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Q9UBZ4 (APEX2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:APEX2
Synonyms:APE2, APEXL2, XTH2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length518 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.8 Ref.10

Catalytic activity

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.

Cofactor

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

Enzyme regulation

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

Subunit structure

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

Subcellular location

Nucleus. Cytoplasm. Mitochondrion Probable. Note: Together with PCNA, is redistributed in discrete nuclear foci in presence of oxidative DNA damaging agents. Ref.1 Ref.10

Tissue specificity

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

Sequence similarities

Belongs to the DNA repair enzymes AP/ExoA family.

Biophysicochemical properties

pH dependence:

Optimum pH is 6.0-8.0. Ref.8

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 518518DNA-(apurinic or apyrimidinic site) lyase 2
PRO_0000200014

Regions

Region390 – 3978Required for the colocalization with PCNA in nuclear foci in presence of oxidative-induced DNA damaging agents

Sites

Active site1561 By similarity
Active site1971Proton donor/acceptor By similarity
Metal binding81Magnesium 1 By similarity
Metal binding481Magnesium 1 By similarity
Metal binding1971Magnesium 2 By similarity
Metal binding1991Magnesium 2 By similarity
Metal binding3031Magnesium 1 By similarity
Site1991Transition state stabilizer By similarity
Site2771Important for catalytic activity By similarity
Site3041Interaction with DNA substrate By similarity

Natural variations

Natural variant1411R → C. Ref.5
Corresponds to variant rs2301416 [ dbSNP | Ensembl ].
VAR_023390
Natural variant1411R → W.
Corresponds to variant rs2301416 [ dbSNP | Ensembl ].
VAR_048261
Natural variant2691H → Y Identified in a patient with mtDNA maintenance disorders. Ref.11
VAR_064033
Natural variant3921N → H Identified in a patient with mtDNA maintenance disorders. Ref.11
VAR_064034

Experimental info

Mutagenesis2691H → A: Abolishes AP endodeoxyribonuclease, 3'-5' exonuclease activity and 3'-phosphodiesterase activities.
Mutagenesis2771D → A: Abolishes AP endodeoxyribonuclease, 3'-5' exonuclease activity and 3'-phosphodiesterase activities. Ref.8
Mutagenesis3961Y → 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. Ref.10
Mutagenesis3971F → 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. Ref.10
Sequence conflict3991P → S in AAD43041. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q9UBZ4 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 08464806153F8832

FASTA51857,401
        10         20         30         40         50         60 
MLRVVSWNIN GIRRPLQGVA NQEPSNCAAV AVGRILDELD ADIVCLQETK VTRDALTEPL 

        70         80         90        100        110        120 
AIVEGYNSYF SFSRNRSGYS GVATFCKDNA TPVAAEEGLS GLFATQNGDV GCYGNMDEFT 

       130        140        150        160        170        180 
QEELRALDSE GRALLTQHKI RTWEGKEKTL TLINVYCPHA DPGRPERLVF KMRFYRLLQI 

       190        200        210        220        230        240 
RAEALLAAGS HVIILGDLNT AHRPIDHWDA VNLECFEEDP GRKWMDSLLS NLGCQSASHV 

       250        260        270        280        290        300 
GPFIDSYRCF QPKQEGAFTC WSAVTGARHL NYGSRLDYVL GDRTLVIDTF QASFLLPEVM 

       310        320        330        340        350        360 
GSDHCPVGAV LSVSSVPAKQ CPPLCTRFLP EFAGTQLKIL RFLVPLEQSP VLEQSTLQHN 

       370        380        390        400        410        420 
NQTRVQTCQN KAQVRSTRPQ PSQVGSSRGQ KNLKSYFQPS PSCPQASPDI ELPSLPLMSA 

       430        440        450        460        470        480 
LMTPKTPEEK AVAKVVKGQA KTSEAKDEKE LRTSFWKSVL AGPLRTPLCG GHREPCVMRT 

       490        500        510 
VKKPGPNLGR RFYMCARPRG PPTDPSSRCN FFLWSRPS 

« Hide

References

« Hide 'large scale' references
[1]"Human APE2 protein is mostly localized in the nuclei and to some extent in the mitochondria, while nuclear APE2 is partly associated with proliferating cell nuclear antigen."
Tsuchimoto D., Sakai Y., Sakumi K., Nishioka K., Sasaki M., Fujiwara T., Nakabeppu Y.
Nucleic Acids Res. 29:2349-2360(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Leukemia.
[2]"Putative human AP endonuclease XTH2."
Luna L., Rognes T., Henriksen A.C., Bjoras M., Seeberg E.
Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lung tumor.
[3]"cDNA cloning and characterization of human APEX nuclease-like 2 (APEXL2) protein."
Akiyama K., Sarker A.H., Yao M., Tsutsui K., Seki S.
Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Bone marrow.
[4]Hadi M.Z., Erzberger J.P., Ramirez M.H., Thelen M.P., Wilson D.M. III
Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lung tumor.
[5]NIEHS SNPs program
Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT CYS-141.
[6]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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].
Tissue: Lung.
[8]"Human Ape2 protein has a 3'-5' exonuclease activity that acts preferentially on mismatched base pairs."
Burkovics P., Szukacsov V., Unk I., Haracska L.
Nucleic Acids Res. 34:2508-2515(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASP-277.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Role of PCNA-dependent stimulation of 3'-phosphodiesterase and 3'-5' exonuclease activities of human Ape2 in repair of oxidative DNA damage."
Burkovics P., Hajdu I., Szukacsov V., Unk I., Haracska L.
Nucleic Acids Res. 37:4247-4255(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-396 AND PHE-397.
[11]"Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing."
Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R., Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M., Speed T.P., Scharfe C.
Nucleic Acids Res. 39:44-58(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TYR-269 AND HIS-392.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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. Translation: CAI43126.1.
BC002959 mRNA. Translation: AAH02959.1.
RefSeqNP_055296.2. NM_014481.3.
UniGeneHs.659558.

3D structure databases

ProteinModelPortalQ9UBZ4.
SMRQ9UBZ4. Positions 1-308.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118124. 13 interactions.
IntActQ9UBZ4. 7 interactions.
MINTMINT-1439290.
STRING9606.ENSP00000364126.

PTM databases

PhosphoSiteQ9UBZ4.

Polymorphism databases

DMDM73921676.

Proteomic databases

PaxDbQ9UBZ4.
PeptideAtlasQ9UBZ4.
PRIDEQ9UBZ4.

Protocols and materials databases

DNASU27301.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000374987; ENSP00000364126; ENSG00000169188.
GeneID27301.
KEGGhsa:27301.
UCSCuc004dtz.4. human.

Organism-specific databases

CTD27301.
GeneCardsGC0XP055043.
HGNCHGNC:17889. APEX2.
HPAHPA030872.
MIM300773. gene.
neXtProtNX_Q9UBZ4.
PharmGKBPA38474.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0708.
HOGENOMHOG000231386.
HOVERGENHBG054715.
InParanoidQ9UBZ4.
KOK10772.
OMADHWDAVN.
OrthoDBEOG7NKKJZ.
PhylomeDBQ9UBZ4.
TreeFamTF328442.

Gene expression databases

ArrayExpressQ9UBZ4.
BgeeQ9UBZ4.
CleanExHS_APEX2.
GenevestigatorQ9UBZ4.

Family and domain databases

Gene3D3.60.10.10. 1 hit.
InterProIPR004808. AP_endonuc_1.
IPR020847. AP_endonuclease_F1_BS.
IPR005135. Endo/exonuclease/phosphatase.
IPR010666. Znf_GRF.
[Graphical view]
PANTHERPTHR22748. PTHR22748. 1 hit.
PfamPF03372. Exo_endo_phos. 1 hit.
PF06839. zf-GRF. 1 hit.
[Graphical view]
SUPFAMSSF56219. SSF56219. 1 hit.
TIGRFAMsTIGR00633. xth. 1 hit.
PROSITEPS00726. AP_NUCLEASE_F1_1. 1 hit.
PS51435. AP_NUCLEASE_F1_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi27301.
NextBio50285.
PROQ9UBZ4.
SOURCESearch...

Entry information

Entry nameAPEX2_HUMAN
AccessionPrimary (citable) accession number: Q9UBZ4
Secondary accession number(s): Q9Y5X7
Entry history
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: May 1, 2000
Last modified: February 19, 2014
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM