APTX_SCHPO
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 03-AUG-2022, entry version 123.
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}.
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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; 4896.SPCC18.09c.1; -.
DR MaxQB; O74859; -.
DR PaxDb; O74859; -.
DR PRIDE; O74859; -.
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; HPFDAFE; -.
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:0006302; P:double-strand break repair; IBA:GO_Central.
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; -; 1.
DR InterPro; IPR026963; Aprataxin-like.
DR InterPro; IPR011146; HIT-like.
DR InterPro; IPR036265; HIT-like_sf.
DR InterPro; IPR032566; Znf-C2HE.
DR PANTHER; PTHR12486:SF4; PTHR12486:SF4; 1.
DR Pfam; PF01230; HIT; 1.
DR Pfam; PF16278; zf-C2HE; 1.
DR SUPFAM; SSF54197; SSF54197; 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
