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Database: UniProt
Entry: Q68G58
LinkDB: Q68G58
Original site: Q68G58 
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-OCT-2014, entry version 85.
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. {ECO:0000269|PubMed:12573260,
CC       ECO:0000269|PubMed:15319281, ECO:0000269|PubMed:18025127,
CC       ECO:0000269|PubMed:19556307}.
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. {ECO:0000255|PROSITE-ProRule:PRU00764}.
CC   -!- COFACTOR: Magnesium. Can also utilize manganese. Probably binds
CC       two magnesium or manganese ions per subunit (By similarity).
CC       {ECO:0000250}.
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       {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
CC       {ECO:0000305}. Note=Together with PCNA, is redistributed in
CC       discrete nuclear foci in presence of oxidative DNA damaging
CC       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. {ECO:0000269|PubMed:12573260,
CC       ECO:0000269|PubMed:15319281}.
CC   -!- INDUCTION: Up-regulated in both the nucleus and the cytosol of B
CC       cells stimulated to switch. {ECO:0000269|PubMed:18025127}.
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       {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_029943.1.
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. [Q68G58-5]
DR   Ensembl; ENSMUST00000112727; ENSMUSP00000108347; ENSMUSG00000025269. [Q68G58-4]
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   OMA; REIMEGF; -.
DR   OrthoDB; EOG7NKKJZ; -.
DR   NextBio; 347242; -.
DR   PRO; PR:Q68G58; -.
DR   Bgee; Q68G58; -.
DR   CleanEx; MM_APEX2; -.
DR   Genevestigator; Q68G58; -.
DR   GO; GO:0005743; C:mitochondrial inner membrane; IDA:MGI.
DR   GO; GO:0005739; C:mitochondrion; 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; IBA:RefGenome.
DR   GO; GO:0008311; F:double-stranded DNA 3'-5' exodeoxyribonuclease activity; IBA:RefGenome.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0006284; P:base-excision repair; IBA:RefGenome.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0000737; P:DNA catabolic process, endonucleolytic; IBA:GOC.
DR   GO; GO:0000738; P:DNA catabolic process, exonucleolytic; IBA:GOC.
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; 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; 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.
FT                                {ECO:0000250}.
FT   ACT_SITE    155    155       {ECO:0000250}.
FT   ACT_SITE    196    196       Proton donor/acceptor. {ECO:0000250}.
FT   METAL         8      8       Magnesium 1. {ECO:0000250}.
FT   METAL        47     47       Magnesium 1. {ECO:0000250}.
FT   METAL       196    196       Magnesium 2. {ECO:0000250}.
FT   METAL       198    198       Magnesium 2. {ECO:0000250}.
FT   METAL       302    302       Magnesium 1. {ECO:0000250}.
FT   SITE        198    198       Transition state stabilizer.
FT                                {ECO:0000250}.
FT   SITE        276    276       Important for catalytic activity.
FT                                {ECO:0000250}.
FT   SITE        303    303       Interaction with DNA substrate.
FT                                {ECO:0000250}.
FT   VAR_SEQ      79     79       S -> SECSCPSP (in isoform 2).
FT                                {ECO:0000305}.
FT                                /FTId=VSP_015346.
FT   VAR_SEQ     213    266       ECFEEDPGRKWMDGLLSNPGDEAGPHIGLFMDSYRYLHPKQ
FT                                QRAFTCWSVVSGA -> LPVAACGHTNLVPEWEAGPVWERT
FT                                MREIMEGFCDLLHSVRIFHHHTASLLRPSY (in
FT                                isoform 4). {ECO:0000305}.
FT                                /FTId=VSP_015347.
FT   VAR_SEQ     213    260       ECFEEDPGRKWMDGLLSNPGDEAGPHIGLFMDSYRYLHPKQ
FT                                QRAFTCW -> LPVAACGHTNLVPEWEAGPVWERTMREIME
FT                                VKTRFCSRPLKFTESPCL (in isoform 5).
FT                                {ECO:0000305}.
FT                                /FTId=VSP_015348.
FT   VAR_SEQ     213    246       ECFEEDPGRKWMDGLLSNPGDEAGPHIGLFMDSY -> VRF
FT                                PLNHRPQFCSVHPASQNWEFGTRGSFFYGKK (in
FT                                isoform 3).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_015349.
FT   VAR_SEQ     247    516       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_015350.
FT   VAR_SEQ     261    516       Missing (in isoform 5). {ECO:0000305}.
FT                                /FTId=VSP_015351.
FT   VAR_SEQ     267    516       Missing (in isoform 4). {ECO:0000305}.
FT                                /FTId=VSP_015352.
FT   CONFLICT    110    110       G -> S (in Ref. 2; BAC38077).
FT                                {ECO:0000305}.
FT   CONFLICT    183    183       A -> P (in Ref. 2; BAB32346).
FT                                {ECO:0000305}.
FT   CONFLICT    372    372       C -> F (in Ref. 3; AAH78633).
FT                                {ECO:0000305}.
FT   CONFLICT    433    433       V -> M (in Ref. 3; AAH78633).
FT                                {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
//
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