APEX1_DANRE
ID APEX1_DANRE Reviewed; 310 AA.
AC A0MTA1; Q4V955; Q5RHZ7; Q7SXL6;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=DNA-(apurinic or apyrimidinic site) endonuclease;
DE EC=3.1.11.2 {ECO:0000250|UniProtKB:P27695};
DE AltName: Full=APEX nuclease;
DE Short=APEN;
DE AltName: Full=Apurinic-apyrimidinic endonuclease 1;
DE Short=AP endonuclease 1;
DE Short=zAP1;
GN Name=apex1; Synonyms=apex1a, apex1b;
GN ORFNames=si:ch211-214j24.12, zgc:66204;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Embryo;
RX PubMed=16966376; DOI=10.1128/mcb.01216-06;
RA Wang Y., Shupenko C.C., Melo L.F., Strauss P.R.;
RT "DNA repair protein involved in heart and blood development.";
RL Mol. Cell. Biol. 26:9083-9093(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 33-310, FUNCTION, AND MUTAGENESIS
RP OF THR-58.
RX PubMed=18579163; DOI=10.1016/j.mrfmmm.2008.04.008;
RA Georgiadis M.M., Luo M., Gaur R.K., Delaplane S., Li X., Kelley M.R.;
RT "Evolution of the redox function in mammalian apurinic/apyrimidinic
RT endonuclease.";
RL Mutat. Res. 643:54-63(2008).
CC -!- FUNCTION: Functions as a apurinic/apyrimidinic (AP)
CC endodeoxyribonuclease in the DNA base excision repair (BER) pathway of
CC DNA lesions induced by oxidative and alkylating agents. Initiates
CC repair of AP sites in DNA by catalyzing hydrolytic incision of the
CC phosphodiester backbone immediately adjacent to the damage, generating
CC a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl
CC ends. May also play a role in the epigenetic regulation of gene
CC expression by participating in DNA demethylation. Required for passage
CC through the midblastula transition MBT. May also act as an
CC endoribonuclease involved in the control of single-stranded RNA
CC metabolism. Has no redox activity. Binds DNA and RNA.
CC {ECO:0000269|PubMed:16966376, ECO:0000269|PubMed:18579163}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage in the 3'- to 5'-direction to yield
CC nucleoside 5'-phosphates.; EC=3.1.11.2;
CC Evidence={ECO:0000250|UniProtKB:P27695};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Probably binds two magnesium or manganese ions per subunit.
CC {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00764}.
CC Nucleus, nucleolus {ECO:0000250}. Nucleus speckle {ECO:0000255|PROSITE-
CC ProRule:PRU00764}. Endoplasmic reticulum {ECO:0000250}. Cytoplasm
CC {ECO:0000255|PROSITE-ProRule:PRU00764}. Mitochondrion {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Expressed in unfertilized eggs and embryos at two
CC stages (at protein level). Expressed throughout embryogenesis.
CC {ECO:0000269|PubMed:16966376}.
CC -!- SIMILARITY: Belongs to the DNA repair enzymes AP/ExoA family.
CC {ECO:0000305}.
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; EF041101; ABK35081.1; -; mRNA.
DR EMBL; EF041102; ABK35082.1; -; mRNA.
DR EMBL; EF041103; ABK35083.1; -; Genomic_DNA.
DR EMBL; EF041104; ABK35084.1; -; Genomic_DNA.
DR EMBL; BX323558; CAI11781.1; -; Genomic_DNA.
DR EMBL; BC055545; AAH55545.1; -; mRNA.
DR EMBL; BC097053; AAH97053.1; -; mRNA.
DR EMBL; BC164240; AAI64240.1; -; mRNA.
DR PDB; 2O3C; X-ray; 2.30 A; A/B/C=33-310.
DR PDBsum; 2O3C; -.
DR AlphaFoldDB; A0MTA1; -.
DR SMR; A0MTA1; -.
DR STRING; 7955.ENSDARP00000067373; -.
DR PaxDb; A0MTA1; -.
DR PeptideAtlas; A0MTA1; -.
DR PRIDE; A0MTA1; -.
DR ZFIN; ZDB-GENE-040426-2761; apex1.
DR eggNOG; KOG1294; Eukaryota.
DR InParanoid; A0MTA1; -.
DR PhylomeDB; A0MTA1; -.
DR TreeFam; TF315048; -.
DR Reactome; R-DRE-110357; Displacement of DNA glycosylase by APEX1.
DR Reactome; R-DRE-110362; POLB-Dependent Long Patch Base Excision Repair.
DR Reactome; R-DRE-110373; Resolution of AP sites via the multiple-nucleotide patch replacement pathway.
DR Reactome; R-DRE-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR Reactome; R-DRE-73930; Abasic sugar-phosphate removal via the single-nucleotide replacement pathway.
DR Reactome; R-DRE-73933; Resolution of Abasic Sites (AP sites).
DR EvolutionaryTrace; A0MTA1; -.
DR PRO; PR:A0MTA1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0052720; F:class II DNA-(apurinic or apyrimidinic site) endonuclease activity; ISS:UniProtKB.
DR GO; GO:0140431; F:DNA-(abasic site) binding; ISS:UniProtKB.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IBA:GO_Central.
DR GO; GO:0008311; F:double-stranded DNA 3'-5' exodeoxyribonuclease activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0006284; P:base-excision repair; IBA:GO_Central.
DR GO; GO:0080111; P:DNA demethylation; ISS:UniProtKB.
DR GO; GO:0060047; P:heart contraction; IMP:ZFIN.
DR GO; GO:0001947; P:heart looping; IMP:ZFIN.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:ZFIN.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ZFIN.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR004808; AP_endonuc_1.
DR InterPro; IPR020847; AP_endonuclease_F1_BS.
DR InterPro; IPR020848; AP_endonuclease_F1_CS.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR PANTHER; PTHR22748; PTHR22748; 1.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR TIGRFAMs; TIGR00633; xth; 1.
DR PROSITE; PS00726; AP_NUCLEASE_F1_1; 1.
DR PROSITE; PS00728; AP_NUCLEASE_F1_3; 1.
DR PROSITE; PS51435; AP_NUCLEASE_F1_4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; DNA damage; DNA repair; DNA-binding; Endonuclease;
KW Endoplasmic reticulum; Hydrolase; Magnesium; Metal-binding; Mitochondrion;
KW Nuclease; Nucleus; Reference proteome; RNA-binding.
FT CHAIN 1..310
FT /note="DNA-(apurinic or apyrimidinic site) endonuclease"
FT /id="PRO_0000402575"
FT REGION 1..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..50
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 164
FT /evidence="ECO:0000250"
FT ACT_SITE 203
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 63
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 89
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 203
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 205
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 300
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT SITE 205
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT SITE 275
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT SITE 301
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250"
FT MUTAGEN 58
FT /note="T->C: Confers redox activity."
FT /evidence="ECO:0000269|PubMed:18579163"
FT CONFLICT 16
FT /note="A -> S (in Ref. 2; CAI11781)"
FT /evidence="ECO:0000305"
FT CONFLICT 80..93
FT /note="Missing (in Ref. 3; AAI64240/AAH97053)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="G -> A (in Ref. 3; AAH55545)"
FT /evidence="ECO:0000305"
FT STRAND 55..61
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 65..70
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 73..80
FT /evidence="ECO:0007829|PDB:2O3C"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:2O3C"
FT STRAND 108..113
FT /evidence="ECO:0007829|PDB:2O3C"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:2O3C"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:2O3C"
FT TURN 142..146
FT /evidence="ECO:0007829|PDB:2O3C"
FT STRAND 150..154
FT /evidence="ECO:0007829|PDB:2O3C"
FT STRAND 159..164
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 175..195
FT /evidence="ECO:0007829|PDB:2O3C"
FT STRAND 198..203
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 210..212
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 216..219
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 227..238
FT /evidence="ECO:0007829|PDB:2O3C"
FT STRAND 241..243
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 244..248
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 265..268
FT /evidence="ECO:0007829|PDB:2O3C"
FT STRAND 275..280
FT /evidence="ECO:0007829|PDB:2O3C"
FT HELIX 281..286
FT /evidence="ECO:0007829|PDB:2O3C"
FT STRAND 287..292
FT /evidence="ECO:0007829|PDB:2O3C"
FT STRAND 298..301
FT /evidence="ECO:0007829|PDB:2O3C"
FT STRAND 304..308
FT /evidence="ECO:0007829|PDB:2O3C"
SQ SEQUENCE 310 AA; 34881 MW; F57493D443106F4B CRC64;
MPKRAKKNEE GVDGEADNGT AAAKKEKKGK EPEAPILYED PPEKLTSKDG RAANMKITSW
NVDGLRAWVK KNGLDWVRKE DPDILCLQET KCAEKALPAD ITGMPEYPHK YWAGSEDKEG
YSGVAMLCKT EPLNVTYGIG KEEHDKEGRV ITAEFPDFFL VTAYVPNASR GLVRLDYRKT
WDVDFRAYLC GLDARKPLVL CGDLNVAHQE IDLKNPKGNR KNAGFTPEER EGFTQLLEAG
FTDSFRELYP DQAYAYTFWT YMMNARSKNV GWRLDYFVLS SALLPGLCDS KIRNTAMGSD
HCPITLFLAV