APEX2_MOUSE
ID APEX2_MOUSE Reviewed; 516 AA.
AC Q68G58; Q8BJP7; Q8BTR7; Q8BUZ2; Q8BYE9; Q8R018; Q8R328; Q9CS12;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 132.
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; Synonyms=Ape2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, INTERACTION
RP WITH PCNA, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=129/Sv, and C57BL/6J; TISSUE=B-cell;
RX PubMed=12573260; DOI=10.1016/s0888-7543(02)00009-5;
RA Ide Y., Tsuchimoto D., Tominaga Y., Iwamoto Y., Nakabeppu Y.;
RT "Characterization of the genomic structure and expression of the mouse
RT Apex2 gene.";
RL Genomics 81:47-57(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1/2/4/5).
RC STRAIN=NOD; TISSUE=Adipose tissue, Head, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=FVB/N-3; TISSUE=Mammary tumor;
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).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=15319281; DOI=10.1182/blood-2004-04-1476;
RA Ide Y., Tsuchimoto D., Tominaga Y., Nakashima M., Watanabe T., Sakumi K.,
RA Ohno M., Nakabeppu Y.;
RT "Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in
RT APEX2-null mice.";
RL Blood 104:4097-4103(2004).
RN [5]
RP FUNCTION, INDUCTION, DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
RX PubMed=18025127; DOI=10.1084/jem.20071289;
RA Guikema J.E., Linehan E.K., Tsuchimoto D., Nakabeppu Y., Strauss P.R.,
RA Stavnezer J., Schrader C.E.;
RT "APE1- and APE2-dependent DNA breaks in immunoglobulin class switch
RT recombination.";
RL J. Exp. Med. 204:3017-3026(2007).
RN [6]
RP FUNCTION.
RX PubMed=19556307; DOI=10.1093/intimm/dxp061;
RA Sabouri Z., Okazaki I.M., Shinkura R., Begum N., Nagaoka H., Tsuchimoto D.,
RA Nakabeppu Y., Honjo T.;
RT "Apex2 is required for efficient somatic hypermutation but not for class
RT switch recombination of immunoglobulin genes.";
RL Int. Immunol. 21:947-955(2009).
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. 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. Also displays double-stranded DNA 3'-5' exonuclease, 3'-
CC phosphodiesterase activities. Shows robust 3'-5' exonuclease activity
CC on 3'-recessed heteroduplex DNA and is able to remove mismatched
CC nucleotides preferentially. Shows fairly strong 3'-phosphodiesterase
CC activity involved in the removal of 3'-damaged termini formed in DNA by
CC oxidative agents. In the nucleus functions in the PCNA-dependent BER
CC pathway. Required for somatic hypermutation (SHM) and DNA cleavage step
CC of class switch recombination (CSR) of immunoglobulin genes. Required
CC for proper cell cycle progression during proliferation of peripheral
CC lymphocytes. {ECO:0000269|PubMed:12573260, ECO:0000269|PubMed:15319281,
CC ECO:0000269|PubMed:18025127, ECO:0000269|PubMed:19556307}.
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 -!- ACTIVITY REGULATION: 3'-5' exonuclease activity is activated by sodium
CC and manganese. 3'-5' exonuclease and 3'-phosphodiesterase activities
CC are stimulated in presence of PCNA (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PCNA. This interaction is increased by
CC misincorporation of uracil in nuclear DNA (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Mitochondrion {ECO:0000305}.
CC Note=Together with PCNA, is redistributed in discrete nuclear foci in
CC presence of oxidative DNA damaging agents.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q68G58-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q68G58-2; Sequence=VSP_015346;
CC Name=3;
CC IsoId=Q68G58-3; Sequence=VSP_015349, VSP_015350;
CC Name=4;
CC IsoId=Q68G58-4; Sequence=VSP_015347, VSP_015352;
CC Name=5;
CC IsoId=Q68G58-5; Sequence=VSP_015348, VSP_015351;
CC -!- TISSUE SPECIFICITY: Expressed in lymphocytes, thymocytes and
CC splenocytes (at protein level). Highly expressed in the thymus and
CC weakly expressed in the bone marrow, spleen, eye, kidney, lung, brain
CC and uterus. {ECO:0000269|PubMed:12573260, ECO:0000269|PubMed:15319281}.
CC -!- INDUCTION: Up-regulated in both the nucleus and the cytosol of B cells
CC stimulated to switch. {ECO:0000269|PubMed:18025127}.
CC -!- DISRUPTION PHENOTYPE: Mice show abnormalities in proliferating
CC haemopoietic organs, such as dyshematopoiesis, defect in lymphopoiesis,
CC and delayed S-phase and G2/M-phase arrest.
CC {ECO:0000269|PubMed:15319281, ECO:0000269|PubMed:18025127}.
CC -!- SIMILARITY: Belongs to the DNA repair enzymes AP/ExoA family.
CC {ECO:0000305}.
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DR EMBL; AB072498; BAB88654.1; -; mRNA.
DR EMBL; AB085235; BAC11807.1; -; Genomic_DNA.
DR EMBL; AK021248; BAB32346.1; -; mRNA.
DR EMBL; AK040145; BAC30522.1; -; mRNA.
DR EMBL; AK050858; BAC34436.1; -; mRNA.
DR EMBL; AK080916; BAC38077.1; -; mRNA.
DR EMBL; AK081677; BAC38287.1; -; mRNA.
DR EMBL; AK088918; BAC40652.1; -; mRNA.
DR EMBL; BC026769; AAH26769.1; -; mRNA.
DR EMBL; BC078633; AAH78633.1; -; mRNA.
DR CCDS; CCDS30463.1; -. [Q68G58-1]
DR RefSeq; NP_084219.1; NM_029943.2.
DR RefSeq; XP_011246180.1; XM_011247878.2. [Q68G58-5]
DR AlphaFoldDB; Q68G58; -.
DR SMR; Q68G58; -.
DR BioGRID; 218805; 3.
DR IntAct; Q68G58; 1.
DR STRING; 10090.ENSMUSP00000108341; -.
DR iPTMnet; Q68G58; -.
DR PhosphoSitePlus; Q68G58; -.
DR MaxQB; Q68G58; -.
DR PaxDb; Q68G58; -.
DR PRIDE; Q68G58; -.
DR ProteomicsDB; 281794; -. [Q68G58-1]
DR ProteomicsDB; 281795; -. [Q68G58-2]
DR ProteomicsDB; 281796; -. [Q68G58-3]
DR ProteomicsDB; 281797; -. [Q68G58-4]
DR ProteomicsDB; 281798; -. [Q68G58-5]
DR Antibodypedia; 26902; 163 antibodies from 24 providers.
DR DNASU; 77622; -.
DR Ensembl; ENSMUST00000112725; ENSMUSP00000108345; ENSMUSG00000025269. [Q68G58-5]
DR Ensembl; ENSMUST00000112727; ENSMUSP00000108347; ENSMUSG00000025269. [Q68G58-4]
DR GeneID; 77622; -.
DR KEGG; mmu:77622; -.
DR UCSC; uc009uoi.1; mouse. [Q68G58-5]
DR CTD; 27301; -.
DR MGI; MGI:1924872; Apex2.
DR VEuPathDB; HostDB:ENSMUSG00000025269; -.
DR eggNOG; KOG1294; Eukaryota.
DR GeneTree; ENSGT00530000063540; -.
DR InParanoid; Q68G58; -.
DR OrthoDB; 1352540at2759; -.
DR BioGRID-ORCS; 77622; 13 hits in 109 CRISPR screens.
DR ChiTaRS; Apex2; mouse.
DR PRO; PR:Q68G58; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q68G58; protein.
DR Bgee; ENSMUSG00000025269; Expressed in epiblast (generic) and 151 other tissues.
DR ExpressionAtlas; Q68G58; baseline and differential.
DR Genevisible; Q68G58; MM.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
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' exodeoxyribonuclease 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 Gene3D; 3.60.10.10; -; 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 PANTHER; PTHR22748; PTHR22748; 1.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF06839; zf-GRF; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
DR TIGRFAMs; TIGR00633; xth; 1.
DR PROSITE; PS00726; AP_NUCLEASE_F1_1; 1.
DR PROSITE; PS51435; AP_NUCLEASE_F1_4; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Cytoplasm; DNA damage; DNA recombination;
KW DNA repair; DNA-binding; Endonuclease; Exonuclease; Hydrolase; Magnesium;
KW Metal-binding; Mitochondrion; Nuclease; Nucleus; Reference proteome; Zinc;
KW Zinc-finger.
FT CHAIN 1..516
FT /note="DNA-(apurinic or apyrimidinic site) endonuclease 2"
FT /id="PRO_0000200015"
FT ZN_FING 465..513
FT /note="GRF-type"
FT REGION 357..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 389..396
FT /note="Required for the colocalization with PCNA in nuclear
FT foci in presence of oxidative-induced DNA damaging agents"
FT /evidence="ECO:0000250"
FT COMPBIAS 372..386
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 155
FT /evidence="ECO:0000250"
FT ACT_SITE 196
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 8
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 47
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 196
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 198
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 302
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT SITE 198
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT SITE 276
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT SITE 303
FT /note="Interaction with DNA substrate"
FT /evidence="ECO:0000250"
FT VAR_SEQ 79
FT /note="S -> SECSCPSP (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_015346"
FT VAR_SEQ 213..266
FT /note="ECFEEDPGRKWMDGLLSNPGDEAGPHIGLFMDSYRYLHPKQQRAFTCWSVVS
FT GA -> LPVAACGHTNLVPEWEAGPVWERTMREIMEGFCDLLHSVRIFHHHTASLLRPS
FT Y (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_015347"
FT VAR_SEQ 213..260
FT /note="ECFEEDPGRKWMDGLLSNPGDEAGPHIGLFMDSYRYLHPKQQRAFTCW ->
FT LPVAACGHTNLVPEWEAGPVWERTMREIMEVKTRFCSRPLKFTESPCL (in
FT isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_015348"
FT VAR_SEQ 213..246
FT /note="ECFEEDPGRKWMDGLLSNPGDEAGPHIGLFMDSY -> VRFPLNHRPQFCSV
FT HPASQNWEFGTRGSFFYGKK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015349"
FT VAR_SEQ 247..516
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015350"
FT VAR_SEQ 261..516
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_015351"
FT VAR_SEQ 267..516
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_015352"
FT CONFLICT 110
FT /note="G -> S (in Ref. 2; BAC38077)"
FT /evidence="ECO:0000305"
FT CONFLICT 183
FT /note="A -> P (in Ref. 2; BAB32346)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="C -> F (in Ref. 3; AAH78633)"
FT /evidence="ECO:0000305"
FT CONFLICT 433
FT /note="V -> M (in Ref. 3; AAH78633)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 516 AA; 57340 MW; ED32A88D9CEABB85 CRC64;
MLRVVSWNIN GIRSPLQGLA CQEPSSCPTA LRRVLDELDA DIVCLQETKV TRDVLTEPLA
IVEGYNSYFS FSRSRSGYSG VATFCKDSAT PVAAEEGLSG VFATLNGDIG CYGNMDEFTQ
EELRVLDSEG RALLTQHKIR TLEGKEKTLT LINVYCPHAD PGKPERLTFK MRFYRLLQMR
AEALLAAGSH VIILGDLNTA HRPIDHCDAS SLECFEEDPG RKWMDGLLSN PGDEAGPHIG
LFMDSYRYLH PKQQRAFTCW SVVSGARHLN YGSRLDYVLG DRALVIDTFQ ASFLLPEVMG
SDHCPVGAVL NVSCVPAKQC PALCTRFLPE FAGTQLKILR FLVPLEQEPV REQQVLQPSH
QIQAQRQPRK ACMHSTRLRK SQGGPKRKQK NLMSYFQPSS SLSQTSGVEL PTLPLVGPLT
TPKTAEEVAT ATVLEEKNKV PESKDEKGER TAFWKSMLSG PSPMPLCGGH REPCVMRTVK
KTGPNFGRQF YMCARPRGPP SDPSSRCNFF LWSRPS
