Q8CAS9 · PARP9_MOUSE

  • Protein
    Protein mono-ADP-ribosyltransferase PARP9
  • Gene
    Parp9
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Activity regulation

Binding to poly(ADP-ribose) does not affect its activity.

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentmitochondrion
Cellular Componentnucleoplasm
Cellular Componentnucleus
Cellular Componentprotein-containing complex
Cellular Componentsite of DNA damage
Molecular FunctionADP-D-ribose binding
Molecular Functionenzyme inhibitor activity
Molecular Functionhistone binding
Molecular FunctionNAD+ ADP-ribosyltransferase activity
Molecular FunctionNAD+-protein ADP-ribosyltransferase activity
Molecular FunctionNAD+-protein-C-terminal glycine ADP-ribosyltransferase activity
Molecular Functionnucleotidyltransferase activity
Molecular FunctionSTAT family protein binding
Molecular Functiontranscription corepressor activity
Molecular Functionubiquitin-like protein ligase binding
Biological Processdefense response to virus
Biological ProcessDNA damage checkpoint signaling
Biological Processdouble-strand break repair
Biological Processinnate immune response
Biological Processnegative regulation of gene expression
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processpositive regulation of defense response to virus by host
Biological Processpositive regulation of DNA-templated transcription
Biological Processpositive regulation of protein localization to nucleus
Biological Processpositive regulation of type II interferon-mediated signaling pathway
Biological Processpositive regulation of tyrosine phosphorylation of STAT protein
Biological Processpost-transcriptional regulation of gene expression
Biological Processregulation of response to type II interferon

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Protein mono-ADP-ribosyltransferase PARP9
  • EC number
  • Alternative names
    • ADP-ribosyltransferase diphtheria toxin-like 9 (ARTD9)
    • B aggressive lymphoma protein homolog
    • Poly [ADP-ribose] polymerase 9 (PARP-9)

Gene names

    • Name
      Parp9
    • Synonyms
      Bal

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q8CAS9
  • Secondary accessions
    • Q6IRT6
    • Q99LF9

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm, cytosol
Nucleus
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

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.

TypeIDPosition(s)Description
ChainPRO_00002113401-866Protein mono-ADP-ribosyltransferase PARP9
Modified residue42Phosphoserine

Post-translational modification

ADP-ribosylated by PARP14.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Highly expressed in the thymus and intestine (PubMed:18069692).
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.

TypeIDPosition(s)Description
Domain109-298Macro 1
Domain313-492Macro 2
Domain635-853PARP catalytic

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

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete

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.

  • Length
    866
  • Mass (Da)
    96,659
  • Last updated
    2003-10-10 v2
  • Checksum
    790AF1968F6C035D
MAYYMDTWAAAPAERPGMIASLSLSFKKAFAELFPQRRRGHSEGDYPPLRGSANNSLEEHYRWQIPIKHNVFEILKSNESQLCEVLQNKFGCISTLSCPTLAGSSSPAQRVFRRTLIPGIELSVWKDDLTRHVVDAVVNAANENLLHGSGLAGSLVKTGGFEIQEESKRIIANVGKISVGGIAITGAGRLPCHLIIHAVGPRWTVTNSQTAIELLKFAIRNILDYVTKYDLRIKTVAIPALSSGIFQFPLDLCTSIILETIRLYFQDKQMFGNLREIHLVSNEDPTVASFKSASESILGRDLSSWGGPETDPASTMTLRIGRGLTLQIVQGCIEMQTTDVIVNSGYMQDFKSGRVAQSILRQAGVEMEKELDKVNLSTDYQEVWVTKGFKLSCQYVFHVAWHSQINKYQILKDAMKSCLEKCLKPDINSISFPALGTGLMDLKKSTAAQIMFEEVFAFAKEHKEKTLTVKIVIFPVDVETYKIFYAEMTKRSNELNLSGNSGALALQWSSGEQRRGGLEAGSPAINLMGVKVGEMCEAQEWIERLLVSLDHHIIENNHILYLGKKEHDVLSELQTSTRVSISETVSPRTATLEIKGPQADLIDAVMRIECMLCDVQEEVAGKREKNLWSLSGQGTNQQEKLDKMEESYTFQRYPASLTQELQDRKKQFEKCGLWVVQVEQIDNKVLLAAFQEKKKMMEERTPKGSGSQRLFQQVPHQFCNTVCRVGFHRMYSTSYNPVYGAGIYFTKSLKNLADKVKKTSSTDKLIYVFEAEVLTGSFCQGNSSNIIPPPLSPGALDVNDSVVDNVSSPETIVVFNGMQAMPLYLWTCTQDRTFSQHPMWSQGYSSGPGMVSSLQSWEWVLNGSSV

Q8CAS9-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q8CAS9-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
H7BWY5H7BWY5_MOUSEParp9597
E0CYZ7E0CYZ7_MOUSEParp958
F6U1Y8F6U1Y8_MOUSEParp9104

Features

Showing features for alternative sequence.

TypeIDPosition(s)Description
Alternative sequenceVSP_00850617-52in isoform 2
Alternative sequenceVSP_008507679-866in isoform 3

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp