APTX_CANLF
ID APTX_CANLF Reviewed; 342 AA.
AC P61797;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 1.
DT 25-MAY-2022, entry version 105.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Chen Y., Huang C.-H.;
RT "Identification of human FHA-HIT gene homolog in dog.";
RL Submitted (DEC-2002) 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 -!- 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; AY208843; AAP86333.1; -; mRNA.
DR RefSeq; NP_001003355.1; NM_001003355.1.
DR AlphaFoldDB; P61797; -.
DR SMR; P61797; -.
DR STRING; 9615.ENSCAFP00000051773; -.
DR PaxDb; P61797; -.
DR GeneID; 442943; -.
DR KEGG; cfa:442943; -.
DR CTD; 54840; -.
DR eggNOG; KOG0562; Eukaryota.
DR eggNOG; KOG2134; Eukaryota.
DR InParanoid; P61797; -.
DR OrthoDB; 1290702at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0033699; F:DNA 5'-adenosine monophosphate hydrolase activity; IBA:GO_Central.
DR GO; GO:0120108; F:DNA-3'-diphospho-5'-guanosine diphosphatase; IEA:UniProtKB-EC.
DR GO; GO:0003725; F:double-stranded RNA binding; IBA:GO_Central.
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: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:0006302; P:double-strand break repair; IBA:GO_Central.
DR GO; GO:0000012; P:single strand break repair; IBA:GO_Central.
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 DNA damage; DNA repair; DNA-binding; Hydrolase; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..342
FT /note="Aprataxin"
FT /id="PRO_0000109837"
FT DOMAIN 24..73
FT /note="FHA-like"
FT DOMAIN 168..273
FT /note="HIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT ZN_FING 317..339
FT /note="C2H2-type"
FT REGION 1..96
FT /note="Interactions with ADPRT/PARP1 and NCL"
FT /evidence="ECO:0000250"
FT REGION 105..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..197
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT REGION 255..256
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT MOTIF 112..117
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 258..262
FT /note="Histidine triad motif"
FT COMPBIAS 105..129
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 135..152
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 260
FT /note="Tele-AMP-histidine intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT SITE 174
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT SITE 251
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT SITE 262
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT SITE 277
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z2E3"
FT MOD_RES 123
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TQC5"
SQ SEQUENCE 342 AA; 39057 MW; 3F22AA913B3ED8FA CRC64;
MMRMCWLVRQ DNQHQRIKLP HLEAVMVGRG PETKIIDKKC SRQQVQLKAE CNKGYVKVKQ
VGVNPTSIDS VIIGKDQEAK LQPGQVLHMV NELYPYIVEF EEEAESPGLE THRKRKRSGN
SDSIERDAAQ EAESSTGLEP GSDSSQCSVP LNKGKDAPTK KESLGHWSQG LKISMQDPKM
QVYKDEQVVV IKDKYPKARY HWLVLPWASV SSLKAVTGEH LELLKHMHTV GEKMIADFAG
SSKLRFRLGY HAIPSMSHVH LHVISQDFDS PCLKNKKHWN SFNTEYFLES QAVIEMVQHA
GRVSVRDGMP ELLKLPLRCH ECQQLLPSIP QLKEHLRRHW PK
