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 01-MAY-2013, entry version 74.
DE RecName: Full=DNA-(apurinic or apyrimidinic site) lyase 2;
DE EC=3.1.-.-;
DE EC=4.2.99.18;
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;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muroidea; Muridae; Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION,
RP INTERACTION WITH PCNA, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=129/Sv, and C57BL/6; 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.,
RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA 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.,
RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA 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
RT project: 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.,
RA Sakumi K., 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.,
RA Tsuchimoto D., Nakabeppu Y., Honjo T.;
RT "Apex2 is required for efficient somatic hypermutation but not for
RT class switch recombination of immunoglobulin genes.";
RL Int. Immunol. 21:947-955(2009).
CC -!- FUNCTION: Function as a weak apurinic/apyrimidinic (AP)
CC endodeoxyribonuclease in the DNA base excision repair (BER)
CC pathway of DNA lesions induced by oxidative and alkylating agents.
CC Initiates repair of AP sites in DNA by catalyzing hydrolytic
CC incision of the phosphodiester backbone immediately adjacent to
CC the damage, generating a single-strand break with 5'-deoxyribose
CC phosphate and 3'-hydroxyl ends. Displays also double-stranded DNA
CC 3'-5' exonuclease, 3'-phosphodiesterase activities. Shows robust
CC 3'-5' exonuclease activity on 3'-recessed heteroduplex DNA and is
CC able to remove mismatched nucleotides preferentially. Shows fairly
CC strong 3'-phosphodiesterase activity involved in the removal of
CC 3'-damaged termini formed in DNA by oxidative agents. In the
CC nucleus functions in the PCNA-dependent BER pathway. Required for
CC somatic hypermutation (SHM) and DNA cleavage step of class switch
CC recombination (CSR) of immunoglobulin genes. Required for proper
CC cell cycle progression during proliferation of peripheral
CC lymphocytes.
CC -!- CATALYTIC ACTIVITY: The C-O-P bond 3' to the apurinic or
CC apyrimidinic site in DNA is broken by a beta-elimination reaction,
CC leaving a 3'-terminal unsaturated sugar and a product with a
CC terminal 5'-phosphate.
CC -!- COFACTOR: Magnesium. Can also utilize manganese. Probably binds
CC two magnesium or manganese ions per subunit (By similarity).
CC -!- ENZYME REGULATION: 3'-5' exonuclease activity is activated by
CC sodium and manganese. 3'-5' exonuclease and 3'-phosphodiesterase
CC activities are stimulated in presence of PCNA (By similarity).
CC -!- SUBUNIT: Interacts with PCNA. This interaction is increased by
CC misincorporation of uracil in nuclear DNA (By similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Mitochondrion
CC (Probable). Note=Together with PCNA, is redistributed in discrete
CC nuclear foci in 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 Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q68G58-3; Sequence=VSP_015349, VSP_015350;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=Q68G58-4; Sequence=VSP_015347, VSP_015352;
CC Note=No experimental confirmation available;
CC Name=5;
CC IsoId=Q68G58-5; Sequence=VSP_015348, VSP_015351;
CC Note=No experimental confirmation available;
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,
CC brain and uterus.
CC -!- INDUCTION: Up-regulated in both the nucleus and the cytosol of B
CC cells stimulated to switch.
CC -!- DISRUPTION PHENOTYPE: Mice show abnormalities in proliferating
CC haemopoietic organs, such as dyshematopoiesis, defect in
CC lymphopoiesis, and delayed S-phase and G2/M-phase arrest.
CC -!- SIMILARITY: Belongs to the DNA repair enzymes AP/ExoA family.
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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 IPI; IPI00225176; -.
DR IPI; IPI00473955; -.
DR IPI; IPI00473962; -.
DR IPI; IPI00474999; -.
DR IPI; IPI00828973; -.
DR RefSeq; NP_084219.1; NM_029943.1.
DR UniGene; Mm.440275; -.
DR ProteinModelPortal; Q68G58; -.
DR SMR; Q68G58; 1-307.
DR PhosphoSite; Q68G58; -.
DR PaxDb; Q68G58; -.
DR PRIDE; Q68G58; -.
DR Ensembl; ENSMUST00000112725; ENSMUSP00000108345; ENSMUSG00000025269.
DR Ensembl; ENSMUST00000112727; ENSMUSP00000108347; ENSMUSG00000025269.
DR GeneID; 77622; -.
DR KEGG; mmu:77622; -.
DR CTD; 27301; -.
DR MGI; MGI:1924872; Apex2.
DR eggNOG; COG0708; -.
DR GeneTree; ENSGT00530000063540; -.
DR HOVERGEN; HBG054715; -.
DR KO; K10772; -.
DR OrthoDB; EOG4NS3BQ; -.
DR NextBio; 347242; -.
DR ArrayExpress; Q68G58; -.
DR Bgee; Q68G58; -.
DR CleanEx; MM_APEX2; -.
DR Genevestigator; Q68G58; -.
DR GermOnline; ENSMUSG00000025269; Mus musculus.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA: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) lyase activity; IEA:EC.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0004527; F:exonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IEA:GOC.
DR InterPro; IPR020847; AP_endonuclease_F1_BS.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR004808; ExoDNase_III.
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; Exo_endo_phos; 1.
DR TIGRFAMs; TIGR00633; xth; 1.
DR PROSITE; PS00726; AP_NUCLEASE_F1_1; 1.
DR PROSITE; PS00727; AP_NUCLEASE_F1_2; FALSE_NEG.
DR PROSITE; PS00728; AP_NUCLEASE_F1_3; FALSE_NEG.
DR PROSITE; PS51435; AP_NUCLEASE_F1_4; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Complete proteome; Cytoplasm;
KW DNA damage; DNA recombination; DNA repair; DNA-binding; Endonuclease;
KW Exonuclease; Hydrolase; Lyase; Magnesium; Metal-binding;
KW Mitochondrion; Nuclease; Nucleus; Reference proteome.
FT CHAIN 1 516 DNA-(apurinic or apyrimidinic site) lyase
FT 2.
FT /FTId=PRO_0000200015.
FT REGION 389 396 Required for the colocalization with PCNA
FT in nuclear foci in presence of oxidative-
FT induced DNA damaging agents (By
FT similarity).
FT ACT_SITE 155 155 By similarity.
FT ACT_SITE 196 196 Proton donor/acceptor (By similarity).
FT METAL 8 8 Magnesium 1 (By similarity).
FT METAL 47 47 Magnesium 1 (By similarity).
FT METAL 196 196 Magnesium 2 (By similarity).
FT METAL 198 198 Magnesium 2 (By similarity).
FT METAL 302 302 Magnesium 1 (By similarity).
FT SITE 198 198 Transition state stabilizer (By
FT similarity).
FT SITE 276 276 Important for catalytic activity (By
FT similarity).
FT SITE 303 303 Interaction with DNA substrate (By
FT similarity).
FT VAR_SEQ 79 79 S -> SECSCPSP (in isoform 2).
FT /FTId=VSP_015346.
FT VAR_SEQ 213 266 ECFEEDPGRKWMDGLLSNPGDEAGPHIGLFMDSYRYLHPKQ
FT QRAFTCWSVVSGA -> LPVAACGHTNLVPEWEAGPVWERT
FT MREIMEGFCDLLHSVRIFHHHTASLLRPSY (in
FT isoform 4).
FT /FTId=VSP_015347.
FT VAR_SEQ 213 260 ECFEEDPGRKWMDGLLSNPGDEAGPHIGLFMDSYRYLHPKQ
FT QRAFTCW -> LPVAACGHTNLVPEWEAGPVWERTMREIME
FT VKTRFCSRPLKFTESPCL (in isoform 5).
FT /FTId=VSP_015348.
FT VAR_SEQ 213 246 ECFEEDPGRKWMDGLLSNPGDEAGPHIGLFMDSY -> VRF
FT PLNHRPQFCSVHPASQNWEFGTRGSFFYGKK (in
FT isoform 3).
FT /FTId=VSP_015349.
FT VAR_SEQ 247 516 Missing (in isoform 3).
FT /FTId=VSP_015350.
FT VAR_SEQ 261 516 Missing (in isoform 5).
FT /FTId=VSP_015351.
FT VAR_SEQ 267 516 Missing (in isoform 4).
FT /FTId=VSP_015352.
FT CONFLICT 110 110 G -> S (in Ref. 2; BAC38077).
FT CONFLICT 183 183 A -> P (in Ref. 2; BAB32346).
FT CONFLICT 372 372 C -> F (in Ref. 3; AAH78633).
FT CONFLICT 433 433 V -> M (in Ref. 3; AAH78633).
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
//
