APEX1_HUMAN - dbPTM
APEX1_HUMAN - PTM Information in dbPTM
Basic Information of Protein
UniProt ID APEX1_HUMAN
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
Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations Modification Substrate Peptides
&
Secondary Structure
ASA (%) Reference Orthologous
Protein Cluster
3Acetylation-----MPKRGKKGAV
-----CCCCCCCCCC
72.9214633989
6Acetylation--MPKRGKKGAVAED
--CCCCCCCCCCCCC
52.6614633989
6Methylation--MPKRGKKGAVAED
--CCCCCCCCCCCCC
52.6614633989
7Ubiquitination-MPKRGKKGAVAEDG
-CCCCCCCCCCCCCC
55.7314633989
7Acetylation-MPKRGKKGAVAEDG
-CCCCCCCCCCCCCC
55.7314633989
18MethylationAEDGDELRTEPEAKK
CCCCCHHCCCHHHHH
34.69-
19PhosphorylationEDGDELRTEPEAKKS
CCCCHHCCCHHHHHH
69.3928348404
19O-linked_GlycosylationEDGDELRTEPEAKKS
CCCCHHCCCHHHHHH
69.3923301498
24AcetylationLRTEPEAKKSKTAAK
HCCCHHHHHHHHHHH
56.7923954790
24UbiquitinationLRTEPEAKKSKTAAK
HCCCHHHHHHHHHHH
56.79-
24SuccinylationLRTEPEAKKSKTAAK
HCCCHHHHHHHHHHH
56.7923954790
25AcetylationRTEPEAKKSKTAAKK
CCCHHHHHHHHHHHH
65.3230586001
25UbiquitinationRTEPEAKKSKTAAKK
CCCHHHHHHHHHHHH
65.3219219073
27AcetylationEPEAKKSKTAAKKND
CHHHHHHHHHHHHHC
51.5720699270
27UbiquitinationEPEAKKSKTAAKKND
CHHHHHHHHHHHHHC
51.5720231292
31AcetylationKKSKTAAKKNDKEAA
HHHHHHHHHHCHHHC
50.0420699270
32AcetylationKSKTAAKKNDKEAAG
HHHHHHHHHCHHHCC
66.7020699270
35AcetylationTAAKKNDKEAAGEGP
HHHHHHCHHHCCCCC
59.6620699270
45PhosphorylationAGEGPALYEDPPDQK
CCCCCCCCCCCCCCC
22.0121945579
52UbiquitinationYEDPPDQKTSPSGKP
CCCCCCCCCCCCCCC
59.35-
52SumoylationYEDPPDQKTSPSGKP
CCCCCCCCCCCCCCC
59.35-
53PhosphorylationEDPPDQKTSPSGKPA
CCCCCCCCCCCCCCC
39.9925159151
54PhosphorylationDPPDQKTSPSGKPAT
CCCCCCCCCCCCCCE
24.8925159151
56PhosphorylationPDQKTSPSGKPATLK
CCCCCCCCCCCCEEE
60.2523663014
58MethylationQKTSPSGKPATLKIC
CCCCCCCCCCEEEEE
35.50-
58AcetylationQKTSPSGKPATLKIC
CCCCCCCCCCEEEEE
35.5025953088
58"N6,N6-dimethyllysine"QKTSPSGKPATLKIC
CCCCCCCCCCEEEEE
35.50-
58UbiquitinationQKTSPSGKPATLKIC
CCCCCCCCCCEEEEE
35.50-
582-HydroxyisobutyrylationQKTSPSGKPATLKIC
CCCCCCCCCCEEEEE
35.50-
61PhosphorylationSPSGKPATLKICSWN
CCCCCCCEEEEEEEE
36.7923663014
63AcetylationSGKPATLKICSWNVD
CCCCCEEEEEEEECH
36.9926051181
63"N6,N6-dimethyllysine"SGKPATLKICSWNVD
CCCCCEEEEEEEECH
36.99-
63MethylationSGKPATLKICSWNVD
CCCCCEEEEEEEECH
36.99-
65S-nitrosylationKPATLKICSWNVDGL
CCCEEEEEEEECHHH
3.5417403694
65GlutathionylationKPATLKICSWNVDGL
CCCEEEEEEEECHHH
3.5422833525
65S-nitrosocysteineKPATLKICSWNVDGL
CCCEEEEEEEECHHH
3.54-
66PhosphorylationPATLKICSWNVDGLR
CCEEEEEEEECHHHH
25.7626074081
73MethylationSWNVDGLRAWIKKKG
EEECHHHHHHHHHCC
33.14-
79UbiquitinationLRAWIKKKGLDWVKE
HHHHHHHCCCHHHHH
60.75-
85AcetylationKKGLDWVKEEAPDIL
HCCCHHHHHHCCCEE
45.6526051181
85SumoylationKKGLDWVKEEAPDIL
HCCCHHHHHHCCCEE
45.65-
85SumoylationKKGLDWVKEEAPDIL
HCCCHHHHHHCCCEE
45.65-
85UbiquitinationKKGLDWVKEEAPDIL
HCCCHHHHHHCCCEE
45.65-
93S-nitrosylationEEAPDILCLQETKCS
HHCCCEEEEECCCCC
3.6317403694
93S-nitrosocysteineEEAPDILCLQETKCS
HHCCCEEEEECCCCC
3.63-
93GlutathionylationEEAPDILCLQETKCS
HHCCCEEEEECCCCC
3.6322555962
98UbiquitinationILCLQETKCSENKLP
EEEEECCCCCCCCCC
34.70-
103UbiquitinationETKCSENKLPAELQE
CCCCCCCCCCHHHHH
52.36-
103AcetylationETKCSENKLPAELQE
CCCCCCCCCCHHHHH
52.3625953088
123PhosphorylationHQYWSAPSDKEGYSG
CCCCCCCCCCCCCCC
62.1225159151
125UbiquitinationYWSAPSDKEGYSGVG
CCCCCCCCCCCCCCH
58.332190698
125AcetylationYWSAPSDKEGYSGVG
CCCCCCCCCCCCCCH
58.3323954790
128PhosphorylationAPSDKEGYSGVGLLS
CCCCCCCCCCCHHHH
11.8925159151
129PhosphorylationPSDKEGYSGVGLLSR
CCCCCCCCCCHHHHC
37.5528102081
136MethylationSGVGLLSRQCPLKVS
CCCHHHHCCCCCEEE
41.93-
141AcetylationLSRQCPLKVSYGIGD
HHCCCCCEEEECCCC
17.8026051181
1412-HydroxyisobutyrylationLSRQCPLKVSYGIGD
HHCCCCCEEEECCCC
17.80-
143PhosphorylationRQCPLKVSYGIGDEE
CCCCCEEEECCCCCC
18.9621406692
144PhosphorylationQCPLKVSYGIGDEEH
CCCCEEEECCCCCCC
18.7521406692
171PhosphorylationSFVLVTAYVPNAGRG
CEEEEEEECCCCCCC
13.6921253578
184PhosphorylationRGLVRLEYRQRWDEA
CCEEEHHHHHHHHHH
19.3522817900
197UbiquitinationEAFRKFLKGLASRKP
HHHHHHHHHHHHCCC
55.8219608861
197MalonylationEAFRKFLKGLASRKP
HHHHHHHHHHHHCCC
55.8226320211
197AcetylationEAFRKFLKGLASRKP
HHHHHHHHHHHHCCC
55.8219608861
1972-HydroxyisobutyrylationEAFRKFLKGLASRKP
HHHHHHHHHHHHCCC
55.82-
2032-HydroxyisobutyrylationLKGLASRKPLVLCGD
HHHHHHCCCEEEECC
39.96-
203AcetylationLKGLASRKPLVLCGD
HHHHHHCCCEEEECC
39.9626051181
227AcetylationLRNPKGNKKNAGFTP
CCCCCCCCCCCCCCH
56.9526051181
228UbiquitinationRNPKGNKKNAGFTPQ
CCCCCCCCCCCCCHH
56.90-
233PhosphorylationNKKNAGFTPQERQGF
CCCCCCCCHHHHCCH
24.1219060867
252PhosphorylationQAVPLADSFRHLYPN
HHCHHHHHHHHHCCC
20.6924275569
260PhosphorylationFRHLYPNTPYAYTFW
HHHHCCCCCCHHHHH
17.1122210691
262PhosphorylationHLYPNTPYAYTFWTY
HHCCCCCCHHHHHHH
15.3622817900
265PhosphorylationPNTPYAYTFWTYMMN
CCCCCHHHHHHHHHC
12.4322210691
270SulfoxidationAYTFWTYMMNARSKN
HHHHHHHHHCCCCCC
0.9928183972
271SulfoxidationYTFWTYMMNARSKNV
HHHHHHHHCCCCCCC
2.2128183972
276SuccinylationYMMNARSKNVGWRLD
HHHCCCCCCCCCCHH
50.5323954790
276MalonylationYMMNARSKNVGWRLD
HHHCCCCCCCCCCHH
50.5326320211
290PhosphorylationDYFLLSHSLLPALCD
HHHHHCCCHHHHHCC
28.3810023679
296GlutathionylationHSLLPALCDSKIRSK
CCHHHHHCCHHHHHH
6.3622555962
299AcetylationLPALCDSKIRSKALG
HHHHCCHHHHHHHHC
28.9626051181
310S-palmitoylationKALGSDHCPITLYLA
HHHCCCCCCEEEEEE
2.9029575903
310S-nitrosylationKALGSDHCPITLYLA
HHHCCCCCCEEEEEE
2.9017403694
310S-nitrosocysteineKALGSDHCPITLYLA
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
233TPhosphorylationKinaseCDK5Q00535
Uniprot
290SPhosphorylationKinaseCK2-FAMILY-GPS
290SPhosphorylationKinaseCK2_GROUP-PhosphoELM
-KUbiquitinationE3 ubiquitin ligaseMDM2Q00987
PMID:19219073

Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference
6KAcetylation

14633989
6KAcetylation

14633989
7KAcetylation

14633989
7KAcetylation

14633989
233TPhosphorylation

11452037

Disease-associated PTM Sites based on SAP

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

Modified Location Modification Variant Position
(Distance <= 10)
Residue Change SAP Related Disease Reference

Oops, there are no SNP-PTM records of APEX1_HUMAN !!

Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
HIF1A_HUMANHIF1Aphysical
10594042
AN32A_HUMANANP32Aphysical
12524539
SET_HUMANSETphysical
12524539
XRCC5_HUMANXRCC5physical
8621488
XRCC1_HUMANXRCC1physical
11707423
RPC4_HUMANPOLR3Dphysical
20211142
HXC13_HUMANHOXC13physical
20211142
TCF21_HUMANTCF21physical
20211142
MDM2_HUMANMDM2physical
19219073
RNF4_HUMANRNF4physical
20696907
P53_HUMANTP53physical
15824742
NPM_HUMANNPM1physical
19188445
PRP19_HUMANPRPF19physical
19188445
MEP50_HUMANWDR77physical
19188445
PRDX6_HUMANPRDX6physical
19188445
TCPA_HUMANTCP1physical
19188445
K2C8_HUMANKRT8physical
19188445
RSSA_HUMANRPSAphysical
19188445
TRAF2_HUMANTRAF2physical
17599408
UBC9_HUMANUBE2Iphysical
12110916
A4_HUMANAPPphysical
21832049
SFPQ_HUMANSFPQphysical
22939629
SMD1_HUMANSNRPD1physical
22939629
STAT3_HUMANSTAT3physical
15735682
EP300_HUMANEP300physical
20856196
ASCL2_HUMANASCL2physical
20856196
YBOX1_HUMANYBX1physical
20856196
HMGA1_HUMANHMGA1physical
18850631
MUTYH_HUMANMUTYHphysical
24209961
ELOC_HUMANTCEB1physical
22863883
TWF2_HUMANTWF2physical
22863883
TRXR1_HUMANTXNRD1physical
22863883
DPOLB_HUMANPOLBphysical
9207062
SIR1_HUMANSIRT1physical
19934257
IMA4_HUMANKPNA3physical
26186194
KLH36_HUMANKLHL36physical
26186194
CFA74_HUMANCFAP74physical
26186194
BUB3_HUMANBUB3physical
26344197
CGBP1_HUMANCGGBP1physical
26344197
CLVS2_HUMANCLVS2physical
26344197
DDB1_HUMANDDB1physical
26344197
NXF1_HUMANNXF1physical
26344197
PDE12_HUMANPDE12physical
26344197
ZFR2_HUMANZFR2physical
26344197
PRKN_HUMANPARK2physical
27148961
KLH36_HUMANKLHL36physical
28514442

Drug and Disease Associations
Kegg Disease
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.
Regulatory Network of APEX1_HUMAN

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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"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
ReferencePubMed
"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
ReferencePubMed
"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.

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