true2002-03-272024-01-24219TNKS1_HUMANTankyrase, a poly(ADP-ribose) polymerase at human telomeres.Smith S.Giriat I.Schmitt A.de Lange T.doi:10.1126/science.282.5393.14841998Science2821484-1487NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2)TestisDNA sequence and analysis of human chromosome 8.Nusbaum C.Mikkelsen T.S.Zody M.C.Asakawa S.Taudien S.Garber M.Kodira C.D.Schueler M.G.Shimizu A.Whittaker C.A.Chang J.L.Cuomo C.A.Dewar K.FitzGerald M.G.Yang X.Allen N.R.Anderson S.Asakawa T.Blechschmidt K.Bloom T.Borowsky M.L.Butler J.Cook A.Corum B.DeArellano K.DeCaprio D.Dooley K.T.Dorris L. IIIEngels R.Gloeckner G.Hafez N.Hagopian D.S.Hall J.L.Ishikawa S.K.Jaffe D.B.Kamat A.Kudoh J.Lehmann R.Lokitsang T.Macdonald P.Major J.E.Matthews C.D.Mauceli E.Menzel U.Mihalev A.H.Minoshima S.Murayama Y.Naylor J.W.Nicol R.Nguyen C.O'Leary S.B.O'Neill K.Parker S.C.J.Polley A.Raymond C.K.Reichwald K.Rodriguez J.Sasaki T.Schilhabel M.Siddiqui R.Smith C.L.Sneddon T.P.Talamas J.A.Tenzin P.Topham K.Venkataraman V.Wen G.Yamazaki S.Young S.K.Zeng Q.Zimmer A.R.Rosenthal A.Birren B.W.Platzer M.Shimizu N.Lander E.S.doi:10.1038/nature044062006Nature439331-335NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]Homo sapiens protein coding cDNA.Totoki Y.Toyoda A.Takeda T.Sakaki Y.Tanaka A.Yokoyama S.Ohara O.Nagase T.Kikuno R.F.2005-03EMBL/GenBank/DDBJNUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 273-1327BrainThe status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).The MGC Project Teamdoi:10.1101/gr.25965042004Genome Res.142121-2127NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]Cell cycle dependent localization of the telomeric PARP, tankyrase, to nuclear pore complexes and centrosomes.Smith S.de Lange T.doi:10.1242/jcs.112.21.36491999J. Cell Sci.1123649-3656SUBCELLULAR LOCATIONTankyrase is a Golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles.Chi N.-W.Lodish H.F.doi:10.1074/jbc.m0076352002000J. Biol. Chem.27538437-38444FUNCTIONPHOSPHORYLATIONIdentification of a tankyrase-binding motif shared by IRAP, TAB182, and human TRF1 but not mouse TRF1. NuMA contains this RXXPDG motif and is a novel tankyrase partner.Sbodio J.I.Chi N.W.doi:10.1074/jbc.m2039162002002J. Biol. Chem.27731887-31892INTERACTION WITH NUMA1Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres.Cook B.D.Dynek J.N.Chang W.Shostak G.Smith S.doi:10.1128/mcb.22.1.332-342.20022002Mol. Cell. Biol.22332-342FUNCTIONMUTAGENESIS OF HIS-1184 AND GLU-1291POT1 as a terminal transducer of TRF1 telomere length control.Loayza D.De Lange T.doi:10.1038/nature016882003Nature4231013-1018IDENTIFICATION IN A COMPLEX WITH POT1; TERF1 AND TINF2NuMA is a major acceptor of poly(ADP-ribosyl)ation by tankyrase 1 in mitosis.Chang W.Dynek J.N.Smith S.doi:10.1042/bj200508852005Biochem. J.391177-184FUNCTIONSUBCELLULAR LOCATIONTankyrase inhibition stabilizes axin and antagonizes Wnt signalling.Huang S.M.Mishina Y.M.Liu S.Cheung A.Stegmeier F.Michaud G.A.Charlat O.Wiellette E.Zhang Y.Wiessner S.Hild M.Shi X.Wilson C.J.Mickanin C.Myer V.Fazal A.Tomlinson R.Serluca F.Shao W.Cheng H.Shultz M.Rau C.Schirle M.Schlegl J.Ghidelli S.Fawell S.Lu C.Curtis D.Kirschner M.W.Lengauer C.Finan P.M.Tallarico J.A.Bouwmeester T.Porter J.A.Bauer A.Cong F.doi:10.1038/nature083562009Nature461614-620FUNCTIONCATALYTIC ACTIVITYACTIVITY REGULATIONINTERACTION WITH AXIN1 AND AXIN2Toward a unified nomenclature for mammalian ADP-ribosyltransferases.Hottiger M.O.Hassa P.O.Luscher B.Schuler H.Koch-Nolte F.doi:10.1016/j.tibs.2009.12.0032010Trends Biochem. Sci.35208-219NOMENCLATURERNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling.Zhang Y.Liu S.Mickanin C.Feng Y.Charlat O.Michaud G.A.Schirle M.Shi X.Hild M.Bauer A.Myer V.E.Finan P.M.Porter J.A.Huang S.M.Cong F.doi:10.1038/ncb22222011Nat. Cell Biol.13623-629FUNCTIONINTERACTION WITH AXIN1; AXIN2; BLZF1 AND CASC3UBIQUITINATIONUbiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt signaling.Callow M.G.Tran H.Phu L.Lau T.Lee J.Sandoval W.N.Liu P.S.Bheddah S.Tao J.Lill J.R.Hongo J.A.Davis D.Kirkpatrick D.S.Polakis P.Costa M.doi:10.1371/journal.pone.00225952011PLoS ONE6E22595INTERACTION WITH AXIN1SUBCELLULAR LOCATIONPoly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation.Ozaki Y.Matsui H.Asou H.Nagamachi A.Aki D.Honda H.Yasunaga S.Takihara Y.Yamamoto T.Izumi S.Ohsugi M.Inaba T.doi:10.1016/j.molcel.2012.06.0332012Mol. Cell47694-706FUNCTIONSUBCELLULAR LOCATIONProteasome regulation by ADP-ribosylation.Cho-Park P.F.Steller H.doi:10.1016/j.cell.2013.03.0402013Cell153614-627FUNCTIONFamily-wide analysis of poly(ADP-ribose) polymerase activity.Vyas S.Matic I.Uchima L.Rood J.Zaja R.Hay R.T.Ahel I.Chang P.doi:10.1038/ncomms54262014Nat. Commun.54426FUNCTIONZinc binding catalytic domain of human tankyrase 1.Lehtio L.Collins R.van den Berg S.Johansson A.Dahlgren L.G.Hammarstrom M.Helleday T.Holmberg-Schiavone L.Karlberg T.Weigelt J.doi:10.1016/j.jmb.2008.03.0582008J. Mol. Biol.379136-145X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1091-1325ZINC-BINDING SITESDissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1.Ryan K.Bolanos B.Smith M.Palde P.B.Cuenca P.D.VanArsdale T.L.Niessen S.Zhang L.Behenna D.Ornelas M.A.Tran K.T.Kaiser S.Lum L.Stewart A.Gajiwala K.S.doi:10.1074/jbc.ra120.0165732021J. Biol. Chem.296100251X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 1104-1314 IN COMPLEX WITH TALAZOPARIB INHIBITOR; OLAPARIB; NIRAPARIB AND VELIPARIBAtlas of Genetics and Cytogenetics in Oncology and Haematology2.30A=1091-13251.95A/B=1105-13272.00A/B=1105-13272.00A/B=1105-13271.90A/B=1104-13142.40A/B/C/D=1104-13142.30A/B=1104-13142.90A/B=1104-13142.29A/B=1105-13272.05A/B=1105-13272.20A/B=1105-13272.52A/B=1105-13271.80A/B=1104-13142.30A/B/C/D=1104-13142.00A/B=1104-13141.90A/B=1104-13142.00A/B=1104-13142.30A/B/C/D=1105-13131.50A/B/C/D=1105-13151.80A/B=1105-13152.37A=1091-13252.52A=1091-13253.37A/B/C/D/E/F/G/H=1091-13252.80A=1105-13141.95A=1106-13142.24A/B/C/D=1106-13142.20A/B/C/D=1105-13162.90A/B/C/D=1091-13241.50A=799-9573.20A/B/C/D=174-6492.90A/B/C/D/E/F=1018-10932.50A/B/C/D/E/F=1018-10932.50A/B/C/D/E/F/G=1026-10911.20A=1104-13142.05A/B=328-6461.58A/B/C/D=1104-13141.48A/B/C/D=1104-13141.56A/B/C=1104-13141.40A/B=1104-13141.59A/B/C/D=1104-13141.43A=1104-131410361the nuclear pore complex (npc) family1 sequenced antibody405 antibodies from 36 providershumanTNKSLow tissue specificitygeneEukaryota2681TCF dependent signaling in response to WNTDegradation of AXINXAV939 stabilizes AXINUb-specific processing proteasesRegulation of PTEN stability and activity14 hits in 1163 CRISPR screenshumanTchemProteinExpressed in middle temporal gyrus and 204 other cell types or tissuesbaseline and differentialHSSAM_tankyrase1_2tankyrase_likeAnkyrin repeat-containing domainTranscription Factor, Ets-1Ankyrin_rptAnkyrin_rpt-contain_sfPoly(ADP-ribose)pol_cat_domSAMSAM/pointed_sfMYOTROPHINSI:CH211-203B8.6AnkAnk_2Ank_4PARPSAM_2ANKYRINANKSAMADP-ribosylationAnkyrin repeatSAM/Pointed domainANK_REP_REGIONANK_REPEATPARP_CATALYTICSAM_DOMAINPoly [ADP-ribose] polymerase tankyrase-12.4.2.30ADP-ribosyltransferase diphtheria toxin-like 5ARTD5Poly [ADP-ribose] polymerase 5AProtein poly-ADP-ribosyltransferase tankyrase-12.4.2.-TNKS-1TRF1-interacting ankyrin-related ADP-ribose polymeraseTankyrase ITankyrase-1TANK1TNKSPARP5APARPLTIN1TINF1TNKS1Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking (PubMed:10988299, PubMed:11739745, PubMed:16076287, PubMed:19759537, PubMed:21478859, PubMed:22864114, PubMed:23622245, PubMed:25043379). Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation (PubMed:19759537, PubMed:21478859). Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination (PubMed:21478859). Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length (PubMed:11739745). Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI (PubMed:22864114). May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles (PubMed:10988299). May be involved in spindle pole assembly through PARsylation of NUMA1 (PubMed:16076287). Stimulates 26S proteasome activity (PubMed:23622245).Specifically inhibited by XAV939, a small molecule, leading to inhibit the Wnt signaling pathway by stabilizing AXIN1 and AXIN2 (PubMed:19759537). Inhibited by talazoparib (PubMed:33361107). Not inhibited by olaparib, niraparib and veliparib (PubMed:33361107).Oligomerizes and associates with TNKS2. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles. Binds to the N-terminus of telomeric TERF1 via the ANK repeats. Found in a complex with POT1; TERF1 and TINF2 (PubMed:12768206). Interacts with AXIN1 (PubMed:19759537, PubMed:21478859, PubMed:21799911). Interacts with AXIN2 (PubMed:19759537, PubMed:21478859). Interacts with BLZF1 and CASC3 (PubMed:21478859). Interacts with NUMA1 (PubMed:12080061).Associated with the Golgi and with juxtanuclear SLC2A4/GLUT4-vesicles (PubMed:22864114). A minor proportion is also found at nuclear pore complexes and around the pericentriolar matrix of mitotic centromeres (PubMed:10523501). During interphase, a small fraction of TNKS is found in the nucleus, associated with TERF1 (PubMed:12768206). Localizes to spindle poles at mitosis onset via interaction with NUMA1 (PubMed:12080061).Ubiquitous; highest levels in testis.Phosphorylated on serine residues by MAPK kinases upon insulin stimulation. Phosphorylated during mitosis.Ubiquitinated by RNF146 when auto-poly-ADP-ribosylated, leading to its degradation.ADP-ribosylated (-auto). Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination.Belongs to the ARTD/PARP family.Poly [ADP-ribose] polymerase tankyrase-114203911327ANK 1181209ANK 2215244ANK 3248277ANK 4281310ANK 5335364ANK 6368397ANK 7401430ANK 8434463ANK 9521553ANK 10557586ANK 11590619ANK 12621647ANK 13649679ANK 14683712ANK 15716745ANK 16749778ANK 17782810ANK 18836865ANK 19869898ANK 20902931ANK 21935964SAM10301089PARP catalytic11121317Disordered91Disordered112173Basic residues16Pro residues2241Basic and acidic residues6680Polar residues1561234123712421245In isoform 2.GHS641643In isoform 2.644Loss of activity; when associated with A-1291.A1184Loss of activity; when associated with A-1184.A1291Q83K802KG1001I12661821921952012042082122192252292372522582622702852912953033183213243293303323343453483543573613723783823904054114154234384444484564714744784985025105135155195255315375465615675715795946016046126286306336407998138168228258298338408468508588738808838919069139169249399429469551031103710411043104410491054105810621067107310861107111011161127113311391145115411561172117311751179118911951199120112021205120912171218122212231226122812301235124312471255125812641268127012761280128212841286128912961297129913001310false3false4false3false4false5false6false3false6false5false3false6false2false3true4ADPRSCENPJEPM2AIP1FNBP1HIF1ANMACROH2A1OARD1RNF146SDCBPTCL1ATERF1TNKS1BP1UBASH3BAxin12009-04-142142039e8674de8c7dedc9625ba57a8e50e32f21MAASRRSQHHHHHHQQQLQPAPGASAPPPPPPPPLSPGLAPGTTPASPTASGLAPFASPRHGLALPEGDGSRDPPDRPRSPDPVDGTSCCSTTSTICTVAAAPVVPAVSTSSAAGVAPNPAGSGSNNSPSSSSSPTSSSSSSPSSPGSSLAESPEAAGVSSTAPLGPGAAGPGTGVPAVSGALRELLEACRNGDVSRVKRLVDAANVNAKDMAGRKSSPLHFAAGFGRKDVVEHLLQMGANVHARDDGGLIPLHNACSFGHAEVVSLLLCQGADPNARDNWNYTPLHEAAIKGKIDVCIVLLQHGADPNIRNTDGKSALDLADPSAKAVLTGEYKKDELLEAARSGNEEKLMALLTPLNVNCHASDGRKSTPLHLAAGYNRVRIVQLLLQHGADVHAKDKGGLVPLHNACSYGHYEVTELLLKHGACVNAMDLWQFTPLHEAASKNRVEVCSLLLSHGADPTLVNCHGKSAVDMAPTPELRERLTYEFKGHSLLQAAREADLAKVKKTLALEIINFKQPQSHETALHCAVASLHPKRKQVTELLLRKGANVNEKNKDFMTPLHVAAERAHNDVMEVLHKHGAKMNALDTLGQTALHRAALAGHLQTCRLLLSYGSDPSIISLQGFTAAQMGNEAVQQILSESTPIRTSDVDYRLLEASKAGDLETVKQLCSSQNVNCRDLEGRHSTPLHFAAGYNRVSVVEYLLHHGADVHAKDKGGLVPLHNACSYGHYEVAELLVRHGASVNVADLWKFTPLHEAAAKGKYEICKLLLKHGADPTKKNRDGNTPLDLVKEGDTDIQDLLRGDAALLDAAKKGCLARVQKLCTPENINCRDTQGRNSTPLHLAAGYNNLEVAEYLLEHGADVNAQDKGGLIPLHNAASYGHVDIAALLIKYNTCVNATDKWAFTPLHEAAQKGRTQLCALLLAHGADPTMKNQEGQTPLDLATADDIRALLIDAMPPEALPTCFKPQATVVSASLISPASTPSCLSAASSIDNLTGPLAELAVGGASNAGDGAAGTERKEGEVAGLDMNISQFLKSLGLEHLRDIFETEQITLDVLADMGHEELKEIGINAYGHRHKLIKGVERLLGGQQGTNPYLTFHCVNQGTILLDLAPEDKEYQSVEEEMQSTIREHRDGGNAGGIFNRYNVIRIQKVVNKKLRERFCHRQKEVSEENHNHHNERMLFHGSPFINAIIHKGFDERHAYIGGMFGAGIYFAENSSKSNQYVYGIGGGTGCPTHKDRSCYICHRQMLFCRVTLGKSFLQFSTMKMAHAPPGHHSVIGRPSVNGLAYAEYVIYRGEQAYPEYLITYQIMKPEAPSQTATAAEQKT2MAASRRSQHHHHHHQQQLQPAPGASAPPPPPPPPLSPGLAPGTTPASPTASGLAPFASPRHGLALPEGDGSRDPPDRPRSPDPVDGTSCCSTTSTICTVAAAPVVPAVSTSSAAGVAPNPAGSGSNNSPSSSSSPTSSSSSSPSSPGSSLAESPEAAGVSSTAPLGPGAAGPGTGVPAVSGALRELLEACRNGDVSRVKRLVDAANVNAKDMAGRKSSPLHFAAGFGRKDVVEHLLQMGANVHARDDGGLIPLHNACSFGHAEVVSLLLCQGADPNARDNWNYTPLHEAAIKGKIDVCIVLLQHGADPNIRNTDGKSALDLADPSAKAVLTGEYKKDELLEAARSGNEEKLMALLTPLNVNCHASDGRKSTPLHLAAGYNRVRIVQLLLQHGADVHAKDKGGLVPLHNACSYGHYEVTELLLKHGACVNAMDLWQFTPLHEAASKNRVEVCSLLLSHGADPTLVNCHGKSAVDMAPTPELRERLTYEFKGHSLLQAAREADLAKVKKTLALEIINFKQPQSHETALHCAVASLHPKRKQVTELLLRKGANVNEKNKDFMTPLHVAAERAHNDVMEVLHKHGAKMNALDTLGQTALHRAALAGHLQTCRLLLSYGSDPSIISLQGFTAAQMGNEAVQQILSGHStruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetrue