Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7K4494)

DOT Name Protein mono-ADP-ribosyltransferase PARP9 (PARP9)
Synonyms EC 2.4.2.-; ADP-ribosyltransferase diphtheria toxin-like 9; ARTD9; B aggressive lymphoma protein; Poly polymerase 9; PARP-9
Gene Name PARP9
Related Disease
B-cell neoplasm ( )
Rheumatoid arthritis ( )
Acute lymphocytic leukaemia ( )
Acute monocytic leukemia ( )
Acute myelogenous leukaemia ( )
Adult respiratory distress syndrome ( )
Allergic asthma ( )
Anca-associated vasculitis ( )
B-cell lymphoma ( )
Bacterial infection ( )
Bipolar disorder ( )
Breast cancer ( )
Breast carcinoma ( )
Childhood acute lymphoblastic leukemia ( )
Chronic obstructive pulmonary disease ( )
Cutaneous porphyria ( )
Hepatocellular carcinoma ( )
Hypersensitivity pneumonitis ( )
Leukopenia ( )
Liver failure ( )
Malignant soft tissue neoplasm ( )
Metastatic prostate carcinoma ( )
Obesity ( )
Pneumonitis ( )
Prostate cancer ( )
Prostate carcinoma ( )
Pulmonary sarcoidosis ( )
Pulmonary tuberculosis ( )
Sarcoidosis ( )
Sarcoma ( )
Schizophrenia ( )
Substance abuse ( )
Tuberculosis ( )
Alcohol dependence ( )
Methicillin-resistant staphylococci infection ( )
Small lymphocytic lymphoma ( )
Systemic sclerosis ( )
Adult lymphoma ( )
Cystic fibrosis ( )
Invasive aspergillosis ( )
Lymphoma ( )
Lymphoproliferative syndrome ( )
MALT lymphoma ( )
Pediatric lymphoma ( )
Pneumocystis pneumonia ( )
Pulmonary disease ( )
UniProt ID
PARP9_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5AIL
EC Number
2.4.2.-
Pfam ID
PF01661
Sequence
MDFSMVAGAAAYNEKSGRITSLSLLFQKVFAQIFPQWRKGNTEECLPYKCSETGALGENY
SWQIPINHNDFKILKNNERQLCEVLQNKFGCISTLVSPVQEGNSKSLQVFRKMLTPRIEL
SVWKDDLTTHAVDAVVNAANEDLLHGGGLALALVKAGGFEIQEESKQFVARYGKVSAGEI
AVTGAGRLPCKQIIHAVGPRWMEWDKQGCTGKLQRAIVSILNYVIYKNTHIKTVAIPALS
SGIFQFPLNLCTKTIVETIRVSLQGKPMMSNLKEIHLVSNEDPTVAAFKAASEFILGKSE
LGQETTPSFNAMVVNNLTLQIVQGHIEWQTADVIVNSVNPHDITVGPVAKSILQQAGVEM
KSEFLATKAKQFQRSQLVLVTKGFNLFCKYIYHVLWHSEFPKPQILKHAMKECLEKCIEQ
NITSISFPALGTGNMEIKKETAAEILFDEVLTFAKDHVKHQLTVKFVIFPTDLEIYKAFS
SEMAKRSKMLSLNNYSVPQSTREEKRENGLEARSPAINLMGFNVEEMYEAHAWIQRILSL
QNHHIIENNHILYLGRKEHDILSQLQKTSSVSITEIISPGRTELEIEGARADLIEVVMNI
EDMLCKVQEEMARKKERGLWRSLGQWTIQQQKTQDEMKENIIFLKCPVPPTQELLDQKKQ
FEKCGLQVLKVEKIDNEVLMAAFQRKKKMMEEKLHRQPVSHRLFQQVPYQFCNVVCRVGF
QRMYSTPCDPKYGAGIYFTKNLKNLAEKAKKISAADKLIYVFEAEVLTGFFCQGHPLNIV
PPPLSPGAIDGHDSVVDNVSSPETFVIFSGMQAIPQYLWTCTQEYVQSQDYSSGPMRPFA
QHPWRGFASGSPVD
Function
ADP-ribosyltransferase which, in association with E3 ligase DTX3L, plays a role in DNA damage repair and in immune responses including interferon-mediated antiviral defenses. Within the complex, enhances DTX3L E3 ligase activity which is further enhanced by PARP9 binding to poly(ADP-ribose). In association with DTX3L and in presence of E1 and E2 enzymes, mediates NAD(+)-dependent mono-ADP-ribosylation of ubiquitin which prevents ubiquitin conjugation to substrates such as histones. During DNA repair, PARP1 recruits PARP9/BAL1-DTX3L complex to DNA damage sites via PARP9 binding to ribosylated PARP1. Subsequent PARP1-dependent PARP9/BAL1-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites. In response to DNA damage, PARP9-DTX3L complex is required for efficient non-homologous end joining (NHEJ); the complex function is negatively modulated by PARP9 activity. Dispensable for B-cell receptor (BCR) assembly through V(D)J recombination and class switch recombination (CSR). In macrophages, positively regulates pro-inflammatory cytokines production in response to IFNG stimulation by suppressing PARP14-mediated STAT1 ADP-ribosylation and thus promoting STAT1 phosphorylation. Also suppresses PARP14-mediated STAT6 ADP-ribosylation.
Tissue Specificity
Expressed in lymphocyte-rich tissues, spleen, lymph nodes, peripheral blood lymphocytes and colonic mucosa . Expressed in macrophages . Also expressed in nonhematopoietic tissues such as heart and skeletal muscle . Isoform 2 is the predominant form . Most abundantly expressed in lymphomas with a brisk host inflammatory response . In diffuse large B-cell lymphomas tumors, expressed specifically by malignant B-cells .
Reactome Pathway
Maturation of nucleoprotein (R-HSA-9683610 )
Maturation of nucleoprotein (R-HSA-9694631 )
Nicotinamide salvaging (R-HSA-197264 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
B-cell neoplasm DISVY326 Definitive Biomarker [1]
Rheumatoid arthritis DISTSB4J Definitive Posttranslational Modification [2]
Acute lymphocytic leukaemia DISPX75S Strong Genetic Variation [3]
Acute monocytic leukemia DIS28NEL Strong Genetic Variation [3]
Acute myelogenous leukaemia DISCSPTN Strong Genetic Variation [4]
Adult respiratory distress syndrome DISIJV47 Strong Biomarker [5]
Allergic asthma DISHF0H3 Strong Biomarker [6]
Anca-associated vasculitis DISU3CNU Strong Altered Expression [7]
B-cell lymphoma DISIH1YQ Strong Biomarker [8]
Bacterial infection DIS5QJ9S Strong Biomarker [9]
Bipolar disorder DISAM7J2 Strong Genetic Variation [10]
Breast cancer DIS7DPX1 Strong Biomarker [11]
Breast carcinoma DIS2UE88 Strong Biomarker [11]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Genetic Variation [3]
Chronic obstructive pulmonary disease DISQCIRF Strong Biomarker [12]
Cutaneous porphyria DISUQTL2 Strong Biomarker [13]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [14]
Hypersensitivity pneumonitis DIS5IW5K Strong Biomarker [15]
Leukopenia DISJMBMM Strong Biomarker [16]
Liver failure DISLGEL6 Strong Biomarker [17]
Malignant soft tissue neoplasm DISTC6NO Strong Biomarker [18]
Metastatic prostate carcinoma DISVBEZ9 Strong Altered Expression [8]
Obesity DIS47Y1K Strong Biomarker [19]
Pneumonitis DIS88E0K Strong Biomarker [20]
Prostate cancer DISF190Y Strong Biomarker [11]
Prostate carcinoma DISMJPLE Strong Biomarker [11]
Pulmonary sarcoidosis DIS1XQCN Strong Biomarker [21]
Pulmonary tuberculosis DIS6FLUM Strong Altered Expression [22]
Sarcoidosis DISE5B8Z Strong Biomarker [23]
Sarcoma DISZDG3U Strong Biomarker [18]
Schizophrenia DISSRV2N Strong Genetic Variation [24]
Substance abuse DIS327VW Strong Genetic Variation [25]
Tuberculosis DIS2YIMD Strong Biomarker [22]
Alcohol dependence DIS4ZSCO moderate Genetic Variation [26]
Methicillin-resistant staphylococci infection DIS6DRDZ moderate Biomarker [27]
Small lymphocytic lymphoma DIS30POX moderate Altered Expression [28]
Systemic sclerosis DISF44L6 moderate Biomarker [29]
Adult lymphoma DISK8IZR Limited Genetic Variation [30]
Cystic fibrosis DIS2OK1Q Limited Biomarker [31]
Invasive aspergillosis DISAI029 Limited Biomarker [32]
Lymphoma DISN6V4S Limited Genetic Variation [30]
Lymphoproliferative syndrome DISMVL8O Limited Biomarker [33]
MALT lymphoma DIS1AVVE Limited Genetic Variation [33]
Pediatric lymphoma DIS51BK2 Limited Genetic Variation [30]
Pneumocystis pneumonia DISFSOM3 Limited Genetic Variation [34]
Pulmonary disease DIS6060I Limited Biomarker [35]
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⏷ Show the Full List of 46 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 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 Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [36]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [37]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [38]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [39]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [40]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [41]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [37]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [42]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [43]
Triclosan DMZUR4N Approved Triclosan increases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [44]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [45]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [46]
Belinostat DM6OC53 Phase 2 Belinostat decreases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [47]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [48]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [49]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Protein mono-ADP-ribosyltransferase PARP9 (PARP9). [50]
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⏷ Show the Full List of 16 Drug(s)

References

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