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Q8IXQ6 Proteins Macro domain Repeats
Uniprot ID:Q8IXQ6
Protein name: Poly [ADP-ribose] polymerase 9
Gene : PARP9 BAL BAL1
Protein Family:
Squence Length : 854
Sequnce
>Q8IXQ6 855 MDFSMVAGAAAYNEKSGRITSLSLLFQKVFAQIFPQWRKGNTEECLPYKCSETGALGENYSWQIPINHNDFKILKNNERQLCEVLQNKFGCISTLVSPVQEGNSKSLQVFRKMLTPRIELSVWKDDLTTHAVDAVVNAANEDLLHGGGLALALVKAGGFEIQEESKQFVARYGKVSAGEIAVTGAGRLPCKQIIHAVGPRWMEWDKQGCTGKLQRAIVSILNYVIYKNTHIKTVAIPALSSGIFQFPLNLCTKTIVETIRVSLQGKPMMSNLKEIHLVSNEDPTVAAFKAASEFILGKSELGQETTPSFNAMVVNNLTLQIVQGHIEWQTADVIVNSVNPHDITVGPVAKSILQQAGVEMKSEFLATKAKQFQRSQLVLVTKGFNLFCKYIYHVLWHSEFPKPQILKHAMKECLEKCIEQNITSISFPALGTGNMEIKKETAAEILFDEVLTFAKDHVKHQLTVKFVIFPTDLEIYKAFSSEMAKRSKMLSLNNYSVPQSTREEKRENGLEARSPAINLMGFNVEEMYEAHAWIQRILSLQNHHIIENNHILYLGRKEHDILSQLQKTSSVSITEIISPGRTELEIEGARADLIEVVMNIEDMLCKVQEEMARKKERGLWRSLGQWTIQQQKTQDEMKENIIFLKCPVPPTQELLDQKKQFEKCGLQVLKVEKIDNEVLMAAFQRKKKMMEEKLHRQPVSHRLFQQVPYQFCNVVCRVGFQRMYSTPCDPKYGAGIYFTKNLKNLAEKAKKISAADKLIYVFEAEVLTGFFCQGHPLNIVPPPLSPGAIDGHDSVVDNVSSPETFVIFSGMQAIPQYLWTCTQEYVQSQDYSSGPMRPFAQHPWRGFASGSPVD
Domains
DOMAIN 107 296 Macro 1 DOMAIN 306 487 Macro 2 DOMAIN 628 850 PARP catalytic
Macro sequence regions
107 - 296 VFRKMLTPRIELSVWKDDLTTHAVDAVVNAANEDLLHGGGLALALVKAGGFEIQEESKQFVARYGKVSAGEIAVTGAGRLPCKQIIHAVGPRWMEWDKQGCTGKLQRAIVSILNYVIYKNTHIKTVAIPALSSGIFQFPLNLCTKTIVETIRVSLQGKPMMSNLKEIHLVSNEDPTVAAFKAASEFILGK 306 - 487 SFNAMVVNNLTLQIVQGHIEWQTADVIVNSVNPHDITVGPVAKSILQQAGVEMKSEFLATKAKQFQRSQLVLVTKGFNLFCKYIYHVLWHSEFPKPQILKHAMKECLEKCIEQNITSISFPALGTGNMEIKKETAAEILFDEVLTFAKDHVKHQLTVKFVIFPTDLEIYKAFSSEMAKRSKM
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)"
Mutation
"147 147 G->E: Reduces the binding to poly(ADP-ribose) by 50 percent and prevents increase in DTX3L-mediated histone ubiquitination without affecting ubiquitin ADP ribosylation, interaction with DTX3L and STAT1 and DTX3L catalytic activity when associated with E-346 346 346 G->E: Reduces the binding to poly(ADP-ribose) by 50 percent and prevents increase in DTX3L-mediated histone ubiquitination without affecting ubiquitin ADP ribosylation, interaction with DTX3L and STAT1 and DTX3L catalytic activity when associated with E-147 719 722 Missing: Loss of ADP ribosylation activity and interaction with DTX3L 737 737 Y->A: No defect in ubiquitin ADP ribosylation and the interaction with DTX3L 738 738 F->K: Severe reduction in ubiquitin ADP ribosylation 766 769 Missing: Loss of ADP ribosylation activity and interaction with DTX3L 780 784 Missing: Reduces ADP ribosylation activity and interaction with DTX3L 802 803 PE->AA: No defect in ADP ribosylation and interaction with DTX3L 831 854 Missing: No defect in ADP ribosylation and interaction with DTX3L"
Disease
DISEASE: Note=Overexpressed at significantly higher levels in fatal high-risk diffuse large B-cell lymphomas (DLB-CL) compared to cured low-risk tumors Overexpression in B-cell lymphoma transfectants may promote malignant B-cell migration May therefore be involved in promoting B-cell migration and dissemination of high-risk DLB-CL tumors (PubMed:11110709)