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Protein

Poly [ADP-ribose] polymerase 9

Gene

Parp9

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity2 Publications

Catalytic activityi

NAD+ + (ADP-D-ribosyl)(n)-acceptor = nicotinamide + (ADP-D-ribosyl)(n+1)-acceptor.PROSITE-ProRule annotation

Enzyme regulationi

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processAntiviral defense, DNA damage, DNA repair, Immunity, Innate immunity
LigandNAD

Enzyme and pathway databases

ReactomeiR-MMU-197264 Nicotinamide salvaging

Names & Taxonomyi

Protein namesi
Recommended name:
Poly [ADP-ribose] polymerase 9 (EC:2.4.2.30PROSITE-ProRule annotation)
Short name:
PARP-9
Alternative name(s):
ADP-ribosyltransferase diphtheria toxin-like 9
Short name:
ARTD9
B aggressive lymphoma protein homolog
Gene namesi
Name:Parp9
Synonyms:Bal
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1933117 Parp9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002113401 – 866Poly [ADP-ribose] polymerase 9Add BLAST866

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei42PhosphoserineCombined sources1

Post-translational modificationi

ADP-ribosylated by PARP14.By similarity

Keywords - PTMi

ADP-ribosylation, Phosphoprotein

Proteomic databases

EPDiQ8CAS9
PaxDbiQ8CAS9
PeptideAtlasiQ8CAS9
PRIDEiQ8CAS9

PTM databases

iPTMnetiQ8CAS9
PhosphoSitePlusiQ8CAS9

Expressioni

Tissue specificityi

Highly expressed in the thymus and intestine (PubMed:18069692). Expressed in macrophages (PubMed:27796300).2 Publications

Developmental stagei

Developmentally regulated. Expressed prominently in the developing thymus and the gut, and also weakly expressed in specific regions of the developing brain.1 Publication

Inductioni

Up-regulated by IFNG in macrophages. Down-regulated by IL4 in macrophages.1 Publication

Gene expression databases

BgeeiENSMUSG00000022906
CleanExiMM_PARP9
ExpressionAtlasiQ8CAS9 baseline and differential
GenevisibleiQ8CAS9 MM

Interactioni

Subunit structurei

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 HIST1H2BH/H2BJ; the interaction is likely to induce HIST1H2BH/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).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ8CAS9, 2 interactors
MINTiQ8CAS9
STRINGi10090.ENSMUSP00000110528

Structurei

3D structure databases

ProteinModelPortaliQ8CAS9
SMRiQ8CAS9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini109 – 298Macro 1PROSITE-ProRule annotationAdd BLAST190
Domaini313 – 492Macro 2PROSITE-ProRule annotationAdd BLAST180
Domaini635 – 853PARP catalyticPROSITE-ProRule annotationAdd BLAST219

Domaini

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.By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2633 Eukaryota
COG2110 LUCA
GeneTreeiENSGT00760000119084
HOGENOMiHOG000115452
HOVERGENiHBG045406
InParanoidiQ8CAS9
KOiK15260
OMAiSGIFQFP
OrthoDBiEOG091G02AK
PhylomeDBiQ8CAS9
TreeFamiTF328965

Family and domain databases

InterProiView protein in InterPro
IPR002589 Macro_dom
IPR012317 Poly(ADP-ribose)pol_cat_dom
PfamiView protein in Pfam
PF01661 Macro, 2 hits
SMARTiView protein in SMART
SM00506 A1pp, 2 hits
PROSITEiView protein in PROSITE
PS51154 MACRO, 2 hits
PS51059 PARP_CATALYTIC, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8CAS9-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAYYMDTWAA APAERPGMIA SLSLSFKKAF AELFPQRRRG HSEGDYPPLR
60 70 80 90 100
GSANNSLEEH YRWQIPIKHN VFEILKSNES QLCEVLQNKF GCISTLSCPT
110 120 130 140 150
LAGSSSPAQR VFRRTLIPGI ELSVWKDDLT RHVVDAVVNA ANENLLHGSG
160 170 180 190 200
LAGSLVKTGG FEIQEESKRI IANVGKISVG GIAITGAGRL PCHLIIHAVG
210 220 230 240 250
PRWTVTNSQT AIELLKFAIR NILDYVTKYD LRIKTVAIPA LSSGIFQFPL
260 270 280 290 300
DLCTSIILET IRLYFQDKQM FGNLREIHLV SNEDPTVASF KSASESILGR
310 320 330 340 350
DLSSWGGPET DPASTMTLRI GRGLTLQIVQ GCIEMQTTDV IVNSGYMQDF
360 370 380 390 400
KSGRVAQSIL RQAGVEMEKE LDKVNLSTDY QEVWVTKGFK LSCQYVFHVA
410 420 430 440 450
WHSQINKYQI LKDAMKSCLE KCLKPDINSI SFPALGTGLM DLKKSTAAQI
460 470 480 490 500
MFEEVFAFAK EHKEKTLTVK IVIFPVDVET YKIFYAEMTK RSNELNLSGN
510 520 530 540 550
SGALALQWSS GEQRRGGLEA GSPAINLMGV KVGEMCEAQE WIERLLVSLD
560 570 580 590 600
HHIIENNHIL YLGKKEHDVL SELQTSTRVS ISETVSPRTA TLEIKGPQAD
610 620 630 640 650
LIDAVMRIEC MLCDVQEEVA GKREKNLWSL SGQGTNQQEK LDKMEESYTF
660 670 680 690 700
QRYPASLTQE LQDRKKQFEK CGLWVVQVEQ IDNKVLLAAF QEKKKMMEER
710 720 730 740 750
TPKGSGSQRL FQQVPHQFCN TVCRVGFHRM YSTSYNPVYG AGIYFTKSLK
760 770 780 790 800
NLADKVKKTS STDKLIYVFE AEVLTGSFCQ GNSSNIIPPP LSPGALDVND
810 820 830 840 850
SVVDNVSSPE TIVVFNGMQA MPLYLWTCTQ DRTFSQHPMW SQGYSSGPGM
860
VSSLQSWEWV LNGSSV
Note: No experimental confirmation available.
Length:866
Mass (Da):96,659
Last modified:October 10, 2003 - v2
Checksum:i790AF1968F6C035D
GO
Isoform 2 (identifier: Q8CAS9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     17-52: Missing.

Show »
Length:830
Mass (Da):92,669
Checksum:i779197039E99D012
GO
Isoform 3 (identifier: Q8CAS9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     679-866: Missing.

Note: No experimental confirmation available.
Show »
Length:678
Mass (Da):75,739
Checksum:i19EBC4E623A9C48B
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00850617 – 52Missing in isoform 2. 2 PublicationsAdd BLAST36
Alternative sequenceiVSP_008507679 – 866Missing in isoform 3. 1 PublicationAdd BLAST188

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK037903 mRNA Translation: BAC29897.1
AK050032 mRNA Translation: BAC34040.1
BC003281 mRNA Translation: AAH03281.1
BC070466 mRNA Translation: AAH70466.1
CCDSiCCDS37326.1 [Q8CAS9-2]
RefSeqiNP_084529.1, NM_030253.3 [Q8CAS9-2]
XP_006522818.1, XM_006522755.2 [Q8CAS9-1]
XP_006522819.1, XM_006522756.3 [Q8CAS9-1]
XP_006522820.1, XM_006522757.3 [Q8CAS9-2]
UniGeneiMm.49074

Genome annotation databases

EnsembliENSMUST00000114877; ENSMUSP00000110527; ENSMUSG00000022906 [Q8CAS9-3]
ENSMUST00000114878; ENSMUSP00000110528; ENSMUSG00000022906 [Q8CAS9-2]
GeneIDi80285
KEGGimmu:80285
UCSCiuc007zbx.1 mouse [Q8CAS9-1]
uc007zby.2 mouse [Q8CAS9-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPARP9_MOUSE
AccessioniPrimary (citable) accession number: Q8CAS9
Secondary accession number(s): Q6IRT6, Q99LF9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: October 10, 2003
Last modified: May 23, 2018
This is version 125 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health