ID A0A8L2Q612_RAT Unreviewed; 308 AA. AC A0A8L2Q612; DT 03-AUG-2022, integrated into UniProtKB/TrEMBL. DT 03-AUG-2022, sequence version 1. DT 08-NOV-2023, entry version 8. DE RecName: Full=DNA-(apurinic or apyrimidinic site) endonuclease {ECO:0000256|ARBA:ARBA00014704, ECO:0000256|RuleBase:RU362131}; DE EC=3.1.-.- {ECO:0000256|RuleBase:RU362131}; GN Name=Apex1 {ECO:0000313|Ensembl:ENSRNOP00000013176.4, GN ECO:0000313|RGD:2126}; 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 {ECO:0000313|Ensembl:ENSRNOP00000013176.4, ECO:0000313|Proteomes:UP000002494}; RN [1] {ECO:0000313|Ensembl:ENSRNOP00000013176.4, ECO:0000313|Proteomes:UP000002494} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000013176.4, RC ECO:0000313|Proteomes:UP000002494}; RX PubMed=15057822; DOI=10.1038/nature02426; RG Rat Genome Sequencing Project Consortium; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [2] {ECO:0000313|Ensembl:ENSRNOP00000013176.4} RP IDENTIFICATION. RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000013176.4}; RG Ensembl; RL Submitted (JUL-2023) to UniProtKB. CC -!- FUNCTION: Initiates repair of AP sites in DNA by catalyzing hydrolytic CC incision of the phosphodiester backbone immediately adjacent to the CC damage, generating a single-strand break with 5'-deoxyribose phosphate CC and 3'-hydroxyl ends. {ECO:0000256|RuleBase:RU362131}. 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:0000256|ARBA:ARBA00000493}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000256|PIRSR:PIRSR604808-2, CC ECO:0000256|RuleBase:RU362131}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000256|PIRSR:PIRSR604808-2, CC ECO:0000256|RuleBase:RU362131}; CC Note=Probably binds two magnesium or manganese ions per subunit. CC {ECO:0000256|PIRSR:PIRSR604808-2, ECO:0000256|RuleBase:RU362131}; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000256|RuleBase:RU362131}. CC Cytoplasm {ECO:0000256|RuleBase:RU362131}. Mitochondrion CC {ECO:0000256|RuleBase:RU362131}. CC -!- SIMILARITY: Belongs to the DNA repair enzymes AP/ExoA family. CC {ECO:0000256|ARBA:ARBA00007092, ECO:0000256|RuleBase:RU362131}. 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 RefSeq; XP_017455294.1; XM_017599805.1. DR Ensembl; ENSRNOT00000013176.6; ENSRNOP00000013176.4; ENSRNOG00000009663.6. DR GeneID; 79116; -. DR CTD; 328; -. DR RGD; 2126; Apex1. DR GeneTree; ENSGT00530000063540; -. DR Proteomes; UP000002494; Chromosome 15. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR CDD; cd09087; Ape1-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; IPR020848; AP_endonuclease_F1_CS. DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf. DR InterPro; IPR005135; Endo/exonuclease/phosphatase. DR NCBIfam; TIGR00195; exoDNase_III; 1. DR NCBIfam; TIGR00633; xth; 1. DR PANTHER; PTHR22748; AP ENDONUCLEASE; 1. DR PANTHER; PTHR22748:SF6; DNA-(APURINIC OR APYRIMIDINIC SITE) ENDONUCLEASE; 1. DR Pfam; PF03372; Exo_endo_phos; 1. DR SUPFAM; SSF56219; DNase I-like; 1. DR PROSITE; PS00726; AP_NUCLEASE_F1_1; 1. DR PROSITE; PS00727; AP_NUCLEASE_F1_2; 1. DR PROSITE; PS00728; AP_NUCLEASE_F1_3; 1. DR PROSITE; PS51435; AP_NUCLEASE_F1_4; 1. PE 1: Evidence at protein level; KW Cytoplasm {ECO:0000256|RuleBase:RU362131}; KW DNA damage {ECO:0000256|RuleBase:RU362131}; KW DNA recombination {ECO:0000256|ARBA:ARBA00023172}; KW DNA repair {ECO:0000256|RuleBase:RU362131}; KW DNA-binding {ECO:0000256|RuleBase:RU362131}; KW Endonuclease {ECO:0000256|ARBA:ARBA00022759, KW ECO:0000256|RuleBase:RU362131}; Hydrolase {ECO:0000256|RuleBase:RU362131}; KW Magnesium {ECO:0000256|PIRSR:PIRSR604808-2, ECO:0000256|RuleBase:RU362131}; KW Manganese {ECO:0000256|PIRSR:PIRSR604808-2}; KW Metal-binding {ECO:0000256|PIRSR:PIRSR604808-2, KW ECO:0000256|RuleBase:RU362131}; KW Mitochondrion {ECO:0000256|RuleBase:RU362131}; KW Nuclease {ECO:0000256|ARBA:ARBA00022722, ECO:0000256|RuleBase:RU362131}; KW Nucleus {ECO:0000256|RuleBase:RU362131}; KW Proteomics identification {ECO:0007829|PeptideAtlas:A0A8L2Q612}; KW Reference proteome {ECO:0000313|Proteomes:UP000002494}; KW S-nitrosylation {ECO:0000256|ARBA:ARBA00022799}. FT DOMAIN 56..299 FT /note="Endonuclease/exonuclease/phosphatase" FT /evidence="ECO:0000259|Pfam:PF03372" FT REGION 1..47 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 14..31 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 161 FT /evidence="ECO:0000256|PIRSR:PIRSR604808-1" FT ACT_SITE 200 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000256|PIRSR:PIRSR604808-1" FT ACT_SITE 299 FT /note="Proton acceptor" FT /evidence="ECO:0000256|PIRSR:PIRSR604808-1" FT BINDING 58 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR604808-2" FT BINDING 86 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR604808-2" FT BINDING 200 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR604808-2" FT BINDING 202 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR604808-2" FT BINDING 298 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR604808-2" FT BINDING 299 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT /evidence="ECO:0000256|PIRSR:PIRSR604808-2" FT SITE 202 FT /note="Transition state stabilizer" FT /evidence="ECO:0000256|PIRSR:PIRSR604808-3" FT SITE 273 FT /note="Important for catalytic activity" FT /evidence="ECO:0000256|PIRSR:PIRSR604808-3" FT SITE 299 FT /note="Interaction with DNA substrate" FT /evidence="ECO:0000256|PIRSR:PIRSR604808-3" SQ SEQUENCE 308 AA; 34590 MW; AA051A975629586F CRC64; MNRIAPLPPE PETKKSKGAA KKTEKEAAGE GPVLYEDPPD QKTSASGKSA TLKICSWNVD GLRAWIKKKG LDWVKEEAPD ILCLQETKCS ENKLPAELQE LPGLTHQYWS APSDKEGYSG VGLLSRQCPL KVSYGIGEEE HDQEGRVIVA EFESFILVTA YVPNAGRGLV RLEYRQRWDE AFRKFLKDLA SRKPLVLCGD LNVAHEEIDL RNPKGNKKNA GFTPQERQGF GEMLQAVPLA DSFRHLYPNT AYAYTFWTYM MNARSKNVGW RLDYFLLSHS LLPALCDSKI RSKALGSDHC PITLYLAL //