CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005682
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 DNA-(apurinic or apyrimidinic site) lyase 
Protein Synonyms/Alias
 APEX nuclease; APEN; Apurinic-apyrimidinic endonuclease 1; AP endonuclease 1; REF-1; Redox factor-1; DNA-(apurinic or apyrimidinic site) lyase, mitochondrial 
Gene Name
 Apex1 
Gene Synonyms/Alias
 Ape; Apex; Ref1 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
227RNPKGNKKNAGFTPQubiquitination[1]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 
Functional Description
 Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 in DNA repair and redox regulation of transcriptional factors. Functions as a 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. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'- phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA. 
Sequence Annotation
 REGION 2 32 Necessary for interaction with YBX1,
 REGION 8 12 Nuclear localization signal (NLS) (By
 REGION 22 32 Necessary for interaction with NPM1 and
 REGION 63 79 Nuclear export signal (NES) (By
 REGION 288 317 Mitochondrial targeting sequence (MTS)
 ACT_SITE 170 170 By similarity.
 ACT_SITE 209 209 Proton donor/acceptor (By similarity).
 METAL 69 69 Magnesium 1 (By similarity).
 METAL 95 95 Magnesium 1 (By similarity).
 METAL 209 209 Magnesium 2 (By similarity).
 METAL 211 211 Magnesium 2 (By similarity).
 METAL 307 307 Magnesium 1 (By similarity).
 MOD_RES 6 6 N6-acetyllysine; by EP300 (By
 MOD_RES 7 7 N6-acetyllysine; by EP300 (By
 MOD_RES 26 26 N6-acetyllysine (By similarity).
 MOD_RES 30 30 N6-acetyllysine (By similarity).
 MOD_RES 31 31 N6-acetyllysine (By similarity).
 MOD_RES 34 34 N6-acetyllysine (By similarity).
 MOD_RES 64 64 S-nitrosocysteine (By similarity).
 MOD_RES 92 92 S-nitrosocysteine (By similarity).
 MOD_RES 196 196 N6-acetyllysine (By similarity).
 MOD_RES 232 232 Phosphothreonine; by CDK5.
 MOD_RES 309 309 S-nitrosocysteine (By similarity).
 DISULFID 64 92 By similarity.  
Keyword
 Acetylation; Activator; Cleavage on pair of basic residues; Complete proteome; Cytoplasm; Direct protein sequencing; Disulfide bond; DNA damage; DNA recombination; DNA repair; DNA-binding; Endonuclease; Endoplasmic reticulum; Exonuclease; Hydrolase; Lyase; Magnesium; Metal-binding; Mitochondrion; Nuclease; Nucleus; Phosphoprotein; Reference proteome; Repressor; RNA-binding; S-nitrosylation; Transcription; Transcription regulation; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 317 AA 
Protein Sequence
MPKRGKKAAA DDGEEPKSEP ETKKSKGAAK KTEKEAAGEG PVLYEDPPDQ KTSPSGKSAT 60
LKICSWNVDG LRAWIKKKGL DWVKEEAPDI LCLQETKCSE NKLPAELQEL PGLTHQYWSA 120
PSDKEGYSGV GLLSRQCPLK VSYGIGEEEH DQEGRVIVAE FESFVLVTAY VPNAGRGLVR 180
LEYRQRWDEA FRKFLKDLAS RKPLVLCGDL NVAHEEIDLR NPKGNKKNAG FTPQERQGFG 240
ELLQAVPLAD SFRHLYPNTA YAYTFWTYMM NARSKNVGWR LDYFLLSHSL LPALCDSKIR 300
SKALGSDHCP ITLYLAL 317 
Gene Ontology
 GO:0005813; C:centrosome; IEA:Compara.
 GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
 GO:0005739; C:mitochondrion; ISS:UniProtKB.
 GO:0016607; C:nuclear speck; ISS:UniProtKB.
 GO:0005730; C:nucleolus; ISS:UniProtKB.
 GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
 GO:0005667; C:transcription factor complex; IEA:Compara.
 GO:0008408; F:3'-5' exonuclease activity; ISS:UniProtKB.
 GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
 GO:0003684; F:damaged DNA binding; ISS:UniProtKB.
 GO:0003906; F:DNA-(apurinic or apyrimidinic site) lyase activity; ISS:UniProtKB.
 GO:0004521; F:endoribonuclease activity; IEA:Compara.
 GO:0046872; F:metal ion binding; ISS:UniProtKB.
 GO:0016491; F:oxidoreductase activity; ISS:UniProtKB.
 GO:0008081; F:phosphoric diester hydrolase activity; IEA:Compara.
 GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
 GO:0016890; F:site-specific endodeoxyribonuclease activity, specific for altered base; ISS:UniProtKB.
 GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
 GO:0007568; P:aging; IEA:Compara.
 GO:0045454; P:cell redox homeostasis; IDA:MGI.
 GO:0071320; P:cellular response to cAMP; IEA:Compara.
 GO:0070301; P:cellular response to hydrogen peroxide; IEA:Compara.
 GO:0071375; P:cellular response to peptide hormone stimulus; IEA:Compara.
 GO:0080111; P:DNA demethylation; ISS:UniProtKB.
 GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
 GO:0006281; P:DNA repair; ISS:UniProtKB.
 GO:0014912; P:negative regulation of smooth muscle cell migration; IEA:Compara.
 GO:0045739; P:positive regulation of DNA repair; ISS:UniProtKB.
 GO:0043488; P:regulation of mRNA stability; ISS:UniProtKB.
 GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR020847; AP_endonuclease_F1_BS.
 IPR020848; AP_endonuclease_F1_CS.
 IPR005135; Endo/exonuclease/phosphatase.
 IPR004808; ExoDNase_III. 
Pfam
 PF03372; Exo_endo_phos 
SMART
  
PROSITE
 PS00726; AP_NUCLEASE_F1_1
 PS00727; AP_NUCLEASE_F1_2
 PS00728; AP_NUCLEASE_F1_3
 PS51435; AP_NUCLEASE_F1_4 
PRINTS