A0MTA1 (APEX1_DANRE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA-(apurinic or apyrimidinic site) lyase
EC=3.1.-.-
EC=4.2.99.18

Alternative name(s):
APEX nuclease
Short name=APEN
Apurinic-apyrimidinic endonuclease 1
Short name=AP endonuclease 1
Short name=zAP1

Gene names

Name:	apex1
Synonyms:	apex1a, apex1b
ORF Names:	si:ch211-214j24.12, zgc:66204

Organism

Danio rerio (Zebrafish) (Brachydanio rerio) [Reference proteome]

Taxonomic identifier

7955 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Actinopterygii › Actinopteri › Neopterygii › Teleostei › Elopocephala › Clupeocephala › Otocephala › Ostariophysi › Otophysi › Cypriniphysi › Cypriniformes › Cyprinoidea › Cyprinidae › Danio

Protein attributes

Sequence length	310 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Function 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. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Required for passage through the midblastula transition MBT. May also acts as a endoribonuclease involved in the control of single-stranded RNA metabolism. Has no redox activity. Binds DNA and RNA. Ref.1 Ref.4
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.
Cofactor	Magnesium. Can also utilize manganese. Probably binds two magnesium or manganese ions per subunit By similarity.
Subcellular location	Nucleus By similarity. Nucleus › nucleolus By similarity. Nucleus speckle By similarity. Endoplasmic reticulum By similarity. Cytoplasm By similarity. Mitochondrion By similarity.
Developmental stage	Expressed in unfertilized eggs and embryos at two stages (at protein level). Expressed throughout embryogenesis. Ref.1
Sequence similarities	Belongs to the DNA repair enzymes AP/ExoA family.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Cytoplasm Endoplasmic reticulum Mitochondrion Nucleus
Ligand	DNA-binding Magnesium Metal-binding RNA-binding
Molecular function	Endonuclease Hydrolase Lyase Nuclease
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA demethylation Inferred from sequence or structural similarity. Source: UniProtKB DNA repair Inferred from electronic annotation. Source: UniProtKB-KW heart contraction Inferred from mutant phenotype Ref.1. Source: ZFIN heart looping Inferred from mutant phenotype Ref.1. Source: ZFIN negative regulation of apoptotic process Inferred from mutant phenotype Ref.1. Source: ZFIN nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC positive regulation of gene expression Inferred from mutant phenotype PubMed 21172930. Source: ZFIN
Cellular_component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW DNA-(apurinic or apyrimidinic site) lyase activity Inferred from electronic annotation. Source: EC RNA binding Inferred from electronic annotation. Source: UniProtKB-KW endonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 310

310

DNA-(apurinic or apyrimidinic site) lyase

PRO_0000402575

Sites

Active site

164

1

By similarity

Active site

203

1

Proton donor/acceptor By similarity

Metal binding

63

1

Magnesium 1 By similarity

Metal binding

89

1

Magnesium 1 By similarity

Metal binding

203

1

Magnesium 2 By similarity

Metal binding

205

1

Magnesium 2 By similarity

Metal binding

300

1

Magnesium 1 By similarity

Site

205

1

Transition state stabilizer By similarity

Site

275

1

Important for catalytic activity By similarity

Site

301

1

Interaction with DNA substrate By similarity

Experimental info

Mutagenesis

58

1

T → C: Confers redox activity. Ref.4

Sequence conflict

16

1

A → S in CAI11781. Ref.2

Sequence conflict

80 – 93

14

Missing in AAI64240. Ref.3

Sequence conflict

80 – 93

14

Missing in AAH97053. Ref.3

Sequence conflict

103

1

G → A in AAH55545. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

310

Helix Strand Turn

Details...

Beta strand

55 – 61

7

Helix

65 – 70

6

Helix

73 – 80

8

Beta strand

83 – 88

6

Helix

94 – 96

3

Helix

99 – 102

4

Beta strand

108 – 113

6

Beta strand

124 – 130

7

Beta strand

133 – 138

6

Turn

142 – 146

5

Beta strand

150 – 154

5

Beta strand

159 – 164

6

Helix

170 – 172

3

Helix

175 – 195

21

Beta strand

198 – 203

6

Helix

210 – 212

3

Helix

216 – 219

4

Helix

227 – 238

12

Beta strand

241 – 243

3

Helix

244 – 248

5

Helix

262 – 264

3

Helix

265 – 268

4

Beta strand

275 – 280

6

Helix

281 – 286

6

Beta strand

287 – 292

6

Beta strand

298 – 301

4

Beta strand

304 – 308

5

Sequences

	Sequence		Length	Mass (Da)
	A0MTA1 [UniParc]. Last modified December 12, 2006. Version 1. Checksum: F57493D443106F4B	FASTA	310	34,881
	10 20 30 40 50 60 MPKRAKKNEE GVDGEADNGT AAAKKEKKGK EPEAPILYED PPEKLTSKDG RAANMKITSW 70 80 90 100 110 120 NVDGLRAWVK KNGLDWVRKE DPDILCLQET KCAEKALPAD ITGMPEYPHK YWAGSEDKEG 130 140 150 160 170 180 YSGVAMLCKT EPLNVTYGIG KEEHDKEGRV ITAEFPDFFL VTAYVPNASR GLVRLDYRKT 190 200 210 220 230 240 WDVDFRAYLC GLDARKPLVL CGDLNVAHQE IDLKNPKGNR KNAGFTPEER EGFTQLLEAG 250 260 270 280 290 300 FTDSFRELYP DQAYAYTFWT YMMNARSKNV GWRLDYFVLS SALLPGLCDS KIRNTAMGSD 310 HCPITLFLAV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DNA repair protein involved in heart and blood development." Wang Y., Shupenko C.C., Melo L.F., Strauss P.R. Mol. Cell. Biol. 26:9083-9093(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, DEVELOPMENTAL STAGE. Tissue: Embryo.
[2]	The Danio rerio sequencing project at the Sanger Institute Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Tuebingen.
[3]	NIH - Zebrafish Gene Collection (ZGC) project Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Olfactory epithelium.
[4]	"Evolution of the redox function in mammalian apurinic/apyrimidinic endonuclease." Georgiadis M.M., Luo M., Gaur R.K., Delaplane S., Li X., Kelley M.R. Mutat. Res. 643:54-63(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 33-310, FUNCTION, MUTAGENESIS OF THR-58.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

EF041101 mRNA. Translation: ABK35081.1.
EF041102 mRNA. Translation: ABK35082.1.
EF041103 Genomic DNA. Translation: ABK35083.1.
EF041104 Genomic DNA. Translation: ABK35084.1.
BX323558 Genomic DNA. Translation: CAI11781.1.
BC055545 mRNA. Translation: AAH55545.1.
BC097053 mRNA. Translation: AAH97053.1.
BC164240 mRNA. Translation: AAI64240.1.

IPI

IPI00498781.

RefSeq

NP_998586.1. NM_213421.1.

UniGene

Dr.20170.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2O3C	X-ray	2.30	A/B/C	33-310	[»]

ProteinModelPortal

A0MTA1.

SMR

A0MTA1. Positions 33-310.

ModBase

Search...

Protein-protein interaction databases

STRING

7955.ENSDARP00000067373.

Proteomic databases

PRIDE

A0MTA1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSDART00000067374; ENSDARP00000067373; ENSDARG00000045843.

GeneID

406730.

KEGG

dre:406730.

Organism-specific databases

CTD

328.

ZFIN

ZDB-GENE-040426-2761. apex1.

Phylogenomic databases

eggNOG

COG0708.

GeneTree

ENSGT00530000063540.

HOGENOM

HOG000034586.

HOVERGEN

HBG050531.

InParanoid

Q7SXL6.

KO

K10771.

OrthoDB

EOG44J2JD.

Gene expression databases

ArrayExpress

A0MTA1.

Bgee

A0MTA1.

Family and domain databases

InterPro

IPR020847. AP_endonuclease_F1_BS.
IPR020848. AP_endonuclease_F1_CS.
IPR005135. Endo/exonuclease/phosphatase.
IPR004808. ExoDNase_III.
[Graphical view]

PANTHER

PTHR22748. PTHR22748. 1 hit.

Pfam

PF03372. Exo_endo_phos. 1 hit.
[Graphical view]

SUPFAM

SSF56219. Exo_endo_phos. 1 hit.

TIGRFAMs

TIGR00633. xth. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

EvolutionaryTrace

A0MTA1.

NextBio

20818249.

Entry information

Entry name

APEX1_DANRE

Accession

Primary (citable) accession number: A0MTA1
Secondary accession number(s): Q4V955, Q5RHZ7, Q7SXL6

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2011
Last sequence update:	December 12, 2006
Last modified:	April 3, 2013
This is version 50 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program