Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOVM4D4)

• DOT Name: Spectrin beta chain, non-erythrocytic 1 (SPTBN1)
• Synonyms: Beta-II spectrin; Fodrin beta chain; Spectrin, non-erythroid beta chain 1
• Gene Name: SPTBN1
• Related Disease: Developmental delay, impaired speech, and behavioral abnormalities
• UniProt ID: SPTB2_HUMAN
• PDB ID: 1AA2; 1BKR; 3EDV
• Pfam ID: PF00307 ; PF15410 ; PF00435
• Sequence:
  MTTTVATDYDNIEIQQQYSDVNNRWDVDDWDNENSSARLFERSRIKALADEREAVQKKTF
  TKWVNSHLARVSCRITDLYTDLRDGRMLIKLLEVLSGERLPKPTKGRMRIHCLENVDKAL
  QFLKEQRVHLENMGSHDIVDGNHRLTLGLIWTIILRFQIQDISVETEDNKEKKSAKDALL
  LWCQMKTAGYPNVNIHNFTTSWRDGMAFNALIHKHRPDLIDFDKLKKSNAHYNLQNAFNL
  AEQHLGLTKLLDPEDISVDHPDEKSIITYVVTYYHYFSKMKALAVEGKRIGKVLDNAIET
  EKMIEKYESLASDLLEWIEQTIIILNNRKFANSLVGVQQQLQAFNTYRTVEKPPKFTEKG
  NLEVLLFTIQSKMRANNQKVYMPREGKLISDINKAWERLEKAEHERELALRNELIRQEKL
  EQLARRFDRKAAMRETWLSENQRLVSQDNFGFDLPAVEAATKKHEAIETDIAAYEERVQA
  VVAVARELEAENYHDIKRITARKDNVIRLWEYLLELLRARRQRLEMNLGLQKIFQEMLYI
  MDWMDEMKVLVLSQDYGKHLLGVEDLLQKHTLVEADIGIQAERVRGVNASAQKFATDGEG
  YKPCDPQVIRDRVAHMEFCYQELCQLAAERRARLEESRRLWKFFWEMAEEEGWIREKEKI
  LSSDDYGKDLTSVMRLLSKHRAFEDEMSGRSGHFEQAIKEGEDMIAEEHFGSEKIRERII
  YIREQWANLEQLSAIRKKRLEEASLLHQFQADADDIDAWMLDILKIVSSSDVGHDEYSTQ
  SLVKKHKDVAEEIANYRPTLDTLHEQASALPQEHAESPDVRGRLSGIEERYKEVAELTRL
  RKQALQDTLALYKMFSEADACELWIDEKEQWLNNMQIPEKLEDLEVIQHRFESLEPEMNN
  QASRVAVVNQIARQLMHSGHPSEKEIKAQQDKLNTRWSQFRELVDRKKDALLSALSIQNY
  HLECNETKSWIREKTKVIESTQDLGNDLAGVMALQRKLTGMERDLVAIEAKLSDLQKEAE
  KLESEHPDQAQAILSRLAEISDVWEEMKTTLKNREASLGEASKLQQFLRDLDDFQSWLSR
  TQTAIASEDMPNTLTEAEKLLTQHENIKNEIDNYEEDYQKMRDMGEMVTQGQTDAQYMFL
  RQRLQALDTGWNELHKMWENRQNLLSQSHAYQQFLRDTKQAEAFLNNQEYVLAHTEMPTT
  LEGAEAAIKKQEDFMTTMDANEEKINAVVETGRRLVSDGNINSDRIQEKVDSIDDRHRKN
  RETASELLMRLKDNRDLQKFLQDCQELSLWINEKMLTAQDMSYDEARNLHSKWLKHQAFM
  AELASNKEWLDKIEKEGMQLISEKPETEAVVKEKLTGLHKMWEVLESTTQTKAQRLFDAN
  KAELFTQSCADLDKWLHGLESQIQSDDYGKDLTSVNILLKKQQMLENQMEVRKKEIEELQ
  SQAQALSQEGKSTDEVDSKRLTVQTKFMELLEPLNERKHNLLASKEIHQFNRDVEDEILW
  VGERMPLATSTDHGHNLQTVQLLIKKNQTLQKEIQGHQPRIDDIFERSQNIVTDSSSLSA
  EAIRQRLADLKQLWGLLIEETEKRHRRLEEAHRAQQYYFDAAEAEAWMSEQELYMMSEEK
  AKDEQSAVSMLKKHQILEQAVEDYAETVHQLSKTSRALVADSHPESERISMRQSKVDKLY
  AGLKDLAEERRGKLDERHRLFQLNREVDDLEQWIAEREVVAGSHELGQDYEHVTMLQERF
  REFARDTGNIGQERVDTVNHLADELINSGHSDAATIAEWKDGLNEAWADLLELIDTRTQI
  LAASYELHKFYHDAKEIFGRIQDKHKKLPEELGRDQNTVETLQRMHTTFEHDIQALGTQV
  RQLQEDAARLQAAYAGDKADDIQKRENEVLEAWKSLLDACESRRVRLVDTGDKFRFFSMV
  RDLMLWMEDVIRQIEAQEKPRDVSSVELLMNNHQGIKAEIDARNDSFTTCIELGKSLLAR
  KHYASEEIKEKLLQLTEKRKEMIDKWEDRWEWLRLILEVHQFSRDASVAEAWLLGQEPYL
  SSREIGQSVDEVEKLIKRHEAFEKSAATWDERFSALERLTTLELLEVRRQQEEEERKRRP
  PSPEPSTKVSEEAESQQQWDTSKGEQVSQNGLPAEQGSPRMAETVDTSEMVNGATEQRTS
  SKESSPIPSPTSDRKAKTALPAQSAATLPARTQETPSAQMEGFLNRKHEWEAHNKKASSR
  SWHNVYCVINNQEMGFYKDAKTAASGIPYHSEVPVSLKEAVCEVALDYKKKKHVFKLRLN
  DGNEYLFQAKDDEEMNTWIQAISSAISSDKHEVSASTQSTPASSRAQTLPTSVVTITSES
  SPGKREKDKEKDKEKRFSLFGKKK
• Function: Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane. Plays a critical role in central nervous system development and function.
• Tissue Specificity: Isoform 2 is present in brain, lung and kidney (at protein level).
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway:
  NCAM signaling for neurite out-growth (R-HSA-375165)
  Interaction between L1 and Ankyrins (R-HSA-445095)
  RAF/MAP kinase cascade (R-HSA-5673001)
  COPI-mediated anterograde transport (R-HSA-6807878)
  RHOU GTPase cycle (R-HSA-9013420)
  RHOV GTPase cycle (R-HSA-9013424)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  Signaling by FLT3 fusion proteins (R-HSA-9703465)
  Nephrin family interactions (R-HSA-373753)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Developmental delay, impaired speech, and behavioral abnormalities	DISMMGYR	Strong	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[13]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[16]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[17]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[18]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[19]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[20]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[23]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[24]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[28]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[29]
AM251	DMTAWHL	Investigative	AM251 decreases the expression of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol decreases the phosphorylation of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[10]
G1	DMTV42K	Phase 1/2	G1 decreases the phosphorylation of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[22]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[25]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Spectrin beta chain, non-erythrocytic 1 (SPTBN1).	[25]

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