Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT83ZH5U)

• DOT Name: Inactive serine protease PAMR1 (PAMR1)
• Synonyms: Peptidase domain-containing protein associated with muscle regeneration 1; Regeneration-associated muscle protease homolog
• Gene Name: PAMR1
• Related Disease:
  Hepatocellular carcinoma
  Acute myocardial infarction
  Asthma
  Breast cancer
  Duchenne muscular dystrophy
  Glomerulonephritis
  Neoplasm
  Type-1/2 diabetes
  Breast carcinoma
  Myeloproliferative neoplasm
  X-linked intellectual disability
• UniProt ID: PAMR1_HUMAN
• Pfam ID: PF00431 ; PF00008 ; PF00084 ; PF00089
• Sequence:
  MELGCWTQLGLTFLQLLLISSLPREYTVINEACPGAEWNIMCRECCEYDQIECVCPGKRE
  VVGYTIPCCRNEENECDSCLIHPGCTIFENCKSCRNGSWGGTLDDFYVKGFYCAECRAGW
  YGGDCMRCGQVLRAPKGQILLESYPLNAHCEWTIHAKPGFVIQLRFVMLSLEFDYMCQYD
  YVEVRDGDNRDGQIIKRVCGNERPAPIQSIGSSLHVLFHSDGSKNFDGFHAIYEEITACS
  SSPCFHDGTCVLDKAGSYKCACLAGYTGQRCENLLEERNCSDPGGPVNGYQKITGGPGLI
  NGRHAKIGTVVSFFCNNSYVLSGNEKRTCQQNGEWSGKQPICIKACREPKISDLVRRRVL
  PMQVQSRETPLHQLYSAAFSKQKLQSAPTKKPALPFGDLPMGYQHLHTQLQYECISPFYR
  RLGSSRRTCLRTGKWSGRAPSCIPICGKIENITAPKTQGLRWPWQAAIYRRTSGVHDGSL
  HKGAWFLVCSGALVNERTVVVAAHCVTDLGKVTMIKTADLKVVLGKFYRDDDRDEKTIQS
  LQISAIILHPNYDPILLDADIAILKLLDKARISTRVQPICLAASRDLSTSFQESHITVAG
  WNVLADVRSPGFKNDTLRSGVVSVVDSLLCEEQHEDHGIPVSVTDNMFCASWEPTAPSDI
  CTAETGGIAAVSFPGRASPEPRWHLMGLVSWSYDKTCSHRLSTAFTKVLPFKDWIERNMK
• Function: May play a role in regeneration of skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[1]
Acute myocardial infarction	DISE3HTG	Strong	Biomarker	[2]
Asthma	DISW9QNS	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[4]
Duchenne muscular dystrophy	DISRQ3NV	Strong	Biomarker	[5]
Glomerulonephritis	DISPZIQ3	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[8]
Myeloproliferative neoplasm	DIS5KAPA	Limited	Biomarker	[9]
X-linked intellectual disability	DISYJBY3	Limited	Biomarker	[9]

3 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 Inactive serine protease PAMR1 (PAMR1).	[10]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Inactive serine protease PAMR1 (PAMR1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Inactive serine protease PAMR1 (PAMR1).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Inactive serine protease PAMR1 (PAMR1).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Inactive serine protease PAMR1 (PAMR1).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Inactive serine protease PAMR1 (PAMR1).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Inactive serine protease PAMR1 (PAMR1).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Inactive serine protease PAMR1 (PAMR1).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Inactive serine protease PAMR1 (PAMR1).	[16]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Inactive serine protease PAMR1 (PAMR1).	[17]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Inactive serine protease PAMR1 (PAMR1).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Inactive serine protease PAMR1 (PAMR1).	[18]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Inactive serine protease PAMR1 (PAMR1).	[20]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Inactive serine protease PAMR1 (PAMR1).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Inactive serine protease PAMR1 (PAMR1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Inactive serine protease PAMR1 (PAMR1).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Inactive serine protease PAMR1 (PAMR1).	[24]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Inactive serine protease PAMR1 (PAMR1).	[25]

References

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• [3] Deficiency of RAMP1 attenuates antigen-induced airway hyperresponsiveness in mice.PLoS One. 2014 Jul 10;9(7):e102356. doi: 10.1371/journal.pone.0102356. eCollection 2014.
• [4] Identification of novel epigenetically inactivated gene PAMR1 in breast carcinoma.Oncol Rep. 2015 Jan;33(1):267-73. doi: 10.3892/or.2014.3581. Epub 2014 Nov 3.
• [5] Cloning of cDNA encoding a regeneration-associated muscle protease whose expression is attenuated in cell lines derived from Duchenne muscular dystrophy patients.Am J Pathol. 2004 May;164(5):1773-82. doi: 10.1016/S0002-9440(10)63735-2.
• [6] Adrenomedullin (AM) and receptor-activity-modifying proteins in glomeruli with Thy.1 glomerulonephritis.Clin Exp Nephrol. 2004 Dec;8(4):316-21. doi: 10.1007/s10157-004-0309-8.
• [7] Cost-effectiveness of a primary care multidisciplinary Risk Assessment and Management Program for patients with diabetes mellitus (RAMP-DM) over lifetime.Endocrine. 2019 Feb;63(2):259-269. doi: 10.1007/s12020-018-1727-9. Epub 2018 Aug 28.
• [8] Development of diagnostic SCAR markers for genomic DNA amplifications in breast carcinoma by DNA cloning of high-GC RAMP-PCR fragments.Oncotarget. 2017 Jul 4;8(27):43866-43877. doi: 10.18632/oncotarget.16704.
• [9] The t(8;13)(p11;q11-12) rearrangement associated with an atypical myeloproliferative disorder fuses the fibroblast growth factor receptor 1 gene to a novel gene RAMP.Hum Mol Genet. 1998 Apr;7(4):637-42. doi: 10.1093/hmg/7.4.637.
• [10] 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.
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• [13] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [14] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [15] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
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• [17] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [18] 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.
• [19] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [20] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [21] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [22] 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.
• [23] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [24] 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.
• [25] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.