CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-022870
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 DNA-(apurinic or apyrimidinic site) lyase 2 
Protein Synonyms/Alias
 AP endonuclease XTH2; APEX nuclease 2; APEX nuclease-like 2; Apurinic-apyrimidinic endonuclease 2; AP endonuclease 2 
Gene Name
 APEX2 
Gene Synonyms/Alias
 APE2; APEXL2; XTH2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
253SYRCFQPKQEGAFTCubiquitination[1]
338EFAGTQLKILRFLVPubiquitination[1, 2, 3, 4, 5]
371RVQTCQNKAQVRSTRubiquitination[1, 5]
457ELRTSFWKSVLAGPLubiquitination[1, 3]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 
Functional Description
 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. 
Sequence Annotation
 REGION 390 397 Required for the colocalization with PCNA
 ACT_SITE 156 156 By similarity.
 ACT_SITE 197 197 Proton donor/acceptor (By similarity).
 METAL 8 8 Magnesium 1 (By similarity).
 METAL 48 48 Magnesium 1 (By similarity).
 METAL 197 197 Magnesium 2 (By similarity).
 METAL 199 199 Magnesium 2 (By similarity).
 METAL 303 303 Magnesium 1 (By similarity).  
Keyword
 Cell cycle; Complete proteome; Cytoplasm; DNA damage; DNA recombination; DNA repair; DNA-binding; Endonuclease; Exonuclease; Hydrolase; Lyase; Magnesium; Metal-binding; Mitochondrion; Nuclease; Nucleus; Polymorphism; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 518 AA 
Protein Sequence
MLRVVSWNIN GIRRPLQGVA NQEPSNCAAV AVGRILDELD ADIVCLQETK VTRDALTEPL 60
AIVEGYNSYF SFSRNRSGYS GVATFCKDNA TPVAAEEGLS GLFATQNGDV GCYGNMDEFT 120
QEELRALDSE GRALLTQHKI RTWEGKEKTL TLINVYCPHA DPGRPERLVF KMRFYRLLQI 180
RAEALLAAGS HVIILGDLNT AHRPIDHWDA VNLECFEEDP GRKWMDSLLS NLGCQSASHV 240
GPFIDSYRCF QPKQEGAFTC WSAVTGARHL NYGSRLDYVL GDRTLVIDTF QASFLLPEVM 300
GSDHCPVGAV LSVSSVPAKQ CPPLCTRFLP EFAGTQLKIL RFLVPLEQSP VLEQSTLQHN 360
NQTRVQTCQN KAQVRSTRPQ PSQVGSSRGQ KNLKSYFQPS PSCPQASPDI ELPSLPLMSA 420
LMTPKTPEEK AVAKVVKGQA KTSEAKDEKE LRTSFWKSVL AGPLRTPLCG GHREPCVMRT 480
VKKPGPNLGR RFYMCARPRG PPTDPSSRCN FFLWSRPS 518 
Gene Ontology
 GO:0005743; C:mitochondrial inner membrane; IEA:Compara.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
 GO:0003906; F:DNA-(apurinic or apyrimidinic site) lyase activity; IEA:EC.
 GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
 GO:0004527; F:exonuclease activity; IEA:UniProtKB-KW.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
 GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
 GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IEA:GOC. 
Interpro
 IPR020847; AP_endonuclease_F1_BS.
 IPR005135; Endo/exonuclease/phosphatase.
 IPR004808; ExoDNase_III.
 IPR010666; Znf_GRF. 
Pfam
 PF03372; Exo_endo_phos
 PF06839; zf-GRF 
SMART
  
PROSITE
 PS00726; AP_NUCLEASE_F1_1
 PS00727; AP_NUCLEASE_F1_2
 PS00728; AP_NUCLEASE_F1_3
 PS51435; AP_NUCLEASE_F1_4 
PRINTS