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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)DescriptionActionsGraphical viewLength
Metal bindingi8Magnesium 1By similarity1
Metal bindingi47Magnesium 1By similarity1
Active sitei155By similarity1
Active sitei196Proton donor/acceptorBy similarity1
Metal bindingi196Magnesium 2By similarity1
Metal bindingi198Magnesium 2By similarity1
Sitei198Transition state stabilizerBy similarity1
Sitei276Important for catalytic activityBy similarity1
Metal bindingi302Magnesium 1By similarity1

GO - Molecular functioni

GO - Biological processi

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
Proteomesi
  • UP000000589 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

  • intracellular membrane-bounded organelle Source: MGI
  • mitochondrial inner membrane Source: MGI
  • mitochondrion Source: MGI
  • nucleolus Source: MGI
  • 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)DescriptionActionsGraphical viewLength
ChainiPRO_00002000151 – 516DNA-(apurinic or apyrimidinic site) lyase 2Add BLAST516

Proteomic databases

PaxDbiQ68G58.
PRIDEiQ68G58.

PTM databases

iPTMnetiQ68G58.
PhosphoSitePlusiQ68G58.

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

BgeeiENSMUSG00000025269.
CleanExiMM_APEX2.
ExpressionAtlasiQ68G58. baseline and differential.
GenevisibleiQ68G58. MM.

Interactioni

Subunit structurei

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei303Interaction with DNA substrateBy similarity1

Protein-protein interaction databases

IntActiQ68G58. 1 interactor.
STRINGi10090.ENSMUSP00000026303.

Structurei

3D structure databases

ProteinModelPortaliQ68G58.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni389 – 396Required for the colocalization with PCNA in nuclear foci in presence of oxidative-induced DNA damaging agentsBy similarity8

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG1294. Eukaryota.
COG0708. LUCA.
GeneTreeiENSGT00530000063540.
HOVERGENiHBG054715.
InParanoidiQ68G58.
KOiK10772.
OMAiREIMEGF.

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)DescriptionActionsGraphical viewLength
Sequence conflicti110G → S in BAC38077 (PubMed:16141072).Curated1
Sequence conflicti183A → P in BAB32346 (PubMed:16141072).Curated1
Sequence conflicti372C → F in AAH78633 (PubMed:15489334).Curated1
Sequence conflicti433V → M in AAH78633 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01534679S → SECSCPSP in isoform 2. Curated1
Alternative sequenceiVSP_015347213 – 266ECFEE…VVSGA → LPVAACGHTNLVPEWEAGPV WERTMREIMEGFCDLLHSVR IFHHHTASLLRPSY in isoform 4. CuratedAdd BLAST54
Alternative sequenceiVSP_015348213 – 260ECFEE…AFTCW → LPVAACGHTNLVPEWEAGPV WERTMREIMEVKTRFCSRPL KFTESPCL in isoform 5. CuratedAdd BLAST48
Alternative sequenceiVSP_015349213 – 246ECFEE…FMDSY → VRFPLNHRPQFCSVHPASQN WEFGTRGSFFYGKK in isoform 3. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_015350247 – 516Missing in isoform 3. 1 PublicationAdd BLAST270
Alternative sequenceiVSP_015351261 – 516Missing in isoform 5. CuratedAdd BLAST256
Alternative sequenceiVSP_015352267 – 516Missing in isoform 4. CuratedAdd BLAST250

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_029943.2.
XP_011246180.1. XM_011247878.2. [Q68G58-5]
UniGeneiMm.440275.

Genome annotation databases

EnsembliENSMUST00000112725; ENSMUSP00000108345; ENSMUSG00000025269. [Q68G58-5]
ENSMUST00000112727; ENSMUSP00000108347; ENSMUSG00000025269. [Q68G58-4]
GeneIDi77622.
KEGGimmu:77622.
UCSCiuc009uoi.1. mouse. [Q68G58-5]

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_029943.2.
XP_011246180.1. XM_011247878.2. [Q68G58-5]
UniGeneiMm.440275.

3D structure databases

ProteinModelPortaliQ68G58.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ68G58. 1 interactor.
STRINGi10090.ENSMUSP00000026303.

PTM databases

iPTMnetiQ68G58.
PhosphoSitePlusiQ68G58.

Proteomic databases

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.
UCSCiuc009uoi.1. mouse. [Q68G58-5]

Organism-specific databases

CTDi27301.
MGIiMGI:1924872. Apex2.

Phylogenomic databases

eggNOGiKOG1294. Eukaryota.
COG0708. LUCA.
GeneTreeiENSGT00530000063540.
HOVERGENiHBG054715.
InParanoidiQ68G58.
KOiK10772.
OMAiREIMEGF.

Miscellaneous databases

PROiQ68G58.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025269.
CleanExiMM_APEX2.
ExpressionAtlasiQ68G58. baseline and differential.
GenevisibleiQ68G58. MM.

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...

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: November 2, 2016
This is version 103 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

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 one 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.