Protein: 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) (Q8IXQ6)
Organism: Homo sapiens (Human)
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) (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. Also suppresses PARP14-mediated STAT6 ADP-ribosylation.
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}.
Interaction partners:
- E3 ubiquitin-protein ligase DTX3L
- Signal transducer and activator of transcription 1-alpha/beta
- Protein mono-ADP-ribosyltransferase PARP14
- Interferon-induced protein 44-like
- Interferon-induced protein 44
- Interferon-induced protein with tetratricopeptide repeats 3
- Epithelial-stromal interaction protein 1
- XIAP-associated factor 1
- Interferon-induced helicase C domain-containing protein 1
- Probable ATP-dependent RNA helicase DDX60
Sequence:
MDFSMVAGAAAYNEKSGRITSLSLLFQKVFAQIFPQWRKGNTEECLPYKCSETGALGENYSWQIPINHNDFKILKNNERQLCEVLQNKFGCISTLVSPVQEGNSKSLQVFRKMLTPRIELSVWKDDLTTHAVDAVVNAANEDLLHGGGLALALVKAGGFEIQEESKQFVARYGKVSAGEIAVTGAGRLPCKQIIHAVGPRWMEWDKQGCTGKLQRAIVSILNYVIYKNTHIKTVAIPALSSGIFQFPLNLCTKTIVETIRVSLQGKPMMSNLKEIHLVSNEDPTVAAFKAASEFILGKSELGQETTPSFNAMVVNNLTLQIVQGHIEWQTADVIVNSVNPHDITVGPVAKSILQQAGVEMKSEFLATKAKQFQRSQLVLVTKGFNLFCKYIYHVLWHSEFPKPQILKHAMKECLEKCIEQNITSISFPALGTGNMEIKKETAAEILFDEVLTFAKDHVKHQLTVKFVIFPTDLEIYKAFSSEMAKRSKMLSLNNYSVPQSTREEKRENGLEARSPAINLMGFNVEEMYEAHAWIQRILSLQNHHIIENNHILYLGRKEHDILSQLQKTSSVSITEIISPGRTELEIEGARADLIEVVMNIEDMLCKVQEEMARKKERGLWRSLGQWTIQQQKTQDEMKENIIFLKCPVPPTQELLDQKKQFEKCGLQVLKVEKIDNEVLMAAFQRKKKMMEEKLHRQPVSHRLFQQVPYQFCNVVCRVGFQRMYSTPCDPKYGAGIYFTKNLKNLAEKAKKISAADKLIYVFEAEVLTGFFCQGHPLNIVPPPLSPGAIDGHDSVVDNVSSPETFVIFSGMQAIPQYLWTCTQEYVQSQDYSSGPMRPFAQHPWRGFASGSPVD