APTX_HUMAN
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 03-AUG-2022, entry version 189.
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 ---------------------------------------------------------------------------
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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; CCDS56568.1; -. [Q7Z2E3-5]
DR CCDS; CCDS6532.1; -. [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. [Q7Z2E3-4]
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; 76.
DR IntAct; Q7Z2E3; 29.
DR MINT; Q7Z2E3; -.
DR STRING; 9606.ENSP00000400806; -.
DR ChEMBL; CHEMBL4523362; -.
DR GlyGen; Q7Z2E3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q7Z2E3; -.
DR PhosphoSitePlus; Q7Z2E3; -.
DR BioMuta; APTX; -.
DR DMDM; 48428038; -.
DR EPD; Q7Z2E3; -.
DR jPOST; Q7Z2E3; -.
DR MassIVE; Q7Z2E3; -.
DR MaxQB; Q7Z2E3; -.
DR PaxDb; Q7Z2E3; -.
DR PeptideAtlas; Q7Z2E3; -.
DR PRIDE; 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 TopDownProteomics; Q7Z2E3-5; -. [Q7Z2E3-5]
DR Antibodypedia; 10716; 252 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 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; PLCWLIS; -.
DR OrthoDB; 297700at2759; -.
DR PhylomeDB; Q7Z2E3; -.
DR TreeFam; TF313308; -.
DR BioCyc; MetaCyc:ENSG00000137074-MON; -.
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 1081 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 190 other tissues.
DR ExpressionAtlas; Q7Z2E3; baseline and differential.
DR Genevisible; Q7Z2E3; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
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:0047485; F:protein N-terminus binding; IPI: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:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0006266; P:DNA ligation; IEA:Ensembl.
DR GO; GO:0006302; P:double-strand break repair; IDA:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB.
DR GO; GO:0042542; P:response to hydrogen peroxide; IDA:UniProtKB.
DR GO; GO:0000012; P:single strand break repair; IDA:UniProtKB.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 3.30.428.10; -; 1.
DR InterPro; IPR026963; Aprataxin-like.
DR InterPro; IPR041388; FHA_2.
DR InterPro; IPR000253; FHA_dom.
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; PTHR12486:SF4; 2.
DR Pfam; PF17913; FHA_2; 1.
DR Pfam; PF16278; zf-C2HE; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR SUPFAM; SSF54197; SSF54197; 1.
DR PROSITE; PS00892; HIT_1; 1.
DR PROSITE; PS51084; HIT_2; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
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 adenosine-5'-
FT diphospho-5'-(DNA) and deadenylation 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
