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Protein

DNA-(apurinic or apyrimidinic site) lyase 2

Gene

Apex2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Mg2+By similarity, Mn2+By similarityNote: Probably binds two magnesium or manganese ions per subunit.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: GO_Central
  2. DNA binding Source: UniProtKB-KW
  3. double-stranded DNA 3'-5' exodeoxyribonuclease activity Source: GO_Central
  4. zinc ion binding Source: InterPro

GO - Biological processi

  1. base-excision repair Source: GO_Central
  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
Complete GO annotation...

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 Componenti: 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. intracellular membrane-bounded organelle Source: MGI
  2. mitochondrial inner membrane Source: MGI
  3. mitochondrion Source: MGI
  4. nucleolus Source: MGI
  5. nucleus Source: MGI
Complete GO annotation...

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

MaxQBiQ68G58.
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.
ExpressionAtlasiQ68G58. baseline and differential.
GenevestigatoriQ68G58.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi218805. 1 interaction.

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.
InParanoidiQ68G58.
KOiK10772.
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. AlignAdd to basket

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

        10         20         30         40         50
MLRVVSWNIN GIRSPLQGLA CQEPSSCPTA LRRVLDELDA DIVCLQETKV
60 70 80 90 100
TRDVLTEPLA IVEGYNSYFS FSRSRSGYSG VATFCKDSAT PVAAEEGLSG
110 120 130 140 150
VFATLNGDIG CYGNMDEFTQ EELRVLDSEG RALLTQHKIR TLEGKEKTLT
160 170 180 190 200
LINVYCPHAD PGKPERLTFK MRFYRLLQMR AEALLAAGSH VIILGDLNTA
210 220 230 240 250
HRPIDHCDAS SLECFEEDPG RKWMDGLLSN PGDEAGPHIG LFMDSYRYLH
260 270 280 290 300
PKQQRAFTCW SVVSGARHLN YGSRLDYVLG DRALVIDTFQ ASFLLPEVMG
310 320 330 340 350
SDHCPVGAVL NVSCVPAKQC PALCTRFLPE FAGTQLKILR FLVPLEQEPV
360 370 380 390 400
REQQVLQPSH QIQAQRQPRK ACMHSTRLRK SQGGPKRKQK NLMSYFQPSS
410 420 430 440 450
SLSQTSGVEL PTLPLVGPLT TPKTAEEVAT ATVLEEKNKV PESKDEKGER
460 470 480 490 500
TAFWKSMLSG PSPMPLCGGH REPCVMRTVK KTGPNFGRQF YMCARPRGPP
510
SDPSSRCNFF LWSRPS
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi218805. 1 interaction.

PTM databases

PhosphoSiteiQ68G58.

Proteomic databases

MaxQBiQ68G58.
PaxDbiQ68G58.
PRIDEiQ68G58.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi27301.
MGIiMGI:1924872. Apex2.

Phylogenomic databases

eggNOGiCOG0708.
GeneTreeiENSGT00530000063540.
HOVERGENiHBG054715.
InParanoidiQ68G58.
KOiK10772.
OrthoDBiEOG7NKKJZ.

Miscellaneous databases

NextBioi347242.
PROiQ68G58.
SOURCEiSearch...

Gene expression databases

BgeeiQ68G58.
CleanExiMM_APEX2.
ExpressionAtlasiQ68G58. baseline and differential.
GenevestigatoriQ68G58.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(2002) [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(2004) [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(2003) [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(2003) [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(2006) [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(2008) [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: March 4, 2015
This is version 90 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.