Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFPU6W8)

• DOT Name: Laminin subunit beta-3 (LAMB3)
• Synonyms: Epiligrin subunit bata; Kalinin B1 chain; Kalinin subunit beta; Laminin B1k chain; Laminin-5 subunit beta; Nicein subunit beta
• Gene Name: LAMB3
• Related Disease:
  Junctional epidermolysis bullosa
  Junctional epidermolysis bullosa Herlitz type
  Junctional epidermolysis bullosa, non-Herlitz type
  Amelogenesis imperfecta type 1A
  Amelogenesis imperfecta type 1
  Generalized junctional epidermolysis bullosa non-Herlitz type
• UniProt ID: LAMB3_HUMAN
• Pfam ID: PF00053 ; PF00055
• Sequence:
  MRPFFLLCFALPGLLHAQQACSRGACYPPVGDLLVGRTRFLRASSTCGLTKPETYCTQYG
  EWQMKCCKCDSRQPHNYYSHRVENVASSSGPMRWWQSQNDVNPVSLQLDLDRRFQLQEVM
  MEFQGPMPAGMLIERSSDFGKTWRVYQYLAADCTSTFPRVRQGRPQSWQDVRCQSLPQRP
  NARLNGGKVQLNLMDLVSGIPATQSQKIQEVGEITNLRVNFTRLAPVPQRGYHPPSAYYA
  VSQLRLQGSCFCHGHADRCAPKPGASAGPSTAVQVHDVCVCQHNTAGPNCERCAPFYNNR
  PWRPAEGQDAHECQRCDCNGHSETCHFDPAVFAASQGAYGGVCDNCRDHTEGKNCERCQL
  HYFRNRRPGASIQETCISCECDPDGAVPGAPCDPVTGQCVCKEHVQGERCDLCKPGFTGL
  TYANPQGCHRCDCNILGSRRDMPCDEESGRCLCLPNVVGPKCDQCAPYHWKLASGQGCEP
  CACDPHNSLSPQCNQFTGQCPCREGFGGLMCSAAAIRQCPDRTYGDVATGCRACDCDFRG
  TEGPGCDKASGRCLCRPGLTGPRCDQCQRGYCNRYPVCVACHPCFQTYDADLREQALRFG
  RLRNATASLWSGPGLEDRGLASRILDAKSKIEQIRAVLSSPAVTEQEVAQVASAILSLRR
  TLQGLQLDLPLEEETLSLPRDLESLDRSFNGLLTMYQRKREQFEKISSADPSGAFRMLST
  AYEQSAQAAQQVSDSSRLLDQLRDSRREAERLVRQAGGGGGTGSPKLVALRLEMSSLPDL
  TPTFNKLCGNSRQMACTPISCPGELCPQDNGTACGSRCRGVLPRAGGAFLMAGQVAEQLR
  GFNAQLQRTRQMIRAAEESASQIQSSAQRLETQVSASRSQMEEDVRRTRLLIQQVRDFLT
  DPDTDAATIQEVSEAVLALWLPTDSATVLQKMNEIQAIAARLPNVDLVLSQTKQDIARAR
  RLQAEAEEARSRAHAVEGQVEDVVGNLRQGTVALQEAQDTMQGTSRSLRLIQDRVAEVQQ
  VLRPAEKLVTSMTKQLGDFWTRMEELRHQARQQGAEAVQAQQLAEGASEQALSAQEGFER
  IKQKYAELKDRLGQSSMLGEQGARIQSVKTEAEELFGETMEMMDRMKDMELELLRGSQAI
  MLRSADLTGLEKRVEQIRDHINGRVLYYATCK
• Function: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
• Tissue Specificity: Found in the basement membranes (major component).
• KEGG Pathway:
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  ECM-receptor interaction (hsa04512)
  Toxoplasmosis (hsa05145)
  Amoebiasis (hsa05146)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Small cell lung cancer (hsa05222)
• Reactome Pathway:
  Assembly of collagen fibrils and other multimeric structures (R-HSA-2022090)
  Anchoring fibril formation (R-HSA-2214320)
  Laminin interactions (R-HSA-3000157)
  Non-integrin membrane-ECM interactions (R-HSA-3000171)
  Type I hemidesmosome assembly (R-HSA-446107)
  MET activates PTK2 signaling (R-HSA-8874081)
  Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Junctional epidermolysis bullosa	DISJRXWU	Definitive	Autosomal recessive	[1]
Junctional epidermolysis bullosa Herlitz type	DIS6X2W8	Definitive	Autosomal recessive	[2]
Junctional epidermolysis bullosa, non-Herlitz type	DISQM23S	Definitive	Autosomal recessive	[3]
Amelogenesis imperfecta type 1A	DISQHD6O	Strong	Autosomal dominant	[4]
Amelogenesis imperfecta type 1	DISVEG5A	Supportive	Autosomal dominant	[4]
Generalized junctional epidermolysis bullosa non-Herlitz type	DISSD3MX	Supportive	Autosomal recessive	[5]

31 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 Laminin subunit beta-3 (LAMB3).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Laminin subunit beta-3 (LAMB3).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Laminin subunit beta-3 (LAMB3).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Laminin subunit beta-3 (LAMB3).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Laminin subunit beta-3 (LAMB3).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Laminin subunit beta-3 (LAMB3).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Laminin subunit beta-3 (LAMB3).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Laminin subunit beta-3 (LAMB3).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Laminin subunit beta-3 (LAMB3).	[14]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Laminin subunit beta-3 (LAMB3).	[15]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Laminin subunit beta-3 (LAMB3).	[16]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Laminin subunit beta-3 (LAMB3).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Laminin subunit beta-3 (LAMB3).	[18]
Selenium	DM25CGV	Approved	Selenium increases the expression of Laminin subunit beta-3 (LAMB3).	[19]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Laminin subunit beta-3 (LAMB3).	[20]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Laminin subunit beta-3 (LAMB3).	[21]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Laminin subunit beta-3 (LAMB3).	[17]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Laminin subunit beta-3 (LAMB3).	[17]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Laminin subunit beta-3 (LAMB3).	[22]
Palbociclib	DMD7L94	Approved	Palbociclib increases the expression of Laminin subunit beta-3 (LAMB3).	[23]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the expression of Laminin subunit beta-3 (LAMB3).	[17]
Methylprednisolone	DM4BDON	Approved	Methylprednisolone decreases the expression of Laminin subunit beta-3 (LAMB3).	[17]
Coprexa	DMA0WEK	Phase 3	Coprexa decreases the expression of Laminin subunit beta-3 (LAMB3).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Laminin subunit beta-3 (LAMB3).	[26]
Sphingosine-1-Phosphate	DMJCQKA	Phase 1	Sphingosine-1-Phosphate increases the expression of Laminin subunit beta-3 (LAMB3).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Laminin subunit beta-3 (LAMB3).	[29]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Laminin subunit beta-3 (LAMB3).	[30]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Laminin subunit beta-3 (LAMB3).	[31]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Laminin subunit beta-3 (LAMB3).	[32]
LPA	DMI5XR1	Investigative	LPA increases the expression of Laminin subunit beta-3 (LAMB3).	[28]
Lysophosphatidylcholine	DMOGFVH	Investigative	Lysophosphatidylcholine increases the expression of Laminin subunit beta-3 (LAMB3).	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Laminin subunit beta-3 (LAMB3).	[25]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Laminin subunit beta-3 (LAMB3).	[27]

References

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