia
  Dementia
  Developmental and epileptic encephalopathy, 53
  Early-onset Parkinson disease 20
  Familial Alzheimer disease
  Glioblastoma multiforme
  Joubert syndrome
  Juvenile-onset Parkinson disease
  Muscular dystrophy
  Retinitis pigmentosa
  Tauopathy
  Alzheimer disease
  Intellectual disability
  Parkinsonian disorder
  Rhabdomyosarcoma
  Atypical juvenile parkinsonism
  Undetermined early-onset epileptic encephalopathy
  Young-onset Parkinson disease
  Amyotrophic lateral sclerosis
  Bipolar disorder
  Cognitive impairment
  Neuroblastoma
• UniProt ID: SYNJ1_HUMAN
• PDB ID: 1W80; 2DNR; 2VJ0; 7A0V
• EC Number: 3.1.3.36
• Pfam ID: PF08952 ; PF02383
• Sequence:
  MAFSKGFRIYHKLDPPPFSLIVETRHKEECLMFESGAVAVLSSAEKEAIKGTYSKVLDAY
  GLLGVLRLNLGDTMLHYLVLVTGCMSVGKIQESEVFRVTSTEFISLRIDSSDEDRISEVR
  KVLNSGNFYFAWSASGISLDLSLNAHRSMQEQTTDNRFFWNQSLHLHLKHYGVNCDDWLL
  RLMCGGVEIRTIYAAHKQAKACLISRLSCERAGTRFNVRGTNDDGHVANFVETEQVVYLD
  DSVSSFIQIRGSVPLFWEQPGLQVGSHRVRMSRGFEANAPAFDRHFRTLKNLYGKQIIVN
  LLGSKEGEHMLSKAFQSHLKASEHAADIQMVNFDYHQMVKGGKAEKLHSVLKPQVQKFLD
  YGFFYFNGSEVQRCQSGTVRTNCLDCLDRTNSVQAFLGLEMLAKQLEALGLAEKPQLVTR
  FQEVFRSMWSVNGDSISKIYAGTGALEGKAKLKDGARSVTRTIQNNFFDSSKQEAIDVLL
  LGNTLNSDLADKARALLTTGSLRVSEQTLQSASSKVLKSMCENFYKYSKPKKIRVCVGTW
  NVNGGKQFRSIAFKNQTLTDWLLDAPKLAGIQEFQDKRSKPTDIFAIGFEEMVELNAGNI
  VSASTTNQKLWAVELQKTISRDNKYVLLASEQLVGVCLFVFIRPQHAPFIRDVAVDTVKT
  GMGGATGNKGAVAIRMLFHTTSLCFVCSHFAAGQSQVKERNEDFIEIARKLSFPMGRMLF
  SHDYVFWCGDFNYRIDLPNEEVKELIRQQNWDSLIAGDQLINQKNAGQVFRGFLEGKVTF
  APTYKYDLFSDDYDTSEKCRTPAWTDRVLWRRRKWPFDRSAEDLDLLNASFQDESKILYT
  WTPGTLLHYGRAELKTSDHRPVVALIDIDIFEVEAEERQNIYKEVIAVQGPPDGTVLVSI
  KSSLPENNFFDDALIDELLQQFASFGEVILIRFVEDKMWVTFLEGSSALNVLSLNGKELL
  NRTITIALKSPDWIKNLEEEMSLEKISIALPSSTSSTLLGEDAEVAADFDMEGDVDDYSA
  EVEELLPQHLQPSSSSGLGTSPSSSPRTSPCQSPTISEGPVPSLPIRPSRAPSRTPGPPS
  AQSSPIDAQPATPLPQKDPAQPLEPKRPPPPRPVAPPTRPAPPQRPPPPSGARSPAPTRK
  EFGGIGAPPSPGVARREMEAPKSPGTTRKDNIGRSQPSPQAGLAGPGPAGYSTARPTIPP
  RAGVISAPQSHARASAGRLTPESQSKTSETSKGSTFLPEPLKPQAAFPPQSSLPPPAQRL
  QEPLVPVAAPMPQSGPQPNLETPPQPPPRSRSSHSLPSEASSQPQVKTNGISDGKRESPL
  KIDPFEDLSFNLLAVSKAQLSVQTSPVPTPDPKRLIQLPSATQSNVLSSVSCMPTMPPIP
  ARSQSQENMRSSPNPFITGLTRTNPFSDRTAAPGNPFRAKSEESEATSWFSKEEPVTISP
  FPSLQPLGHNKSRASSSLDGFKDSFDLQGQSTLKISNPKGWVTFEEEEDFGVKGKSKSAC
  SDLLGNQPSSFSGSNLTLNDDWNKGTNVSFCVLPSRRPPPPPVPLLPPGTSPPVDPFTTL
  ASKASPTLDFTER
• Function: Phosphatase that acts on various phosphoinositides, including phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate. Has a role in clathrin-mediated endocytosis. Hydrolyzes PIP2 bound to actin regulatory proteins resulting in the rearrangement of actin filaments downstream of tyrosine kinase and ASH/GRB2.
• KEGG Pathway:
  Inositol phosphate metabolism (hsa00562)
  Metabolic pathways (hsa01100)
  Phosphatidylinositol sig.ling system (hsa04070)
• Reactome Pathway:
  Synthesis of IP2, IP, and Ins in the cytosol (R-HSA-1855183)
  Synthesis of IP3 and IP4 in the cytosol (R-HSA-1855204)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Synthesis of PIPs at the plasma membrane (R-HSA-1660499)
• BioCyc Pathway: MetaCyc:HS08354-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epilepsy	DISBB28L	Definitive	Genetic Variation	[1]
Infantile spasm	DISZSKDG	Definitive	Autosomal recessive	[2]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[3]
Autosomal recessive juvenile Parkinson disease 2	DISNSTD1	Strong	Genetic Variation	[4]
Bronchopulmonary dysplasia	DISO0BY5	Strong	Biomarker	[5]
Dementia	DISXL1WY	Strong	Biomarker	[6]
Developmental and epileptic encephalopathy, 53	DISESJ1V	Strong	Autosomal recessive	[7]
Early-onset Parkinson disease 20	DISIBMD3	Strong	Autosomal recessive	[8]
Familial Alzheimer disease	DISE75U4	Strong	Genetic Variation	[9]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[3]
Joubert syndrome	DIS7P5CO	Strong	Biomarker	[10]
Juvenile-onset Parkinson disease	DISNT5BI	Strong	Genetic Variation	[1]
Muscular dystrophy	DISJD6P7	Strong	Genetic Variation	[11]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[12]
Tauopathy	DISY2IPA	Strong	Genetic Variation	[13]
Alzheimer disease	DISF8S70	moderate	Biomarker	[9]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[14]
Parkinsonian disorder	DISHGY45	moderate	Genetic Variation	[15]
Rhabdomyosarcoma	DISNR7MS	moderate	Biomarker	[16]
Atypical juvenile parkinsonism	DISYXFE3	Supportive	Autosomal recessive	[17]
Undetermined early-onset epileptic encephalopathy	DISISEI2	Supportive	Autosomal dominant	[14]
Young-onset Parkinson disease	DIS05LFS	Supportive	Autosomal recessive	[18]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Genetic Variation	[19]
Bipolar disorder	DISAM7J2	Limited	Biomarker	[20]
Cognitive impairment	DISH2ERD	Limited	Altered Expression	[21]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[22]

15 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 Synaptojanin-1 (SYNJ1).	[23]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Synaptojanin-1 (SYNJ1).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Synaptojanin-1 (SYNJ1).	[25]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Synaptojanin-1 (SYNJ1).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Synaptojanin-1 (SYNJ1).	[27]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Synaptojanin-1 (SYNJ1).	[28]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Synaptojanin-1 (SYNJ1).	[29]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Synaptojanin-1 (SYNJ1).	[30]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Synaptojanin-1 (SYNJ1).	[31]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Synaptojanin-1 (SYNJ1).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Synaptojanin-1 (SYNJ1).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Synaptojanin-1 (SYNJ1).	[34]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Synaptojanin-1 (SYNJ1).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Synaptojanin-1 (SYNJ1).	[37]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Synaptojanin-1 (SYNJ1).	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Synaptojanin-1 (SYNJ1).	[35]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Synaptojanin-1 (SYNJ1).	[35]

References

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• [16] The essential role of clathrin-mediated endocytosis in the infectious entry of human enterovirus 71.J Biol Chem. 2011 Jan 7;286(1):309-21. doi: 10.1074/jbc.M110.168468. Epub 2010 Oct 18.
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• [21] Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer's disease pathogenesis.Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):11965-70. doi: 10.1073/pnas.1510011112. Epub 2015 Sep 8.
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