ID APEX2_BOVIN Reviewed; 514 AA. AC Q5E9N9; Q58D90; DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot. DT 15-MAR-2005, sequence version 1. DT 08-NOV-2023, entry version 98. DE RecName: Full=DNA-(apurinic or apyrimidinic site) endonuclease 2; DE EC=3.1.11.2 {ECO:0000250|UniProtKB:P27695}; DE AltName: Full=APEX nuclease 2; DE AltName: Full=Apurinic-apyrimidinic endonuclease 2; DE Short=AP endonuclease 2; GN Name=APEX2; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=16305752; DOI=10.1186/1471-2164-6-166; RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L., RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.; RT "Characterization of 954 bovine full-CDS cDNA sequences."; RL BMC Genomics 6:166-166(2005). CC -!- FUNCTION: Functions as a weak apurinic/apyrimidinic (AP) CC endodeoxyribonuclease in the DNA base excision repair (BER) pathway of CC DNA lesions induced by oxidative and alkylating agents (By similarity). CC Initiates repair of AP sites in DNA by catalyzing hydrolytic incision CC of the phosphodiester backbone immediately adjacent to the damage, CC generating a single-strand break with 5'-deoxyribose phosphate and 3'- CC hydroxyl ends (By similarity). Also displays double-stranded DNA 3'-5' CC exonuclease, 3'-phosphodiesterase activities. Shows robust 3'-5' CC exonuclease activity on 3'-recessed heteroduplex DNA and is able to CC remove mismatched nucleotides preferentially (By similarity). Shows CC fairly strong 3'-phosphodiesterase activity involved in the removal of CC 3'-damaged termini formed in DNA by oxidative agents. In the nucleus CC functions in the PCNA-dependent BER pathway (By similarity). Plays a CC role in reversing blocked 3' DNA ends, problematic lesions that CC preclude DNA synthesis (By similarity). Required for somatic CC hypermutation (SHM) and DNA cleavage step of class switch recombination CC (CSR) of immunoglobulin genes (By similarity). Required for proper cell CC cycle progression during proliferation of peripheral lymphocytes (By CC similarity). {ECO:0000250|UniProtKB:Q68G58, CC ECO:0000250|UniProtKB:Q9UBZ4}. 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; CC Evidence={ECO:0000250|UniProtKB:P27695}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:P27695}; CC Note=Probably binds two magnesium or manganese ions per subunit. CC {ECO:0000250|UniProtKB:P27695}; CC -!- ACTIVITY REGULATION: 3'-5' exonuclease activity is activated by sodium CC and manganese (By similarity). 3'-5' exonuclease and 3'- CC phosphodiesterase activities are stimulated in presence of PCNA (By CC similarity). {ECO:0000250|UniProtKB:Q9UBZ4}. CC -!- SUBUNIT: Interacts with PCNA; this interaction is triggered by reactive CC oxygen species and increased by misincorporation of uracil in nuclear CC DNA. {ECO:0000250|UniProtKB:Q9UBZ4}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00764}. CC Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU00764}. Mitochondrion CC {ECO:0000250|UniProtKB:Q9UBZ4}. Note=Together with PCNA, is CC redistributed in discrete nuclear foci in presence of oxidative DNA CC damaging agents. {ECO:0000250|UniProtKB:Q9UBZ4}. CC -!- SIMILARITY: Belongs to the DNA repair enzymes AP/ExoA family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAX46554.1; Type=Frameshift; Evidence={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; BT020881; AAX08898.1; -; mRNA. DR EMBL; BT021707; AAX46554.1; ALT_FRAME; mRNA. DR RefSeq; NP_001015577.1; NM_001015577.1. DR AlphaFoldDB; Q5E9N9; -. DR SMR; Q5E9N9; -. DR STRING; 9913.ENSBTAP00000017537; -. DR PaxDb; 9913-ENSBTAP00000017537; -. DR GeneID; 511790; -. DR KEGG; bta:511790; -. DR CTD; 27301; -. DR eggNOG; KOG1294; Eukaryota. DR InParanoid; Q5E9N9; -. DR OrthoDB; 169291at2759; -. DR Proteomes; UP000009136; Unplaced. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. 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' DNA exonuclease activity; IBA:GO_Central. DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW. DR GO; GO:0008081; F:phosphoric diester hydrolase activity; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0006284; P:base-excision repair; IBA:GO_Central. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW. DR CDD; cd09088; Ape2-like_AP-endo; 1. DR Gene3D; 3.60.10.10; Endonuclease/exonuclease/phosphatase; 1. DR InterPro; IPR004808; AP_endonuc_1. DR InterPro; IPR020847; AP_endonuclease_F1_BS. DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf. DR InterPro; IPR005135; Endo/exonuclease/phosphatase. DR InterPro; IPR010666; Znf_GRF. DR NCBIfam; TIGR00633; xth; 1. DR PANTHER; PTHR22748; AP ENDONUCLEASE; 1. DR PANTHER; PTHR22748:SF4; DNA-(APURINIC OR APYRIMIDINIC SITE) ENDONUCLEASE 2; 1. DR Pfam; PF03372; Exo_endo_phos; 1. DR Pfam; PF06839; zf-GRF; 1. DR SUPFAM; SSF56219; DNase I-like; 1. DR PROSITE; PS00726; AP_NUCLEASE_F1_1; 1. DR PROSITE; PS51435; AP_NUCLEASE_F1_4; 1. DR PROSITE; PS51999; ZF_GRF; 1. PE 2: Evidence at transcript level; KW Cell cycle; Cytoplasm; DNA damage; DNA recombination; DNA repair; KW DNA-binding; Endonuclease; Exonuclease; Hydrolase; Magnesium; KW Metal-binding; Mitochondrion; Nuclease; Nucleus; Reference proteome; Zinc; KW Zinc-finger. FT CHAIN 1..514 FT /note="DNA-(apurinic or apyrimidinic site) endonuclease 2" FT /id="PRO_0000200013" FT ZN_FING 465..514 FT /note="GRF-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT REGION 359..417 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 390..397 FT /note="Required for the interaction and colocalization with FT PCNA in nuclear foci in presence of oxidative-induced DNA FT damaging agents" FT /evidence="ECO:0000250|UniProtKB:Q9UBZ4" FT COMPBIAS 379..417 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 156 FT /evidence="ECO:0000250|UniProtKB:P27695" FT ACT_SITE 197 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000250" FT ACT_SITE 304 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 8 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 48 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 197 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 199 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 303 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 304 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00764" FT BINDING 465 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 468 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 491 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 505 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT SITE 199 FT /note="Transition state stabilizer" FT /evidence="ECO:0000250|UniProtKB:P27695" FT SITE 277 FT /note="Important for catalytic activity" FT /evidence="ECO:0000250|UniProtKB:P27695" FT SITE 304 FT /note="Interaction with DNA substrate" FT /evidence="ECO:0000250|UniProtKB:P27695" FT CONFLICT 369 FT /note="K -> Q (in Ref. 1; AAX46554)" FT /evidence="ECO:0000305" SQ SEQUENCE 514 AA; 56938 MW; D22E64035623C993 CRC64; MLRLVSWNIN GIRSPLQGVR CEEPSSCSAM AMGRILDKLD ADIVCLQETK VTRDVLTEPL AIIEGYNSYF SFSRNRSGYS GVATFCKDSA TPVAAEEGLS GLLSTQNGDV GCYGNMDDFT QEELRALDSE GRALLTQHKI CTWEGKEKTL TLINVYCPHA DPGKPERLTF KMRFYRLLQI RAEALLAAGS HVIILGDLNT AHRPIDHWDA VNMECFEEDP GRKWMDGLLS NLGCESGSHM GPFIDSYRCF QPKQKGAFTC WSTVSGARHL NYGSRLDYVL GDRTLVIDTF QSSFLLPEVM GSDHCPVGAV LSVSSVPAKQ CPPLCTCFLP EFAGTQLKIL RFLVHFKQDP VFKQSALQPS NQTQVHMRKN KARVRSTRSR PSKTGSSRGQ KNLMSYFQPS SSGPQTSNLD LPSLGTLITP KTSEEDVMAN VVEGQTKASE AKDEKEIRTS FWKSLLGGPS PMPLCGGHRE PCVMRTVKKP GPNLGRHFYM CARPQGPPTD PSSRCNFFLW SRPS //