APEX1
DNA repair nuclease/redox regulator APEX1
Also known as: APE, APE-1, APEN, APEX, APEX1_HUMAN, APX, HAP1, REF-1, REF1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P27695
- Gene
- APEX1
- Ensembl
- ENSG00000100823
- Chromosome
- 14
- Canonical length
- 318 aa
- Protein class
- Cancer-related genes, Enzymes, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Centrosome
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The APEX gene encodes the major AP endonuclease in human cells. It encodes the APEX endonuclease, a DNA repair enzyme with apurinic/apyrimidinic (AP) activity. Such AP activity sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. The AP sites are the most frequent pre-mutagenic lesions that can prevent normal DNA replication. Splice variants have been found for this gene; all encode the same protein. Disruptions in the biological functions related to APEX are associated with many various malignancies and neurodegenerative diseases.[provided by RefSeq, Dec 2019]
Canonical amino-acid sequenceUniProt
318 residues, UniProt reviewed canonical sequence.
>P27695|APEX1
1 MPKRGKKGAV AEDGDELRTE PEAKKSKTAA KKNDKEAAGE GPALYEDPPD QKTSPSGKPA
61 TLKICSWNVD GLRAWIKKKG LDWVKEEAPD ILCLQETKCS ENKLPAELQE LPGLSHQYWS
121 APSDKEGYSG VGLLSRQCPL KVSYGIGDEE HDQEGRVIVA EFDSFVLVTA YVPNAGRGLV
181 RLEYRQRWDE AFRKFLKGLA SRKPLVLCGD LNVAHEEIDL RNPKGNKKNA GFTPQERQGF
241 GELLQAVPLA DSFRHLYPNT PYAYTFWTYM MNARSKNVGW RLDYFLLSHS LLPALCDSKI
301 RSKALGSDHC PITLYLALLocalizationUniProt · AlphaFold · HPA
Whether an antibody against APEX1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.3
- Highest tissue expression
- 174 nTPM
Expression across tissuesHPA
Tissue
- ovary: 174 nTPM
- bone marrow: 146 nTPM
- thymus: 117 nTPM
- tonsil: 114 nTPM
- lymph node: 105 nTPM
- adrenal gland: 102 nTPM
Single-cell type
- decidual stromal cells: 277 nCPM
- migrating cytotrophoblasts: 263 nCPM
- extravillous trophoblasts: 237 nCPM
- cytotrophoblasts: 236 nCPM
- esophageal basal cells: 218 nCPM
- enteric stem cells: 211 nCPM
Immune cell
- plasmacytoid DC: 236 nTPM
- myeloid DC: 209 nTPM
- total PBMC: 200 nTPM
- memory B-cell: 155 nTPM
- naive B-cell: 141 nTPM
- naive CD4 T-cell: 134 nTPM
Brain region
- white matter: 54 nTPM
- thalamus: 51 nTPM
- hypothalamus: 50 nTPM
- cerebellum: 49 nTPM
- spinal cord: 48 nTPM
- medulla oblongata: 48 nTPM
ReferencesPubMed · IEDB
Publications for APEX1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
2 publications
- Serum APE1 autoantibodies: a novel potential tumor marker and predictor of chemotherapeutic efficacy in non-small cell lung cancer.
2013 · PLoS One · RCR 1.5 · 48 citations - Identification of three new autoantibodies associated with systemic lupus erythematosus using two proteomic approaches.
2011 · Mol Cell Proteomics · RCR 1.2 · 40 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.27
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.12
- DepMap mean gene effect
- -0.09
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- base-excision repair
- base-excision repair, gap-filling
- cell redox homeostasis
- DNA catabolic process
- DNA recombination
- DNA repair
- positive regulation of gene expression via chromosomal CpG island demethylation
- positive regulation of transcription by RNA polymerase II
- regulation of apoptotic process
- regulation of mRNA stability
- telomere maintenance
- telomere maintenance via base-excision repair
Molecular functions
- 3'-5' exonuclease activity
- 3'-5'-DNA exonuclease activity
- chromatin DNA binding
- damaged DNA binding
- deoxyribonuclease (pyrimidine dimer) activity
- DNA binding
- DNA endonuclease activity
- DNA-(abasic site) binding
- DNA-(apurinic or apyrimidinic site) endonuclease activity
- double-stranded DNA 3'-5' DNA exonuclease activity
- double-stranded DNA exodeoxyribonuclease activity
- double-stranded telomeric DNA binding
- endonuclease activity
- metal ion binding
- oxidoreductase activity
- phosphodiesterase I activity
- phosphoric diester hydrolase activity
- RNA binding
- RNA-DNA hybrid ribonuclease activity
- transcription coactivator activity
- transcription corepressor activity
- uracil DNA N-glycosylase activity
- class II DNA-(apurinic or apyrimidinic site) endonuclease activity
- phosphodiesterase activity, acting on 3'-phosphoglycolate-terminated DNA strands
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
- Acetylation
- Activator
- Cleavage on pair of basic residues
- Cytoplasm
- Disulfide bond
- DNA damage
- DNA recombination
- DNA repair
- DNA-binding
- Endonuclease
- Endoplasmic reticulum
- Exonuclease
- Hydrolase
- Magnesium
- Metal-binding
- Mitochondrion
- Nuclease
- Nucleus
- Phosphoprotein
- Repressor
- RNA-binding
- S-nitrosylation
- Transcription
- Transcription regulation
- Ubl conjugation
InteractionsUniProt · HPA
Protein binding partners of APEX1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads APEX1 as an antibody target. Whether an autoantibody or antibody against APEX1 could matter depends on whether native APEX1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
APEX1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label APEX1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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