ID APTX_SCHPO Reviewed; 232 AA. AC O74859; DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 24-JAN-2024, entry version 129. DE RecName: Full=Aprataxin-like protein; DE EC=3.6.1.71 {ECO:0000269|PubMed:21984210, ECO:0000269|PubMed:24362567}; DE EC=3.6.1.72 {ECO:0000269|PubMed:26007660}; DE AltName: Full=Hit family protein 3; GN Name=hnt3; ORFNames=SPCC18.09c; OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina; OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae; OC Schizosaccharomyces. OX NCBI_TaxID=284812; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=972 / ATCC 24843; RX PubMed=11859360; DOI=10.1038/nature724; RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A., RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S., RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M., RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S., RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S., RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D., RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P., RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K., RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M., RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N., RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A., RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R., RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M., RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A., RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A., RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H., RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S., RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C., RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A., RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M., RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S., RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R., RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G., RA Nurse P.; RT "The genome sequence of Schizosaccharomyces pombe."; RL Nature 415:871-880(2002). RN [2] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=16823372; DOI=10.1038/nbt1222; RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S., RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S., RA Yoshida M.; RT "ORFeome cloning and global analysis of protein localization in the fission RT yeast Schizosaccharomyces pombe."; RL Nat. Biotechnol. 24:841-847(2006). RN [3] RP FUNCTION, AND CATALYTIC ACTIVITY. 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 [4] {ECO:0007744|PDB:3SZQ} RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 31-232 IN COMPLEX WITH ZINC IONS RP AND SUBSTRATE DNA, FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, SUBUNIT, AND RP MUTAGENESIS OF PHE-65; LYS-67; HIS-138; SER-142; HIS-147; LYS-161; HIS-165 RP AND SER-168. RX PubMed=21984210; DOI=10.1038/nsmb.2146; RA Tumbale P., Appel C.D., Kraehenbuehl R., Robertson P.D., Williams J.S., RA Krahn J., Ahel I., Williams R.S.; RT "Structure of an aprataxin-DNA complex with insights into AOA1 RT neurodegenerative disease."; RL Nat. Struct. Mol. Biol. 18:1189-1195(2011). RN [5] {ECO:0007744|PDB:3SP4, ECO:0007744|PDB:3SPD, ECO:0007744|PDB:3SPL} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 33-232 IN COMPLEXES WITH ZINC RP IONS AND SUBSTRATE DNA, SUBUNIT, AND MUTAGENESIS OF PHE-34; CYS-130; RP HIS-138; SER-142 AND LYS-161. RX PubMed=21984208; DOI=10.1038/nsmb.2145; RA Gong Y., Zhu D., Ding J., Dou C.N., Ren X., Gu L., Jiang T., Wang D.C.; RT "Crystal structures of aprataxin ortholog Hnt3 reveal the mechanism for RT reversal of 5'-adenylated DNA."; RL Nat. Struct. Mol. Biol. 18:1297-1299(2011). RN [6] {ECO:0007744|PDB:4XBA, ECO:0007744|PDB:4YKL} RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 33-232 IN COMPLEXES WITH ZINC RP IONS; GMP AND SUBSTRATE DNA, CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF RP TYR-41; ASP-63; HIS-147 AND HIS-149, AND ACTIVE SITE. RX PubMed=26007660; DOI=10.1093/nar/gkv501; RA Chauleau M., Jacewicz A., Shuman S.; RT "DNA3'pp5'G de-capping activity of aprataxin: effect of cap nucleoside RT analogs and structural basis for guanosine recognition."; RL Nucleic Acids Res. 43:6075-6083(2015). CC -!- FUNCTION: DNA-binding protein involved in single-strand DNA break CC repair, double-strand DNA break repair and base excision repair. CC Resolves abortive DNA ligation intermediates formed either at base CC excision sites, or when DNA ligases attempt to repair non-ligatable CC breaks induced by reactive oxygen species (PubMed:24362567, CC PubMed:21984208). Catalyzes the release of adenylate groups covalently CC linked to 5'-phosphate termini, resulting in the production of 5'- CC phosphate termini that can be efficiently rejoined (PubMed:24362567, CC PubMed:21984210). 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) (PubMed:26007660). CC {ECO:0000269|PubMed:21984210, ECO:0000269|PubMed:24362567, CC ECO:0000269|PubMed:26007660, ECO:0000305, ECO:0000305|PubMed:21984208}. 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:21984210, ECO:0000269|PubMed:24362567}; 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:21984210}; 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:0000269|PubMed:26007660}; CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:21984208, CC ECO:0000269|PubMed:21984210}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16823372}. Cytoplasm CC {ECO:0000269|PubMed:16823372}. 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; CU329672; CAA21423.1; -; Genomic_DNA. DR PIR; T41152; T41152. DR RefSeq; NP_588388.1; NM_001023379.2. DR PDB; 3SP4; X-ray; 1.80 A; A/B=33-232. DR PDB; 3SPD; X-ray; 1.91 A; A/B/C/D=33-232. DR PDB; 3SPL; X-ray; 2.10 A; A/B/C/D=33-232. DR PDB; 3SZQ; X-ray; 2.35 A; A=31-232. DR PDB; 4XBA; X-ray; 1.50 A; A/B=33-232. DR PDB; 4YKL; X-ray; 2.25 A; B=33-232. DR PDBsum; 3SP4; -. DR PDBsum; 3SPD; -. DR PDBsum; 3SPL; -. DR PDBsum; 3SZQ; -. DR PDBsum; 4XBA; -. DR PDBsum; 4YKL; -. DR AlphaFoldDB; O74859; -. DR SMR; O74859; -. DR BioGRID; 275769; 4. DR STRING; 284812.O74859; -. DR iPTMnet; O74859; -. DR MaxQB; O74859; -. DR PaxDb; 4896-SPCC18-09c-1; -. DR EnsemblFungi; SPCC18.09c.1; SPCC18.09c.1:pep; SPCC18.09c. DR GeneID; 2539198; -. DR KEGG; spo:SPCC18.09c; -. DR PomBase; SPCC18.09c; hnt3. DR VEuPathDB; FungiDB:SPCC18.09c; -. DR eggNOG; KOG0562; Eukaryota. DR HOGENOM; CLU_066882_0_0_1; -. DR InParanoid; O74859; -. DR OMA; IHDMFPK; -. DR PhylomeDB; O74859; -. DR BRENDA; 3.6.1.70; 5613. DR BRENDA; 3.6.1.71; 5613. DR BRENDA; 3.6.1.72; 5613. DR PRO; PR:O74859; -. DR Proteomes; UP000002485; Chromosome III. DR GO; GO:0005829; C:cytosol; HDA:PomBase. DR GO; GO:0005634; C:nucleus; HDA:PomBase. DR GO; GO:0033699; F:DNA 5'-adenosine monophosphate hydrolase activity; IDA:PomBase. DR GO; GO:0120108; F:DNA-3'-diphospho-5'-guanosine diphosphatase; IDA:PomBase. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:PomBase. DR GO; GO:0003725; F:double-stranded RNA binding; IBA:GO_Central. DR GO; GO:0019002; F:GMP binding; IDA:PomBase. DR GO; GO:1905108; F:guanosine binding; IDA:PomBase. DR GO; GO:0030983; F:mismatched DNA binding; IDA:PomBase. DR GO; GO:1990165; F:single-strand break-containing DNA binding; IDA:PomBase. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:PomBase. DR GO; GO:0008270; F:zinc ion binding; IDA:PomBase. DR GO; GO:0006298; P:mismatch repair; IDA:PomBase. DR GO; GO:0000012; P:single strand break repair; IBA:GO_Central. DR Gene3D; 3.30.428.10; HIT-like; 1. DR InterPro; IPR011146; HIT-like. DR InterPro; IPR036265; HIT-like_sf. DR InterPro; IPR032566; Znf-C2HE. DR PANTHER; PTHR12486:SF4; APRATAXIN; 1. DR PANTHER; PTHR12486; APRATAXIN-RELATED; 1. DR Pfam; PF01230; HIT; 1. DR Pfam; PF16278; zf-C2HE; 1. DR SUPFAM; SSF54197; HIT-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; DNA damage; DNA repair; DNA-binding; Hydrolase; KW Metal-binding; Nucleus; Reference proteome; Zinc. FT CHAIN 1..232 FT /note="Aprataxin-like protein" FT /id="PRO_0000314650" FT DOMAIN 38..160 FT /note="HIT" FT REGION 63..67 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:21984208, FT ECO:0000269|PubMed:21984210, ECO:0000269|PubMed:26007660" FT REGION 138..149 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:21984208, FT ECO:0000269|PubMed:21984210, ECO:0000269|PubMed:26007660" FT REGION 161..165 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:21984208, FT ECO:0000269|PubMed:21984210, ECO:0000269|PubMed:26007660" FT REGION 209..212 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:21984208, FT ECO:0000269|PubMed:21984210, ECO:0000269|PubMed:26007660" FT ACT_SITE 147 FT /note="Nucleophile" FT /evidence="ECO:0000305|PubMed:21984210, FT ECO:0000305|PubMed:26007660" FT BINDING 200 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:21984210, FT ECO:0000269|PubMed:26007660, ECO:0007744|PDB:3SPD, FT ECO:0007744|PDB:3SPL, ECO:0007744|PDB:4XBA" FT BINDING 203 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:21984210, FT ECO:0000269|PubMed:26007660, ECO:0007744|PDB:3SPD, FT ECO:0007744|PDB:3SPL, ECO:0007744|PDB:4XBA" FT BINDING 217 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:21984210, FT ECO:0000269|PubMed:26007660, ECO:0007744|PDB:3SPD, FT ECO:0007744|PDB:3SPL, ECO:0007744|PDB:4XBA" FT BINDING 221 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:21984210, FT ECO:0000269|PubMed:26007660, ECO:0007744|PDB:3SPD, FT ECO:0007744|PDB:3SPL, ECO:0007744|PDB:4XBA" FT SITE 41 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:21984210, FT ECO:0000269|PubMed:26007660" FT MUTAGEN 34 FT /note="F->A: Decreased affinity for DNA." FT /evidence="ECO:0000269|PubMed:21984208" FT MUTAGEN 41 FT /note="Y->A: Mildly decreased DNAppG decapping activity." FT /evidence="ECO:0000269|PubMed:26007660" FT MUTAGEN 63 FT /note="D->A: Strongly decreased DNAppG decapping activity." FT /evidence="ECO:0000269|PubMed:26007660" FT MUTAGEN 65 FT /note="F->A: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:21984210" FT MUTAGEN 67 FT /note="K->E: Loss of enzyme activity. Strongly reduced FT affinity for DNA." FT /evidence="ECO:0000269|PubMed:21984210" FT MUTAGEN 130 FT /note="C->A: Decreased affinity for DNA." FT /evidence="ECO:0000269|PubMed:21984208" FT MUTAGEN 138 FT /note="H->A: Decreased enzyme activity. Mildly decreases FT affinity for DNA." FT /evidence="ECO:0000269|PubMed:21984208, FT ECO:0000269|PubMed:21984210" FT MUTAGEN 142 FT /note="S->A,E: Nearly abolishes enzyme activity. Mildly FT decreases affinity for DNA." FT /evidence="ECO:0000269|PubMed:21984208, FT ECO:0000269|PubMed:21984210" FT MUTAGEN 147 FT /note="H->A: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:26007660" FT MUTAGEN 147 FT /note="H->N: Loss of enzyme activity." FT /evidence="ECO:0000269|PubMed:21984210" FT MUTAGEN 149 FT /note="H->A: Nearly abolishes enzyme activity." FT /evidence="ECO:0000269|PubMed:26007660" FT MUTAGEN 161 FT /note="K->A: Strongly decreases abolishes enzyme activity. FT Decreased affinity for DNA." FT /evidence="ECO:0000269|PubMed:21984208, FT ECO:0000269|PubMed:21984210" FT MUTAGEN 161 FT /note="K->E: Nearly abolishes enzyme activity. Strongly FT reduced affinity for DNA." FT /evidence="ECO:0000269|PubMed:21984210" FT MUTAGEN 165 FT /note="H->A: Slightly decreased enzyme activity." FT /evidence="ECO:0000269|PubMed:21984210" FT MUTAGEN 165 FT /note="H->E: Nearly abolishes enzyme activity. Strongly FT reduced affinity for DNA." FT /evidence="ECO:0000269|PubMed:21984210" FT MUTAGEN 168 FT /note="S->A: Decreased enzyme activity." FT /evidence="ECO:0000269|PubMed:21984210" FT HELIX 34..38 FT /evidence="ECO:0007829|PDB:4XBA" FT HELIX 39..43 FT /evidence="ECO:0007829|PDB:4XBA" FT HELIX 45..47 FT /evidence="ECO:0007829|PDB:4XBA" FT STRAND 51..54 FT /evidence="ECO:0007829|PDB:4XBA" FT STRAND 56..62 FT /evidence="ECO:0007829|PDB:4XBA" FT STRAND 67..76 FT /evidence="ECO:0007829|PDB:4XBA" FT TURN 79..83 FT /evidence="ECO:0007829|PDB:4XBA" FT HELIX 86..92 FT /evidence="ECO:0007829|PDB:4XBA" FT HELIX 94..105 FT /evidence="ECO:0007829|PDB:4XBA" FT TURN 106..108 FT /evidence="ECO:0007829|PDB:4XBA" FT HELIX 109..119 FT /evidence="ECO:0007829|PDB:4XBA" FT HELIX 126..130 FT /evidence="ECO:0007829|PDB:4XBA" FT STRAND 133..140 FT /evidence="ECO:0007829|PDB:4XBA" FT STRAND 142..145 FT /evidence="ECO:0007829|PDB:4XBA" FT STRAND 148..153 FT /evidence="ECO:0007829|PDB:4XBA" FT HELIX 163..169 FT /evidence="ECO:0007829|PDB:4XBA" FT STRAND 174..176 FT /evidence="ECO:0007829|PDB:4XBA" FT HELIX 181..183 FT /evidence="ECO:0007829|PDB:4XBA" FT HELIX 190..192 FT /evidence="ECO:0007829|PDB:4XBA" FT HELIX 193..195 FT /evidence="ECO:0007829|PDB:4YKL" FT TURN 201..203 FT /evidence="ECO:0007829|PDB:4XBA" FT STRAND 206..208 FT /evidence="ECO:0007829|PDB:3SPD" FT HELIX 211..229 FT /evidence="ECO:0007829|PDB:4XBA" SQ SEQUENCE 232 AA; 26922 MW; 7B448C953ED13CFB CRC64; MSVHKTNDAF KVLMNSAKEP IVEDIPKKYR KQSFRDNLKV YIESPESYKN VIYYDDDVVL VRDMFPKSKM HLLLMTRDPH LTHVHPLEIM MKHRSLVEKL VSYVQGDLSG LIFDEARNCL SQQLTNEALC NYIKVGFHAG PSMNNLHLHI MTLDHVSPSL KNSAHYISFT SPFFVKIDTP TSNLPTRGTL TSLFQEDLKC WRCGETFGRH FTKLKAHLQE EYDDWLDKSV SM //