Reviewed, UniProtKB/Swiss-Prot P27695 (APEX1_HUMAN)

Names and origin

Protein names

Recommended name:
    DNA-(apurinic or apyrimidinic site) lyase
    EC=4.2.99.18
Alternative name(s):
    Apurinic-apyrimidinic endonuclease 1
      Short name=AP endonuclease 1
    APEX nuclease
      Short name=APEN
    Protein REF-1

Gene names

Name:	APEX1
Synonyms:	APE, APEX, APX, HAP1, REF1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	318 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Repairs oxidative DNA damages in vitro. May have a role in protection against cell lethality and suppression of mutations. Removes the blocking groups from the 3'-termini of the DNA strand breaks generated by ionizing radiations and bleomycin.
Catalytic activity	The C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar and a product with a terminal 5'-phosphate.
Subunit structure	Monomer. Component of the SET complex, which also contains SET, ANP32A, HMGB2 and NME1.
Subcellular location	Nucleus.
Sequence similarities	Belongs to the DNA repair enzymes AP/exoA family.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Lyase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	base-excision repair Ref.18 Traceable author statement. Source: UniProtKB regulation of DNA binding Inferred from direct assay. Source: UniProtKB transcription from RNA polymerase II promoter Ref.3 Traceable author statement. Source: ProtInc
Cellular component	centrosome Inferred from direct assay. Source: HPA endoplasmic reticulum Ref.21 Traceable author statement. Source: UniProtKB nucleoplasm Inferred from Experiment. Source: Reactome perinuclear region of cytoplasm Ref.21 Inferred from direct assay. Source: UniProtKB ribosome Ref.21 Traceable author statement. Source: UniProtKB
Molecular function	3'-5' exonuclease activity Ref.18 Traceable author statement. Source: UniProtKB DNA binding Ref.18 Inferred from direct assay. Source: UniProtKB DNA-(apurinic or apyrimidinic site) lyase activity Traceable author statement. Source: UniProtKB endodeoxyribonuclease activity Ref.7 Traceable author statement. Source: ProtInc magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity Inferred from direct assay. Source: UniProtKB phosphodiesterase I activity Traceable author statement. Source: UniProtKB ribonuclease H activity Ref.18 Traceable author statement. Source: UniProtKB transcription coactivator activity Inferred from direct assay. Source: UniProtKB transcription corepressor activity Traceable author statement. Source: ProtInc uracil DNA N-glycosylase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.3

Chain

2 – 318

317

DNA-(apurinic or apyrimidinic site) lyase

PRO_0000200010

Sites

Active site

309

1

Proton acceptor By similarity

Metal binding

68

1

Magnesium or manganese

Metal binding

96

1

Magnesium or manganese

Metal binding

210

1

Magnesium or manganese

Metal binding

212

1

Magnesium or manganese

Metal binding

308

1

Magnesium or manganese

Metal binding

309

1

Magnesium or manganese

Amino acid modifications

Modified residue

197

1

N6-acetyllysine Ref.17

Modified residue

262

1

Phosphotyrosine Ref.15

Natural variations

Natural variant

51

1

Q → H: dbSNP rs1048945. Ref.11

VAR_013455

Natural variant

64

1

I → V: dbSNP rs2307486. Ref.11

VAR_014823

Natural variant

148

1

D → E: dbSNP rs1130409. Ref.11 Ref.12

VAR_019790

Experimental info

Mutagenesis

212

1

N → A: Abolishes the AP endonuclease activity. Ref.14

Mutagenesis

212

1

N → Q or D: Decreases the AP endonuclease activity. Ref.14

Sequence conflict

57

1

G → A in AAA58371. Ref.7

Sequence conflict

306

1

G → A in AAA58371. Ref.7

Secondary structure

1

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318

Helix Strand Turn

Details...

Beta strand

62 – 68

7

Helix

72 – 77

6

Helix

80 – 87

8

Beta strand

90 – 95

6

Helix

106 – 109

4

Beta strand

116 – 120

5

Beta strand

126 – 128

3

Beta strand

131 – 137

7

Beta strand

140 – 145

6

Helix

149 – 151

3

Beta strand

152 – 154

3

Beta strand

157 – 161

5

Beta strand

166 – 171

6

Helix

177 – 179

3

Helix

182 – 200

19

Beta strand

205 – 210

6

Helix

217 – 219

3

Helix

223 – 226

4

Helix

234 – 246

13

Helix

252 – 256

5

Helix

270 – 272

3

Turn

273 – 277

5

Beta strand

283 – 287

5

Helix

289 – 294

6

Beta strand

295 – 300

6

Beta strand

306 – 309

4

Beta strand

312 – 316

5

Sequences

	Sequence		Length	Mass (Da)
	P27695-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: B88579C01BAF80C6	FASTA	318	35,555
	10 20 30 40 50 60 MPKRGKKGAV AEDGDELRTE PEAKKSKTAA KKNDKEAAGE GPALYEDPPD QKTSPSGKPA 70 80 90 100 110 120 TLKICSWNVD GLRAWIKKKG LDWVKEEAPD ILCLQETKCS ENKLPAELQE LPGLSHQYWS 130 140 150 160 170 180 APSDKEGYSG VGLLSRQCPL KVSYGIGDEE HDQEGRVIVA EFDSFVLVTA YVPNAGRGLV 190 200 210 220 230 240 RLEYRQRWDE AFRKFLKGLA SRKPLVLCGD LNVAHEEIDL RNPKGNKKNA GFTPQERQGF 250 260 270 280 290 300 GELLQAVPLA DSFRHLYPNT PYAYTFWTYM MNARSKNVGW RLDYFLLSHS LLPALCDSKI 310 RSKALGSDHC PITLYLAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure of the human DNA repair gene HAP1 and its localisation to chromosome 14q 11.2-12." Robson C.N., Hocchauser D., Craig R., Rack K., Buckle I.D., Hickson I.D. Nucleic Acids Res. 20:4417-4421(1992) [PubMed: 1383925] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Isolation of cDNA clones encoding a human apurinic/apyrimidinic endonuclease that corrects DNA repair and mutagenesis defects in E. coli xth (exonuclease III) mutants." Robson C.N., Hickson I.D. Nucleic Acids Res. 19:5519-5523(1991) [PubMed: 1719477] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Melanocyte.
[3]	"Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme." Xanthoudakis S., Miao G., Wang F., Pan Y.-C.E., Curran T. EMBO J. 11:3323-3335(1992) [PubMed: 1380454] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-21.
[4]	"The human gene for apurinic/apyrimidinic endonuclease (HAP1): sequence and localization to chromosome 14 band q12." Zhao B., Grandy D.K., Hagerup J.M., Magenis R.E., Smith L., Chauhan B.C., Henner W.D. Nucleic Acids Res. 20:4097-4098(1992) [PubMed: 1380694] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III." Seki S., Hatsushika M., Watanabe S., Akiyama K., Nagao K., Tsutsui K. Biochim. Biophys. Acta 1131:287-299(1992) [PubMed: 1627644] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[6]	"Structure, promoter analysis and chromosomal assignment of the human APEX gene." Akiyama K., Seki S., Oshida T., Yoshida M. Biochim. Biophys. Acta 1219:15-25(1994) [PubMed: 8086453] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes." Demple B., Herman T., Chen D.S. Proc. Natl. Acad. Sci. U.S.A. 88:11450-11454(1991) [PubMed: 1722334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[8]	"Nucleotide sequence of a cDNA for an apurinic/apyrimidinic endonuclease from HeLa cells." Cheng X.B., Bunville J., Patterson T.A. Nucleic Acids Res. 20:370-370(1992) [PubMed: 1371347] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[9]	"Large-scale concatenation cDNA sequencing." Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W., Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A. Genome Res. 7:353-358(1997) [PubMed: 9110174] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[10]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[11]	NIEHS SNPs program Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-51; VAL-64 AND GLU-148.
[12]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLU-148. Tissue: Brain, Lung and Skin.
[13]	"Human apurinic endonuclease gene (APE): structure and genomic mapping (chromosome 14q11.2-12)." Harrison L., Ascione G., Menninger J.C., Ward D.C., Demple B. Hum. Mol. Genet. 1:677-680(1992) [PubMed: 1284593] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-146. Tissue: Placenta.
[14]	"Asparagine 212 is essential for abasic site recognition by the human DNA repair endonuclease HAP1." Rothwell D.G., Hickson I.D. Nucleic Acids Res. 24:4217-4221(1996) [PubMed: 8932375] [Abstract] Cited for: MUTAGENESIS OF ASN-212.
[15]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." 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) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-262, MASS SPECTROMETRY.
[16]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[17]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-197, MASS SPECTROMETRY.
[18]	"Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, ape1: implications for the catalytic mechanism." Beernink P.T., Segelke B.W., Hadi M.Z., Erzberger J.P., Wilson D.M. III, Rupp B. J. Mol. Biol. 307:1023-1034(2001) [PubMed: 11286553] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
[19]	"The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites." Gorman M.A., Morera S., Rothwell D.G., de La Fortelle E., Mol C.D., Tainer J.A., Hickson I.D., Freemont P.S. EMBO J. 16:6548-6558(1997) [PubMed: 9351835] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 32-318.
[20]	"DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination." Mol C.D., Izumi T., Mitra S., Tainer J.A. Nature 403:451-456(2000) [PubMed: 10667800] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 40-318.
[21]	"Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A." Fan Z., Beresford P.J., Zhang D., Xu Z., Novina C.D., Yoshida A., Pommier Y., Lieberman J. Nat. Immunol. 4:145-153(2003) [PubMed: 12524539] [Abstract] Cited for: IDENTIFICATION IN THE SET COMPLEX.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X66133 Genomic DNA. Translation: CAA46925.1.
X59764 mRNA. Translation: CAA42437.1.
M92444 Genomic DNA. Translation: AAA58629.1.
M99703 Genomic DNA. Translation: AAA58373.1.
D90373 mRNA. Translation: BAA14381.1.
D13370 Genomic DNA. Translation: BAA02633.1.
M80261 mRNA. Translation: AAA58371.1.
M81955 mRNA. Translation: AAA58372.1.
U79268 mRNA. Translation: AAB50212.1.
BT007236 mRNA. Translation: AAP35900.1.
AF488551 Genomic DNA. Translation: AAL86909.1.
BC002338 mRNA. Translation: AAH02338.1.
BC004979 mRNA. Translation: AAH04979.1.
BC008145 mRNA. Translation: AAH08145.1.
BC019291 mRNA. Translation: AAH19291.1.
S43127 mRNA. Translation: AAB22977.1.

IPI

IPI00215911.

PIR

S23550.

RefSeq

NP_001632.2.
NP_542379.1.
NP_542380.1.

UniGene

Hs.73722

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BIX	X-ray	2.20	A	32-318	[»]
1CQG	NMR	-	B	59-71	[»]
1CQH	NMR	-	B	59-71	[»]
1DE8	X-ray	2.95	A/B	43-318	[»]
1DE9	X-ray	3.00	A/B	43-318	[»]
1DEW	X-ray	2.65	A/B	40-318	[»]
1E9N	X-ray	2.20	A/B	1-318	[»]
1HD7	X-ray	1.95	A	1-318	[»]
2ISI	X-ray	2.76	A/B/C	2-317	[»]
2O3H	X-ray	1.90	A	40-318	[»]

DisProt

DP00007.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6130N.

IntAct

P27695. 8 interactions.

STRING

P27695.

PTM databases

PhosphoSite

P27695.

Proteomic databases

PeptideAtlas

P27695.

PRIDE

P27695.

Genome annotation databases

Ensembl

ENST00000216714; ENSP00000216714; ENSG00000100823; Homo sapiens. [Genome view]
ENST00000398030; ENSP00000381111; ENSG00000100823; Homo sapiens. [Genome view]
ENST00000442613; ENSP00000400658; ENSG00000100823; Homo sapiens. [Genome view]

GeneID

328.

KEGG

hsa:328.

UCSC

uc001vxg.1. human.

Organism-specific databases

CTD

328.

GeneCards

GC14P019993.

H-InvDB

HIX0011489.

HGNC

HGNC:587. APEX1.

HPA

CAB004294.
HPA002564.

MIM

107748. gene.

PharmGKB

PA201059.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08118.

HOGENOM

HBG704164.

HOVERGEN

P27695.

InParanoid

P27695.

OMA

YTWWSYM.

OrthoDB

EOG97M4HB.

PhylomeDB

P27695.

Enzyme and pathway databases

BRENDA

4.2.99.18. 247.

Reactome

REACT_216. DNA Repair.

Gene expression databases

ArrayExpress

P27695.

Bgee

P27695.

CleanEx

HS_APEX1.
HS_HAP1.

Genevestigator

P27695.

GermOnline

ENSG00000100823. Homo sapiens.

Family and domain databases

InterPro

IPR000097. AP_endonuclease_F1.
IPR020847. AP_endonuclease_F1_BS.
IPR020848. AP_endonuclease_F1_CS.
IPR005135. Endo/exonuclease/phosphatase.
IPR004808. exoDNase_III.
[Graphical view]

PANTHER

PTHR22748. ExoIII_xth. 1 hit.

Pfam

PF03372. Exo_endo_phos. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00195. exoDNase_III. 1 hit.
TIGR00633. xth. 1 hit.

PROSITE

PS00726. AP_NUCLEASE_F1_1. 1 hit.
PS00727. AP_NUCLEASE_F1_2. 1 hit.
PS00728. AP_NUCLEASE_F1_3. 1 hit.
PS51435. AP_NUCLEASE_F1_4. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB04967. Lucanthone.

NextBio

1347.

PMAP-CutDB

P27695.

SOURCE

Search...

Entry information

Entry name

APEX1_HUMAN

Accession

Primary (citable) accession number: P27695
Secondary accession number(s): Q969L5, Q99775

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 137 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.