APTX_RAT
ID APTX_RAT Reviewed; 329 AA.
AC Q8K4H4;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 125.
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Huang C.-H., Chen H., Peng J., Chen Y.;
RT "Identification of FHA-HIT as a novel nuclear protein involved in cell-
RT cycle regulation.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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).
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 -!- 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; AF398235; AAM90583.1; -; mRNA.
DR EMBL; BC078716; AAH78716.1; -; mRNA.
DR RefSeq; NP_683687.1; NM_148889.2.
DR RefSeq; XP_006238089.1; XM_006238027.3.
DR RefSeq; XP_006238090.1; XM_006238028.3.
DR AlphaFoldDB; Q8K4H4; -.
DR SMR; Q8K4H4; -.
DR STRING; 10116.ENSRNOP00000046400; -.
DR PhosphoSitePlus; Q8K4H4; -.
DR PaxDb; Q8K4H4; -.
DR Ensembl; ENSRNOT00000046463; ENSRNOP00000046400; ENSRNOG00000006582.
DR GeneID; 259271; -.
DR KEGG; rno:259271; -.
DR UCSC; RGD:628740; rat.
DR CTD; 54840; -.
DR RGD; 628740; Aptx.
DR eggNOG; KOG0562; Eukaryota.
DR eggNOG; KOG2134; Eukaryota.
DR GeneTree; ENSGT00940000156806; -.
DR HOGENOM; CLU_066882_2_0_1; -.
DR InParanoid; Q8K4H4; -.
DR OMA; PLCWLIS; -.
DR OrthoDB; 1290702at2759; -.
DR PhylomeDB; Q8K4H4; -.
DR PRO; PR:Q8K4H4; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000006582; Expressed in testis and 19 other tissues.
DR Genevisible; Q8K4H4; RN.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005730; C:nucleolus; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0003684; F:damaged DNA binding; ISO:RGD.
DR GO; GO:0033699; F:DNA 5'-adenosine monophosphate hydrolase activity; ISO:RGD.
DR GO; GO:0120108; F:DNA-3'-diphospho-5'-guanosine diphosphatase; IEA:UniProtKB-EC.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:RGD.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0006266; P:DNA ligation; ISO:RGD.
DR GO; GO:0006302; P:double-strand break repair; IBA:GO_Central.
DR GO; GO:0031647; P:regulation of protein stability; ISO:RGD.
DR GO; GO:0042542; P:response to hydrogen peroxide; ISO:RGD.
DR GO; GO:0000012; P:single strand break repair; ISO:RGD.
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.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 1.
PE 2: Evidence at transcript level;
KW DNA damage; DNA repair; DNA-binding; Hydrolase; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..329
FT /note="Aprataxin"
FT /id="PRO_0000109842"
FT DOMAIN 23..72
FT /note="FHA-like"
FT DOMAIN 155..260
FT /note="HIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT ZN_FING 304..326
FT /note="C2H2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..95
FT /note="Interactions with ADPRT/PARP1 and NCL"
FT /evidence="ECO:0000250"
FT REGION 106..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 180..184
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT REGION 242..243
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT MOTIF 111..115
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 245..249
FT /note="Histidine triad motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT COMPBIAS 106..122
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 247
FT /note="Tele-AMP-histidine intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT SITE 161
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT SITE 238
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT SITE 249
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT SITE 264
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT MOD_RES 120
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TQC5"
SQ SEQUENCE 329 AA; 37720 MW; 636B827F661B14FD CRC64;
MRVCWLVRQD CWHQRIKLPH LEAVVIGRSP ETKITDKKCS RQQVQLKAEC NKRYVNVKQM
GVNPTSIDEV VIGKDREMKL LPGQVLHMVN ELYPYMVEFE EVAESPNVTQ RKRKRPDCDS
QEMEAEAGAS PSQCSVSPKT GKHGAAKEES LGHWSQGLKI SMKDPKMQVY KDDQVVVIKD
KYPKARHHWL VLPWASISSL KVVTSEHLEL LKHMHAVGEK VIADFTGSSK LRFRLGYHAI
PSMSHVHLHV ISQDFDSPCL KNKKHWNSFN TEYFLESQAV IKMVQEAGRV TVKDGTCELL
KLPLRCHECQ QLLPSIPQLK EHLRKHWGG
