Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJMTM72)

• DOT Name: Laminin subunit gamma-2 (LAMC2)
• Synonyms: Cell-scattering factor 140 kDa subunit; CSF 140 kDa subunit; Epiligrin subunit gamma; Kalinin subunit gamma; Kalinin/nicein/epiligrin 100 kDa subunit; Ladsin 140 kDa subunit; Laminin B2t chain; Laminin-5 subunit gamma; Large adhesive scatter factor 140 kDa subunit; Nicein subunit gamma
• Gene Name: LAMC2
• Related Disease:
  Junctional epidermolysis bullosa
  Junctional epidermolysis bullosa Herlitz type
  Junctional epidermolysis bullosa, non-Herlitz type
  Generalized junctional epidermolysis bullosa non-Herlitz type
• UniProt ID: LAMC2_HUMAN
• Pfam ID: PF00052 ; PF00053
• Sequence:
  MPALWLGCCLCFSLLLPAARATSRREVCDCNGKSRQCIFDRELHRQTGNGFRCLNCNDNT
  DGIHCEKCKNGFYRHRERDRCLPCNCNSKGSLSARCDNSGRCSCKPGVTGARCDRCLPGF
  HMLTDAGCTQDQRLLDSKCDCDPAGIAGPCDAGRCVCKPAVTGERCDRCRSGYYNLDGGN
  PEGCTQCFCYGHSASCRSSAEYSVHKITSTFHQDVDGWKAVQRNGSPAKLQWSQRHQDVF
  SSAQRLDPVYFVAPAKFLGNQQVSYGQSLSFDYRVDRGGRHPSAHDVILEGAGLRITAPL
  MPLGKTLPCGLTKTYTFRLNEHPSNNWSPQLSYFEYRRLLRNLTALRIRATYGEYSTGYI
  DNVTLISARPVSGAPAPWVEQCICPVGYKGQFCQDCASGYKRDSARLGPFGTCIPCNCQG
  GGACDPDTGDCYSGDENPDIECADCPIGFYNDPHDPRSCKPCPCHNGFSCSVMPETEEVV
  CNNCPPGVTGARCELCADGYFGDPFGEHGPVRPCQPCQCNNNVDPSASGNCDRLTGRCLK
  CIHNTAGIYCDQCKAGYFGDPLAPNPADKCRACNCNPMGSEPVGCRSDGTCVCKPGFGGP
  NCEHGAFSCPACYNQVKIQMDQFMQQLQRMEALISKAQGGDGVVPDTELEGRMQQAEQAL
  QDILRDAQISEGASRSLGLQLAKVRSQENSYQSRLDDLKMTVERVRALGSQYQNRVRDTH
  RLITQMQLSLAESEASLGNTNIPASDHYVGPNGFKSLAQEATRLAESHVESASNMEQLTR
  ETEDYSKQALSLVRKALHEGVGSGSGSPDGAVVQGLVEKLEKTKSLAQQLTREATQAEIE
  ADRSYQHSLRLLDSVSRLQGVSDQSFQVEEAKRIKQKADSLSSLVTRHMDEFKRTQKNLG
  NWKEEAQQLLQNGKSGREKSDQLLSRANLAKSRAQEALSMGNATFYEVESILKNLREFDL
  QVDNRKAEAEEAMKRLSYISQKVSDASDKTQQAERALGSAAADAQRAKNGAGEALEISSE
  IEQEIGSLNLEANVTADGALAMEKGLASLKSEMREVEGELERKELEFDTNMDAVQMVITE
  AQKVDTRAKNAGVTIQDTLNTLDGLLHLMDQPLSVDEEGLVLLEQKLSRAKTQINSQLRP
  MMSELEERARQQRGHLHLLETSIDGILADVKNLENIRDNLPPGCYNTQALEQQ
• 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. Ladsin exerts cell-scattering activity toward a wide variety of cells, including epithelial, endothelial, and fibroblastic cells.
• Tissue Specificity: The large variant is expressed only in specific epithelial cells of embryonic and neonatal tissues. In 17-week old embryo the small variant is found in cerebral cortex, lung, and distal tubes of kidney, but not in epithelia except for distal tubuli.
• 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

4 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	Strong	Autosomal recessive	[2]
Junctional epidermolysis bullosa, non-Herlitz type	DISQM23S	Strong	Autosomal recessive	[2]
Generalized junctional epidermolysis bullosa non-Herlitz type	DISSD3MX	Supportive	Autosomal recessive	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Laminin subunit gamma-2 (LAMC2) decreases the response to substance of Arsenic trioxide.	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Laminin subunit gamma-2 (LAMC2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Laminin subunit gamma-2 (LAMC2).	[17]

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 Laminin subunit gamma-2 (LAMC2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Laminin subunit gamma-2 (LAMC2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Laminin subunit gamma-2 (LAMC2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Laminin subunit gamma-2 (LAMC2).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Laminin subunit gamma-2 (LAMC2).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Laminin subunit gamma-2 (LAMC2).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Laminin subunit gamma-2 (LAMC2).	[11]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Laminin subunit gamma-2 (LAMC2).	[12]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Laminin subunit gamma-2 (LAMC2).	[13]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Laminin subunit gamma-2 (LAMC2).	[14]
Palbociclib	DMD7L94	Approved	Palbociclib increases the expression of Laminin subunit gamma-2 (LAMC2).	[15]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Laminin subunit gamma-2 (LAMC2).	[13]
Mechlorethamine	DM0CVXA	Approved	Mechlorethamine decreases the expression of Laminin subunit gamma-2 (LAMC2).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Laminin subunit gamma-2 (LAMC2).	[18]
Sphingosine-1-Phosphate	DMJCQKA	Phase 1	Sphingosine-1-Phosphate increases the expression of Laminin subunit gamma-2 (LAMC2).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Laminin subunit gamma-2 (LAMC2).	[20]
Roxithromycin	DMVMIK2	Withdrawn from market	Roxithromycin decreases the expression of Laminin subunit gamma-2 (LAMC2).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Laminin subunit gamma-2 (LAMC2).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Laminin subunit gamma-2 (LAMC2).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Laminin subunit gamma-2 (LAMC2).	[24]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Laminin subunit gamma-2 (LAMC2).	[25]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Laminin subunit gamma-2 (LAMC2).	[26]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Laminin subunit gamma-2 (LAMC2).	[27]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Laminin subunit gamma-2 (LAMC2).	[28]
LPA	DMI5XR1	Investigative	LPA increases the expression of Laminin subunit gamma-2 (LAMC2).	[19]
Lysophosphatidylcholine	DMOGFVH	Investigative	Lysophosphatidylcholine increases the expression of Laminin subunit gamma-2 (LAMC2).	[19]

References

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