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Q68G58

- APEX2_MOUSE

UniProt

Q68G58 - APEX2_MOUSE

Protein

DNA-(apurinic or apyrimidinic site) lyase 2

Gene

Apex2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 85 (01 Oct 2014)
      Sequence version 1 (11 Oct 2004)
      Previous versions | rss
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    Functioni

    Function as a weak apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Displays also double-stranded DNA 3'-5' exonuclease, 3'-phosphodiesterase activities. Shows robust 3'-5' exonuclease activity on 3'-recessed heteroduplex DNA and is able to remove mismatched nucleotides preferentially. Shows fairly strong 3'-phosphodiesterase activity involved in the removal of 3'-damaged termini formed in DNA by oxidative agents. In the nucleus functions in the PCNA-dependent BER pathway. Required for somatic hypermutation (SHM) and DNA cleavage step of class switch recombination (CSR) of immunoglobulin genes. Required for proper cell cycle progression during proliferation of peripheral lymphocytes.4 Publications

    Catalytic activityi

    The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.PROSITE-ProRule annotation

    Cofactori

    Magnesium. Can also utilize manganese. Probably binds two magnesium or manganese ions per subunit By similarity.By similarity

    Enzyme regulationi

    3'-5' exonuclease activity is activated by sodium and manganese. 3'-5' exonuclease and 3'-phosphodiesterase activities are stimulated in presence of PCNA By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi8 – 81Magnesium 1By similarity
    Metal bindingi47 – 471Magnesium 1By similarity
    Active sitei155 – 1551By similarity
    Active sitei196 – 1961Proton donor/acceptorBy similarity
    Metal bindingi196 – 1961Magnesium 2By similarity
    Metal bindingi198 – 1981Magnesium 2By similarity
    Sitei198 – 1981Transition state stabilizerBy similarity
    Sitei276 – 2761Important for catalytic activityBy similarity
    Metal bindingi302 – 3021Magnesium 1By similarity
    Sitei303 – 3031Interaction with DNA substrateBy similarity

    GO - Molecular functioni

    1. DNA-(apurinic or apyrimidinic site) lyase activity Source: RefGenome
    2. DNA binding Source: UniProtKB-KW
    3. double-stranded DNA 3'-5' exodeoxyribonuclease activity Source: RefGenome
    4. zinc ion binding Source: InterPro

    GO - Biological processi

    1. base-excision repair Source: RefGenome
    2. cell cycle Source: UniProtKB-KW
    3. DNA catabolic process, endonucleolytic Source: GOC
    4. DNA catabolic process, exonucleolytic Source: GOC
    5. DNA recombination Source: UniProtKB-KW

    Keywords - Molecular functioni

    Endonuclease, Exonuclease, Hydrolase, Lyase, Nuclease

    Keywords - Biological processi

    Cell cycle, DNA damage, DNA recombination, DNA repair

    Keywords - Ligandi

    DNA-binding, Magnesium, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DNA-(apurinic or apyrimidinic site) lyase 2 (EC:3.1.-.-, EC:4.2.99.18)
    Alternative name(s):
    APEX nuclease 2
    Apurinic-apyrimidinic endonuclease 2
    Short name:
    AP endonuclease 2
    Gene namesi
    Name:Apex2
    Synonyms:Ape2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome X

    Organism-specific databases

    MGIiMGI:1924872. Apex2.

    Subcellular locationi

    Nucleus. Cytoplasm. Mitochondrion Curated
    Note: Together with PCNA, is redistributed in discrete nuclear foci in presence of oxidative DNA damaging agents.

    GO - Cellular componenti

    1. mitochondrial inner membrane Source: MGI
    2. mitochondrion Source: MGI
    3. nucleus Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    Mice show abnormalities in proliferating haemopoietic organs, such as dyshematopoiesis, defect in lymphopoiesis, and delayed S-phase and G2/M-phase arrest.2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 516516DNA-(apurinic or apyrimidinic site) lyase 2PRO_0000200015Add
    BLAST

    Proteomic databases

    PaxDbiQ68G58.
    PRIDEiQ68G58.

    PTM databases

    PhosphoSiteiQ68G58.

    Expressioni

    Tissue specificityi

    Expressed in lymphocytes, thymocytes and splenocytes (at protein level). Highly expressed in the thymus and weakly expressed in the bone marrow, spleen, eye, kidney, lung, brain and uterus.2 Publications

    Inductioni

    Up-regulated in both the nucleus and the cytosol of B cells stimulated to switch.1 Publication

    Gene expression databases

    BgeeiQ68G58.
    CleanExiMM_APEX2.
    GenevestigatoriQ68G58.

    Interactioni

    Subunit structurei

    Interacts with PCNA. This interaction is increased by misincorporation of uracil in nuclear DNA By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliQ68G58.
    SMRiQ68G58. Positions 1-307.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni389 – 3968Required for the colocalization with PCNA in nuclear foci in presence of oxidative-induced DNA damaging agentsBy similarity

    Sequence similaritiesi

    Belongs to the DNA repair enzymes AP/ExoA family.Curated

    Phylogenomic databases

    eggNOGiCOG0708.
    GeneTreeiENSGT00530000063540.
    HOVERGENiHBG054715.
    KOiK10772.
    OMAiREIMEGF.
    OrthoDBiEOG7NKKJZ.

    Family and domain databases

    Gene3Di3.60.10.10. 1 hit.
    InterProiIPR004808. AP_endonuc_1.
    IPR020847. AP_endonuclease_F1_BS.
    IPR005135. Endo/exonuclease/phosphatase.
    IPR010666. Znf_GRF.
    [Graphical view]
    PANTHERiPTHR22748. PTHR22748. 1 hit.
    PfamiPF03372. Exo_endo_phos. 1 hit.
    PF06839. zf-GRF. 1 hit.
    [Graphical view]
    SUPFAMiSSF56219. SSF56219. 1 hit.
    TIGRFAMsiTIGR00633. xth. 1 hit.
    PROSITEiPS00726. AP_NUCLEASE_F1_1. 1 hit.
    PS51435. AP_NUCLEASE_F1_4. 1 hit.
    [Graphical view]

    Sequences (5)i

    Sequence statusi: Complete.

    This entry describes 5 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q68G58-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MLRVVSWNIN GIRSPLQGLA CQEPSSCPTA LRRVLDELDA DIVCLQETKV    50
    TRDVLTEPLA IVEGYNSYFS FSRSRSGYSG VATFCKDSAT PVAAEEGLSG 100
    VFATLNGDIG CYGNMDEFTQ EELRVLDSEG RALLTQHKIR TLEGKEKTLT 150
    LINVYCPHAD PGKPERLTFK MRFYRLLQMR AEALLAAGSH VIILGDLNTA 200
    HRPIDHCDAS SLECFEEDPG RKWMDGLLSN PGDEAGPHIG LFMDSYRYLH 250
    PKQQRAFTCW SVVSGARHLN YGSRLDYVLG DRALVIDTFQ ASFLLPEVMG 300
    SDHCPVGAVL NVSCVPAKQC PALCTRFLPE FAGTQLKILR FLVPLEQEPV 350
    REQQVLQPSH QIQAQRQPRK ACMHSTRLRK SQGGPKRKQK NLMSYFQPSS 400
    SLSQTSGVEL PTLPLVGPLT TPKTAEEVAT ATVLEEKNKV PESKDEKGER 450
    TAFWKSMLSG PSPMPLCGGH REPCVMRTVK KTGPNFGRQF YMCARPRGPP 500
    SDPSSRCNFF LWSRPS 516
    Length:516
    Mass (Da):57,340
    Last modified:October 11, 2004 - v1
    Checksum:iED32A88D9CEABB85
    GO
    Isoform 2 (identifier: Q68G58-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         79-79: S → SECSCPSP

    Note: No experimental confirmation available.

    Show »
    Length:523
    Mass (Da):58,043
    Checksum:i50712632B2D818F7
    GO
    Isoform 3 (identifier: Q68G58-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         213-246: ECFEEDPGRKWMDGLLSNPGDEAGPHIGLFMDSY → VRFPLNHRPQFCSVHPASQNWEFGTRGSFFYGKK
         247-516: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:246
    Mass (Da):27,389
    Checksum:i194A612EF3CB1D8F
    GO
    Isoform 4 (identifier: Q68G58-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         213-266: ECFEEDPGRK...FTCWSVVSGA → LPVAACGHTN...HTASLLRPSY
         267-516: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:266
    Mass (Da):29,575
    Checksum:i7EBE161284108FD5
    GO
    Isoform 5 (identifier: Q68G58-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         213-260: ECFEEDPGRK...PKQQRAFTCW → LPVAACGHTN...PLKFTESPCL
         261-516: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:260
    Mass (Da):28,880
    Checksum:i0186A39DE091BA93
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti110 – 1101G → S in BAC38077. (PubMed:16141072)Curated
    Sequence conflicti183 – 1831A → P in BAB32346. (PubMed:16141072)Curated
    Sequence conflicti372 – 3721C → F in AAH78633. (PubMed:15489334)Curated
    Sequence conflicti433 – 4331V → M in AAH78633. (PubMed:15489334)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei79 – 791S → SECSCPSP in isoform 2. CuratedVSP_015346
    Alternative sequencei213 – 26654ECFEE…VVSGA → LPVAACGHTNLVPEWEAGPV WERTMREIMEGFCDLLHSVR IFHHHTASLLRPSY in isoform 4. CuratedVSP_015347Add
    BLAST
    Alternative sequencei213 – 26048ECFEE…AFTCW → LPVAACGHTNLVPEWEAGPV WERTMREIMEVKTRFCSRPL KFTESPCL in isoform 5. CuratedVSP_015348Add
    BLAST
    Alternative sequencei213 – 24634ECFEE…FMDSY → VRFPLNHRPQFCSVHPASQN WEFGTRGSFFYGKK in isoform 3. 1 PublicationVSP_015349Add
    BLAST
    Alternative sequencei247 – 516270Missing in isoform 3. 1 PublicationVSP_015350Add
    BLAST
    Alternative sequencei261 – 516256Missing in isoform 5. CuratedVSP_015351Add
    BLAST
    Alternative sequencei267 – 516250Missing in isoform 4. CuratedVSP_015352Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB072498 mRNA. Translation: BAB88654.1.
    AB085235 Genomic DNA. Translation: BAC11807.1.
    AK021248 mRNA. Translation: BAB32346.1.
    AK040145 mRNA. Translation: BAC30522.1.
    AK050858 mRNA. Translation: BAC34436.1.
    AK080916 mRNA. Translation: BAC38077.1.
    AK081677 mRNA. Translation: BAC38287.1.
    AK088918 mRNA. Translation: BAC40652.1.
    BC026769 mRNA. Translation: AAH26769.1.
    BC078633 mRNA. Translation: AAH78633.1.
    CCDSiCCDS30463.1. [Q68G58-1]
    RefSeqiNP_084219.1. NM_029943.1.
    UniGeneiMm.440275.

    Genome annotation databases

    EnsembliENSMUST00000112725; ENSMUSP00000108345; ENSMUSG00000025269. [Q68G58-5]
    ENSMUST00000112727; ENSMUSP00000108347; ENSMUSG00000025269. [Q68G58-4]
    GeneIDi77622.
    KEGGimmu:77622.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB072498 mRNA. Translation: BAB88654.1 .
    AB085235 Genomic DNA. Translation: BAC11807.1 .
    AK021248 mRNA. Translation: BAB32346.1 .
    AK040145 mRNA. Translation: BAC30522.1 .
    AK050858 mRNA. Translation: BAC34436.1 .
    AK080916 mRNA. Translation: BAC38077.1 .
    AK081677 mRNA. Translation: BAC38287.1 .
    AK088918 mRNA. Translation: BAC40652.1 .
    BC026769 mRNA. Translation: AAH26769.1 .
    BC078633 mRNA. Translation: AAH78633.1 .
    CCDSi CCDS30463.1. [Q68G58-1 ]
    RefSeqi NP_084219.1. NM_029943.1.
    UniGenei Mm.440275.

    3D structure databases

    ProteinModelPortali Q68G58.
    SMRi Q68G58. Positions 1-307.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei Q68G58.

    Proteomic databases

    PaxDbi Q68G58.
    PRIDEi Q68G58.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000112725 ; ENSMUSP00000108345 ; ENSMUSG00000025269 . [Q68G58-5 ]
    ENSMUST00000112727 ; ENSMUSP00000108347 ; ENSMUSG00000025269 . [Q68G58-4 ]
    GeneIDi 77622.
    KEGGi mmu:77622.

    Organism-specific databases

    CTDi 27301.
    MGIi MGI:1924872. Apex2.

    Phylogenomic databases

    eggNOGi COG0708.
    GeneTreei ENSGT00530000063540.
    HOVERGENi HBG054715.
    KOi K10772.
    OMAi REIMEGF.
    OrthoDBi EOG7NKKJZ.

    Miscellaneous databases

    NextBioi 347242.
    PROi Q68G58.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q68G58.
    CleanExi MM_APEX2.
    Genevestigatori Q68G58.

    Family and domain databases

    Gene3Di 3.60.10.10. 1 hit.
    InterProi IPR004808. AP_endonuc_1.
    IPR020847. AP_endonuclease_F1_BS.
    IPR005135. Endo/exonuclease/phosphatase.
    IPR010666. Znf_GRF.
    [Graphical view ]
    PANTHERi PTHR22748. PTHR22748. 1 hit.
    Pfami PF03372. Exo_endo_phos. 1 hit.
    PF06839. zf-GRF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56219. SSF56219. 1 hit.
    TIGRFAMsi TIGR00633. xth. 1 hit.
    PROSITEi PS00726. AP_NUCLEASE_F1_1. 1 hit.
    PS51435. AP_NUCLEASE_F1_4. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of the genomic structure and expression of the mouse Apex2 gene."
      Ide Y., Tsuchimoto D., Tominaga Y., Iwamoto Y., Nakabeppu Y.
      Genomics 81:47-57(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Strain: 129/Sv and C57BL/6.
      Tissue: B-cell.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1/2/4/5).
      Strain: NOD.
      Tissue: Adipose tissue, Head and Thymus.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
      Strain: FVB/N-3.
      Tissue: Mammary tumor.
    4. "Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice."
      Ide Y., Tsuchimoto D., Tominaga Y., Nakashima M., Watanabe T., Sakumi K., Ohno M., Nakabeppu Y.
      Blood 104:4097-4103(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
    5. "APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination."
      Guikema J.E., Linehan E.K., Tsuchimoto D., Nakabeppu Y., Strauss P.R., Stavnezer J., Schrader C.E.
      J. Exp. Med. 204:3017-3026(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION.
    6. "Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes."
      Sabouri Z., Okazaki I.M., Shinkura R., Begum N., Nagaoka H., Tsuchimoto D., Nakabeppu Y., Honjo T.
      Int. Immunol. 21:947-955(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiAPEX2_MOUSE
    AccessioniPrimary (citable) accession number: Q68G58
    Secondary accession number(s): Q8BJP7
    , Q8BTR7, Q8BUZ2, Q8BYE9, Q8R018, Q8R328, Q9CS12
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 30, 2005
    Last sequence update: October 11, 2004
    Last modified: October 1, 2014
    This is version 85 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3