APEX1 APEX nuclease (multifunctional DNA repair enzyme) 1 [Homo sapiens] - Gene

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Summary

Official Symbol: APEX1provided by HGNC
Official Full Name: APEX nuclease (multifunctional DNA repair enzyme) 1provided by HGNC
Primary source: HGNC:587
See related: Ensembl:ENSG00000100823; HPRD:00136; MIM:107748; Vega:OTTHUMG00000029544
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: APE; APX; APE1; APEN; APEX; HAP1; REF1
Summary: Apurinic/apyrimidinic (AP) sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can prevent normal DNA replication so the cell contains systems to identify and repair such sites. Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site. This gene encodes the major AP endonuclease in human cells. Splice variants have been found for this gene; all encode the same protein. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 14q11.2

Sequence :: Chromosome: 14; NC_000014.8 (20923290..20925926)

See APEX1 in Epigenomics, MapViewer

Chromosome 14 - NC_000014.8 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

On the basis of enzyme fluorescence changes over time, the APE1 molecule is shown to undergo at least four conformational transitions along the reaction coordinate. The data reveal a conformational flexibility of the abasic DNA being processed by APE1.
Title: Conformational dynamics of abasic DNA upon interactions with AP endonuclease 1 revealed by stopped-flow fluorescence analysis.
APE1 T1349G polymorphism may be a marker for the development of gastric cancer in the Chinese population
Title: The DNA repair gene APE1 T1349G polymorphism and risk of gastric cancer in a Chinese population.
Lucanthone and its derivative hycanthone inhibit apurinic endonuclease-1 (APE1) by direct protein binding
Title: Lucanthone and its derivative hycanthone inhibit apurinic endonuclease-1 (APE1) by direct protein binding.
the meta-analysis suggests that APE1 -656 T > G polymorphism has a possible protective effect on cancer risk particularly among Asian populations whereas 1349 T > G polymorphism does not contribute to the development of cancer.
Title: The association of APE1 -656T > G and 1349 T > G polymorphisms and cancer risk: a meta-analysis based on 37 case-control studies.
The human E3 ubiquitin ligase UBR3 has a major activity that polyubiquitylates APE1 at multiple lysine residues clustered on the N-terminal tail.
Title: Ubiquitin ligase UBR3 regulates cellular levels of the essential DNA repair protein APE1 and is required for genome stability.
APE1 is a unique redox factor with properties distinct from those of other redox factors
Title: Characterization of the redox activity and disulfide bond formation in apurinic/apyrimidinic endonuclease.
Nm23-H1 protects cells against oxidative stress through the engagement of DNA BER enzyme APE1
Title: Nm23-H1 protein binds to APE1 at AP sites and stimulates AP endonuclease activity following ionizing radiation of the human lung cancer A549 cells.
We found that haplotypes in APEX1, BRCA2, ERCC2, and RAD51 were significantly associated with total childhood acute lymphoblastic leukemia
Title: Haplotypes of DNA repair and cell cycle control genes, X-ray exposure, and risk of childhood acute lymphoblastic leukemia.
Cysteine residue (Cis-65) of the APE1 protein controls APE1 subcellular trafficking and plays important role in tumorigenesis.
Title: Knock-in reconstitution studies reveal an unexpected role of Cys-65 in regulating APE1/Ref-1 subcellular trafficking and function.
Cigarette smoke modulated the activity and distribution of the BER enzymes 8-oxoguanine-DNA-glycosylase (OGG1) and apyrimidinic/apurinic endonuclease (APE1) in several brain regions.
Title: Cigarette smoke induces DNA damage and alters base-excision repair and tau levels in the brain of neonatal mice.

Submit: New GeneRIF Correction See all (210)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_001632.2	NC_000006.9	CDKN1A	BIND	PubMed	Ref1 interacts weakly with p21 promoter.
NP_001632.2	AAH03178.1	MUTYH	BIND	PubMed	hMYH is associated in vivo with apurinic/apyrimidinic endonuclease (APE1)
NP_001632.2	NP_000537.2	TP53	BIND	PubMed	p53 interacts with Ref-1.
P27695	P39687	ANP32A	HPRD	PubMed
P27695	O43423	ANP32C	HPRD	PubMed
P27695	P27695	APEX1	HPRD	PubMed
P27695	P68400	CSNK2A1	HPRD	PubMed
P27695	Q14203	DCTN1	HPRD	PubMed
P27695	Q09472	EP300	HPRD	PubMed
P27695	P39748	FEN1	HPRD	PubMed
P27695	P12544	GZMA	HPRD	PubMed
P27695	Q13547	HDAC1	HPRD	PubMed
P27695	Q16665	HIF1A	HPRD	PubMed
P27695	P26583	HMGB2	HPRD	PubMed
P27695	P14866	HNRNPL	HPRD	PubMed
P27695	Heat shock 70 KD protein 1A	HSPA1A	HPRD	PubMed
P27695	Q9UIF7	MUTYH	HPRD	PubMed
P27695	P15531	NME1	HPRD	PubMed
P27695	Q9GZY0	NXF2	HPRD	PubMed
P27695	P12004	PCNA	HPRD	PubMed
P27695	P06746	POLB	HPRD	PubMed
P27695	Q01105	SET	HPRD	PubMed
P27695	P04637	TP53	HPRD	PubMed
P27695	P10599	TXN	HPRD	PubMed
P27695	P63279	UBE2I	HPRD	PubMed
P27695	P18887	XRCC1	HPRD	PubMed
P27695	P12956	XRCC6	HPRD	PubMed
BioGRID:106825	BioGRID:113791	ANP32A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106825	BioGRID:108528	FEN1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:106825	BioGRID:109338	HIF1A	BioGRID	PubMed	Reconstituted Complex
BioGRID:106825	BioGRID:109432	HNRNPL	BioGRID	PubMed	Reconstituted Complex
BioGRID:106825	BioGRID:109469	HOXC13	BioGRID	PubMed	Two-hybrid
BioGRID:106825	BioGRID:110358	MDM2	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity
BioGRID:106825	BioGRID:110681	MUTYH	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:106825	BioGRID:116336	NUDT3	BioGRID	PubMed	Two-hybrid
BioGRID:106825	BioGRID:111142	PCNA	BioGRID	PubMed	Reconstituted Complex
BioGRID:106825	BioGRID:107129	POLR3D	BioGRID	PubMed	Two-hybrid
BioGRID:106825	BioGRID:112316	SET	BioGRID	PubMed	Affinity Capture-Western
BioGRID:106825	BioGRID:112497	SUMO2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:106825	BioGRID:112803	TCF21	BioGRID	PubMed	Two-hybrid
BioGRID:106825	BioGRID:113010	TP53	BioGRID	PubMed	Co-purification
BioGRID:106825	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:106825	BioGRID:113349	XRCC1	BioGRID	PubMed	Far Western; Two-hybrid
BioGRID:106825	BioGRID:113353	XRCC5	BioGRID	PubMed	Reconstituted Complex

Function	Evidence Code	Pubs
3'-5' exonuclease activity	IDA Inferred from Direct Assay more info	PubMed
3'-5' exonuclease activity	TAS Traceable Author Statement more info	PubMed
DNA binding	IDA Inferred from Direct Assay more info	PubMed
DNA-(apurinic or apyrimidinic site) lyase activity	IDA Inferred from Direct Assay more info	PubMed
DNA-(apurinic or apyrimidinic site) lyase activity	TAS Traceable Author Statement more info	PubMed
RNA binding	IEA Inferred from Electronic Annotation more info
chromatin DNA binding	IDA Inferred from Direct Assay more info	PubMed
damaged DNA binding	IDA Inferred from Direct Assay more info	PubMed
endodeoxyribonuclease activity	TAS Traceable Author Statement more info	PubMed
endonuclease activity	IDA Inferred from Direct Assay more info	PubMed
hydrolase activity	IEA Inferred from Electronic Annotation more info
lyase activity	IEA Inferred from Electronic Annotation more info
metal ion binding	IDA Inferred from Direct Assay more info	PubMed
oxidoreductase activity	IDA Inferred from Direct Assay more info	PubMed
phosphodiesterase I activity	TAS Traceable Author Statement more info	PubMed
phosphoric diester hydrolase activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info
ribonuclease H activity	TAS Traceable Author Statement more info	PubMed
site-specific endodeoxyribonuclease activity, specific for altered base	IDA Inferred from Direct Assay more info	PubMed
transcription coactivator activity	IDA Inferred from Direct Assay more info	PubMed
transcription corepressor activity	TAS Traceable Author Statement more info	PubMed
uracil DNA N-glycosylase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
DNA demethylation	IDA Inferred from Direct Assay more info
DNA recombination	IEA Inferred from Electronic Annotation more info
DNA repair	IDA Inferred from Direct Assay more info	PubMed
DNA repair	TAS Traceable Author Statement more info
base-excision repair	TAS Traceable Author Statement more info
oxidation-reduction process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of DNA repair	IDA Inferred from Direct Assay more info	PubMed
positive regulation of anti-apoptosis	IDA Inferred from Direct Assay more info	PubMed
regulation of mRNA stability	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of transcription, DNA-dependent	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
centrosome	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum	TAS Traceable Author Statement more info	PubMed
intracellular	IEA Inferred from Electronic Annotation more info
mitochondrion	IDA Inferred from Direct Assay more info
nuclear speck	IDA Inferred from Direct Assay more info	PubMed
nucleolus	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IDA Inferred from Direct Assay more info	PubMed
perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
ribosome	TAS Traceable Author Statement more info	PubMed

General protein information

Preferred Names: DNA-(apurinic or apyrimidinic site) lyase

Names: DNA-(apurinic or apyrimidinic site) lyase; AP lyase; protein REF-1; redox factor-1; AP endonuclease class I; apurinic-apyrimidinic endonuclease 1; apurinic/apyrimidinic (abasic) endonuclease; deoxyribonuclease (apurinic or apyrimidinic)

NP_001632.2

EC 4.2.99.18

NP_542379.1

EC 4.2.99.18

NP_542380.1

EC 4.2.99.18

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008718.1 RefSeqGene

Range

5001..7642

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001244249.1 → NP_001231178.1 DNA-(apurinic or apyrimidinic site) lyase

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses a donor splice site for exon 1 downstream of that used by variant 3.

Source sequence(s)

AI554786, AK291100, AL355075, CB139337

UniProtKB/Swiss-Prot

P27695

UniProtKB/TrEMBL

Q5TZP7

Conserved Domains (1) summary

cd09087
Location:62 – 316
Blast Score: 1163

Ape1-like_AP-endo; Human Ape1-like subfamily of the ExoIII family purinic/apyrimidinic (AP) endonucleases
NM_001641.3 → NP_001632.2 DNA-(apurinic or apyrimidinic site) lyase

Status: REVIEWED

Description

Transcript Variant: This variant (1) contains the full-length first exon and is the longest transcript.

Source sequence(s)

AI554786, AK291100, AL355075

Consensus CDS

CCDS9550.1

UniProtKB/Swiss-Prot

P27695

UniProtKB/TrEMBL

Q5TZP7

Related

ENSP00000216714, OTTHUMP00000163989, ENST00000216714, OTTHUMT00000073641

Conserved Domains (1) summary

cd09087
Location:62 – 316
Blast Score: 1163

Ape1-like_AP-endo; Human Ape1-like subfamily of the ExoIII family purinic/apyrimidinic (AP) endonucleases
NM_080648.2 → NP_542379.1 DNA-(apurinic or apyrimidinic site) lyase

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses a different donor splice site for exon 1 when compared to variant 1.

Source sequence(s)

AI554786, AL355075, BC004979

Consensus CDS

CCDS9550.1

UniProtKB/Swiss-Prot

P27695

UniProtKB/TrEMBL

Q5TZP7

Related

ENSP00000381111, OTTHUMP00000244793, ENST00000398030, OTTHUMT00000411060

Conserved Domains (1) summary

cd09087
Location:62 – 316
Blast Score: 1163

Ape1-like_AP-endo; Human Ape1-like subfamily of the ExoIII family purinic/apyrimidinic (AP) endonucleases
NM_080649.2 → NP_542380.1 DNA-(apurinic or apyrimidinic site) lyase

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses a donor splice site for exon 1 downstream of that used by variant 2.

Source sequence(s)

AI554786, AL355075, BC095428

Consensus CDS

CCDS9550.1

UniProtKB/Swiss-Prot

P27695

UniProtKB/TrEMBL

Q5TZP7

Related

ENSP00000451979, OTTHUMP00000163988, ENST00000555414, OTTHUMT00000073640

Conserved Domains (1) summary

cd09087
Location:62 – 316
Blast Score: 1163

Ape1-like_AP-endo; Human Ape1-like subfamily of the ExoIII family purinic/apyrimidinic (AP) endonucleases

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000014.8 Reference GRCh37.p5 Primary Assembly

Range

20923290..20925926

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000146.1 Alternate HuRef

Range

1044909..1047545

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF488551.1	AAL86909.1
genomic	AL355075.6 (62197..64833)	None
genomic	CH471078.2	EAW66463.1
		EAW66464.1
		EAW66465.1
		EAW66466.1
		EAW66467.1
		EAW66468.1
genomic	D13370.1	BAA02633.1
genomic	M92444.1	AAA58629.1
genomic	M99703.1	AAA58373.1
genomic	X66133.1	CAA46925.1
mRNA	AI554786.1	None
mRNA	AK098588.1	None
mRNA	AK291100.1	BAF83789.1
mRNA	BC002338.2	AAH02338.1
mRNA	BC004979.1	AAH04979.1
mRNA	BC008145.1	AAH08145.1
mRNA	BC019291.1	AAH19291.1
mRNA	BC095428.1	AAH95428.1
mRNA	BT007236.1	AAP35900.1
mRNA	BT020133.1	AAV38935.1
mRNA	BX161454.1	CAD61917.1
mRNA	CB139337.1	None
mRNA	D90373.1	BAA14381.1
mRNA	M80261.1	AAA58371.1
mRNA	M81955.1	AAA58372.1
mRNA	S43127.1	AAB22977.1
mRNA	U79268.1	AAB50212.1
mRNA	X59764.1	CAA42437.1
other-genetic	DQ891814.2	ABM82740.1
other-genetic	DQ894998.2	ABM85924.1