Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXR5PQ8)

• DOT Name: PAXIP1-associated glutamate-rich protein 1 (PAGR1)
• Synonyms: Glutamate-rich coactivator interacting with SRC1; GAS; PAXIP1-associated protein 1; PTIP-associated protein 1
• Gene Name: PAGR1
• Related Disease:
  Adenocarcinoma
  Anxiety
  Anxiety disorder
  Cardiac disease
  Parkinson disease
  Abscess
  Acute otitis media
  Advanced cancer
  Age-related macular degeneration
  Alzheimer disease
  Amyloidosis
  Anthrax
  Bacteremia
  Breast cancer
  Breast carcinoma
  Cardiovascular disease
  Cholangiocarcinoma
  Gastric cancer
  Glomerulonephritis
  Impetigo
  Mental disorder
  Myocardial infarction
  Myositis disease
  Necrotizing soft tissue infection
  Prostate cancer
  Prostate carcinoma
  Pyoderma
  Skin and skin-structure infection
  Small lymphocytic lymphoma
  Stomach cancer
  Streptococcal toxic-shock syndrome
  Streptococcus infection
  Tuberculosis
  Venous thromboembolism
  Vulvovaginitis
  Wilson disease
  Chronic obstructive pulmonary disease
  Influenza
  Bacterial meningitis
  Meningitis
  Non-small-cell lung cancer
  Rheumatic fever
  Rheumatic heart disease
  Type-1/2 diabetes
• UniProt ID: PAGR1_HUMAN
• Pfam ID: PF15364
• Sequence:
  MSLARGHGDTAASTAAPLSEEGEVTSGLQALAVEDTGGPSASAGKAEDEGEGGREETERE
  GSGGEEAQGEVPSAGGEEPAEEDSEDWCVPCSDEEVELPADGQPWMPPPSEIQRLYELLA
  AHGTLELQAEILPRRPPTPEAQSEEERSDEEPEAKEEEEEKPHMPTEFDFDDEPVTPKDS
  LIDRRRTPGSSARSQKREARLDKVLSDMKRHKKLEEQILRTGRDLFSLDSEDPSPASPPL
  RSSGSSLFPRQRKY
• Function: Its association with the histone methyltransferase MLL2/MLL3 complex is suggesting a role in epigenetic transcriptional activation. However, in association with PAXIP1/PTIP is proposed to function at least in part independently of the MLL2/MLL3 complex. Proposed to be recruited by PAXIP1 to sites of DNA damage where the PAGR1:PAXIP1 complex is required for cell survival in response to DNA damage independently of the MLL2/MLL3 complex. However, its function in DNA damage has been questioned. During immunoglobulin class switching in activated B-cells is involved in transcription regulation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus independently of the MLL2/MLL3 complex. Involved in both estrogen receptor-regulated gene transcription and estrogen-stimulated G1/S cell-cycle transition. Acts as a transcriptional cofactor for nuclear hormone receptors. Inhibits the induction properties of several steroid receptors such as NR3C1, AR and PPARG; the mechanism of inhibition appears to be gene-dependent.
• Tissue Specificity: Ubiquitously expressed.
• Reactome Pathway:
  Formation of WDR5-containing histone-modifying complexes (R-HSA-9772755)
  Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Biomarker	[1]
Anxiety	DISIJDBA	Definitive	Genetic Variation	[2]
Anxiety disorder	DISBI2BT	Definitive	Genetic Variation	[2]
Cardiac disease	DISVO1I5	Definitive	Genetic Variation	[2]
Parkinson disease	DISQVHKL	Definitive	Genetic Variation	[2]
Abscess	DISAP982	Strong	Biomarker	[3]
Acute otitis media	DISL8D8G	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Amyloidosis	DISHTAI2	Strong	Altered Expression	[7]
Anthrax	DISFPT78	Strong	Biomarker	[8]
Bacteremia	DIS6N9RZ	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[11]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[12]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[13]
Glomerulonephritis	DISPZIQ3	Strong	Biomarker	[14]
Impetigo	DISOF023	Strong	Biomarker	[15]
Mental disorder	DIS3J5R8	Strong	Biomarker	[16]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[11]
Myositis disease	DISCIXF0	Strong	Biomarker	[17]
Necrotizing soft tissue infection	DISTLZ8K	Strong	Biomarker	[18]
Prostate cancer	DISF190Y	Strong	Altered Expression	[19]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[19]
Pyoderma	DISZ6M7Y	Strong	Biomarker	[20]
Skin and skin-structure infection	DIS3F9EY	Strong	Biomarker	[21]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[22]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[13]
Streptococcal toxic-shock syndrome	DISCVXCW	Strong	Biomarker	[23]
Streptococcus infection	DIS04U9T	Strong	Biomarker	[24]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[25]
Venous thromboembolism	DISUR7CR	Strong	Genetic Variation	[11]
Vulvovaginitis	DISS1UT7	Strong	Biomarker	[26]
Wilson disease	DISVS9H7	Strong	Biomarker	[27]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Genetic Variation	[28]
Influenza	DIS3PNU3	moderate	Genetic Variation	[29]
Bacterial meningitis	DISRP9SL	Limited	Genetic Variation	[30]
Meningitis	DISQABAA	Limited	Biomarker	[30]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[31]
Rheumatic fever	DISLUF66	Limited	Biomarker	[32]
Rheumatic heart disease	DISCI8JQ	Limited	Biomarker	[33]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[34]

13 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 PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[37]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[38]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[39]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[40]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[44]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[45]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[46]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[48]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[49]

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 PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[42]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of PAXIP1-associated glutamate-rich protein 1 (PAGR1).	[47]

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