General Information of Target

Target ID LDTP08610
Target Name Protein mono-ADP-ribosyltransferase PARP9 (PARP9)
Gene Name PARP9
Gene ID 83666
Synonyms
BAL; BAL1; Protein mono-ADP-ribosyltransferase PARP9; EC 2.4.2.-; ADP-ribosyltransferase diphtheria toxin-like 9; ARTD9; B aggressive lymphoma protein; Poly [ADP-ribose] polymerase 9; PARP-9
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MDFSMVAGAAAYNEKSGRITSLSLLFQKVFAQIFPQWRKGNTEECLPYKCSETGALGENY
SWQIPINHNDFKILKNNERQLCEVLQNKFGCISTLVSPVQEGNSKSLQVFRKMLTPRIEL
SVWKDDLTTHAVDAVVNAANEDLLHGGGLALALVKAGGFEIQEESKQFVARYGKVSAGEI
AVTGAGRLPCKQIIHAVGPRWMEWDKQGCTGKLQRAIVSILNYVIYKNTHIKTVAIPALS
SGIFQFPLNLCTKTIVETIRVSLQGKPMMSNLKEIHLVSNEDPTVAAFKAASEFILGKSE
LGQETTPSFNAMVVNNLTLQIVQGHIEWQTADVIVNSVNPHDITVGPVAKSILQQAGVEM
KSEFLATKAKQFQRSQLVLVTKGFNLFCKYIYHVLWHSEFPKPQILKHAMKECLEKCIEQ
NITSISFPALGTGNMEIKKETAAEILFDEVLTFAKDHVKHQLTVKFVIFPTDLEIYKAFS
SEMAKRSKMLSLNNYSVPQSTREEKRENGLEARSPAINLMGFNVEEMYEAHAWIQRILSL
QNHHIIENNHILYLGRKEHDILSQLQKTSSVSITEIISPGRTELEIEGARADLIEVVMNI
EDMLCKVQEEMARKKERGLWRSLGQWTIQQQKTQDEMKENIIFLKCPVPPTQELLDQKKQ
FEKCGLQVLKVEKIDNEVLMAAFQRKKKMMEEKLHRQPVSHRLFQQVPYQFCNVVCRVGF
QRMYSTPCDPKYGAGIYFTKNLKNLAEKAKKISAADKLIYVFEAEVLTGFFCQGHPLNIV
PPPLSPGAIDGHDSVVDNVSSPETFVIFSGMQAIPQYLWTCTQEYVQSQDYSSGPMRPFA
QHPWRGFASGSPVD
Target Bioclass
Enzyme
Family
ARTD/PARP family
Subcellular location
Cytoplasm, cytosol
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.
Uniprot ID
Q8IXQ6
Ensemble ID
ENST00000360356.6
HGNC ID
HGNC:24118
ChEMBL ID
CHEMBL4295895

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C388(8.23)  LDD0204  [1]
4-Iodoacetamidophenylacetylene
 Probe Info 
C664(0.00); C91(0.00)  LDD0038  [2]
IA-alkyne
 Probe Info 
C664(0.00); C728(0.00); C91(0.00); C82(0.00)  LDD0036  [2]
Lodoacetamide azide
 Probe Info 
C664(0.00); C82(0.00); C251(0.00); C728(0.00)  LDD0037  [2]
NAIA_5
 Probe Info 
N.A.  LDD2223  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0296  AC35 PaTu 8988t C728(1.04)  LDD1175  [4]
 LDCM0297  AC36 PaTu 8988t C728(1.28)  LDD1176  [4]
 LDCM0298  AC37 PaTu 8988t C728(1.36)  LDD1177  [4]
 LDCM0299  AC38 PaTu 8988t C728(1.29)  LDD1178  [4]
 LDCM0300  AC39 PaTu 8988t C728(1.27)  LDD1179  [4]
 LDCM0302  AC40 PaTu 8988t C728(1.41)  LDD1181  [4]
 LDCM0303  AC41 PaTu 8988t C728(1.21)  LDD1182  [4]
 LDCM0304  AC42 PaTu 8988t C728(1.31)  LDD1183  [4]
 LDCM0305  AC43 PaTu 8988t C728(1.19)  LDD1184  [4]
 LDCM0306  AC44 PaTu 8988t C728(1.60)  LDD1185  [4]
 LDCM0307  AC45 PaTu 8988t C728(1.43)  LDD1186  [4]
 LDCM0102  BDHI 8 Jurkat C388(8.23)  LDD0204  [1]
 LDCM0387  CL117 PaTu 8988t C728(1.15)  LDD1266  [4]
 LDCM0388  CL118 PaTu 8988t C728(1.29)  LDD1267  [4]
 LDCM0389  CL119 PaTu 8988t C728(1.23)  LDD1268  [4]
 LDCM0391  CL120 PaTu 8988t C728(1.11)  LDD1270  [4]
 LDCM0420  CL31 PaTu 8988t C728(1.11)  LDD1299  [4]
 LDCM0421  CL32 PaTu 8988t C728(1.14)  LDD1300  [4]
 LDCM0422  CL33 PaTu 8988t C728(1.11)  LDD1301  [4]
 LDCM0423  CL34 PaTu 8988t C728(1.30)  LDD1302  [4]
 LDCM0424  CL35 PaTu 8988t C728(1.33)  LDD1303  [4]
 LDCM0425  CL36 PaTu 8988t C728(1.08)  LDD1304  [4]
 LDCM0426  CL37 PaTu 8988t C728(1.27)  LDD1305  [4]
 LDCM0428  CL39 PaTu 8988t C728(1.25)  LDD1307  [4]
 LDCM0430  CL40 PaTu 8988t C728(1.02)  LDD1309  [4]
 LDCM0431  CL41 PaTu 8988t C728(1.28)  LDD1310  [4]
 LDCM0432  CL42 PaTu 8988t C728(1.23)  LDD1311  [4]
 LDCM0433  CL43 PaTu 8988t C728(1.23)  LDD1312  [4]
 LDCM0434  CL44 PaTu 8988t C728(1.34)  LDD1313  [4]
 LDCM0435  CL45 PaTu 8988t C728(1.35)  LDD1314  [4]
 LDCM0453  CL61 PaTu 8988t C728(1.00)  LDD1332  [4]
 LDCM0454  CL62 PaTu 8988t C728(1.52)  LDD1333  [4]
 LDCM0455  CL63 PaTu 8988t C728(1.72)  LDD1334  [4]
 LDCM0456  CL64 PaTu 8988t C728(1.57)  LDD1335  [4]
 LDCM0457  CL65 PaTu 8988t C728(1.33)  LDD1336  [4]
 LDCM0458  CL66 PaTu 8988t C728(1.37)  LDD1337  [4]
 LDCM0459  CL67 PaTu 8988t C728(1.94)  LDD1338  [4]
 LDCM0460  CL68 PaTu 8988t C728(1.66)  LDD1339  [4]
 LDCM0461  CL69 PaTu 8988t C728(2.07)  LDD1340  [4]
 LDCM0463  CL70 PaTu 8988t C728(1.09)  LDD1342  [4]
 LDCM0464  CL71 PaTu 8988t C728(1.93)  LDD1343  [4]
 LDCM0465  CL72 PaTu 8988t C728(1.28)  LDD1344  [4]
 LDCM0466  CL73 PaTu 8988t C728(1.53)  LDD1345  [4]
 LDCM0467  CL74 PaTu 8988t C728(1.29)  LDD1346  [4]
 LDCM0469  CL76 PaTu 8988t C728(1.11)  LDD1348  [4]
 LDCM0470  CL77 PaTu 8988t C728(1.19)  LDD1349  [4]
 LDCM0471  CL78 PaTu 8988t C728(1.35)  LDD1350  [4]
 LDCM0472  CL79 PaTu 8988t C728(1.52)  LDD1351  [4]
 LDCM0474  CL80 PaTu 8988t C728(1.37)  LDD1353  [4]
 LDCM0475  CL81 PaTu 8988t C728(1.32)  LDD1354  [4]
 LDCM0476  CL82 PaTu 8988t C728(1.53)  LDD1355  [4]
 LDCM0477  CL83 PaTu 8988t C728(1.68)  LDD1356  [4]
 LDCM0478  CL84 PaTu 8988t C728(1.15)  LDD1357  [4]
 LDCM0479  CL85 PaTu 8988t C728(1.13)  LDD1358  [4]
 LDCM0480  CL86 PaTu 8988t C728(1.28)  LDD1359  [4]
 LDCM0481  CL87 PaTu 8988t C728(1.36)  LDD1360  [4]
 LDCM0482  CL88 PaTu 8988t C728(1.57)  LDD1361  [4]
 LDCM0483  CL89 PaTu 8988t C728(1.10)  LDD1362  [4]
 LDCM0485  CL90 PaTu 8988t C728(1.41)  LDD1364  [4]
 LDCM0468  Fragment33 PaTu 8988t C728(1.60)  LDD1347  [4]
 LDCM0427  Fragment51 PaTu 8988t C728(1.39)  LDD1306  [4]
 LDCM0022  KB02 22RV1 C82(1.74); C251(1.59)  LDD2243  [5]
 LDCM0023  KB03 Jurkat C728(4.31)  LDD0209  [1]
 LDCM0024  KB05 COLO792 C728(2.24); C251(1.73)  LDD3310  [5]

References

1 Covalent Inhibition by a Natural Product-Inspired Latent Electrophile. J Am Chem Soc. 2023 May 24;145(20):11097-11109. doi: 10.1021/jacs.3c00598. Epub 2023 May 15.
2 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
3 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
4 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.
5 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840