Q8CAS9 · PARP9_MOUSE
- ProteinProtein mono-ADP-ribosyltransferase PARP9
- GeneParp9
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids866 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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:27796300).
Within the complex, enhances DTX3L E3 ligase activity which is further enhanced by PARP9 binding to poly(ADP-ribose) (By similarity).
In addition, positively regulates DTXL3 protein levels (By similarity).
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 (By similarity).
During DNA repair, PARP1 recruits PARP9/BAL1-DTX3L complex to DNA damage sites via PARP9 binding to ribosylated PARP1 (By similarity).
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 (By similarity).
In response to DNA damage, PARP9-DTX3L complex is required for efficient non-homologous end joining (NHEJ) but the complex function is restrained by PARP9 activity (By similarity).
Dispensable for B-cell receptor (BCR) assembly through V(D)J recombination and class switch recombination (CSR) (PubMed:28105679).
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 (By similarity).
Within the complex, enhances DTX3L E3 ligase activity which is further enhanced by PARP9 binding to poly(ADP-ribose) (By similarity).
In addition, positively regulates DTXL3 protein levels (By similarity).
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 (By similarity).
During DNA repair, PARP1 recruits PARP9/BAL1-DTX3L complex to DNA damage sites via PARP9 binding to ribosylated PARP1 (By similarity).
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 (By similarity).
In response to DNA damage, PARP9-DTX3L complex is required for efficient non-homologous end joining (NHEJ) but the complex function is restrained by PARP9 activity (By similarity).
Dispensable for B-cell receptor (BCR) assembly through V(D)J recombination and class switch recombination (CSR) (PubMed:28105679).
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 (By similarity).
Catalytic activity
- [protein]-C-terminal glycine + NAD+ = [protein]-C-terminal O-(ADP-D-ribosyl)-glycine + nicotinamide
Activity regulation
Binding to poly(ADP-ribose) does not affect its activity.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein mono-ADP-ribosyltransferase PARP9
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8CAS9
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Shuttles between the nucleus and the cytosol. Translocates to the nucleus in response to IFNG or IFNB1 stimulation. Export to the cytosol depends on the interaction with DTX3L. Localizes at sites of DNA damage in a PARP1-dependent manner.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
No visible phenotype. Mice are viable, fertile and are born at the expected Mendelian rate with a slight decrease in male frequency. No defect in B-cell development, maturation and maintenance in periphery. Slight decrease in the number of follicular B-cell associated with an increase in the number of marginal zone B-cells.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000211340 | 1-866 | Protein mono-ADP-ribosyltransferase PARP9 | |||
Sequence: MAYYMDTWAAAPAERPGMIASLSLSFKKAFAELFPQRRRGHSEGDYPPLRGSANNSLEEHYRWQIPIKHNVFEILKSNESQLCEVLQNKFGCISTLSCPTLAGSSSPAQRVFRRTLIPGIELSVWKDDLTRHVVDAVVNAANENLLHGSGLAGSLVKTGGFEIQEESKRIIANVGKISVGGIAITGAGRLPCHLIIHAVGPRWTVTNSQTAIELLKFAIRNILDYVTKYDLRIKTVAIPALSSGIFQFPLDLCTSIILETIRLYFQDKQMFGNLREIHLVSNEDPTVASFKSASESILGRDLSSWGGPETDPASTMTLRIGRGLTLQIVQGCIEMQTTDVIVNSGYMQDFKSGRVAQSILRQAGVEMEKELDKVNLSTDYQEVWVTKGFKLSCQYVFHVAWHSQINKYQILKDAMKSCLEKCLKPDINSISFPALGTGLMDLKKSTAAQIMFEEVFAFAKEHKEKTLTVKIVIFPVDVETYKIFYAEMTKRSNELNLSGNSGALALQWSSGEQRRGGLEAGSPAINLMGVKVGEMCEAQEWIERLLVSLDHHIIENNHILYLGKKEHDVLSELQTSTRVSISETVSPRTATLEIKGPQADLIDAVMRIECMLCDVQEEVAGKREKNLWSLSGQGTNQQEKLDKMEESYTFQRYPASLTQELQDRKKQFEKCGLWVVQVEQIDNKVLLAAFQEKKKMMEERTPKGSGSQRLFQQVPHQFCNTVCRVGFHRMYSTSYNPVYGAGIYFTKSLKNLADKVKKTSSTDKLIYVFEAEVLTGSFCQGNSSNIIPPPLSPGALDVNDSVVDNVSSPETIVVFNGMQAMPLYLWTCTQDRTFSQHPMWSQGYSSGPGMVSSLQSWEWVLNGSSV | ||||||
Modified residue | 42 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
ADP-ribosylated by PARP14.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in the thymus and intestine (PubMed:18069692).
Expressed in macrophages (PubMed:27796300).
Expressed in macrophages (PubMed:27796300).
Induction
Up-regulated by IFNG in macrophages. Down-regulated by IL4 in macrophages.
Developmental stage
Developmentally regulated. Expressed prominently in the developing thymus and the gut, and also weakly expressed in specific regions of the developing brain.
Gene expression databases
Interaction
Subunit
Forms a stable complex with E3 ligase DTX3L; the interaction is required for PARP9 mediated ADP-ribosylation of ubiquitin. Interacts (via PARP catalytic domain) with DTX3L (via N-terminus). Forms a complex with STAT1 and DTX3L independently of IFNB1 or IFNG-mediated STAT1 'Tyr-701' phosphorylation. Forms a complex with STAT1, DTX3L and histone H2B H2BC9/H2BJ; the interaction is likely to induce H2BC9/H2BJ ubiquitination. Interacts (via N-terminus) with STAT1. Interacts with PARP14 in IFNG-stimulated macrophages; the interaction prevents PARP14-mediated STAT1 and STAT6 ADP-riboslylation. Interacts with PARP1 (when poly-ADP-ribosylated).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 109-298 | Macro 1 | ||||
Sequence: QRVFRRTLIPGIELSVWKDDLTRHVVDAVVNAANENLLHGSGLAGSLVKTGGFEIQEESKRIIANVGKISVGGIAITGAGRLPCHLIIHAVGPRWTVTNSQTAIELLKFAIRNILDYVTKYDLRIKTVAIPALSSGIFQFPLDLCTSIILETIRLYFQDKQMFGNLREIHLVSNEDPTVASFKSASESIL | ||||||
Domain | 313-492 | Macro 2 | ||||
Sequence: ASTMTLRIGRGLTLQIVQGCIEMQTTDVIVNSGYMQDFKSGRVAQSILRQAGVEMEKELDKVNLSTDYQEVWVTKGFKLSCQYVFHVAWHSQINKYQILKDAMKSCLEKCLKPDINSISFPALGTGLMDLKKSTAAQIMFEEVFAFAKEHKEKTLTVKIVIFPVDVETYKIFYAEMTKRS | ||||||
Domain | 635-853 | PARP catalytic | ||||
Sequence: TNQQEKLDKMEESYTFQRYPASLTQELQDRKKQFEKCGLWVVQVEQIDNKVLLAAFQEKKKMMEERTPKGSGSQRLFQQVPHQFCNTVCRVGFHRMYSTSYNPVYGAGIYFTKSLKNLADKVKKTSSTDKLIYVFEAEVLTGSFCQGNSSNIIPPPLSPGALDVNDSVVDNVSSPETIVVFNGMQAMPLYLWTCTQDRTFSQHPMWSQGYSSGPGMVSS |
Domain
Macro domains 1 and 2 may be involved in the binding to poly(ADP-ribose). Macro domain 2 is required for recruitment to DNA damage sites. Macro domains 1 and 2 are probably dispensable for the interaction with STAT1 and DTX3L and for STAT1 phosphorylation.
Sequence similarities
Belongs to the ARTD/PARP family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q8CAS9-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length866
- Mass (Da)96,659
- Last updated2003-10-10 v2
- Checksum790AF1968F6C035D
Q8CAS9-2
- Name2
- Differences from canonical
- 17-52: Missing
Q8CAS9-3
- Name3
- Differences from canonical
- 679-866: Missing
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK037903 EMBL· GenBank· DDBJ | BAC29897.1 EMBL· GenBank· DDBJ | mRNA | ||
AK050032 EMBL· GenBank· DDBJ | BAC34040.1 EMBL· GenBank· DDBJ | mRNA | ||
BC003281 EMBL· GenBank· DDBJ | AAH03281.1 EMBL· GenBank· DDBJ | mRNA | ||
BC070466 EMBL· GenBank· DDBJ | AAH70466.1 EMBL· GenBank· DDBJ | mRNA |