APEX1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: APEX1_MOUSE
• UniProt AC: P28352
• Protein Name: DNA-(apurinic or apyrimidinic site) lyase
• Gene Name: Apex1
• Organism: Mus musculus (Mouse).
• Sequence Length: 317
• Subcellular Localization: Nucleus. Nucleus, nucleolus. Nucleus speckle . Endoplasmic reticulum. Cytoplasm. Colocalized with SIRT1 in the nucleus. Colocalized with YBX1 in nuclear speckles after genotoxic stress. Together with OGG1 is recruited to nuclear speckles in UVA-irrad
• Protein 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..
• Protein Sequence: MPKRGKKAAADDGEEPKSEPETKKSKGAAKKTEKEAAGEGPVLYEDPPDQKTSPSGKSATLKICSWNVDGLRAWIKKKGLDWVKEEAPDILCLQETKCSENKLPAELQELPGLTHQYWSAPSDKEGYSGVGLLSRQCPLKVSYGIGEEEHDQEGRVIVAEFESFVLVTAYVPNAGRGLVRLEYRQRWDEAFRKFLKDLASRKPLVLCGDLNVAHEEIDLRNPKGNKKNAGFTPQERQGFGELLQAVPLADSFRHLYPNTAYAYTFWTYMMNARSKNVGWRLDYFLLSHSLLPALCDSKIRSKALGSDHCPITLYLAL

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
6	Acetylation	--MPKRGKKAAADDG --CCCCCCCCCCCCC	43.18	-
7	Acetylation	-MPKRGKKAAADDGE -CCCCCCCCCCCCCC	46.19	-
18	Phosphorylation	DDGEEPKSEPETKKS CCCCCCCCCCCHHHC	69.93	27087446
22	Phosphorylation	EPKSEPETKKSKGAA CCCCCCCHHHCCCCC	55.26	25521595
26	Acetylation	EPETKKSKGAAKKTE CCCHHHCCCCCCHHH	62.54	-
30	Acetylation	KKSKGAAKKTEKEAA HHCCCCCCHHHHHHC	60.74	-
31	Acetylation	KSKGAAKKTEKEAAG HCCCCCCHHHHHHCC	58.13	-
34	Acetylation	GAAKKTEKEAAGEGP CCCCHHHHHHCCCCC	58.86	23806337
52	Phosphorylation	EDPPDQKTSPSGKSA CCCCCCCCCCCCCCC	39.99	25338131
53	Phosphorylation	DPPDQKTSPSGKSAT CCCCCCCCCCCCCCE	24.89	22006019
60	Phosphorylation	SPSGKSATLKICSWN CCCCCCCEEEEEEEE	35.36	23140645
64	S-nitrosocysteine	KSATLKICSWNVDGL CCCEEEEEEEECHHH	3.54	-
64	S-nitrosylation	KSATLKICSWNVDGL CCCEEEEEEEECHHH	3.54	-
92	S-nitrosocysteine	EEAPDILCLQETKCS HHCCCEEEEECCCCC	3.63	-
92	S-nitrosylation	EEAPDILCLQETKCS HHCCCEEEEECCCCC	3.63	-
124	Acetylation	YWSAPSDKEGYSGVG CCCCCCCCCCCCCCH	58.33	23954790
127	Phosphorylation	APSDKEGYSGVGLLS CCCCCCCCCCCHHHH	11.89	25195567
128	Phosphorylation	PSDKEGYSGVGLLSR CCCCCCCCCCHHHHC	37.55	25367039
134	Phosphorylation	YSGVGLLSRQCPLKV CCCCHHHHCCCCCEE	25.91	25367039
196	Acetylation	EAFRKFLKDLASRKP HHHHHHHHHHHHCCC	54.55	22826441
202	Acetylation	LKDLASRKPLVLCGD HHHHHHCCCEEEECC	39.96	22826441
227	Ubiquitination	RNPKGNKKNAGFTPQ CCCCCCCCCCCCCHH	56.90	22790023
232	Phosphorylation	NKKNAGFTPQERQGF CCCCCCCCHHHHCCH	24.12	22817900
275	Malonylation	YMMNARSKNVGWRLD HHHCCCCCCCCCCHH	50.53	26320211
309	S-nitrosocysteine	KALGSDHCPITLYLA HHHCCCCCCEEEEEE	2.90	-
309	S-nitrosylation	KALGSDHCPITLYLA HHHCCCCCCEEEEEE	2.90	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
232	T	Phosphorylation	Kinase	CDK5	Q00535	PSP
232	T	Phosphorylation	Kinase	CDK5	P49615	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Mdm2	P23804	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
6	K	Acetylation	Acetylated on Lys-6 and Lys-7.	-
6	K	Acetylation	Lys-6 and Lys-7 are deacetylated by SIRT1 (By similarity).	-
7	K	Acetylation	Acetylated on Lys-6 and Lys-7.	-
7	K	Acetylation	Lys-6 and Lys-7 are deacetylated by SIRT1 (By similarity).	-
232	T	Phosphorylation	Phosphorylation of Thr-232 by CDK5 in response to MPP(+)/MPTP (1-methyl-4-phenylpyridinium) reduces AP-endodeoxyribonuclease activity resulting in accumulation of DNA damage and contributing to neuronal death.	20473298

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of APEX1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SIN3A_MOUSE	Sin3a	physical	22441348
HDAC1_MOUSE	Hdac1	physical	22441348
HDAC2_MOUSE	Hdac2	physical	22441348
MUTYH_MOUSE	Mutyh	physical	24209961

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"The role of Cdk5-mediated apurinic/apyrimidinic endonuclease 1phosphorylation in neuronal death.";
Huang E., Qu D., Zhang Y., Venderova K., Haque M.E., Rousseaux M.W.C.,Slack R.S., Woulfe J.M., Park D.S.;
Nat. Cell Biol. 12:563-571(2010).
Cited for: PHOSPHORYLATION AT THR-232, INTERACTION WITH CDK5, AND MUTAGENESIS OFTHR-232.
PubMed: 20473298