Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK4FSHR)

• DOT Name: Tenascin (TNC)
• Synonyms: TN; Cytotactin; GMEM; GP 150-225; Glioma-associated-extracellular matrix antigen; Hexabrachion; JI; Myotendinous antigen; Neuronectin; Tenascin-C; TN-C
• Gene Name: TNC
• Related Disease:
  Autosomal dominant nonsyndromic hearing loss 56
  Autosomal dominant nonsyndromic hearing loss
  Nonsyndromic genetic hearing loss
• UniProt ID: TENA_HUMAN
• PDB ID: 1TEN; 2RB8; 2RBL; 5R5T; 5R5U; 5R5V; 5R5W; 5R5X; 5R5Y; 5R5Z; 5R60; 5R61; 5R62; 5R63; 6BRB; 6QNV; 8FN8; 8FNB
• Pfam ID: PF07974 ; PF18720 ; PF00147 ; PF00041
• Sequence:
  MGAMTQLLAGVFLAFLALATEGGVLKKVIRHKRQSGVNATLPEENQPVVFNHVYNIKLPV
  GSQCSVDLESASGEKDLAPPSEPSESFQEHTVDGENQIVFTHRINIPRRACGCAAAPDVK
  ELLSRLEELENLVSSLREQCTAGAGCCLQPATGRLDTRPFCSGRGNFSTEGCGCVCEPGW
  KGPNCSEPECPGNCHLRGRCIDGQCICDDGFTGEDCSQLACPSDCNDQGKCVNGVCICFE
  GYAGADCSREICPVPCSEEHGTCVDGLCVCHDGFAGDDCNKPLCLNNCYNRGRCVENECV
  CDEGFTGEDCSELICPNDCFDRGRCINGTCYCEEGFTGEDCGKPTCPHACHTQGRCEEGQ
  CVCDEGFAGVDCSEKRCPADCHNRGRCVDGRCECDDGFTGADCGELKCPNGCSGHGRCVN
  GQCVCDEGYTGEDCSQLRCPNDCHSRGRCVEGKCVCEQGFKGYDCSDMSCPNDCHQHGRC
  VNGMCVCDDGYTGEDCRDRQCPRDCSNRGLCVDGQCVCEDGFTGPDCAELSCPNDCHGQG
  RCVNGQCVCHEGFMGKDCKEQRCPSDCHGQGRCVDGQCICHEGFTGLDCGQHSCPSDCNN
  LGQCVSGRCICNEGYSGEDCSEVSPPKDLVVTEVTEETVNLAWDNEMRVTEYLVVYTPTH
  EGGLEMQFRVPGDQTSTIIQELEPGVEYFIRVFAILENKKSIPVSARVATYLPAPEGLKF
  KSIKETSVEVEWDPLDIAFETWEIIFRNMNKEDEGEITKSLRRPETSYRQTGLAPGQEYE
  ISLHIVKNNTRGPGLKRVTTTRLDAPSQIEVKDVTDTTALITWFKPLAEIDGIELTYGIK
  DVPGDRTTIDLTEDENQYSIGNLKPDTEYEVSLISRRGDMSSNPAKETFTTGLDAPRNLR
  RVSQTDNSITLEWRNGKAAIDSYRIKYAPISGGDHAEVDVPKSQQATTKTTLTGLRPGTE
  YGIGVSAVKEDKESNPATINAATELDTPKDLQVSETAETSLTLLWKTPLAKFDRYRLNYS
  LPTGQWVGVQLPRNTTSYVLRGLEPGQEYNVLLTAEKGRHKSKPARVKASTEQAPELENL
  TVTEVGWDGLRLNWTAADQAYEHFIIQVQEANKVEAARNLTVPGSLRAVDIPGLKAATPY
  TVSIYGVIQGYRTPVLSAEASTGETPNLGEVVVAEVGWDALKLNWTAPEGAYEYFFIQVQ
  EADTVEAAQNLTVPGGLRSTDLPGLKAATHYTITIRGVTQDFSTTPLSVEVLTEEVPDMG
  NLTVTEVSWDALRLNWTTPDGTYDQFTIQVQEADQVEEAHNLTVPGSLRSMEIPGLRAGT
  PYTVTLHGEVRGHSTRPLAVEVVTEDLPQLGDLAVSEVGWDGLRLNWTAADNAYEHFVIQ
  VQEVNKVEAAQNLTLPGSLRAVDIPGLEAATPYRVSIYGVIRGYRTPVLSAEASTAKEPE
  IGNLNVSDITPESFNLSWMATDGIFETFTIEIIDSNRLLETVEYNISGAERTAHISGLPP
  STDFIVYLSGLAPSIRTKTISATATTEALPLLENLTISDINPYGFTVSWMASENAFDSFL
  VTVVDSGKLLDPQEFTLSGTQRKLELRGLITGIGYEVMVSGFTQGHQTKPLRAEIVTEAE
  PEVDNLLVSDATPDGFRLSWTADEGVFDNFVLKIRDTKKQSEPLEITLLAPERTRDITGL
  REATEYEIELYGISKGRRSQTVSAIATTAMGSPKEVIFSDITENSATVSWRAPTAQVESF
  RITYVPITGGTPSMVTVDGTKTQTRLVKLIPGVEYLVSIIAMKGFEESEPVSGSFTTALD
  GPSGLVTANITDSEALARWQPAIATVDSYVISYTGEKVPEITRTVSGNTVEYALTDLEPA
  TEYTLRIFAEKGPQKSSTITAKFTTDLDSPRDLTATEVQSETALLTWRPPRASVTGYLLV
  YESVDGTVKEVIVGPDTTSYSLADLSPSTHYTAKIQALNGPLRSNMIQTIFTTIGLLYPF
  PKDCSQAMLNGDTTSGLYTIYLNGDKAEALEVFCDMTSDGGGWIVFLRRKNGRENFYQNW
  KAYAAGFGDRREEFWLGLDNLNKITAQGQYELRVDLRDHGETAFAVYDKFSVGDAKTRYK
  LKVEGYSGTAGDSMAYHNGRSFSTFDKDTDSAITNCALSYKGAFWYRNCHRVNLMGRYGD
  NNHSQGVNWFHWKGHEHSIQFAEMKLRPSNFRNLEGRRKRA
• Function: Extracellular matrix protein implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration. Promotes neurite outgrowth from cortical neurons grown on a monolayer of astrocytes. Ligand for integrins alpha-8/beta-1, alpha-9/beta-1, alpha-V/beta-3 and alpha-V/beta-6. In tumors, stimulates angiogenesis by elongation, migration and sprouting of endothelial cells.
• Tissue Specificity: Detected in fibroblasts (at protein level).
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Human papillomavirus infection (hsa05165)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway:
  Syndecan interactions (R-HSA-3000170)
  ECM proteoglycans (R-HSA-3000178)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Integrin cell surface interactions (R-HSA-216083)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal dominant nonsyndromic hearing loss 56	DISOVY34	Moderate	Autosomal dominant	[1]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[1]
Nonsyndromic genetic hearing loss	DISZX61P	Limited	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Tenascin (TNC) affects the response to substance of DTI-015.	[36]

35 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 Tenascin (TNC).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tenascin (TNC).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tenascin (TNC).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tenascin (TNC).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tenascin (TNC).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tenascin (TNC).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tenascin (TNC).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Tenascin (TNC).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Tenascin (TNC).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tenascin (TNC).	[13]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Tenascin (TNC).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Tenascin (TNC).	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tenascin (TNC).	[16]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Tenascin (TNC).	[17]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Tenascin (TNC).	[18]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Tenascin (TNC).	[19]
Capsaicin	DMGMF6V	Approved	Capsaicin decreases the expression of Tenascin (TNC).	[20]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Tenascin (TNC).	[21]
Rofecoxib	DM3P5DA	Approved	Rofecoxib increases the expression of Tenascin (TNC).	[21]
Diazepam	DM08E9O	Approved	Diazepam decreases the expression of Tenascin (TNC).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Tenascin (TNC).	[23]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Tenascin (TNC).	[11]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Tenascin (TNC).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tenascin (TNC).	[25]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Tenascin (TNC).	[26]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tenascin (TNC).	[27]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Tenascin (TNC).	[28]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Tenascin (TNC).	[29]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Tenascin (TNC).	[30]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Tenascin (TNC).	[20]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Tenascin (TNC).	[31]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Tenascin (TNC).	[32]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Tenascin (TNC).	[33]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone increases the expression of Tenascin (TNC).	[34]
Erythropoietin	DM3R8YL	Investigative	Erythropoietin decreases the expression of Tenascin (TNC).	[35]

2 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 Tenascin (TNC).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tenascin (TNC).	[24]

References

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