APTX_MACFA
ID APTX_MACFA Reviewed; 356 AA.
AC Q9BGQ0; Q60HH6;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 25-MAY-2022, entry version 99.
DE RecName: Full=Aprataxin;
DE EC=3.6.1.71 {ECO:0000250|UniProtKB:Q7Z2E3};
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; ORFNames=QflA-13527, QflA-14784;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Frontal cortex;
RA Osada N., Hida M., Kusuda J., Tanuma R., Iseki K., Hirai M., Terao K.,
RA Suzuki Y., Sugano S., Hashimoto K.;
RT "Isolation of full-length cDNA clones from macaque brain cDNA libraries.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Frontal cortex;
RA Kusuda J., Osada N., Tanuma R., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation and characterization of cDNA for macaque neurological disease
RT genes.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
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. Catalyzes the release of
CC adenylate groups covalently linked to 5'-phosphate termini, resulting
CC in the production of 5'-phosphate termini that can be efficiently
CC rejoined. Also able to hydrolyze adenosine 5'-monophosphoramidate (AMP-
CC NH(2)) and diadenosine tetraphosphate (AppppA), but with lower
CC catalytic activity (By similarity). Likewise, catalyzes the release of
CC 3'-linked guanosine (DNAppG) and inosine (DNAppI) from DNA, but has
CC higher specific activity with 5'-linked adenosine (AppDNA) (By
CC similarity). {ECO:0000250|UniProtKB:O74859,
CC ECO:0000250|UniProtKB:Q7Z2E3}.
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:0000250|UniProtKB:Q7Z2E3};
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:0000250|UniProtKB:Q7Z2E3};
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 -!- SUBUNIT: Interacts with single-strand break repair proteins XRCC1,
CC XRCC4, ADPRT/PARP1 and p53/TP53. Interacts with NCL. Interacts (via
CC FHA-like domain) with MDC1 (phosphorylated).
CC {ECO:0000250|UniProtKB:Q7Z2E3}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q7Z2E3}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q7Z2E3}. Note=Upon genotoxic stress, colocalizes
CC with XRCC1 at sites of DNA damage. Colocalizes with MDC1 at sites of
CC DNA double-strand breaks. Interaction with NCL is required for
CC nucleolar localization (By similarity). {ECO:0000250|UniProtKB:Q7Z2E3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BGQ0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BGQ0-2; Sequence=VSP_013358;
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:0000250|UniProtKB:Q7Z2E3}.
CC -!- DOMAIN: The FHA-like domain mediates interaction with NCL; XRCC1 and
CC XRCC4. {ECO:0000250}.
CC -!- DOMAIN: The HIT domain is required for enzymatic activity.
CC {ECO:0000250}.
CC -!- DOMAIN: The C2H2-type zinc finger mediates DNA-binding. {ECO:0000250}.
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DR EMBL; AB056422; BAB33080.1; -; mRNA.
DR EMBL; AB125151; BAD51939.1; -; mRNA.
DR AlphaFoldDB; Q9BGQ0; -.
DR SMR; Q9BGQ0; -.
DR STRING; 9541.XP_005581603.1; -.
DR eggNOG; KOG0562; Eukaryota.
DR eggNOG; KOG2134; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0033699; F:DNA 5'-adenosine monophosphate hydrolase activity; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0120108; F:DNA-3'-diphospho-5'-guanosine diphosphatase; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
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 2: Evidence at transcript level;
KW Alternative splicing; DNA damage; DNA repair; DNA-binding; Hydrolase;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Zinc;
KW Zinc-finger.
FT CHAIN 1..356
FT /note="Aprataxin"
FT /id="PRO_0000109839"
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 REGION 1..110
FT /note="Interactions with ADPRT/PARP1 and NCL"
FT /evidence="ECO:0000250"
FT REGION 122..173
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 207..211
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT REGION 269..270
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT MOTIF 126..131
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 272..276
FT /note="Histidine triad motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT COMPBIAS 122..147
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:0000250|UniProtKB:Q7Z2E3"
FT SITE 188
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT SITE 265
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT SITE 276
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT SITE 291
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT MOD_RES 132
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TQC5"
FT VAR_SEQ 1..188
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_013358"
SQ SEQUENCE 356 AA; 40847 MW; 5C29E1B4D1B9D413 CRC64;
MSNVNLSVSD VWRLMMRVCW LVRQDSRHQR IRLPHLEAVV IGRGPETKIT DKKCSRQQVQ
LKAECNKGYV KVKQVGVNPT SIDSVVIGKD QEVKLQPGQV LHMVNELYPY IVEFEEEAKN
PGLETHRKRK RSGDSDSIER DAAHEAEPGT GLEPGSNHNQ CSVPPKKGKD APIKKESLGH
WSQGLKISMQ DPKMQVYKDE QVVVIKDKYP KARYHWLVLP WTAISSLKAV TREHLELLKH
MHTVGEKVIV DFAGSSKLRF RLGYHAIPSM SHVHLHVISQ DFDSPCLKNK KHWNSFNTEY
FLESQAVIEM VQEAGRVTVR DGMPELLKLP LRCHECQQLL PSIPQLKEHL RKHWTQ
