PARP9_MOUSE
ID PARP9_MOUSE Reviewed; 866 AA.
AC Q8CAS9; Q6IRT6; Q99LF9;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Protein mono-ADP-ribosyltransferase PARP9 {ECO:0000305};
DE EC=2.4.2.- {ECO:0000250|UniProtKB:Q8IXQ6};
DE AltName: Full=ADP-ribosyltransferase diphtheria toxin-like 9;
DE Short=ARTD9;
DE AltName: Full=B aggressive lymphoma protein homolog;
DE AltName: Full=Poly [ADP-ribose] polymerase 9;
DE Short=PARP-9;
GN Name=Parp9; Synonyms=Bal;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Liver, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Eye, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=18069692; DOI=10.1002/dvdy.21399;
RA Hakme A., Huber A., Dolle P., Schreiber V.;
RT "The macroPARP genes Parp-9 and Parp-14 are developmentally and
RT differentially regulated in mouse tissues.";
RL Dev. Dyn. 237:209-215(2008).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=27796300; DOI=10.1038/ncomms12849;
RA Iwata H., Goettsch C., Sharma A., Ricchiuto P., Goh W.W., Halu A.,
RA Yamada I., Yoshida H., Hara T., Wei M., Inoue N., Fukuda D., Mojcher A.,
RA Mattson P.C., Barabasi A.L., Boothby M., Aikawa E., Singh S.A., Aikawa M.;
RT "PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-
RT ribosylation.";
RL Nat. Commun. 7:12849-12849(2016).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28105679; DOI=10.1002/eji.201646757;
RA Robert I., Gaudot L., Yelamos J., Noll A., Wong H.K., Dantzer F.,
RA Schreiber V., Reina-San-Martin B.;
RT "Robust immunoglobulin class switch recombination and end joining in Parp9-
RT deficient mice.";
RL Eur. J. Immunol. 47:665-676(2017).
CC -!- FUNCTION: ADP-ribosyltransferase which, in association with E3 ligase
CC DTX3L, plays a role in DNA damage repair and in immune responses
CC including interferon-mediated antiviral defenses (PubMed:27796300).
CC Within the complex, enhances DTX3L E3 ligase activity which is further
CC enhanced by PARP9 binding to poly(ADP-ribose) (By similarity). In
CC addition, positively regulates DTXL3 protein levels (By similarity). In
CC association with DTX3L and in presence of E1 and E2 enzymes, mediates
CC NAD(+)-dependent mono-ADP-ribosylation of ubiquitin which prevents
CC ubiquitin conjugation to substrates such as histones (By similarity).
CC During DNA repair, PARP1 recruits PARP9/BAL1-DTX3L complex to DNA
CC damage sites via PARP9 binding to ribosylated PARP1 (By similarity).
CC Subsequent PARP1-dependent PARP9/BAL1-DTX3L-mediated ubiquitination
CC promotes the rapid and specific recruitment of 53BP1/TP53BP1,
CC UIMC1/RAP80, and BRCA1 to DNA damage sites (By similarity). In response
CC to DNA damage, PARP9-DTX3L complex is required for efficient non-
CC homologous end joining (NHEJ) but the complex function is restrained by
CC PARP9 activity (By similarity). Dispensable for B-cell receptor (BCR)
CC assembly through V(D)J recombination and class switch recombination
CC (CSR) (PubMed:28105679). In macrophages, positively regulates pro-
CC inflammatory cytokines production in response to IFNG stimulation by
CC suppressing PARP14-mediated STAT1 ADP-ribosylation and thus promoting
CC STAT1 phosphorylation (PubMed:27796300). Also suppresses PARP14-
CC mediated STAT6 ADP-ribosylation (By similarity).
CC {ECO:0000250|UniProtKB:Q8IXQ6, ECO:0000269|PubMed:27796300,
CC ECO:0000269|PubMed:28105679}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-C-terminal glycine + NAD(+) = [protein]-C-terminal
CC O-(ADP-D-ribosyl)-glycine + nicotinamide; Xref=Rhea:RHEA:58268,
CC Rhea:RHEA-COMP:15093, Rhea:RHEA-COMP:15095, ChEBI:CHEBI:17154,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:83148, ChEBI:CHEBI:142558;
CC Evidence={ECO:0000250|UniProtKB:Q8IXQ6};
CC -!- ACTIVITY REGULATION: Binding to poly(ADP-ribose) does not affect its
CC activity. {ECO:0000250|UniProtKB:Q8IXQ6}.
CC -!- SUBUNIT: Forms a stable complex with E3 ligase DTX3L; the interaction
CC is required for PARP9 mediated ADP-ribosylation of ubiquitin. Interacts
CC (via PARP catalytic domain) with DTX3L (via N-terminus). Forms a
CC complex with STAT1 and DTX3L independently of IFNB1 or IFNG-mediated
CC STAT1 'Tyr-701' phosphorylation. Forms a complex with STAT1, DTX3L and
CC histone H2B H2BC9/H2BJ; the interaction is likely to induce H2BC9/H2BJ
CC ubiquitination. Interacts (via N-terminus) with STAT1. Interacts with
CC PARP14 in IFNG-stimulated macrophages; the interaction prevents PARP14-
CC mediated STAT1 and STAT6 ADP-riboslylation. Interacts with PARP1 (when
CC poly-ADP-ribosylated). {ECO:0000250|UniProtKB:Q8IXQ6}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q8IXQ6}. Nucleus {ECO:0000250|UniProtKB:Q8IXQ6}.
CC Note=Shuttles between the nucleus and the cytosol. Translocates to the
CC nucleus in response to IFNG or IFNB1 stimulation. Export to the cytosol
CC depends on the interaction with DTX3L. Localizes at sites of DNA damage
CC in a PARP1-dependent manner. {ECO:0000250|UniProtKB:Q8IXQ6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8CAS9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CAS9-2; Sequence=VSP_008506;
CC Name=3;
CC IsoId=Q8CAS9-3; Sequence=VSP_008507;
CC -!- TISSUE SPECIFICITY: Highly expressed in the thymus and intestine
CC (PubMed:18069692). Expressed in macrophages (PubMed:27796300).
CC {ECO:0000269|PubMed:18069692, ECO:0000269|PubMed:27796300}.
CC -!- DEVELOPMENTAL STAGE: Developmentally regulated. Expressed prominently
CC in the developing thymus and the gut, and also weakly expressed in
CC specific regions of the developing brain.
CC {ECO:0000269|PubMed:18069692}.
CC -!- INDUCTION: Up-regulated by IFNG in macrophages. Down-regulated by IL4
CC in macrophages. {ECO:0000269|PubMed:27796300}.
CC -!- DOMAIN: Macro domains 1 and 2 may be involved in the binding to
CC poly(ADP-ribose). Macro domain 2 is required for recruitment to DNA
CC damage sites. Macro domains 1 and 2 are probably dispensable for the
CC interaction with STAT1 and DTX3L and for STAT1 phosphorylation.
CC {ECO:0000250|UniProtKB:Q8IXQ6}.
CC -!- PTM: ADP-ribosylated by PARP14. {ECO:0000250|UniProtKB:Q8IXQ6}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are viable, fertile
CC and are born at the expected Mendelian rate with a slight decrease in
CC male frequency. No defect in B-cell development, maturation and
CC maintenance in periphery. Slight decrease in the number of follicular
CC B-cell associated with an increase in the number of marginal zone B-
CC cells. {ECO:0000269|PubMed:28105679}.
CC -!- SIMILARITY: Belongs to the ARTD/PARP family. {ECO:0000305}.
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DR EMBL; AK037903; BAC29897.1; -; mRNA.
DR EMBL; AK050032; BAC34040.1; -; mRNA.
DR EMBL; BC003281; AAH03281.1; -; mRNA.
DR EMBL; BC070466; AAH70466.1; -; mRNA.
DR CCDS; CCDS37326.1; -. [Q8CAS9-2]
DR RefSeq; NP_084529.1; NM_030253.3. [Q8CAS9-2]
DR RefSeq; XP_006522818.1; XM_006522755.2. [Q8CAS9-1]
DR RefSeq; XP_006522819.1; XM_006522756.3.
DR RefSeq; XP_006522820.1; XM_006522757.3.
DR AlphaFoldDB; Q8CAS9; -.
DR SMR; Q8CAS9; -.
DR BioGRID; 219773; 6.
DR IntAct; Q8CAS9; 1.
DR STRING; 10090.ENSMUSP00000110528; -.
DR iPTMnet; Q8CAS9; -.
DR PhosphoSitePlus; Q8CAS9; -.
DR EPD; Q8CAS9; -.
DR MaxQB; Q8CAS9; -.
DR PaxDb; Q8CAS9; -.
DR PeptideAtlas; Q8CAS9; -.
DR PRIDE; Q8CAS9; -.
DR ProteomicsDB; 287959; -. [Q8CAS9-1]
DR ProteomicsDB; 287960; -. [Q8CAS9-2]
DR ProteomicsDB; 287961; -. [Q8CAS9-3]
DR Antibodypedia; 32910; 103 antibodies from 28 providers.
DR DNASU; 80285; -.
DR Ensembl; ENSMUST00000114878; ENSMUSP00000110528; ENSMUSG00000022906. [Q8CAS9-2]
DR GeneID; 80285; -.
DR KEGG; mmu:80285; -.
DR UCSC; uc007zbx.1; mouse. [Q8CAS9-1]
DR UCSC; uc007zby.2; mouse. [Q8CAS9-2]
DR CTD; 83666; -.
DR MGI; MGI:1933117; Parp9.
DR VEuPathDB; HostDB:ENSMUSG00000022906; -.
DR eggNOG; KOG2633; Eukaryota.
DR GeneTree; ENSGT00940000158837; -.
DR HOGENOM; CLU_012160_0_0_1; -.
DR InParanoid; Q8CAS9; -.
DR OMA; LSCQYVY; -.
DR OrthoDB; 681829at2759; -.
DR PhylomeDB; Q8CAS9; -.
DR TreeFam; TF328965; -.
DR Reactome; R-MMU-197264; Nicotinamide salvaging.
DR BioGRID-ORCS; 80285; 3 hits in 110 CRISPR screens.
DR PRO; PR:Q8CAS9; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q8CAS9; protein.
DR Bgee; ENSMUSG00000022906; Expressed in small intestine Peyer's patch and 204 other tissues.
DR ExpressionAtlas; Q8CAS9; baseline and differential.
DR Genevisible; Q8CAS9; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0090734; C:site of DNA damage; ISO:MGI.
DR GO; GO:0072570; F:ADP-D-ribose binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0004857; F:enzyme inhibitor activity; ISO:MGI.
DR GO; GO:0042393; F:histone binding; ISO:MGI.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; ISS:UniProtKB.
DR GO; GO:1990404; F:NAD+-protein ADP-ribosyltransferase activity; IBA:GO_Central.
DR GO; GO:0097677; F:STAT family protein binding; ISO:MGI.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:MGI.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; ISO:MGI.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0043086; P:negative regulation of catalytic activity; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0035563; P:positive regulation of chromatin binding; ISO:MGI.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISO:MGI.
DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; ISO:MGI.
DR GO; GO:0060335; P:positive regulation of interferon-gamma-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:MGI.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; ISO:MGI.
DR GO; GO:0006471; P:protein ADP-ribosylation; ISO:MGI.
DR GO; GO:0140289; P:protein mono-ADP-ribosylation; IBA:GO_Central.
DR GO; GO:0070212; P:protein poly-ADP-ribosylation; IBA:GO_Central.
DR GO; GO:0060330; P:regulation of response to interferon-gamma; ISS:UniProtKB.
DR Gene3D; 3.40.220.10; -; 2.
DR InterPro; IPR002589; Macro_dom.
DR InterPro; IPR043472; Macro_dom-like.
DR InterPro; IPR012317; Poly(ADP-ribose)pol_cat_dom.
DR Pfam; PF01661; Macro; 2.
DR SMART; SM00506; A1pp; 2.
DR SUPFAM; SSF52949; SSF52949; 2.
DR PROSITE; PS51154; MACRO; 2.
DR PROSITE; PS51059; PARP_CATALYTIC; 1.
PE 1: Evidence at protein level;
KW ADP-ribosylation; Alternative splicing; Antiviral defense; Cytoplasm;
KW DNA damage; DNA repair; Glycosyltransferase; Immunity; Innate immunity;
KW NAD; Nucleotidyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transferase.
FT CHAIN 1..866
FT /note="Protein mono-ADP-ribosyltransferase PARP9"
FT /id="PRO_0000211340"
FT DOMAIN 109..298
FT /note="Macro 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 313..492
FT /note="Macro 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 635..853
FT /note="PARP catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00397"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT VAR_SEQ 17..52
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_008506"
FT VAR_SEQ 679..866
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008507"
SQ SEQUENCE 866 AA; 96659 MW; 790AF1968F6C035D CRC64;
MAYYMDTWAA APAERPGMIA SLSLSFKKAF AELFPQRRRG HSEGDYPPLR GSANNSLEEH
YRWQIPIKHN VFEILKSNES QLCEVLQNKF GCISTLSCPT LAGSSSPAQR VFRRTLIPGI
ELSVWKDDLT RHVVDAVVNA ANENLLHGSG LAGSLVKTGG FEIQEESKRI IANVGKISVG
GIAITGAGRL PCHLIIHAVG PRWTVTNSQT AIELLKFAIR NILDYVTKYD LRIKTVAIPA
LSSGIFQFPL DLCTSIILET IRLYFQDKQM FGNLREIHLV SNEDPTVASF KSASESILGR
DLSSWGGPET DPASTMTLRI GRGLTLQIVQ GCIEMQTTDV IVNSGYMQDF KSGRVAQSIL
RQAGVEMEKE LDKVNLSTDY QEVWVTKGFK LSCQYVFHVA WHSQINKYQI LKDAMKSCLE
KCLKPDINSI SFPALGTGLM DLKKSTAAQI MFEEVFAFAK EHKEKTLTVK IVIFPVDVET
YKIFYAEMTK RSNELNLSGN SGALALQWSS GEQRRGGLEA GSPAINLMGV KVGEMCEAQE
WIERLLVSLD HHIIENNHIL YLGKKEHDVL SELQTSTRVS ISETVSPRTA TLEIKGPQAD
LIDAVMRIEC MLCDVQEEVA GKREKNLWSL SGQGTNQQEK LDKMEESYTF QRYPASLTQE
LQDRKKQFEK CGLWVVQVEQ IDNKVLLAAF QEKKKMMEER TPKGSGSQRL FQQVPHQFCN
TVCRVGFHRM YSTSYNPVYG AGIYFTKSLK NLADKVKKTS STDKLIYVFE AEVLTGSFCQ
GNSSNIIPPP LSPGALDVND SVVDNVSSPE TIVVFNGMQA MPLYLWTCTQ DRTFSQHPMW
SQGYSSGPGM VSSLQSWEWV LNGSSV
