UniProt ID | APEX1_HUMAN | |
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UniProt AC | P27695 | |
Protein Name | DNA-(apurinic or apyrimidinic site) lyase | |
Gene Name | APEX1 | |
Organism | Homo sapiens (Human). | |
Sequence Length | 318 | |
Subcellular Localization | Nucleus. Nucleus, nucleolus. Nucleus speckle. Endoplasmic reticulum. Cytoplasm. Detected in the cytoplasm of B-cells stimulated to switch (By similarity). Colocalized with SIRT1 in the nucleus. Colocalized with YBX1 in nuclear speckles after genotoxi | |
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 | MPKRGKKGAVAEDGDELRTEPEAKKSKTAAKKNDKEAAGEGPALYEDPPDQKTSPSGKPATLKICSWNVDGLRAWIKKKGLDWVKEEAPDILCLQETKCSENKLPAELQELPGLSHQYWSAPSDKEGYSGVGLLSRQCPLKVSYGIGDEEHDQEGRVIVAEFDSFVLVTAYVPNAGRGLVRLEYRQRWDEAFRKFLKGLASRKPLVLCGDLNVAHEEIDLRNPKGNKKNAGFTPQERQGFGELLQAVPLADSFRHLYPNTPYAYTFWTYMMNARSKNVGWRLDYFLLSHSLLPALCDSKIRSKALGSDHCPITLYLAL | |
Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
---|---|---|---|---|---|
3 | Acetylation | -----MPKRGKKGAV -----CCCCCCCCCC | 72.92 | 14633989 | |
6 | Acetylation | --MPKRGKKGAVAED --CCCCCCCCCCCCC | 52.66 | 14633989 | |
6 | Methylation | --MPKRGKKGAVAED --CCCCCCCCCCCCC | 52.66 | 14633989 | |
7 | Ubiquitination | -MPKRGKKGAVAEDG -CCCCCCCCCCCCCC | 55.73 | 14633989 | |
7 | Acetylation | -MPKRGKKGAVAEDG -CCCCCCCCCCCCCC | 55.73 | 14633989 | |
18 | Methylation | AEDGDELRTEPEAKK CCCCCHHCCCHHHHH | 34.69 | - | |
19 | Phosphorylation | EDGDELRTEPEAKKS CCCCHHCCCHHHHHH | 69.39 | 28348404 | |
19 | O-linked_Glycosylation | EDGDELRTEPEAKKS CCCCHHCCCHHHHHH | 69.39 | 23301498 | |
24 | Acetylation | LRTEPEAKKSKTAAK HCCCHHHHHHHHHHH | 56.79 | 23954790 | |
24 | Ubiquitination | LRTEPEAKKSKTAAK HCCCHHHHHHHHHHH | 56.79 | - | |
24 | Succinylation | LRTEPEAKKSKTAAK HCCCHHHHHHHHHHH | 56.79 | 23954790 | |
25 | Acetylation | RTEPEAKKSKTAAKK CCCHHHHHHHHHHHH | 65.32 | 30586001 | |
25 | Ubiquitination | RTEPEAKKSKTAAKK CCCHHHHHHHHHHHH | 65.32 | 19219073 | |
27 | Acetylation | EPEAKKSKTAAKKND CHHHHHHHHHHHHHC | 51.57 | 20699270 | |
27 | Ubiquitination | EPEAKKSKTAAKKND CHHHHHHHHHHHHHC | 51.57 | 20231292 | |
31 | Acetylation | KKSKTAAKKNDKEAA HHHHHHHHHHCHHHC | 50.04 | 20699270 | |
32 | Acetylation | KSKTAAKKNDKEAAG HHHHHHHHHCHHHCC | 66.70 | 20699270 | |
35 | Acetylation | TAAKKNDKEAAGEGP HHHHHHCHHHCCCCC | 59.66 | 20699270 | |
45 | Phosphorylation | AGEGPALYEDPPDQK CCCCCCCCCCCCCCC | 22.01 | 21945579 | |
52 | Ubiquitination | YEDPPDQKTSPSGKP CCCCCCCCCCCCCCC | 59.35 | - | |
52 | Sumoylation | YEDPPDQKTSPSGKP CCCCCCCCCCCCCCC | 59.35 | - | |
53 | Phosphorylation | EDPPDQKTSPSGKPA CCCCCCCCCCCCCCC | 39.99 | 25159151 | |
54 | Phosphorylation | DPPDQKTSPSGKPAT CCCCCCCCCCCCCCE | 24.89 | 25159151 | |
56 | Phosphorylation | PDQKTSPSGKPATLK CCCCCCCCCCCCEEE | 60.25 | 23663014 | |
58 | Methylation | QKTSPSGKPATLKIC CCCCCCCCCCEEEEE | 35.50 | - | |
58 | Acetylation | QKTSPSGKPATLKIC CCCCCCCCCCEEEEE | 35.50 | 25953088 | |
58 | "N6,N6-dimethyllysine" | QKTSPSGKPATLKIC CCCCCCCCCCEEEEE | 35.50 | - | |
58 | Ubiquitination | QKTSPSGKPATLKIC CCCCCCCCCCEEEEE | 35.50 | - | |
58 | 2-Hydroxyisobutyrylation | QKTSPSGKPATLKIC CCCCCCCCCCEEEEE | 35.50 | - | |
61 | Phosphorylation | SPSGKPATLKICSWN CCCCCCCEEEEEEEE | 36.79 | 23663014 | |
63 | Acetylation | SGKPATLKICSWNVD CCCCCEEEEEEEECH | 36.99 | 26051181 | |
63 | "N6,N6-dimethyllysine" | SGKPATLKICSWNVD CCCCCEEEEEEEECH | 36.99 | - | |
63 | Methylation | SGKPATLKICSWNVD CCCCCEEEEEEEECH | 36.99 | - | |
65 | S-nitrosylation | KPATLKICSWNVDGL CCCEEEEEEEECHHH | 3.54 | 17403694 | |
65 | Glutathionylation | KPATLKICSWNVDGL CCCEEEEEEEECHHH | 3.54 | 22833525 | |
65 | S-nitrosocysteine | KPATLKICSWNVDGL CCCEEEEEEEECHHH | 3.54 | - | |
66 | Phosphorylation | PATLKICSWNVDGLR CCEEEEEEEECHHHH | 25.76 | 26074081 | |
73 | Methylation | SWNVDGLRAWIKKKG EEECHHHHHHHHHCC | 33.14 | - | |
79 | Ubiquitination | LRAWIKKKGLDWVKE HHHHHHHCCCHHHHH | 60.75 | - | |
85 | Acetylation | KKGLDWVKEEAPDIL HCCCHHHHHHCCCEE | 45.65 | 26051181 | |
85 | Sumoylation | KKGLDWVKEEAPDIL HCCCHHHHHHCCCEE | 45.65 | - | |
85 | Sumoylation | KKGLDWVKEEAPDIL HCCCHHHHHHCCCEE | 45.65 | - | |
85 | Ubiquitination | KKGLDWVKEEAPDIL HCCCHHHHHHCCCEE | 45.65 | - | |
93 | S-nitrosylation | EEAPDILCLQETKCS HHCCCEEEEECCCCC | 3.63 | 17403694 | |
93 | S-nitrosocysteine | EEAPDILCLQETKCS HHCCCEEEEECCCCC | 3.63 | - | |
93 | Glutathionylation | EEAPDILCLQETKCS HHCCCEEEEECCCCC | 3.63 | 22555962 | |
98 | Ubiquitination | ILCLQETKCSENKLP EEEEECCCCCCCCCC | 34.70 | - | |
103 | Ubiquitination | ETKCSENKLPAELQE CCCCCCCCCCHHHHH | 52.36 | - | |
103 | Acetylation | ETKCSENKLPAELQE CCCCCCCCCCHHHHH | 52.36 | 25953088 | |
123 | Phosphorylation | HQYWSAPSDKEGYSG CCCCCCCCCCCCCCC | 62.12 | 25159151 | |
125 | Ubiquitination | YWSAPSDKEGYSGVG CCCCCCCCCCCCCCH | 58.33 | 2190698 | |
125 | Acetylation | YWSAPSDKEGYSGVG CCCCCCCCCCCCCCH | 58.33 | 23954790 | |
128 | Phosphorylation | APSDKEGYSGVGLLS CCCCCCCCCCCHHHH | 11.89 | 25159151 | |
129 | Phosphorylation | PSDKEGYSGVGLLSR CCCCCCCCCCHHHHC | 37.55 | 28102081 | |
136 | Methylation | SGVGLLSRQCPLKVS CCCHHHHCCCCCEEE | 41.93 | - | |
141 | Acetylation | LSRQCPLKVSYGIGD HHCCCCCEEEECCCC | 17.80 | 26051181 | |
141 | 2-Hydroxyisobutyrylation | LSRQCPLKVSYGIGD HHCCCCCEEEECCCC | 17.80 | - | |
143 | Phosphorylation | RQCPLKVSYGIGDEE CCCCCEEEECCCCCC | 18.96 | 21406692 | |
144 | Phosphorylation | QCPLKVSYGIGDEEH CCCCEEEECCCCCCC | 18.75 | 21406692 | |
171 | Phosphorylation | SFVLVTAYVPNAGRG CEEEEEEECCCCCCC | 13.69 | 21253578 | |
184 | Phosphorylation | RGLVRLEYRQRWDEA CCEEEHHHHHHHHHH | 19.35 | 22817900 | |
197 | Ubiquitination | EAFRKFLKGLASRKP HHHHHHHHHHHHCCC | 55.82 | 19608861 | |
197 | Malonylation | EAFRKFLKGLASRKP HHHHHHHHHHHHCCC | 55.82 | 26320211 | |
197 | Acetylation | EAFRKFLKGLASRKP HHHHHHHHHHHHCCC | 55.82 | 19608861 | |
197 | 2-Hydroxyisobutyrylation | EAFRKFLKGLASRKP HHHHHHHHHHHHCCC | 55.82 | - | |
203 | 2-Hydroxyisobutyrylation | LKGLASRKPLVLCGD HHHHHHCCCEEEECC | 39.96 | - | |
203 | Acetylation | LKGLASRKPLVLCGD HHHHHHCCCEEEECC | 39.96 | 26051181 | |
227 | Acetylation | LRNPKGNKKNAGFTP CCCCCCCCCCCCCCH | 56.95 | 26051181 | |
228 | Ubiquitination | RNPKGNKKNAGFTPQ CCCCCCCCCCCCCHH | 56.90 | - | |
233 | Phosphorylation | NKKNAGFTPQERQGF CCCCCCCCHHHHCCH | 24.12 | 19060867 | |
252 | Phosphorylation | QAVPLADSFRHLYPN HHCHHHHHHHHHCCC | 20.69 | 24275569 | |
260 | Phosphorylation | FRHLYPNTPYAYTFW HHHHCCCCCCHHHHH | 17.11 | 22210691 | |
262 | Phosphorylation | HLYPNTPYAYTFWTY HHCCCCCCHHHHHHH | 15.36 | 22817900 | |
265 | Phosphorylation | PNTPYAYTFWTYMMN CCCCCHHHHHHHHHC | 12.43 | 22210691 | |
270 | Sulfoxidation | AYTFWTYMMNARSKN HHHHHHHHHCCCCCC | 0.99 | 28183972 | |
271 | Sulfoxidation | YTFWTYMMNARSKNV HHHHHHHHCCCCCCC | 2.21 | 28183972 | |
276 | Succinylation | YMMNARSKNVGWRLD HHHCCCCCCCCCCHH | 50.53 | 23954790 | |
276 | Malonylation | YMMNARSKNVGWRLD HHHCCCCCCCCCCHH | 50.53 | 26320211 | |
290 | Phosphorylation | DYFLLSHSLLPALCD HHHHHCCCHHHHHCC | 28.38 | 10023679 | |
296 | Glutathionylation | HSLLPALCDSKIRSK CCHHHHHCCHHHHHH | 6.36 | 22555962 | |
299 | Acetylation | LPALCDSKIRSKALG HHHHCCHHHHHHHHC | 28.96 | 26051181 | |
310 | S-palmitoylation | KALGSDHCPITLYLA HHHCCCCCCEEEEEE | 2.90 | 29575903 | |
310 | S-nitrosylation | KALGSDHCPITLYLA HHHCCCCCCEEEEEE | 2.90 | 17403694 | |
310 | S-nitrosocysteine | KALGSDHCPITLYLA HHHCCCCCCEEEEEE | 2.90 | - |
Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
---|---|---|---|---|---|---|
233 | T | Phosphorylation | Kinase | CDK5 | Q00535 | Uniprot |
290 | S | Phosphorylation | Kinase | CK2-FAMILY | - | GPS |
290 | S | Phosphorylation | Kinase | CK2_GROUP | - | PhosphoELM |
- | K | Ubiquitination | E3 ubiquitin ligase | MDM2 | Q00987 | PMID:19219073 |
* Distance = the distance between SAP position and PTM sites.
Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
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Oops, there are no SNP-PTM records of APEX1_HUMAN !! |
Kegg Disease | ||||||
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There are no disease associations of PTM sites. | ||||||
OMIM Disease | ||||||
There are no disease associations of PTM sites. | ||||||
Kegg Drug | ||||||
There are no disease associations of PTM sites. | ||||||
DrugBank | ||||||
There are no disease associations of PTM sites. |
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Acetylation | |
Reference | PubMed |
"Critical lysine residues within the overlooked N-terminal domain ofhuman APE1 regulate its biological functions."; Fantini D., Vascotto C., Marasco D., D'Ambrosio C., Romanello M.,Vitagliano L., Pedone C., Poletto M., Cesaratto L., Quadrifoglio F.,Scaloni A., Radicella J.P., Tell G.; Nucleic Acids Res. 38:8239-8256(2010). Cited for: FUNCTION, INTERACTION WITH NPM1, RNA-BINDING, ACETYLATION AT LYS-27;LYS-31; LYS-32 AND LYS-35, MUTAGENESIS OF LYS-24; LYS-25; LYS-27;LYS-31 AND LYS-32, AND MASS SPECTROMETRY. | |
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-197, AND MASS SPECTROMETRY. | |
"Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulationof the parathyroid hormone gene."; Bhakat K.K., Izumi T., Yang S.H., Hazra T.K., Mitra S.; EMBO J. 22:6299-6309(2003). Cited for: INTERACTION WITH HDAC1; HDAC2 AND HDAC3, ACETYLATION AT LYS-6 ANDLYS-7, AND MUTAGENESIS OF LYS-6 AND LYS-7. | |
Phosphorylation | |
Reference | PubMed |
"Immunoaffinity profiling of tyrosine phosphorylation in cancercells."; Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,Zha X.-M., Polakiewicz R.D., Comb M.J.; Nat. Biotechnol. 23:94-101(2005). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-262, AND MASSSPECTROMETRY. | |
S-nitrosylation | |
Reference | PubMed |
"Nitric oxide controls nuclear export of APE1/Ref-1 through S-nitrosation of cysteines 93 and 310."; Qu J., Liu G.H., Huang B., Chen C.; Nucleic Acids Res. 35:2522-2532(2007). Cited for: S-NITROSYLATION AT CYS-65; CYS-93 AND CYS-310 IN RESPONSE TO NITRICOXIDE, AND SUBCELLULAR LOCATION. |