| IED ID | IndEnz0002009980 |
| Enzyme Type ID | protease009980 |
| Protein Name |
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 |
| Gene Name | PARP9 BAL BAL1 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MDFSMVAGAAAYNEKSGRITSLSLLFQKVFAQIFPQWRKGNTEECLPYKCSETGALGENYSWQIPINHNDFKILKNNERQLCEVLQNKFGCISTLVSPVQEGNSKSLQVFRKMLTPRIELSVWKDDLTTHAVDAVVNAANEDLLHGGGLALALVKAGGFEIQEESKQFVARYGKVSAGEIAVTGAGRLPCKQIIHAVGPRWMEWDKQGCTGKLQRAIVSILNYVIYKNTHIKTVAIPALSSGIFQFPLNLCTKTIVETIRVSLQGKPMMSNLKEIHLVSNEDPTVAAFKAASEFILGKSELGQETTPSFNAMVVNNLTLQIVQGHIEWQTADVIVNSVNPHDITVGPVAKSILQQAGVEMKSEFLATKAKQFQRSQLVLVTKGFNLFCKYIYHVLWHSEFPKPQILKHAMKECLEKCIEQNITSISFPALGTGNMEIKKETAAEILFDEVLTFAKDHVKHQLTVKFVIFPTDLEIYKAFSSEMAKRSKMLSLNNYSVPQSTREEKRENGLEARSPAINLMGFNVEEMYEAHAWIQRILSLQNHHIIENNHILYLGRKEHDILSQLQKTSSVSITEIISPGRTELEIEGARADLIEVVMNIEDMLCKVQEEMARKKERGLWRSLGQWTIQQQKTQDEMKENIIFLKCPVPPTQELLDQKKQFEKCGLQVLKVEKIDNEVLMAAFQRKKKMMEEKLHRQPVSHRLFQQVPYQFCNVVCRVGFQRMYSTPCDPKYGAGIYFTKNLKNLAEKAKKISAADKLIYVFEAEVLTGFFCQGHPLNIVPPPLSPGAIDGHDSVVDNVSSPETFVIFSGMQAIPQYLWTCTQEYVQSQDYSSGPMRPFAQHPWRGFASGSPVD |
| Enzyme Length | 854 |
| Uniprot Accession Number | Q8IXQ6 |
| Absorption | |
| Active Site | |
| Activity Regulation | ACTIVITY REGULATION: Binding to poly(ADP-ribose) does not affect its activity. {ECO:0000269|PubMed:28525742}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=[protein]-C-terminal glycine + NAD(+) = [protein]-C-terminal O-(ADP-D-ribosyl)-glycine + nicotinamide; Xref=Rhea:RHEA:58268, Rhea:RHEA-COMP:15093, Rhea:RHEA-COMP:15095, ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:83148, ChEBI:CHEBI:142558; Evidence={ECO:0000269|PubMed:28525742};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58269; Evidence={ECO:0000269|PubMed:28525742}; |
| DNA Binding | |
| EC Number | 2.4.2.- |
| Enzyme Function | 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 (PubMed:16809771, PubMed:23230272, PubMed:26479788, PubMed:27796300). Within the complex, enhances DTX3L E3 ligase activity which is further enhanced by PARP9 binding to poly(ADP-ribose) (PubMed:28525742). 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 (PubMed:28525742). During DNA repair, PARP1 recruits PARP9/BAL1-DTX3L complex to DNA damage sites via PARP9 binding to ribosylated PARP1 (PubMed:23230272). 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 (PubMed:23230272, PubMed:28525742). 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 (PubMed:28525742). Dispensable for B-cell receptor (BCR) assembly through V(D)J recombination and class switch recombination (CSR) (By similarity). 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 (PubMed:27796300). Also suppresses PARP14-mediated STAT6 ADP-ribosylation (PubMed:27796300). {ECO:0000250|UniProtKB:Q8CAS9, ECO:0000269|PubMed:16809771, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:27796300, ECO:0000269|PubMed:28525742}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (3); Beta strand (8); Chain (1); Domain (3); Helix (6); Mutagenesis (9); Natural variant (4); Sequence conflict (2) |
| Keywords | 3D-structure;ADP-ribosylation;Alternative splicing;Antiviral defense;Cytoplasm;DNA damage;DNA repair;Immunity;Innate immunity;NAD;Nucleus;Reference proteome;Repeat;Transferase |
| Interact With | |
| Induction | INDUCTION: Up-regulated by IFNG in macrophages and in B-cell lymphoma cell lines (PubMed:16809771, PubMed:27796300, PubMed:26479788). Up-regulated by IFNB1 or viral infection (PubMed:26479788). Down-regulated by IL4 in macrophages (PubMed:27796300). {ECO:0000269|PubMed:16809771, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:27796300}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:16809771, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:27796300}. Nucleus {ECO:0000269|PubMed:11110709, ECO:0000269|PubMed:16809771, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28525742}. Note=Shuttles between the nucleus and the cytosol (PubMed:16809771). Translocates to the nucleus in response to IFNG or IFNB1 stimulation (PubMed:26479788). Export to the cytosol depends on the interaction with DTX3L (PubMed:16809771). Localizes at sites of DNA damage in a PARP1-dependent manner (PubMed:23230272, PubMed:28525742). {ECO:0000269|PubMed:16809771, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28525742}. |
| Modified Residue | |
| Post Translational Modification | PTM: ADP-ribosylated by PARP14. {ECO:0000269|PubMed:27796300}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 5AIL; |
| Mapped Pubmed ID | 15674325; 18339380; 22701565; 23487038; 24886089; 26496610; 29199039; 30848916; 32020421; 32029454; 32678519; 33060572; 33976187; 33976210; 34358560; |
| Motif | |
| Gene Encoded By | |
| Mass | 96,343 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=196 uM for NAD(+) {ECO:0000269|PubMed:28525742}; |
| Metal Binding | |
| Rhea ID | RHEA:58268; RHEA:58269 |
| Cross Reference Brenda |