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Protein

DNA-(apurinic or apyrimidinic site) lyase 2

Gene

APEX2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.3 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

Activity regulationi

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

pH dependencei

Optimum pH is 6.0-8.0.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi8Magnesium 1By similarity1
Metal bindingi48Magnesium 1By similarity1
Active sitei156By similarity1
Active sitei197Proton donor/acceptorBy similarity1
Metal bindingi197Magnesium 2By similarity1
Metal bindingi199Magnesium 2By similarity1
Sitei199Transition state stabilizerBy similarity1
Sitei277Important for catalytic activityBy similarity1
Metal bindingi303Magnesium 1By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Endonuclease, Exonuclease, Hydrolase, Lyase, Nuclease
Biological processCell cycle, DNA damage, DNA recombination, DNA repair
LigandMagnesium, 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):
AP endonuclease XTH2
APEX nuclease 2
APEX nuclease-like 2
Apurinic-apyrimidinic endonuclease 2
Short name:
AP endonuclease 2
Gene namesi
Name:APEX2
Synonyms:APE2, APEXL2, XTH2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000169188.4
HGNCiHGNC:17889 APEX2
MIMi300773 gene
neXtProtiNX_Q9UBZ4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi269H → A: Abolishes AP endodeoxyribonuclease, 3'-5' exonuclease activity and 3'-phosphodiesterase activities. 1
Mutagenesisi277D → A: Abolishes AP endodeoxyribonuclease, 3'-5' exonuclease activity and 3'-phosphodiesterase activities. 1 Publication1
Mutagenesisi396Y → A: Reduces 3'-5' exonuclease activity in presence of PCNA. Does not abolish the 3'-5' exonuclease activity. Does only partially redistributes together with PCNA in nuclear foci in presence of oxidative-induced DNA damaging agents. 1 Publication1
Mutagenesisi397F → A: Reduces 3'-5' exonuclease activity in presence of PCNA. Does not abolish the 3'-5' exonuclease activity. Does only partially redistributes together with PCNA in nuclear foci in presence of oxidative-induced DNA damaging agents. 1 Publication1

Organism-specific databases

DisGeNETi27301
OpenTargetsiENSG00000169188
PharmGKBiPA38474

Polymorphism and mutation databases

DMDMi73921676

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002000141 – 518DNA-(apurinic or apyrimidinic site) lyase 2Add BLAST518

Proteomic databases

EPDiQ9UBZ4
MaxQBiQ9UBZ4
PaxDbiQ9UBZ4
PeptideAtlasiQ9UBZ4
PRIDEiQ9UBZ4
ProteomicsDBi84104

PTM databases

iPTMnetiQ9UBZ4
PhosphoSitePlusiQ9UBZ4

Expressioni

Tissue specificityi

Highly expressed in brain and kidney. Weakly expressed in the fetal brain.1 Publication

Gene expression databases

BgeeiENSG00000169188 Expressed in 193 organ(s), highest expression level in mucosa of transverse colon
CleanExiHS_APEX2
ExpressionAtlasiQ9UBZ4 baseline and differential
GenevisibleiQ9UBZ4 HS

Organism-specific databases

HPAiHPA048577

Interactioni

Subunit structurei

Interacts with PCNA; this interaction is triggered by reactive oxygen species and increased by misincorporation of uracil in nuclear DNA.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei304Interaction with DNA substrateBy similarity1

Protein-protein interaction databases

BioGridi118124, 21 interactors
IntActiQ9UBZ4, 17 interactors
STRINGi9606.ENSP00000364126

Structurei

3D structure databases

ProteinModelPortaliQ9UBZ4
SMRiQ9UBZ4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni390 – 397Required for the colocalization with PCNA in nuclear foci in presence of oxidative-induced DNA damaging agents8

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG1294 Eukaryota
COG0708 LUCA
GeneTreeiENSGT00530000063540
HOGENOMiHOG000231386
HOVERGENiHBG054715
InParanoidiQ9UBZ4
KOiK10772
OMAiGAFTCWS
OrthoDBiEOG091G0IPG
PhylomeDBiQ9UBZ4
TreeFamiTF328442

Family and domain databases

Gene3Di3.60.10.10, 1 hit
InterProiView protein in InterPro
IPR004808 AP_endonuc_1
IPR020847 AP_endonuclease_F1_BS
IPR036691 Endo/exonu/phosph_ase_sf
IPR005135 Endo/exonuclease/phosphatase
IPR010666 Znf_GRF
PANTHERiPTHR22748 PTHR22748, 1 hit
PfamiView protein in Pfam
PF03372 Exo_endo_phos, 1 hit
PF06839 zf-GRF, 1 hit
SUPFAMiSSF56219 SSF56219, 1 hit
TIGRFAMsiTIGR00633 xth, 1 hit
PROSITEiView protein in PROSITE
PS00726 AP_NUCLEASE_F1_1, 1 hit
PS51435 AP_NUCLEASE_F1_4, 1 hit

Sequencei

Sequence statusi: Complete.

Q9UBZ4-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLRVVSWNIN GIRRPLQGVA NQEPSNCAAV AVGRILDELD ADIVCLQETK
60 70 80 90 100
VTRDALTEPL AIVEGYNSYF SFSRNRSGYS GVATFCKDNA TPVAAEEGLS
110 120 130 140 150
GLFATQNGDV GCYGNMDEFT QEELRALDSE GRALLTQHKI RTWEGKEKTL
160 170 180 190 200
TLINVYCPHA DPGRPERLVF KMRFYRLLQI RAEALLAAGS HVIILGDLNT
210 220 230 240 250
AHRPIDHWDA VNLECFEEDP GRKWMDSLLS NLGCQSASHV GPFIDSYRCF
260 270 280 290 300
QPKQEGAFTC WSAVTGARHL NYGSRLDYVL GDRTLVIDTF QASFLLPEVM
310 320 330 340 350
GSDHCPVGAV LSVSSVPAKQ CPPLCTRFLP EFAGTQLKIL RFLVPLEQSP
360 370 380 390 400
VLEQSTLQHN NQTRVQTCQN KAQVRSTRPQ PSQVGSSRGQ KNLKSYFQPS
410 420 430 440 450
PSCPQASPDI ELPSLPLMSA LMTPKTPEEK AVAKVVKGQA KTSEAKDEKE
460 470 480 490 500
LRTSFWKSVL AGPLRTPLCG GHREPCVMRT VKKPGPNLGR RFYMCARPRG
510
PPTDPSSRCN FFLWSRPS
Length:518
Mass (Da):57,401
Last modified:May 1, 2000 - v1
Checksum:i08464806153F8832
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti399P → S in AAD43041 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023390141R → C1 PublicationCorresponds to variant dbSNP:rs2301416Ensembl.1
Natural variantiVAR_048261141R → W. Corresponds to variant dbSNP:rs2301416Ensembl.1
Natural variantiVAR_064033269H → Y Identified in a patient with mtDNA maintenance disorders. 1 PublicationCorresponds to variant dbSNP:rs145122391Ensembl.1
Natural variantiVAR_064034392N → H Identified in a patient with mtDNA maintenance disorders. 1 PublicationCorresponds to variant dbSNP:rs201964062Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB049211 mRNA Translation: BAB13764.1
AJ011311 mRNA Translation: CAB45242.1
AB021260 mRNA Translation: BAA78422.1
AF119046 mRNA Translation: AAD43041.1
AY884244 Genomic DNA Translation: AAW56941.1
AL020991 Genomic DNA No translation available.
BC002959 mRNA Translation: AAH02959.1
CCDSiCCDS14365.1
RefSeqiNP_055296.2, NM_014481.3
UniGeneiHs.659558

Genome annotation databases

EnsembliENST00000374987; ENSP00000364126; ENSG00000169188
GeneIDi27301
KEGGihsa:27301
UCSCiuc004dtz.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB049211 mRNA Translation: BAB13764.1
AJ011311 mRNA Translation: CAB45242.1
AB021260 mRNA Translation: BAA78422.1
AF119046 mRNA Translation: AAD43041.1
AY884244 Genomic DNA Translation: AAW56941.1
AL020991 Genomic DNA No translation available.
BC002959 mRNA Translation: AAH02959.1
CCDSiCCDS14365.1
RefSeqiNP_055296.2, NM_014481.3
UniGeneiHs.659558

3D structure databases

ProteinModelPortaliQ9UBZ4
SMRiQ9UBZ4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118124, 21 interactors
IntActiQ9UBZ4, 17 interactors
STRINGi9606.ENSP00000364126

PTM databases

iPTMnetiQ9UBZ4
PhosphoSitePlusiQ9UBZ4

Polymorphism and mutation databases

DMDMi73921676

Proteomic databases

EPDiQ9UBZ4
MaxQBiQ9UBZ4
PaxDbiQ9UBZ4
PeptideAtlasiQ9UBZ4
PRIDEiQ9UBZ4
ProteomicsDBi84104

Protocols and materials databases

DNASUi27301
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000374987; ENSP00000364126; ENSG00000169188
GeneIDi27301
KEGGihsa:27301
UCSCiuc004dtz.5 human

Organism-specific databases

CTDi27301
DisGeNETi27301
EuPathDBiHostDB:ENSG00000169188.4
GeneCardsiAPEX2
HGNCiHGNC:17889 APEX2
HPAiHPA048577
MIMi300773 gene
neXtProtiNX_Q9UBZ4
OpenTargetsiENSG00000169188
PharmGKBiPA38474
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1294 Eukaryota
COG0708 LUCA
GeneTreeiENSGT00530000063540
HOGENOMiHOG000231386
HOVERGENiHBG054715
InParanoidiQ9UBZ4
KOiK10772
OMAiGAFTCWS
OrthoDBiEOG091G0IPG
PhylomeDBiQ9UBZ4
TreeFamiTF328442

Miscellaneous databases

ChiTaRSiAPEX2 human
GenomeRNAii27301
PROiPR:Q9UBZ4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169188 Expressed in 193 organ(s), highest expression level in mucosa of transverse colon
CleanExiHS_APEX2
ExpressionAtlasiQ9UBZ4 baseline and differential
GenevisibleiQ9UBZ4 HS

Family and domain databases

Gene3Di3.60.10.10, 1 hit
InterProiView protein in InterPro
IPR004808 AP_endonuc_1
IPR020847 AP_endonuclease_F1_BS
IPR036691 Endo/exonu/phosph_ase_sf
IPR005135 Endo/exonuclease/phosphatase
IPR010666 Znf_GRF
PANTHERiPTHR22748 PTHR22748, 1 hit
PfamiView protein in Pfam
PF03372 Exo_endo_phos, 1 hit
PF06839 zf-GRF, 1 hit
SUPFAMiSSF56219 SSF56219, 1 hit
TIGRFAMsiTIGR00633 xth, 1 hit
PROSITEiView protein in PROSITE
PS00726 AP_NUCLEASE_F1_1, 1 hit
PS51435 AP_NUCLEASE_F1_4, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiAPEX2_HUMAN
AccessioniPrimary (citable) accession number: Q9UBZ4
Secondary accession number(s): Q9Y5X7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: May 1, 2000
Last modified: September 12, 2018
This is version 150 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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