ID APTX_HUMAN Reviewed; 356 AA. AC Q7Z2E3; A8MTN4; D3DRK9; D3DRL0; Q0P662; Q5T781; Q5T782; Q5T784; Q6JV81; AC Q6JV82; Q6JV85; Q7Z2F3; Q7Z336; Q7Z5R5; Q7Z6V7; Q7Z6V8; Q9NXM5; DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot. DT 07-JUN-2004, sequence version 2. DT 27-MAR-2024, entry version 198. DE RecName: Full=Aprataxin; DE EC=3.6.1.71 {ECO:0000269|PubMed:16964241, ECO:0000269|PubMed:17276982, ECO:0000269|PubMed:24362567, ECO:0000305|PubMed:16547001}; DE EC=3.6.1.72 {ECO:0000250|UniProtKB:O74859}; DE AltName: Full=Forkhead-associated domain histidine triad-like protein; DE Short=FHA-HIT; GN Name=APTX; Synonyms=AXA1; 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 7; 12 AND 13), ALTERNATIVE SPLICING, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=15276230; DOI=10.1016/j.neulet.2004.05.034; RA Hirano M., Nishiwaki T., Kariya S., Furiya Y., Kawahara M., Ueno S.; RT "Novel splice variants increase molecular diversity of aprataxin, the gene RT responsible for early-onset ataxia with ocular motor apraxia and RT hypoalbuminemia."; RL Neurosci. Lett. 366:120-125(2004). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Huang C.-H.; RT "Identification of FHA-HIT as a novel nuclear protein involved in cell- RT cycle regulation."; RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7; 8 AND 10). RC TISSUE=Hypothalamus, Kidney, Lung adenocarcinoma, Lymphoma, Melanoma, RC Muscle, Retinoblastoma, Skin, and Testis; RA Chen Y., Huang C.-H.; RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 11). RC TISSUE=Colon; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 9). RC TISSUE=Endometrium; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 4 AND 7). RC TISSUE=Brain, Lung, and Lymph; 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 [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-261 (ISOFORMS 2; 4; 5 AND 7). RC TISSUE=Brain; RA Hellenbroich Y., Habeck M.; RT "Mutations in the APTX gene."; RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP TISSUE SPECIFICITY, AND VARIANTS AOA LEU-220 AND GLY-277. RX PubMed=11586299; DOI=10.1038/ng1001-184; RA Date H., Onodera O., Tanaka H., Iwabuchi K., Uekawa K., Igarashi S., RA Koike R., Hiroi T., Yuasa T., Awaya Y., Sakai T., Takahashi T., RA Nagatomo H., Sekijima Y., Kawachi I., Takiyama Y., Nishizawa M., RA Fukuhara N., Saito K., Sugano S., Tsuji S.; RT "Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused RT by mutations in a new HIT superfamily gene."; RL Nat. Genet. 29:184-188(2001). RN [11] RP ALTERNATIVE SPLICING, TISSUE SPECIFICITY, AND VARIANTS AOA HIS-213 AND RP LEU-220. RX PubMed=11586300; DOI=10.1038/ng1001-189; RA Moreira M.-C., Barbot C., Tachi N., Kozuka N., Uchida E., Gibson T., RA Mendonca P., Costa M., Barros J., Yanagisawa T., Watanabe M., Ikeda Y., RA Aoki M., Nagata T., Coutinho P., Sequeiros J., Koenig M.; RT "The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger RT protein aprataxin."; RL Nat. Genet. 29:189-193(2001). RN [12] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH XRCC1. RX PubMed=14755728; DOI=10.1002/ana.10808; RA Sano Y., Date H., Igarashi S., Onodera O., Oyake M., Takahashi T., RA Hayashi S., Morimatsu M., Takahashi H., Makifuchi T., Fukuhara N., RA Tsuji S.; RT "Aprataxin, the causative protein for EAOH is a nuclear protein with a RT potential role as a DNA repair protein."; RL Ann. Neurol. 55:241-249(2004). RN [13] RP FUNCTION, INTERACTION WITH XRCC1 AND XRCC4, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF ARG-43. RX PubMed=15380105; DOI=10.1016/j.dnarep.2004.06.017; RA Clements P.M., Breslin C., Deeks E.D., Byrd P.J., Ju L., Bieganowski P., RA Brenner C., Moreira M.-C., Taylor A.M.R., Caldecott K.W.; RT "The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM RT and interacts with the DNA strand break repair proteins XRCC1 and XRCC4."; RL DNA Repair 3:1493-1502(2004). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH XRCC1; PARP1; TP53 AND RP NCL. RX PubMed=15044383; DOI=10.1093/hmg/ddh122; RA Gueven N., Becherel O.J., Kijas A.W., Chen P., Howe O., Rudolph J.H., RA Gatti R., Date H., Onodera O., Taucher-Scholz G., Lavin M.F.; RT "Aprataxin, a novel protein that protects against genotoxic stress."; RL Hum. Mol. Genet. 13:1081-1093(2004). RN [15] RP SUBCELLULAR LOCATION, AND INTERACTION WITH XRCC1 AND NCL. RX PubMed=16777843; DOI=10.1093/hmg/ddl149; RA Becherel O.J., Gueven N., Birrell G.W., Schreiber V., Suraweera A., RA Jakob B., Taucher-Scholz G., Lavin M.F.; RT "Nucleolar localization of aprataxin is dependent on interaction with RT nucleolin and on active ribosomal DNA transcription."; RL Hum. Mol. Genet. 15:2239-2249(2006). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DNA-BINDING, RP AND CHARACTERIZATION OF VARIANT GLY-277. RX PubMed=16547001; DOI=10.1074/jbc.m507946200; RA Kijas A.W., Harris J.L., Harris J.M., Lavin M.F.; RT "Aprataxin forms a discrete branch in the HIT (histidine triad) superfamily RT of proteins with both DNA/RNA binding and nucleotide hydrolase RT activities."; RL J. Biol. Chem. 281:13939-13948(2006). RN [17] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-274. RX PubMed=16964241; DOI=10.1038/nature05164; RA Ahel I., Rass U., El-Khamisy S.F., Katyal S., Clements P.M., McKinnon P.J., RA Caldecott K.W., West S.C.; RT "The neurodegenerative disease protein aprataxin resolves abortive DNA RT ligation intermediates."; RL Nature 443:713-716(2006). RN [18] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-274; CYS-333 AND RP CYS-336. RX PubMed=17276982; DOI=10.1074/jbc.m611489200; RA Rass U., Ahel I., West S.C.; RT "Actions of aprataxin in multiple DNA repair pathways."; RL J. Biol. Chem. 282:9469-9474(2007). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [21] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 15-116, SUBCELLULAR LOCATION, RP INTERACTION WITH MDC1, AND MUTAGENESIS OF ARG-43 AND LYS-52. RX PubMed=20008512; DOI=10.1093/nar/gkp1149; RA Becherel O.J., Jakob B., Cherry A.L., Gueven N., Fusser M., Kijas A.W., RA Peng C., Katyal S., McKinnon P.J., Chen J., Epe B., Smerdon S.J., RA Taucher-Scholz G., Lavin M.F.; RT "CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in RT the DNA damage response."; RL Nucleic Acids Res. 38:1489-1503(2010). RN [22] {ECO:0007744|PDB:4NDF, ECO:0007744|PDB:4NDG, ECO:0007744|PDB:4NDH, ECO:0007744|PDB:4NDI} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 179-356 IN COMPLEXES WITH DNA; RP RNA; ZINC; AMP AND ADENOSINE-5'-VANADATE, FUNCTION, CATALYTIC ACTIVITY, RP ACTIVE SITE, AND CHARACTERIZATION OF VARIANT AOA GLN-211. RX PubMed=24362567; DOI=10.1038/nature12824; RA Tumbale P., Williams J.S., Schellenberg M.J., Kunkel T.A., Williams R.S.; RT "Aprataxin resolves adenylated RNA-DNA junctions to maintain genome RT integrity."; RL Nature 506:111-115(2014). RN [23] RP VARIANT AOA ARG-215. RX PubMed=12196655; DOI=10.1212/wnl.59.4.590; RA Shimazaki H., Takiyama Y., Sakoe K., Ikeguchi K., Niijima K., Kaneko J., RA Namekawa M., Ogawa T., Date H., Tsuji S., Nakano I., Nishizawa M.; RT "Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the RT aprataxin gene mutations."; RL Neurology 59:590-595(2002). RN [24] RP VARIANT AOA GLN-211. RX PubMed=12629250; DOI=10.1212/01.wnl.0000048562.88536.a4; RA Tranchant C., Fleury M., Moreira M.-C., Koenig M., Warter J.-M.; RT "Phenotypic variability of aprataxin gene mutations."; RL Neurology 60:868-870(2003). RN [25] RP VARIANTS AOA VAL-212; GLY-277 AND ARG-293. RX PubMed=14506070; DOI=10.1093/brain/awg283; RA Le Ber I., Moreira M.-C., Rivaud-Pechoux S., Chamayou C., Ochsner F., RA Kuntzer T., Tardieu M., Saied G., Habert M.-O., Demarquay G., Tannier C., RA Beis J.-M., Brice A., Koenig M., Duerr A.; RT "Cerebellar ataxia with oculomotor apRAxia type 1: clinical and genetic RT studies."; RL Brain 126:2761-2772(2003). RN [26] RP VARIANT AOA PRO-237. RX PubMed=15852392; DOI=10.1002/ana.20463; RA Criscuolo C., Mancini P., Menchise V., Sacca F., De Michele G., Banfi S., RA Filla A.; RT "Very late onset in ataxia oculomotor apraxia type I."; RL Ann. Neurol. 57:777-777(2005). RN [27] RP INVOLVEMENT IN AOA. RX PubMed=15699391; DOI=10.1212/01.wnl.0000150588.75281.58; RA Quinzii C.M., Kattah A.G., Naini A., Akman H.O., Mootha V.K., DiMauro S., RA Hirano M.; RT "Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin RT mutation."; RL Neurology 64:539-541(2005). CC -!- FUNCTION: DNA-binding protein involved in single-strand DNA break CC repair, double-strand DNA break repair and base excision repair CC (PubMed:15380105, PubMed:15044383, PubMed:16964241, PubMed:17276982, CC PubMed:24362567). Resolves abortive DNA ligation intermediates formed CC either at base excision sites, or when DNA ligases attempt to repair CC non-ligatable breaks induced by reactive oxygen species CC (PubMed:16964241, PubMed:24362567). Catalyzes the release of adenylate CC groups covalently linked to 5'-phosphate termini, resulting in the CC production of 5'-phosphate termini that can be efficiently rejoined CC (PubMed:16964241, PubMed:17276982, PubMed:24362567). Also able to CC hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine CC tetraphosphate (AppppA), but with lower catalytic activity CC (PubMed:16547001). Likewise, catalyzes the release of 3'-linked CC guanosine (DNAppG) and inosine (DNAppI) from DNA, but has higher CC specific activity with 5'-linked adenosine (AppDNA) (By similarity). CC {ECO:0000250|UniProtKB:O74859, ECO:0000269|PubMed:15044383, CC ECO:0000269|PubMed:15380105, ECO:0000269|PubMed:16547001, CC ECO:0000269|PubMed:16964241, ECO:0000269|PubMed:17276982, CC ECO:0000269|PubMed:24362567}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end adenosine-5'-diphospho-5'-(2'-deoxyribonucleoside)- CC DNA + H2O = a 5'-end 5'-monophospho-2'-deoxyribonucleoside-DNA + AMP CC + 2 H(+); Xref=Rhea:RHEA:52128, Rhea:RHEA-COMP:13180, Rhea:RHEA- CC COMP:13181, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:136412, CC ChEBI:CHEBI:136413, ChEBI:CHEBI:456215; EC=3.6.1.71; CC Evidence={ECO:0000269|PubMed:16964241, ECO:0000269|PubMed:17276982, CC ECO:0000269|PubMed:24362567, ECO:0000305|PubMed:16547001}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 5'-end adenosine-5'-diphospho-5'-ribonucleoside-2'- CC deoxyribonucleotide-DNA + H2O = a 5'-end 5'-monophospho- CC ribonucleoside-2'-deoxyribonucleotide-DNA + AMP + 2 H(+); CC Xref=Rhea:RHEA:52132, Rhea:RHEA-COMP:13182, Rhea:RHEA-COMP:13183, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:136414, CC ChEBI:CHEBI:136415, ChEBI:CHEBI:456215; EC=3.6.1.71; CC Evidence={ECO:0000269|PubMed:16964241, ECO:0000269|PubMed:17276982, CC ECO:0000269|PubMed:24362567, ECO:0000305|PubMed:16547001}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 3'-end 2'-deoxyribonucleotide-3'-diphospho-5'-guanosine-DNA CC + H2O = a 3'-end 2'-deoxyribonucleotide 3'-phosphate-DNA + GMP + 2 CC H(+); Xref=Rhea:RHEA:52140, Rhea:RHEA-COMP:13186, Rhea:RHEA- CC COMP:13187, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58115, CC ChEBI:CHEBI:136419, ChEBI:CHEBI:136420; EC=3.6.1.72; CC Evidence={ECO:0000250|UniProtKB:O74859}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=18 uM for AppppA {ECO:0000269|PubMed:16547001}; CC KM=837.5 uM for AMP-NH(2) {ECO:0000269|PubMed:16547001}; CC -!- SUBUNIT: Interacts with single-strand break repair proteins XRCC1, CC XRCC4, ADPRT/PARP1 and p53/TP53 (PubMed:14755728, PubMed:15380105, CC PubMed:15044383, PubMed:16777843). Interacts with NCL (PubMed:15044383, CC PubMed:16777843). Interacts (via FHA-like domain) with MDC1 CC (phosphorylated) (PubMed:20008512). {ECO:0000269|PubMed:14755728, CC ECO:0000269|PubMed:15044383, ECO:0000269|PubMed:15380105, CC ECO:0000269|PubMed:16777843, ECO:0000269|PubMed:20008512}. CC -!- INTERACTION: CC Q7Z2E3; P09874: PARP1; NbExp=8; IntAct=EBI-847814, EBI-355676; CC Q7Z2E3; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-847814, EBI-302345; CC Q7Z2E3; P18887: XRCC1; NbExp=11; IntAct=EBI-847814, EBI-947466; CC Q7Z2E3; Q13426: XRCC4; NbExp=3; IntAct=EBI-847814, EBI-717592; CC Q7Z2E3-7; Q8NFF5-2: FLAD1; NbExp=3; IntAct=EBI-12298187, EBI-11526128; CC Q7Z2E3-7; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-12298187, EBI-302345; CC Q7Z2E3-7; Q9UL41: PNMA3; NbExp=3; IntAct=EBI-12298187, EBI-11278955; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm CC {ECO:0000269|PubMed:14755728, ECO:0000269|PubMed:15044383, CC ECO:0000269|PubMed:15276230, ECO:0000269|PubMed:15380105}. Nucleus, CC nucleolus {ECO:0000269|PubMed:15044383, ECO:0000269|PubMed:16777843}. CC Note=Upon genotoxic stress, colocalizes with XRCC1 at sites of DNA CC damage (PubMed:15380105). Colocalizes with MDC1 at sites of DNA double- CC strand breaks (PubMed:20008512). Interaction with NCL is required for CC nucleolar localization (PubMed:16777843). {ECO:0000269|PubMed:15044383, CC ECO:0000269|PubMed:15380105, ECO:0000269|PubMed:20008512}. CC -!- SUBCELLULAR LOCATION: [Isoform 12]: Cytoplasm CC {ECO:0000269|PubMed:15276230}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=13; CC Name=1; Synonyms=Long {ECO:0000303|PubMed:14755728}; CC IsoId=Q7Z2E3-1; Sequence=Displayed; CC Name=2; Synonyms=Short {ECO:0000303|PubMed:14755728}; CC IsoId=Q7Z2E3-2; Sequence=VSP_010535; CC Name=3; CC IsoId=Q7Z2E3-3; Sequence=VSP_010539; CC Name=4; CC IsoId=Q7Z2E3-4; Sequence=VSP_010536; CC Name=5; CC IsoId=Q7Z2E3-5; Sequence=VSP_010537, VSP_010538; CC Name=6; CC IsoId=Q7Z2E3-6; Sequence=VSP_010534, VSP_010541; CC Name=7; CC IsoId=Q7Z2E3-7; Sequence=VSP_010537; CC Name=8; CC IsoId=Q7Z2E3-8; Sequence=VSP_010540; CC Name=9; CC IsoId=Q7Z2E3-9; Sequence=VSP_010537, VSP_010541; CC Name=10; CC IsoId=Q7Z2E3-10; Sequence=VSP_010538; CC Name=11; CC IsoId=Q7Z2E3-11; Sequence=VSP_010541; CC Name=12; Synonyms=LP2, LP2E5, LP2P3, LP2P3E5; CC IsoId=Q7Z2E3-12; Sequence=VSP_010537, VSP_044091, VSP_044092; CC Name=13; Synonyms=LE5; CC IsoId=Q7Z2E3-13; Sequence=VSP_010537, VSP_044093; CC -!- TISSUE SPECIFICITY: Widely expressed; detected in liver, kidney and CC lymph node (at protein level) (PubMed:14755728). Isoform 1 is highly CC expressed in the cerebral cortex and cerebellum, compared to isoform 2 CC (at protein level) (PubMed:14755728). Widely expressed; detected CC throughout the brain, in liver, kidney, skeletal muscle, fibroblasts, CC lymphocytes and pancreas (PubMed:15276230, PubMed:11586299, CC PubMed:11586300). {ECO:0000269|PubMed:11586299, CC ECO:0000269|PubMed:11586300, ECO:0000269|PubMed:14755728, CC ECO:0000269|PubMed:15276230}. CC -!- DOMAIN: The histidine triad, also called HIT motif, forms part of the CC binding loop for the alpha-phosphate of purine mononucleotide. CC {ECO:0000269|PubMed:24362567}. CC -!- DOMAIN: The FHA-like domain mediates interaction with NCL; XRCC1 and CC XRCC4. CC -!- DOMAIN: The HIT domain is required for enzymatic activity. CC -!- DOMAIN: The C2H2-type zinc finger mediates DNA-binding. CC -!- DISEASE: Ataxia-oculomotor apraxia syndrome (AOA) [MIM:208920]: An CC autosomal recessive syndrome characterized by early-onset cerebellar CC ataxia, oculomotor apraxia, early areflexia and late peripheral CC neuropathy. {ECO:0000269|PubMed:11586299, ECO:0000269|PubMed:11586300, CC ECO:0000269|PubMed:12196655, ECO:0000269|PubMed:12629250, CC ECO:0000269|PubMed:14506070, ECO:0000269|PubMed:15699391, CC ECO:0000269|PubMed:15852392, ECO:0000269|PubMed:24362567}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 1]: Major form. {ECO:0000305|PubMed:14755728}. CC -!- MISCELLANEOUS: [Isoform 2]: Minor form. {ECO:0000305|PubMed:14755728}. CC -!- MISCELLANEOUS: [Isoform 3]: May be an aberrant isoform present in CC cancer cell lines. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: May be an aberrant isoform present in CC cancer cell lines. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: May be an aberrant isoform present in CC cancer cell lines. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 6]: May be an aberrant isoform present in CC cancer cell lines. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 8]: May be an aberrant isoform present in CC cancer cell lines. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 10]: May be an aberrant isoform present in CC cancer cell lines. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY302067; AAQ74130.1; -; mRNA. DR EMBL; AY302068; AAQ74131.1; -; mRNA. DR EMBL; AY302070; AAQ74133.1; -; mRNA. DR EMBL; AY302071; AAQ74134.1; -; mRNA. DR EMBL; AY302072; AAQ74135.1; -; mRNA. DR EMBL; AY302074; AAQ74137.1; -; mRNA. DR EMBL; AY040777; AAK91768.1; -; mRNA. DR EMBL; AY208829; AAP86319.1; -; mRNA. DR EMBL; AY208830; AAP86320.1; -; mRNA. DR EMBL; AY208831; AAP86321.1; -; mRNA. DR EMBL; AY208832; AAP86322.1; -; mRNA. DR EMBL; AY208833; AAP86323.1; -; mRNA. DR EMBL; AY208834; AAP86324.1; -; mRNA. DR EMBL; AY208835; AAP86325.1; -; mRNA. DR EMBL; AY208836; AAP86326.1; -; mRNA. DR EMBL; AY208837; AAP86327.1; -; mRNA. DR EMBL; AY208838; AAP86328.1; -; mRNA. DR EMBL; AY208839; AAP86329.1; -; mRNA. DR EMBL; AY208840; AAP86330.1; -; mRNA. DR EMBL; AY208841; AAP86331.1; -; mRNA. DR EMBL; AY208842; AAP86332.1; -; mRNA. DR EMBL; AK000164; BAA90985.1; -; mRNA. DR EMBL; AK055672; BAG51552.1; -; mRNA. DR EMBL; BX538161; CAD98041.1; -; mRNA. DR EMBL; AL162590; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL353717; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471071; EAW58530.1; -; Genomic_DNA. DR EMBL; CH471071; EAW58529.1; -; Genomic_DNA. DR EMBL; CH471071; EAW58531.1; -; Genomic_DNA. DR EMBL; CH471071; EAW58532.1; -; Genomic_DNA. DR EMBL; CH471071; EAW58534.1; -; Genomic_DNA. DR EMBL; CH471071; EAW58535.1; -; Genomic_DNA. DR EMBL; BC001628; AAH01628.1; -; mRNA. DR EMBL; BC032650; AAH32650.1; -; mRNA. DR EMBL; BC104881; AAI04882.1; -; mRNA. DR EMBL; AJ565850; CAD92454.1; -; mRNA. DR EMBL; AJ565851; CAD92455.1; -; mRNA. DR EMBL; AJ565852; CAD92456.1; -; mRNA. DR EMBL; AJ565853; CAD92457.1; -; mRNA. DR EMBL; AJ565854; CAD92458.1; -; mRNA. DR EMBL; AJ565855; CAD92459.1; -; mRNA. DR EMBL; AJ575566; CAE01427.1; -; mRNA. DR CCDS; CCDS47956.1; -. [Q7Z2E3-7] DR CCDS; CCDS47957.1; -. [Q7Z2E3-4] DR CCDS; CCDS6532.2; -. [Q7Z2E3-9] DR CCDS; CCDS75827.1; -. [Q7Z2E3-5] DR RefSeq; NP_001182177.1; NM_001195248.1. [Q7Z2E3-7] DR RefSeq; NP_001182178.1; NM_001195249.1. [Q7Z2E3-7] DR RefSeq; NP_001182179.1; NM_001195250.1. [Q7Z2E3-5] DR RefSeq; NP_001182180.1; NM_001195251.1. [Q7Z2E3-9] DR RefSeq; NP_001182181.1; NM_001195252.1. DR RefSeq; NP_001182183.1; NM_001195254.1. [Q7Z2E3-5] DR RefSeq; NP_778239.1; NM_175069.2. [Q7Z2E3-9] DR RefSeq; NP_778243.1; NM_175073.2. [Q7Z2E3-7] DR RefSeq; XP_006716854.1; XM_006716791.3. DR RefSeq; XP_006716855.1; XM_006716792.2. DR RefSeq; XP_011516240.1; XM_011517938.1. DR RefSeq; XP_011516241.1; XM_011517939.2. DR RefSeq; XP_016870326.1; XM_017014837.1. DR PDB; 3KT9; X-ray; 1.65 A; A=15-116. DR PDB; 4NDF; X-ray; 1.94 A; A/B=179-356. DR PDB; 4NDG; X-ray; 2.54 A; A/B=179-356. DR PDB; 4NDH; X-ray; 1.85 A; A/B=179-356. DR PDB; 4NDI; X-ray; 1.90 A; A/B=179-356. DR PDB; 6CVO; X-ray; 2.40 A; A/B=179-356. DR PDB; 6CVP; X-ray; 2.00 A; A/B=179-356. DR PDB; 6CVQ; X-ray; 1.65 A; A/B=179-354. DR PDB; 6CVR; X-ray; 1.88 A; A/B=179-356. DR PDB; 6CVS; X-ray; 2.11 A; A/B=179-356. DR PDB; 6CVT; X-ray; 2.94 A; A/B=179-356. DR PDBsum; 3KT9; -. DR PDBsum; 4NDF; -. DR PDBsum; 4NDG; -. DR PDBsum; 4NDH; -. DR PDBsum; 4NDI; -. DR PDBsum; 6CVO; -. DR PDBsum; 6CVP; -. DR PDBsum; 6CVQ; -. DR PDBsum; 6CVR; -. DR PDBsum; 6CVS; -. DR PDBsum; 6CVT; -. DR AlphaFoldDB; Q7Z2E3; -. DR SMR; Q7Z2E3; -. DR BioGRID; 120191; 82. DR ComplexPortal; CPX-793; XRCC1 DNA repair complex. DR IntAct; Q7Z2E3; 31. DR MINT; Q7Z2E3; -. DR STRING; 9606.ENSP00000369145; -. DR ChEMBL; CHEMBL4523362; -. DR GlyCosmos; Q7Z2E3; 1 site, 1 glycan. DR GlyGen; Q7Z2E3; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q7Z2E3; -. DR PhosphoSitePlus; Q7Z2E3; -. DR SwissPalm; Q7Z2E3; -. DR BioMuta; APTX; -. DR DMDM; 48428038; -. DR EPD; Q7Z2E3; -. DR jPOST; Q7Z2E3; -. DR MassIVE; Q7Z2E3; -. DR MaxQB; Q7Z2E3; -. DR PaxDb; 9606-ENSP00000400806; -. DR PeptideAtlas; Q7Z2E3; -. DR ProteomicsDB; 66521; -. DR ProteomicsDB; 66522; -. DR ProteomicsDB; 68945; -. [Q7Z2E3-1] DR ProteomicsDB; 68946; -. [Q7Z2E3-10] DR ProteomicsDB; 68947; -. [Q7Z2E3-11] DR ProteomicsDB; 68948; -. [Q7Z2E3-2] DR ProteomicsDB; 68949; -. [Q7Z2E3-3] DR ProteomicsDB; 68950; -. [Q7Z2E3-4] DR ProteomicsDB; 68951; -. [Q7Z2E3-5] DR ProteomicsDB; 68952; -. [Q7Z2E3-6] DR ProteomicsDB; 68953; -. [Q7Z2E3-7] DR ProteomicsDB; 68954; -. [Q7Z2E3-8] DR ProteomicsDB; 68955; -. [Q7Z2E3-9] DR Pumba; Q7Z2E3; -. DR TopDownProteomics; Q7Z2E3-5; -. [Q7Z2E3-5] DR Antibodypedia; 10716; 278 antibodies from 30 providers. DR DNASU; 54840; -. DR Ensembl; ENST00000309615.8; ENSP00000311547.4; ENSG00000137074.20. [Q7Z2E3-5] DR Ensembl; ENST00000379817.7; ENSP00000369145.2; ENSG00000137074.20. [Q7Z2E3-7] DR Ensembl; ENST00000379819.6; ENSP00000369147.2; ENSG00000137074.20. [Q7Z2E3-7] DR Ensembl; ENST00000379825.7; ENSP00000369153.3; ENSG00000137074.20. [Q7Z2E3-9] DR Ensembl; ENST00000436040.7; ENSP00000400806.4; ENSG00000137074.20. [Q7Z2E3-5] DR Ensembl; ENST00000460940.6; ENSP00000418311.1; ENSG00000137074.20. [Q7Z2E3-12] DR Ensembl; ENST00000463596.6; ENSP00000419846.1; ENSG00000137074.20. [Q7Z2E3-7] DR Ensembl; ENST00000464632.6; ENSP00000418069.2; ENSG00000137074.20. [Q7Z2E3-12] DR Ensembl; ENST00000465003.6; ENSP00000419430.2; ENSG00000137074.20. [Q7Z2E3-12] DR Ensembl; ENST00000467331.6; ENSP00000418733.1; ENSG00000137074.20. [Q7Z2E3-12] DR Ensembl; ENST00000468275.6; ENSP00000420263.2; ENSG00000137074.20. [Q7Z2E3-9] DR Ensembl; ENST00000476858.6; ENSP00000419042.2; ENSG00000137074.20. [Q7Z2E3-5] DR Ensembl; ENST00000479656.6; ENSP00000420071.1; ENSG00000137074.20. [Q7Z2E3-12] DR Ensembl; ENST00000482687.6; ENSP00000419289.2; ENSG00000137074.20. [Q7Z2E3-12] DR Ensembl; ENST00000485479.6; ENSP00000418144.1; ENSG00000137074.20. [Q7Z2E3-12] DR Ensembl; ENST00000494649.5; ENSP00000417634.1; ENSG00000137074.20. [Q7Z2E3-12] DR Ensembl; ENST00000672438.1; ENSP00000499997.1; ENSG00000137074.20. [Q7Z2E3-4] DR Ensembl; ENST00000672519.1; ENSP00000500320.1; ENSG00000137074.20. [Q7Z2E3-12] DR Ensembl; ENST00000672535.1; ENSP00000499872.1; ENSG00000137074.20. [Q7Z2E3-12] DR Ensembl; ENST00000672846.1; ENSP00000500396.1; ENSG00000137074.20. [Q7Z2E3-12] DR Ensembl; ENST00000673248.1; ENSP00000500601.1; ENSG00000137074.20. [Q7Z2E3-4] DR Ensembl; ENST00000673416.1; ENSP00000500738.1; ENSG00000137074.20. [Q7Z2E3-4] DR Ensembl; ENST00000673487.1; ENSP00000500943.1; ENSG00000137074.20. [Q7Z2E3-12] DR Ensembl; ENST00000673598.1; ENSP00000499991.1; ENSG00000137074.20. [Q7Z2E3-2] DR GeneID; 54840; -. DR KEGG; hsa:54840; -. DR MANE-Select; ENST00000379817.7; ENSP00000369145.2; NM_001195248.2; NP_001182177.2. [Q7Z2E3-7] DR UCSC; uc003zrm.4; human. [Q7Z2E3-1] DR AGR; HGNC:15984; -. DR CTD; 54840; -. DR DisGeNET; 54840; -. DR GeneCards; APTX; -. DR GeneReviews; APTX; -. DR HGNC; HGNC:15984; APTX. DR HPA; ENSG00000137074; Low tissue specificity. DR MalaCards; APTX; -. DR MIM; 208920; phenotype. DR MIM; 606350; gene. DR neXtProt; NX_Q7Z2E3; -. DR OpenTargets; ENSG00000137074; -. DR Orphanet; 1168; Ataxia-oculomotor apraxia type 1. DR PharmGKB; PA24915; -. DR VEuPathDB; HostDB:ENSG00000137074; -. DR eggNOG; KOG0562; Eukaryota. DR eggNOG; KOG2134; Eukaryota. DR GeneTree; ENSGT00940000156806; -. DR HOGENOM; CLU_066882_2_1_1; -. DR InParanoid; Q7Z2E3; -. DR OMA; QFRTGYH; -. DR OrthoDB; 12181at2759; -. DR PhylomeDB; Q7Z2E3; -. DR TreeFam; TF313308; -. DR BioCyc; MetaCyc:ENSG00000137074-MONOMER; -. DR BRENDA; 3.1.11.7; 2681. DR BRENDA; 3.6.1.70; 2681. DR BRENDA; 3.6.1.71; 2681. DR BRENDA; 3.6.1.72; 2681. DR PathwayCommons; Q7Z2E3; -. DR SABIO-RK; Q7Z2E3; -. DR SignaLink; Q7Z2E3; -. DR SIGNOR; Q7Z2E3; -. DR BioGRID-ORCS; 54840; 15 hits in 1160 CRISPR screens. DR ChiTaRS; APTX; human. DR EvolutionaryTrace; Q7Z2E3; -. DR GeneWiki; Aprataxin; -. DR GenomeRNAi; 54840; -. DR Pharos; Q7Z2E3; Tbio. DR PRO; PR:Q7Z2E3; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q7Z2E3; Protein. DR Bgee; ENSG00000137074; Expressed in colonic epithelium and 192 other cell types or tissues. DR ExpressionAtlas; Q7Z2E3; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB. DR GO; GO:0033699; F:DNA 5'-adenosine monophosphate hydrolase activity; IDA:UniProtKB. DR GO; GO:0120108; F:DNA-3'-diphospho-5'-guanosine diphosphatase; IEA:UniProtKB-EC. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0030983; F:mismatched DNA binding; IBA:GO_Central. DR GO; GO:0008967; F:phosphoglycolate phosphatase activity; IDA:UniProtKB. DR GO; GO:0051219; F:phosphoprotein binding; IPI:UniProtKB. DR GO; GO:0046403; F:polynucleotide 3'-phosphatase activity; IDA:UniProtKB. DR GO; GO:1990165; F:single-strand break-containing DNA binding; IBA:GO_Central. DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central. DR GO; GO:0006266; P:DNA ligation; IEA:Ensembl. DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB. DR GO; GO:0000012; P:single strand break repair; IDA:UniProtKB. DR CDD; cd01278; aprataxin_related; 1. DR CDD; cd22735; FHA_APTX; 1. DR Gene3D; 2.60.200.20; -; 1. DR Gene3D; 3.30.428.10; HIT-like; 1. DR InterPro; IPR041388; FHA_2. DR InterPro; IPR047289; FHA_APTX. DR InterPro; IPR019808; Histidine_triad_CS. DR InterPro; IPR011146; HIT-like. DR InterPro; IPR036265; HIT-like_sf. DR InterPro; IPR008984; SMAD_FHA_dom_sf. DR InterPro; IPR032566; Znf-C2HE. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR12486:SF4; APRATAXIN; 1. DR PANTHER; PTHR12486; APRATAXIN-RELATED; 1. DR Pfam; PF11969; DcpS_C; 1. DR Pfam; PF17913; FHA_2; 1. DR Pfam; PF16278; zf-C2HE; 1. DR SUPFAM; SSF54197; HIT-like; 1. DR SUPFAM; SSF49879; SMAD/FHA domain; 1. DR PROSITE; PS00892; HIT_1; 1. DR PROSITE; PS51084; HIT_2; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1. DR Genevisible; Q7Z2E3; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; DNA damage; KW DNA repair; DNA-binding; Hydrolase; Metal-binding; Neurodegeneration; KW Nucleus; Phosphoprotein; Reference proteome; Zinc; Zinc-finger. FT CHAIN 1..356 FT /note="Aprataxin" FT /id="PRO_0000109838" FT DOMAIN 38..87 FT /note="FHA-like" FT DOMAIN 182..287 FT /note="HIT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464" FT ZN_FING 331..353 FT /note="C2H2-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042, FT ECO:0000305|PubMed:17276982, ECO:0000305|PubMed:24362567" FT REGION 1..110 FT /note="Interactions with ADPRT/PARP1 and NCL" FT REGION 122..167 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 207..211 FT /note="Interaction with DNA substrate" FT /evidence="ECO:0000269|PubMed:24362567" FT REGION 269..270 FT /note="Interaction with DNA substrate" FT /evidence="ECO:0000269|PubMed:24362567" FT MOTIF 126..131 FT /note="Nuclear localization signal" FT /evidence="ECO:0000305" FT MOTIF 272..276 FT /note="Histidine triad motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464, FT ECO:0000305|PubMed:24362567" FT COMPBIAS 122..143 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 274 FT /note="Tele-AMP-histidine intermediate" FT /evidence="ECO:0000269|PubMed:24362567" FT SITE 188 FT /note="Interaction with DNA substrate" FT /evidence="ECO:0000269|PubMed:24362567" FT SITE 265 FT /note="Interaction with DNA substrate" FT /evidence="ECO:0000269|PubMed:24362567" FT SITE 276 FT /note="Interaction with DNA substrate" FT /evidence="ECO:0000269|PubMed:24362567" FT SITE 291 FT /note="Interaction with DNA substrate" FT /evidence="ECO:0000269|PubMed:24362567" FT MOD_RES 132 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:24275569" FT MOD_RES 137 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q7TQC5" FT VAR_SEQ 1..193 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_010534" FT VAR_SEQ 1..188 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3, FT ECO:0000303|Ref.9" FT /id="VSP_010535" FT VAR_SEQ 1..102 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3, FT ECO:0000303|Ref.9" FT /id="VSP_010536" FT VAR_SEQ 1..14 FT /note="Missing (in isoform 5, isoform 7, isoform 9, isoform FT 12 and isoform 13)" FT /evidence="ECO:0000303|PubMed:15276230, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005, FT ECO:0000303|Ref.3, ECO:0000303|Ref.9" FT /id="VSP_010537" FT VAR_SEQ 59..112 FT /note="Missing (in isoform 5 and isoform 10)" FT /evidence="ECO:0000303|Ref.3, ECO:0000303|Ref.9" FT /id="VSP_010538" FT VAR_SEQ 60..63 FT /note="QLKA -> ESRV (in isoform 12)" FT /evidence="ECO:0000303|PubMed:15276230" FT /id="VSP_044091" FT VAR_SEQ 64..356 FT /note="Missing (in isoform 12)" FT /evidence="ECO:0000303|PubMed:15276230" FT /id="VSP_044092" FT VAR_SEQ 104..175 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_010539" FT VAR_SEQ 175..193 FT /note="Missing (in isoform 8)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_010540" FT VAR_SEQ 196..356 FT /note="VYKDEQVVVIKDKYPKARYHWLVLPWTSISSLKAVAREHLELLKHMHTVGEK FT VIVDFAGSSKLRFRLGYHAIPSMSHVHLHVISQDFDSPCLKNKKHWNSFNTEYFLESQA FT VIEMVQEAGRVTVRDGMPELLKLPLRCHECQQLLPSIPQLKEHLRKHWTQ -> PCTSS FT CDQPGF (in isoform 13)" FT /evidence="ECO:0000303|PubMed:15276230" FT /id="VSP_044093" FT VAR_SEQ 306..356 FT /note="AVIEMVQEAGRVTVRDGMPELLKLPLRCHECQQLLPSIPQLKEHLRKHWTQ FT -> E (in isoform 6, isoform 9 and isoform 11)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:17974005, ECO:0000303|Ref.3" FT /id="VSP_010541" FT VARIANT 211 FT /note="K -> Q (in AOA; impairs binding to FT adenosine-5'-diphospho-5'-(DNA) and deadenylation FT activity)" FT /evidence="ECO:0000269|PubMed:12629250, FT ECO:0000269|PubMed:24362567" FT /id="VAR_018794" FT VARIANT 212 FT /note="A -> V (in AOA; heterozygous; dbSNP:rs748165574)" FT /evidence="ECO:0000269|PubMed:14506070" FT /id="VAR_018795" FT VARIANT 213 FT /note="R -> H (in AOA; dbSNP:rs150886026)" FT /evidence="ECO:0000269|PubMed:11586300" FT /id="VAR_018796" FT VARIANT 215 FT /note="H -> R (in AOA; dbSNP:rs121908133)" FT /evidence="ECO:0000269|PubMed:12196655" FT /id="VAR_018797" FT VARIANT 220 FT /note="P -> L (in AOA; dbSNP:rs121908131)" FT /evidence="ECO:0000269|PubMed:11586299, FT ECO:0000269|PubMed:11586300" FT /id="VAR_018798" FT VARIANT 237 FT /note="L -> P (in AOA; dbSNP:rs267606665)" FT /evidence="ECO:0000269|PubMed:15852392" FT /id="VAR_025365" FT VARIANT 277 FT /note="V -> G (in AOA; abolishes DNA-binding and enzymatic FT activity towards Ap(4)A; dbSNP:rs121908132)" FT /evidence="ECO:0000269|PubMed:11586299, FT ECO:0000269|PubMed:14506070, ECO:0000269|PubMed:16547001" FT /id="VAR_018799" FT VARIANT 281 FT /note="D -> G (in AOA; heterozygous)" FT /id="VAR_018800" FT VARIANT 293 FT /note="W -> R (in AOA; heterozygous; dbSNP:rs773393618)" FT /evidence="ECO:0000269|PubMed:14506070" FT /id="VAR_018801" FT MUTAGEN 43 FT /note="R->A: Impairs interaction with XRCC1 and XRCC4. FT Abolishes localization at sites of DNA double-strand FT breaks. Loss of interaction with MDC1." FT /evidence="ECO:0000269|PubMed:15380105, FT ECO:0000269|PubMed:20008512" FT MUTAGEN 52 FT /note="K->A: Impairs interaction with MDC1 and localization FT at sites of DNA double-strand breaks." FT /evidence="ECO:0000269|PubMed:20008512" FT MUTAGEN 274 FT /note="H->A: Abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:16964241, FT ECO:0000269|PubMed:17276982" FT MUTAGEN 333 FT /note="C->A: Abolishes DNA-binding and enzyme activity; FT when associated with A-336." FT /evidence="ECO:0000269|PubMed:17276982" FT MUTAGEN 336 FT /note="C->A: Abolishes DNA-binding and enzyme activity; FT when associated with A-333." FT /evidence="ECO:0000269|PubMed:17276982" FT STRAND 18..23 FT /evidence="ECO:0007829|PDB:3KT9" FT STRAND 30..32 FT /evidence="ECO:0007829|PDB:3KT9" FT STRAND 38..41 FT /evidence="ECO:0007829|PDB:3KT9" FT TURN 45..47 FT /evidence="ECO:0007829|PDB:3KT9" FT STRAND 59..64 FT /evidence="ECO:0007829|PDB:3KT9" FT TURN 65..68 FT /evidence="ECO:0007829|PDB:3KT9" FT STRAND 69..74 FT /evidence="ECO:0007829|PDB:3KT9" FT STRAND 76..78 FT /evidence="ECO:0007829|PDB:3KT9" FT STRAND 92..95 FT /evidence="ECO:0007829|PDB:3KT9" FT STRAND 101..104 FT /evidence="ECO:0007829|PDB:3KT9" FT STRAND 107..115 FT /evidence="ECO:0007829|PDB:3KT9" FT HELIX 181..183 FT /evidence="ECO:0007829|PDB:6CVQ" FT HELIX 184..188 FT /evidence="ECO:0007829|PDB:6CVQ" FT TURN 192..194 FT /evidence="ECO:0007829|PDB:6CVQ" FT STRAND 195..198 FT /evidence="ECO:0007829|PDB:6CVQ" FT STRAND 200..206 FT /evidence="ECO:0007829|PDB:6CVQ" FT STRAND 211..213 FT /evidence="ECO:0007829|PDB:6CVQ" FT STRAND 215..222 FT /evidence="ECO:0007829|PDB:6CVQ" FT HELIX 227..229 FT /evidence="ECO:0007829|PDB:6CVQ" FT HELIX 232..234 FT /evidence="ECO:0007829|PDB:6CVQ" FT HELIX 235..253 FT /evidence="ECO:0007829|PDB:6CVQ" FT HELIX 254..256 FT /evidence="ECO:0007829|PDB:4NDH" FT STRAND 260..267 FT /evidence="ECO:0007829|PDB:6CVQ" FT STRAND 269..272 FT /evidence="ECO:0007829|PDB:6CVQ" FT STRAND 275..279 FT /evidence="ECO:0007829|PDB:6CVQ" FT HELIX 290..297 FT /evidence="ECO:0007829|PDB:6CVQ" FT STRAND 301..303 FT /evidence="ECO:0007829|PDB:6CVQ" FT HELIX 304..314 FT /evidence="ECO:0007829|PDB:6CVQ" FT HELIX 323..326 FT /evidence="ECO:0007829|PDB:6CVQ" FT TURN 334..336 FT /evidence="ECO:0007829|PDB:6CVQ" FT STRAND 339..342 FT /evidence="ECO:0007829|PDB:4NDH" FT HELIX 343..350 FT /evidence="ECO:0007829|PDB:6CVQ" FT HELIX 351..353 FT /evidence="ECO:0007829|PDB:6CVQ" SQ SEQUENCE 356 AA; 40740 MW; 5B338490E35EC8E4 CRC64; MSNVNLSVSD FWRVMMRVCW LVRQDSRHQR IRLPHLEAVV IGRGPETKIT DKKCSRQQVQ LKAECNKGYV KVKQVGVNPT SIDSVVIGKD QEVKLQPGQV LHMVNELYPY IVEFEEEAKN PGLETHRKRK RSGNSDSIER DAAQEAEAGT GLEPGSNSGQ CSVPLKKGKD APIKKESLGH WSQGLKISMQ DPKMQVYKDE QVVVIKDKYP KARYHWLVLP WTSISSLKAV AREHLELLKH MHTVGEKVIV DFAGSSKLRF RLGYHAIPSM SHVHLHVISQ DFDSPCLKNK KHWNSFNTEY FLESQAVIEM VQEAGRVTVR DGMPELLKLP LRCHECQQLL PSIPQLKEHL RKHWTQ //