Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAAW121)

• DOT Name: Adherens junction-associated protein 1 (AJAP1)
• Synonyms: Membrane protein shrew-1
• Gene Name: AJAP1
• Related Disease:
  Neuroblastoma
  Advanced cancer
  Esophageal squamous cell carcinoma
  Hepatocellular carcinoma
  Malignant glioma
  Glioblastoma multiforme
  Glioma
  Adult glioblastoma
• UniProt ID: AJAP1_HUMAN
• Pfam ID: PF15298
• Sequence:
  MWIQQLLGLSSMSIRWPGRPLGSHAWILIAMFQLAVDLPACEALGPGPEFWLLPRSPPRP
  PRLWSFRSGQPARVPAPVWSPRPPRVERIHGQMQMPRARRAHRPRDQAAALVPKAGLAKP
  PAAAKSSPSLASSSSSSSSAVAGGAPEQQALLRRGKRHLQGDGLSSFDSRGSRPTTETEF
  IAWGPTGDEEALESNTFPGVYGPTTVSILQTRKTTVAATTTTTTTATPMTLQTKGFTESL
  DPRRRIPGGVSTTEPSTSPSNNGEVTQPPRILGEASGLAVHQIITITVSLIMVIAALITT
  LVLKNCCAQSGNTRRNSHQRKTNQQEESCQNLTDFPSARVPSSLDIFTAYNETLQCSHEC
  VRASVPVYTDETLHSTTGEYKSTFNGNRPSSSDRHLIPVAFVSEKWFEISC
• Function: Plays a role in cell adhesion and cell migration.
• Tissue Specificity: Expressed in uterus and pancreas (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[4]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[5]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[6]
Glioma	DIS5RPEH	moderate	Altered Expression	[7]
Adult glioblastoma	DISVP4LU	Limited	Altered Expression	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Adherens junction-associated protein 1 (AJAP1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Adherens junction-associated protein 1 (AJAP1).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Adherens junction-associated protein 1 (AJAP1).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Adherens junction-associated protein 1 (AJAP1).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Adherens junction-associated protein 1 (AJAP1).	[12]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Adherens junction-associated protein 1 (AJAP1).	[11]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Adherens junction-associated protein 1 (AJAP1).	[13]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Adherens junction-associated protein 1 (AJAP1).	[14]
Methamphetamine	DMPM4SK	Approved	Methamphetamine increases the expression of Adherens junction-associated protein 1 (AJAP1).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Adherens junction-associated protein 1 (AJAP1).	[11]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 increases the expression of Adherens junction-associated protein 1 (AJAP1).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Adherens junction-associated protein 1 (AJAP1).	[17]

References

• [1] Complex constitutional subtelomeric 1p36.3 deletion/duplication in a mentally retarded child with neonatal neuroblastoma.Eur J Med Genet. 2008 Nov-Dec;51(6):679-84. doi: 10.1016/j.ejmg.2008.06.004. Epub 2008 Jul 11.
• [2] -Catenin nuclear localization positively feeds back on EGF/EGFR-attenuated AJAP1 expression in breast cancer.J Exp Clin Cancer Res. 2019 Jun 6;38(1):238. doi: 10.1186/s13046-019-1252-6.
• [3] Endogenous AJAP1 associates with the cytoskeleton and attenuates angiogenesis in endothelial cells.Biol Open. 2017 Jun 15;6(6):723-731. doi: 10.1242/bio.022335.
• [4] MiR-552 promotes the proliferation, migration and EMT of hepatocellular carcinoma cells by inhibiting AJAP1 expression.J Cell Mol Med. 2019 Feb;23(2):1541-1552. doi: 10.1111/jcmm.14062. Epub 2018 Dec 30.
• [5] Adherens junctional associated protein-1: a novel 1p36 tumor suppressor candidate in gliomas (Review).Int J Oncol. 2014 Jul;45(1):13-7. doi: 10.3892/ijo.2014.2425. Epub 2014 May 8.
• [6] The adherens junction-associated protein 1 is a negative transcriptional regulator of MAGEA2, which potentiates temozolomide-induced apoptosis in GBM.Int J Oncol. 2014 Apr;44(4):1243-51. doi: 10.3892/ijo.2014.2277. Epub 2014 Jan 24.
• [7] AJAP1 expression modulates glioma cell motility and correlates with tumor growth and survival.Int J Oncol. 2018 Jan;52(1):47-54. doi: 10.3892/ijo.2017.4184. Epub 2017 Nov 1.
• [8] Deletion or epigenetic silencing of AJAP1 on 1p36 in glioblastoma.Mol Cancer Res. 2012 Feb;10(2):208-17. doi: 10.1158/1541-7786.MCR-10-0109. Epub 2012 Jan 12.
• [9] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [10] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [13] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [14] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [15] Methamphetamine alters the normal progression by inducing cell cycle arrest in astrocytes. PLoS One. 2014 Oct 7;9(10):e109603.
• [16] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [17] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.