PARP9_HUMAN
ID PARP9_HUMAN Reviewed; 854 AA.
AC Q8IXQ6; A8KA94; B2R8S9; E9PFM7; Q8TCP3; Q9BZL8; Q9BZL9;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Protein mono-ADP-ribosyltransferase PARP9 {ECO:0000305};
DE EC=2.4.2.- {ECO:0000269|PubMed:28525742};
DE AltName: Full=ADP-ribosyltransferase diphtheria toxin-like 9;
DE Short=ARTD9;
DE AltName: Full=B aggressive lymphoma protein {ECO:0000303|PubMed:11110709};
DE AltName: Full=Poly [ADP-ribose] polymerase 9;
DE Short=PARP-9;
GN Name=PARP9;
GN Synonyms=BAL {ECO:0000303|PubMed:11110709},
GN BAL1 {ECO:0000303|PubMed:11110709};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, VARIANT CYS-528, AND INVOLVEMENT IN B-CELL LYMPHOMAS.
RC TISSUE=B-cell;
RX PubMed=11110709;
RA Aguiar R.C.T., Yakushijin Y., Kharbanda S., Salgia R., Fletcher J.A.,
RA Shipp M.A.;
RT "BAL is a novel risk-related gene in diffuse large B-cell lymphomas that
RT enhances cellular migration.";
RL Blood 96:4328-4334(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP CYS-528.
RC TISSUE=Trachea, and Umbilical cord blood;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANTS
RP VAL-517 AND CYS-528.
RC TISSUE=Mammary gland, and Melanoma;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 525-854.
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP INTERACTION WITH DTX3L.
RX PubMed=12670957; DOI=10.1074/jbc.m301157200;
RA Takeyama K., Aguiar R.C.T., Gu L., He C., Freeman G.J., Kutok J.L.,
RA Aster J.C., Shipp M.A.;
RT "The BAL-binding protein BBAP and related Deltex family members exhibit
RT ubiquitin-protein isopeptide ligase activity.";
RL J. Biol. Chem. 278:21930-21937(2003).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16809771; DOI=10.1128/mcb.02351-05;
RA Juszczynski P., Kutok J.L., Li C., Mitra J., Aguiar R.C.T., Shipp M.A.;
RT "BAL1 and BBAP are regulated by a gamma interferon-responsive bidirectional
RT promoter and are overexpressed in diffuse large B-cell lymphomas with a
RT prominent inflammatory infiltrate.";
RL Mol. Cell. Biol. 26:5348-5359(2006).
RN [8]
RP NOMENCLATURE.
RX PubMed=20106667; DOI=10.1016/j.tibs.2009.12.003;
RA Hottiger M.O., Hassa P.O., Luscher B., Schuler H., Koch-Nolte F.;
RT "Toward a unified nomenclature for mammalian ADP-ribosyltransferases.";
RL Trends Biochem. Sci. 35:208-219(2010).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PARP1, AND DOMAIN MACRO 2.
RX PubMed=23230272; DOI=10.1128/mcb.00990-12;
RA Yan Q., Xu R., Zhu L., Cheng X., Wang Z., Manis J., Shipp M.A.;
RT "BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) activation,
RT ubiquitylation, and double-strand DNA repair independent of ATM, MDC1, and
RT RNF8.";
RL Mol. Cell. Biol. 33:845-857(2013).
RN [10]
RP FUNCTION, INTERACTION WITH DTX3L AND STAT1, IDENTIFICATION IN A COMPLEX
RP WITH DTX3L; STAT1 AND H2BC9, SUBCELLULAR LOCATION, INDUCTION, DOMAIN, AND
RP MUTAGENESIS OF GLY-147 AND GLY-346.
RX PubMed=26479788; DOI=10.1038/ni.3279;
RA Zhang Y., Mao D., Roswit W.T., Jin X., Patel A.C., Patel D.A., Agapov E.,
RA Wang Z., Tidwell R.M., Atkinson J.J., Huang G., McCarthy R., Yu J.,
RA Yun N.E., Paessler S., Lawson T.G., Omattage N.S., Brett T.J.,
RA Holtzman M.J.;
RT "PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C
RT protease to enhance interferon signaling and control viral infection.";
RL Nat. Immunol. 16:1215-1227(2015).
RN [11]
RP FUNCTION, INTERACTION WITH PARP14, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INDUCTION, AND ADP-RIBOSYLATION.
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 [12]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, IDENTIFICATION IN A COMPLEX WITH DTX3L, SUBCELLULAR LOCATION,
RP DOMAIN, AND MUTAGENESIS OF GLY-147; GLY-346; 719-GLY--ARG-722; TYR-737;
RP PHE-738; 766-VAL--GLY-769; 780-VAL--LEU-784; 802-PRO--GLU-803 AND
RP 831-TYR--ASP-854.
RX PubMed=28525742; DOI=10.1016/j.molcel.2017.04.028;
RA Yang C.S., Jividen K., Spencer A., Dworak N., Ni L., Oostdyk L.T.,
RA Chatterjee M., Kusmider B., Reon B., Parlak M., Gorbunova V., Abbas T.,
RA Jeffery E., Sherman N.E., Paschal B.M.;
RT "Ubiquitin Modification by the E3 Ligase/ADP-Ribosyltransferase
RT Dtx3L/Parp9.";
RL Mol. Cell 66:503-516(2017).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 310-493.
RA Elkins J.M.;
RT "Structure of Parp9 2Nd Macrodomain.";
RL Submitted (FEB-2015) to the PDB data bank.
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:16809771,
CC PubMed:23230272, PubMed:26479788, PubMed:27796300). Within the complex,
CC enhances DTX3L E3 ligase activity which is further enhanced by PARP9
CC binding to poly(ADP-ribose) (PubMed:28525742). In association with
CC DTX3L and in presence of E1 and E2 enzymes, mediates NAD(+)-dependent
CC mono-ADP-ribosylation of ubiquitin which prevents ubiquitin conjugation
CC to substrates such as histones (PubMed:28525742). During DNA repair,
CC PARP1 recruits PARP9/BAL1-DTX3L complex to DNA damage sites via PARP9
CC binding to ribosylated PARP1 (PubMed:23230272). Subsequent PARP1-
CC dependent PARP9/BAL1-DTX3L-mediated ubiquitination promotes the rapid
CC and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to
CC DNA damage sites (PubMed:23230272, PubMed:28525742). In response to DNA
CC damage, PARP9-DTX3L complex is required for efficient non-homologous
CC end joining (NHEJ); the complex function is negatively modulated by
CC PARP9 activity (PubMed:28525742). Dispensable for B-cell receptor (BCR)
CC assembly through V(D)J recombination and class switch recombination
CC (CSR) (By similarity). 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 (PubMed:27796300).
CC {ECO:0000250|UniProtKB:Q8CAS9, ECO:0000269|PubMed:16809771,
CC ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26479788,
CC ECO:0000269|PubMed:27796300, ECO:0000269|PubMed:28525742}.
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:0000269|PubMed:28525742};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58269;
CC Evidence={ECO:0000269|PubMed:28525742};
CC -!- ACTIVITY REGULATION: Binding to poly(ADP-ribose) does not affect its
CC activity. {ECO:0000269|PubMed:28525742}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=196 uM for NAD(+) {ECO:0000269|PubMed:28525742};
CC -!- SUBUNIT: Forms a stable complex with E3 ligase DTX3L; the interaction
CC is required for PARP9 mediated ADP-ribosylation of ubiquitin
CC (PubMed:12670957, PubMed:28525742). Interacts (via PARP catalytic
CC domain) with DTX3L (via N-terminus) (PubMed:26479788). Forms a complex
CC with STAT1 and DTX3L independently of IFNB1 or IFNG-mediated STAT1
CC 'Tyr-701' phosphorylation (PubMed:26479788). Forms a complex with
CC STAT1, DTX3L and histone H2B H2BC9/H2BJ; the interaction is likely to
CC induce H2BC9/H2BJ ubiquitination (PubMed:26479788). Interacts (via N-
CC terminus) with STAT1 (PubMed:26479788). Interacts with PARP14 in IFNG-
CC stimulated macrophages; the interaction prevents PARP14-mediated STAT1
CC and STAT6 ADP-riboslylation (PubMed:27796300). Interacts with PARP1
CC (when poly-ADP-ribosylated) (PubMed:23230272).
CC {ECO:0000269|PubMed:12670957, ECO:0000269|PubMed:23230272,
CC ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:27796300,
CC ECO:0000269|PubMed:28525742}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:16809771,
CC ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:27796300}. Nucleus
CC {ECO:0000269|PubMed:11110709, ECO:0000269|PubMed:16809771,
CC ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26479788,
CC ECO:0000269|PubMed:28525742}. Note=Shuttles between the nucleus and the
CC cytosol (PubMed:16809771). Translocates to the nucleus in response to
CC IFNG or IFNB1 stimulation (PubMed:26479788). Export to the cytosol
CC depends on the interaction with DTX3L (PubMed:16809771). Localizes at
CC sites of DNA damage in a PARP1-dependent manner (PubMed:23230272,
CC PubMed:28525742). {ECO:0000269|PubMed:16809771,
CC ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26479788,
CC ECO:0000269|PubMed:28525742}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Long, L;
CC IsoId=Q8IXQ6-1; Sequence=Displayed;
CC Name=2; Synonyms=Short, S;
CC IsoId=Q8IXQ6-2; Sequence=VSP_008505;
CC Name=3;
CC IsoId=Q8IXQ6-3; Sequence=VSP_008505, VSP_046086, VSP_046087;
CC -!- TISSUE SPECIFICITY: Expressed in lymphocyte-rich tissues, spleen, lymph
CC nodes, peripheral blood lymphocytes and colonic mucosa
CC (PubMed:11110709, PubMed:16809771). Expressed in macrophages
CC (PubMed:27796300). Also expressed in nonhematopoietic tissues such as
CC heart and skeletal muscle (PubMed:11110709, PubMed:16809771). Isoform 2
CC is the predominant form (PubMed:11110709). Most abundantly expressed in
CC lymphomas with a brisk host inflammatory response (PubMed:11110709,
CC PubMed:16809771). In diffuse large B-cell lymphomas tumors, expressed
CC specifically by malignant B-cells (PubMed:11110709, PubMed:16809771).
CC {ECO:0000269|PubMed:11110709, ECO:0000269|PubMed:16809771,
CC ECO:0000269|PubMed:27796300}.
CC -!- INDUCTION: Up-regulated by IFNG in macrophages and in B-cell lymphoma
CC cell lines (PubMed:16809771, PubMed:27796300, PubMed:26479788). Up-
CC regulated by IFNB1 or viral infection (PubMed:26479788). Down-regulated
CC by IL4 in macrophages (PubMed:27796300). {ECO:0000269|PubMed:16809771,
CC ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:27796300}.
CC -!- DOMAIN: Macro domains 1 and 2 may be involved in the binding to
CC poly(ADP-ribose) (PubMed:28525742, PubMed:26479788). Macro domain 2 is
CC required for recruitment to DNA damage sites (PubMed:23230272). Macro
CC domains 1 and 2 are probably dispensable for the interaction with STAT1
CC and DTX3L and for STAT1 phosphorylation (PubMed:26479788).
CC {ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:26479788,
CC ECO:0000269|PubMed:28525742}.
CC -!- PTM: ADP-ribosylated by PARP14. {ECO:0000269|PubMed:27796300}.
CC -!- DISEASE: Note=Overexpressed at significantly higher levels in fatal
CC high-risk diffuse large B-cell lymphomas (DLB-CL) compared to cured
CC low-risk tumors. Overexpression in B-cell lymphoma transfectants may
CC promote malignant B-cell migration. May therefore be involved in
CC promoting B-cell migration and dissemination of high-risk DLB-CL tumors
CC (PubMed:11110709). {ECO:0000269|PubMed:11110709}.
CC -!- SIMILARITY: Belongs to the ARTD/PARP family. {ECO:0000305}.
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DR EMBL; AF307338; AAK07558.1; -; mRNA.
DR EMBL; AF307339; AAK07559.1; -; mRNA.
DR EMBL; AK292959; BAF85648.1; -; mRNA.
DR EMBL; AK313494; BAG36276.1; -; mRNA.
DR EMBL; AC092908; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC096861; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017463; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC039580; AAH39580.1; -; mRNA.
DR EMBL; AL713679; CAD28483.1; -; mRNA.
DR CCDS; CCDS3014.1; -. [Q8IXQ6-1]
DR CCDS; CCDS54633.1; -. [Q8IXQ6-3]
DR CCDS; CCDS54634.1; -. [Q8IXQ6-2]
DR RefSeq; NP_001139574.1; NM_001146102.1. [Q8IXQ6-1]
DR RefSeq; NP_001139575.1; NM_001146103.1. [Q8IXQ6-2]
DR RefSeq; NP_001139576.1; NM_001146104.1. [Q8IXQ6-2]
DR RefSeq; NP_001139577.1; NM_001146105.1. [Q8IXQ6-2]
DR RefSeq; NP_113646.2; NM_031458.2. [Q8IXQ6-1]
DR RefSeq; XP_005247877.1; XM_005247820.2. [Q8IXQ6-1]
DR RefSeq; XP_016862793.1; XM_017007304.1. [Q8IXQ6-1]
DR RefSeq; XP_016862794.1; XM_017007305.1. [Q8IXQ6-2]
DR RefSeq; XP_016862795.1; XM_017007306.1. [Q8IXQ6-2]
DR PDB; 5AIL; X-ray; 1.55 A; A/B=310-493.
DR PDBsum; 5AIL; -.
DR AlphaFoldDB; Q8IXQ6; -.
DR SMR; Q8IXQ6; -.
DR BioGRID; 123723; 25.
DR CORUM; Q8IXQ6; -.
DR IntAct; Q8IXQ6; 2.
DR STRING; 9606.ENSP00000353512; -.
DR ChEMBL; CHEMBL4295895; -.
DR iPTMnet; Q8IXQ6; -.
DR MetOSite; Q8IXQ6; -.
DR PhosphoSitePlus; Q8IXQ6; -.
DR BioMuta; PARP9; -.
DR DMDM; 48474734; -.
DR EPD; Q8IXQ6; -.
DR jPOST; Q8IXQ6; -.
DR MassIVE; Q8IXQ6; -.
DR MaxQB; Q8IXQ6; -.
DR PaxDb; Q8IXQ6; -.
DR PeptideAtlas; Q8IXQ6; -.
DR PRIDE; Q8IXQ6; -.
DR ProteomicsDB; 20136; -.
DR ProteomicsDB; 71045; -. [Q8IXQ6-1]
DR ProteomicsDB; 71046; -. [Q8IXQ6-2]
DR Antibodypedia; 32910; 103 antibodies from 28 providers.
DR DNASU; 83666; -.
DR Ensembl; ENST00000360356.6; ENSP00000353512.2; ENSG00000138496.17. [Q8IXQ6-1]
DR Ensembl; ENST00000462315.5; ENSP00000418894.1; ENSG00000138496.17. [Q8IXQ6-3]
DR Ensembl; ENST00000471785.5; ENSP00000419001.1; ENSG00000138496.17. [Q8IXQ6-2]
DR Ensembl; ENST00000477522.6; ENSP00000419506.1; ENSG00000138496.17. [Q8IXQ6-2]
DR Ensembl; ENST00000682323.1; ENSP00000507390.1; ENSG00000138496.17. [Q8IXQ6-2]
DR GeneID; 83666; -.
DR KEGG; hsa:83666; -.
DR MANE-Select; ENST00000682323.1; ENSP00000507390.1; NM_001146105.2; NP_001139577.1. [Q8IXQ6-2]
DR UCSC; uc003efh.5; human. [Q8IXQ6-1]
DR CTD; 83666; -.
DR DisGeNET; 83666; -.
DR GeneCards; PARP9; -.
DR HGNC; HGNC:24118; PARP9.
DR HPA; ENSG00000138496; Low tissue specificity.
DR MIM; 612065; gene.
DR neXtProt; NX_Q8IXQ6; -.
DR OpenTargets; ENSG00000138496; -.
DR PharmGKB; PA134870403; -.
DR VEuPathDB; HostDB:ENSG00000138496; -.
DR eggNOG; KOG2633; Eukaryota.
DR GeneTree; ENSGT00940000158837; -.
DR HOGENOM; CLU_012160_0_0_1; -.
DR InParanoid; Q8IXQ6; -.
DR OMA; LSCQYVY; -.
DR OrthoDB; 681829at2759; -.
DR PhylomeDB; Q8IXQ6; -.
DR TreeFam; TF328965; -.
DR PathwayCommons; Q8IXQ6; -.
DR Reactome; R-HSA-197264; Nicotinamide salvaging.
DR Reactome; R-HSA-9683610; Maturation of nucleoprotein.
DR Reactome; R-HSA-9694631; Maturation of nucleoprotein.
DR SignaLink; Q8IXQ6; -.
DR BioGRID-ORCS; 83666; 8 hits in 1084 CRISPR screens.
DR ChiTaRS; PARP9; human.
DR GenomeRNAi; 83666; -.
DR Pharos; Q8IXQ6; Tbio.
DR PRO; PR:Q8IXQ6; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8IXQ6; protein.
DR Bgee; ENSG00000138496; Expressed in monocyte and 162 other tissues.
DR ExpressionAtlas; Q8IXQ6; baseline and differential.
DR Genevisible; Q8IXQ6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0090734; C:site of DNA damage; IDA:UniProtKB.
DR GO; GO:0072570; F:ADP-D-ribose binding; IMP:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0004857; F:enzyme inhibitor activity; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IPI:UniProtKB.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IDA:UniProtKB.
DR GO; GO:1990404; F:NAD+-protein ADP-ribosyltransferase activity; IBA:GO_Central.
DR GO; GO:0097677; F:STAT family protein binding; IPI:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IMP:UniProtKB.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:UniProtKB.
DR GO; GO:0016477; P:cell migration; TAS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0034356; P:NAD biosynthesis via nicotinamide riboside salvage pathway; TAS:Reactome.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0035563; P:positive regulation of chromatin binding; IGI:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IGI:UniProtKB.
DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
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; IGI:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IGI:UniProtKB.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:UniProtKB.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0006471; P:protein ADP-ribosylation; IDA:UniProtKB.
DR GO; GO:0140289; P:protein mono-ADP-ribosylation; IBA:GO_Central.
DR GO; GO:0060330; P:regulation of response to interferon-gamma; IDA:UniProtKB.
DR GO; GO:0019082; P:viral protein processing; TAS:Reactome.
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 3D-structure; ADP-ribosylation; Alternative splicing; Antiviral defense;
KW Cytoplasm; DNA damage; DNA repair; Glycosyltransferase; Immunity;
KW Innate immunity; NAD; Nucleotidyltransferase; Nucleus; Reference proteome;
KW Repeat; Transferase.
FT CHAIN 1..854
FT /note="Protein mono-ADP-ribosyltransferase PARP9"
FT /id="PRO_0000211339"
FT DOMAIN 107..296
FT /note="Macro 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 306..487
FT /note="Macro 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 628..850
FT /note="PARP catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00397"
FT VAR_SEQ 17..51
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:11110709,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_008505"
FT VAR_SEQ 729..745
FT /note="DPKYGAGIYFTKNLKNL -> GRCQCLIIGATLWNLVS (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046086"
FT VAR_SEQ 746..854
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046087"
FT VARIANT 21
FT /note="S -> L (in dbSNP:rs34006803)"
FT /id="VAR_056654"
FT VARIANT 517
FT /note="I -> V (in dbSNP:rs28365795)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_056655"
FT VARIANT 528
FT /note="Y -> C (in dbSNP:rs9851180)"
FT /evidence="ECO:0000269|PubMed:11110709,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_056656"
FT VARIANT 651
FT /note="T -> A (in dbSNP:rs6780543)"
FT /id="VAR_056657"
FT MUTAGEN 147
FT /note="G->E: Reduces the binding to poly(ADP-ribose) by 50
FT percent and prevents increase in DTX3L-mediated histone
FT ubiquitination without affecting ubiquitin ADP
FT ribosylation, interaction with DTX3L and STAT1 and DTX3L
FT catalytic activity; when associated with E-346."
FT /evidence="ECO:0000269|PubMed:26479788,
FT ECO:0000269|PubMed:28525742"
FT MUTAGEN 346
FT /note="G->E: Reduces the binding to poly(ADP-ribose) by 50
FT percent and prevents increase in DTX3L-mediated histone
FT ubiquitination without affecting ubiquitin ADP
FT ribosylation, interaction with DTX3L and STAT1 and DTX3L
FT catalytic activity; when associated with E-147."
FT /evidence="ECO:0000269|PubMed:26479788,
FT ECO:0000269|PubMed:28525742"
FT MUTAGEN 719..722
FT /note="Missing: Loss of ADP ribosylation activity and
FT interaction with DTX3L."
FT /evidence="ECO:0000269|PubMed:28525742"
FT MUTAGEN 737
FT /note="Y->A: No defect in ubiquitin ADP ribosylation and
FT the interaction with DTX3L."
FT /evidence="ECO:0000269|PubMed:28525742"
FT MUTAGEN 738
FT /note="F->K: Severe reduction in ubiquitin ADP
FT ribosylation. No effect on the interaction with DTX3L and
FT on DTX3L E3 ligase activity. Increases DNA repair."
FT /evidence="ECO:0000269|PubMed:28525742"
FT MUTAGEN 766..769
FT /note="Missing: Loss of ADP ribosylation activity and
FT interaction with DTX3L."
FT /evidence="ECO:0000269|PubMed:28525742"
FT MUTAGEN 780..784
FT /note="Missing: Reduces ADP ribosylation activity and
FT interaction with DTX3L."
FT /evidence="ECO:0000269|PubMed:28525742"
FT MUTAGEN 802..803
FT /note="PE->AA: No defect in ADP ribosylation and
FT interaction with DTX3L."
FT /evidence="ECO:0000269|PubMed:28525742"
FT MUTAGEN 831..854
FT /note="Missing: No defect in ADP ribosylation and
FT interaction with DTX3L."
FT /evidence="ECO:0000269|PubMed:28525742"
FT CONFLICT 487
FT /note="S -> P (in Ref. 2; BAF85648)"
FT /evidence="ECO:0000305"
FT CONFLICT 839
FT /note="F -> S (in Ref. 2; BAG36276)"
FT /evidence="ECO:0000305"
FT STRAND 311..314
FT /evidence="ECO:0007829|PDB:5AIL"
FT STRAND 317..324
FT /evidence="ECO:0007829|PDB:5AIL"
FT HELIX 326..328
FT /evidence="ECO:0007829|PDB:5AIL"
FT STRAND 330..339
FT /evidence="ECO:0007829|PDB:5AIL"
FT HELIX 347..356
FT /evidence="ECO:0007829|PDB:5AIL"
FT HELIX 358..370
FT /evidence="ECO:0007829|PDB:5AIL"
FT STRAND 378..382
FT /evidence="ECO:0007829|PDB:5AIL"
FT STRAND 386..395
FT /evidence="ECO:0007829|PDB:5AIL"
FT HELIX 402..419
FT /evidence="ECO:0007829|PDB:5AIL"
FT STRAND 423..427
FT /evidence="ECO:0007829|PDB:5AIL"
FT STRAND 433..437
FT /evidence="ECO:0007829|PDB:5AIL"
FT HELIX 439..456
FT /evidence="ECO:0007829|PDB:5AIL"
FT STRAND 462..468
FT /evidence="ECO:0007829|PDB:5AIL"
FT HELIX 473..490
FT /evidence="ECO:0007829|PDB:5AIL"
SQ SEQUENCE 854 AA; 96343 MW; CBBB3B4B7CA1CDA4 CRC64;
MDFSMVAGAA AYNEKSGRIT SLSLLFQKVF AQIFPQWRKG NTEECLPYKC SETGALGENY
SWQIPINHND FKILKNNERQ LCEVLQNKFG CISTLVSPVQ EGNSKSLQVF RKMLTPRIEL
SVWKDDLTTH AVDAVVNAAN EDLLHGGGLA LALVKAGGFE IQEESKQFVA RYGKVSAGEI
AVTGAGRLPC KQIIHAVGPR WMEWDKQGCT GKLQRAIVSI LNYVIYKNTH IKTVAIPALS
SGIFQFPLNL CTKTIVETIR VSLQGKPMMS NLKEIHLVSN EDPTVAAFKA ASEFILGKSE
LGQETTPSFN AMVVNNLTLQ IVQGHIEWQT ADVIVNSVNP HDITVGPVAK SILQQAGVEM
KSEFLATKAK QFQRSQLVLV TKGFNLFCKY IYHVLWHSEF PKPQILKHAM KECLEKCIEQ
NITSISFPAL GTGNMEIKKE TAAEILFDEV LTFAKDHVKH QLTVKFVIFP TDLEIYKAFS
SEMAKRSKML SLNNYSVPQS TREEKRENGL EARSPAINLM GFNVEEMYEA HAWIQRILSL
QNHHIIENNH ILYLGRKEHD ILSQLQKTSS VSITEIISPG RTELEIEGAR ADLIEVVMNI
EDMLCKVQEE MARKKERGLW RSLGQWTIQQ QKTQDEMKEN IIFLKCPVPP TQELLDQKKQ
FEKCGLQVLK VEKIDNEVLM AAFQRKKKMM EEKLHRQPVS HRLFQQVPYQ FCNVVCRVGF
QRMYSTPCDP KYGAGIYFTK NLKNLAEKAK KISAADKLIY VFEAEVLTGF FCQGHPLNIV
PPPLSPGAID GHDSVVDNVS SPETFVIFSG MQAIPQYLWT CTQEYVQSQD YSSGPMRPFA
QHPWRGFASG SPVD
