Q68G58 (APEX2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA-(apurinic or apyrimidinic site) lyase 2
EC=3.1.-.-
EC=4.2.99.18

Alternative name(s):
APEX nuclease 2
Apurinic-apyrimidinic endonuclease 2
Short name=AP endonuclease 2

Gene names

Name:	Apex2
Synonyms:	Ape2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	516 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Function as a weak 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. Displays also double-stranded DNA 3'-5' exonuclease, 3'-phosphodiesterase activities. Shows robust 3'-5' exonuclease activity on 3'-recessed heteroduplex DNA and is able to remove mismatched nucleotides preferentially. Shows fairly strong 3'-phosphodiesterase activity involved in the removal of 3'-damaged termini formed in DNA by oxidative agents. In the nucleus functions in the PCNA-dependent BER pathway. Required for somatic hypermutation (SHM) and DNA cleavage step of class switch recombination (CSR) of immunoglobulin genes. Required for proper cell cycle progression during proliferation of peripheral lymphocytes. Ref.1 Ref.4 Ref.5 Ref.6
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.
Enzyme regulation	3'-5' exonuclease activity is activated by sodium and manganese. 3'-5' exonuclease and 3'-phosphodiesterase activities are stimulated in presence of PCNA By similarity.
Subunit structure	Interacts with PCNA. This interaction is increased by misincorporation of uracil in nuclear DNA By similarity. Ref.1
Subcellular location	Nucleus. Cytoplasm. Mitochondrion Probable. Note: Together with PCNA, is redistributed in discrete nuclear foci in presence of oxidative DNA damaging agents. Ref.1 Ref.5
Tissue specificity	Expressed in lymphocytes, thymocytes and splenocytes (at protein level). Highly expressed in the thymus and weakly expressed in the bone marrow, spleen, eye, kidney, lung, brain and uterus. Ref.1 Ref.4
Induction	Up-regulated in both the nucleus and the cytosol of B cells stimulated to switch. Ref.5
Disruption phenotype	Mice show abnormalities in proliferating haemopoietic organs, such as dyshematopoiesis, defect in lymphopoiesis, and delayed S-phase and G2/M-phase arrest. Ref.4 Ref.5
Sequence similarities	Belongs to the DNA repair enzymes AP/ExoA family.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA recombination DNA repair
Cellular component	Cytoplasm Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding Magnesium Metal-binding
Molecular function	Endonuclease Exonuclease Hydrolase Lyase Nuclease
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA recombination Inferred from electronic annotation. Source: UniProtKB-KW DNA repair Inferred from electronic annotation. Source: UniProtKB-KW cell cycle Inferred from electronic annotation. Source: UniProtKB-KW nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC
Cellular_component	mitochondrial inner membrane Inferred from direct assay Ref.1. Source: MGI nucleus Inferred from direct assay Ref.1. Source: MGI
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW DNA-(apurinic or apyrimidinic site) lyase activity Inferred from electronic annotation. Source: EC endonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW exonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q68G58-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q68G58-2)

The sequence of this isoform differs from the canonical sequence as follows:
     79-79: S → SECSCPSP

Note: No experimental confirmation available.

Isoform 3 (identifier: Q68G58-3)

The sequence of this isoform differs from the canonical sequence as follows:
     213-246: ECFEEDPGRKWMDGLLSNPGDEAGPHIGLFMDSY → VRFPLNHRPQFCSVHPASQNWEFGTRGSFFYGKK
     247-516: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q68G58-4)

The sequence of this isoform differs from the canonical sequence as follows:
     213-266: ECFEEDPGRK...FTCWSVVSGA → LPVAACGHTN...HTASLLRPSY
     267-516: Missing.

Note: No experimental confirmation available.

Isoform 5 (identifier: Q68G58-5)

The sequence of this isoform differs from the canonical sequence as follows:
     213-260: ECFEEDPGRK...PKQQRAFTCW → LPVAACGHTN...PLKFTESPCL
     261-516: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 516	516	DNA-(apurinic or apyrimidinic site) lyase 2		PRO_0000200015
Regions
	Region	389 – 396	8	Required for the colocalization with PCNA in nuclear foci in presence of oxidative-induced DNA damaging agents By similarity
Sites
	Active site	155	1	By similarity
	Active site	196	1	Proton donor/acceptor By similarity
	Metal binding	8	1	Magnesium 1 By similarity
	Metal binding	47	1	Magnesium 1 By similarity
	Metal binding	196	1	Magnesium 2 By similarity
	Metal binding	198	1	Magnesium 2 By similarity
	Metal binding	302	1	Magnesium 1 By similarity
	Site	198	1	Transition state stabilizer By similarity
	Site	276	1	Important for catalytic activity By similarity
	Site	303	1	Interaction with DNA substrate By similarity
Natural variations
	Alternative sequence	79	1	S → SECSCPSP in isoform 2.		VSP_015346
	Alternative sequence	213 – 266	54	ECFEE…VVSGA → LPVAACGHTNLVPEWEAGPV WERTMREIMEGFCDLLHSVR IFHHHTASLLRPSY in isoform 4.		VSP_015347
	Alternative sequence	213 – 260	48	ECFEE…AFTCW → LPVAACGHTNLVPEWEAGPV WERTMREIMEVKTRFCSRPL KFTESPCL in isoform 5.		VSP_015348
	Alternative sequence	213 – 246	34	ECFEE…FMDSY → VRFPLNHRPQFCSVHPASQN WEFGTRGSFFYGKK in isoform 3.		VSP_015349
	Alternative sequence	247 – 516	270	Missing in isoform 3.		VSP_015350
	Alternative sequence	261 – 516	256	Missing in isoform 5.		VSP_015351
	Alternative sequence	267 – 516	250	Missing in isoform 4.		VSP_015352
Experimental info
	Sequence conflict	110	1	G → S in BAC38077. Ref.2
	Sequence conflict	183	1	A → P in BAB32346. Ref.2
	Sequence conflict	372	1	C → F in AAH78633. Ref.3
	Sequence conflict	433	1	V → M in AAH78633. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 11, 2004. Version 1. Checksum: ED32A88D9CEABB85	FASTA	516	57,340
	10 20 30 40 50 60 MLRVVSWNIN GIRSPLQGLA CQEPSSCPTA LRRVLDELDA DIVCLQETKV TRDVLTEPLA 70 80 90 100 110 120 IVEGYNSYFS FSRSRSGYSG VATFCKDSAT PVAAEEGLSG VFATLNGDIG CYGNMDEFTQ 130 140 150 160 170 180 EELRVLDSEG RALLTQHKIR TLEGKEKTLT LINVYCPHAD PGKPERLTFK MRFYRLLQMR 190 200 210 220 230 240 AEALLAAGSH VIILGDLNTA HRPIDHCDAS SLECFEEDPG RKWMDGLLSN PGDEAGPHIG 250 260 270 280 290 300 LFMDSYRYLH PKQQRAFTCW SVVSGARHLN YGSRLDYVLG DRALVIDTFQ ASFLLPEVMG 310 320 330 340 350 360 SDHCPVGAVL NVSCVPAKQC PALCTRFLPE FAGTQLKILR FLVPLEQEPV REQQVLQPSH 370 380 390 400 410 420 QIQAQRQPRK ACMHSTRLRK SQGGPKRKQK NLMSYFQPSS SLSQTSGVEL PTLPLVGPLT 430 440 450 460 470 480 TPKTAEEVAT ATVLEEKNKV PESKDEKGER TAFWKSMLSG PSPMPLCGGH REPCVMRTVK 490 500 510 KTGPNFGRQF YMCARPRGPP SDPSSRCNFF LWSRPS
	Isoform 2 [UniParc]. Checksum: 50712632B2D818F7	FASTA	523	58,043
	10 20 30 40 50 60 MLRVVSWNIN GIRSPLQGLA CQEPSSCPTA LRRVLDELDA DIVCLQETKV TRDVLTEPLA 70 80 90 100 110 120 IVEGYNSYFS FSRSRSGYSE CSCPSPGVAT FCKDSATPVA AEEGLSGVFA TLNGDIGCYG 130 140 150 160 170 180 NMDEFTQEEL RVLDSEGRAL LTQHKIRTLE GKEKTLTLIN VYCPHADPGK PERLTFKMRF 190 200 210 220 230 240 YRLLQMRAEA LLAAGSHVII LGDLNTAHRP IDHCDASSLE CFEEDPGRKW MDGLLSNPGD 250 260 270 280 290 300 EAGPHIGLFM DSYRYLHPKQ QRAFTCWSVV SGARHLNYGS RLDYVLGDRA LVIDTFQASF 310 320 330 340 350 360 LLPEVMGSDH CPVGAVLNVS CVPAKQCPAL CTRFLPEFAG TQLKILRFLV PLEQEPVREQ 370 380 390 400 410 420 QVLQPSHQIQ AQRQPRKACM HSTRLRKSQG GPKRKQKNLM SYFQPSSSLS QTSGVELPTL 430 440 450 460 470 480 PLVGPLTTPK TAEEVATATV LEEKNKVPES KDEKGERTAF WKSMLSGPSP MPLCGGHREP 490 500 510 520 CVMRTVKKTG PNFGRQFYMC ARPRGPPSDP SSRCNFFLWS RPS
	Isoform 3 [UniParc]. Checksum: 194A612EF3CB1D8F	FASTA	246	27,389
	10 20 30 40 50 60 MLRVVSWNIN GIRSPLQGLA CQEPSSCPTA LRRVLDELDA DIVCLQETKV TRDVLTEPLA 70 80 90 100 110 120 IVEGYNSYFS FSRSRSGYSG VATFCKDSAT PVAAEEGLSG VFATLNGDIG CYGNMDEFTQ 130 140 150 160 170 180 EELRVLDSEG RALLTQHKIR TLEGKEKTLT LINVYCPHAD PGKPERLTFK MRFYRLLQMR 190 200 210 220 230 240 AEALLAAGSH VIILGDLNTA HRPIDHCDAS SLVRFPLNHR PQFCSVHPAS QNWEFGTRGS FFYGKK
	Isoform 4 [UniParc]. Checksum: 7EBE161284108FD5	FASTA	266	29,575
	10 20 30 40 50 60 MLRVVSWNIN GIRSPLQGLA CQEPSSCPTA LRRVLDELDA DIVCLQETKV TRDVLTEPLA 70 80 90 100 110 120 IVEGYNSYFS FSRSRSGYSG VATFCKDSAT PVAAEEGLSG VFATLNGDIG CYGNMDEFTQ 130 140 150 160 170 180 EELRVLDSEG RALLTQHKIR TLEGKEKTLT LINVYCPHAD PGKPERLTFK MRFYRLLQMR 190 200 210 220 230 240 AEALLAAGSH VIILGDLNTA HRPIDHCDAS SLLPVAACGH TNLVPEWEAG PVWERTMREI 250 260 MEGFCDLLHS VRIFHHHTAS LLRPSY
	Isoform 5 [UniParc]. Checksum: 0186A39DE091BA93	FASTA	260	28,880
	10 20 30 40 50 60 MLRVVSWNIN GIRSPLQGLA CQEPSSCPTA LRRVLDELDA DIVCLQETKV TRDVLTEPLA 70 80 90 100 110 120 IVEGYNSYFS FSRSRSGYSG VATFCKDSAT PVAAEEGLSG VFATLNGDIG CYGNMDEFTQ 130 140 150 160 170 180 EELRVLDSEG RALLTQHKIR TLEGKEKTLT LINVYCPHAD PGKPERLTFK MRFYRLLQMR 190 200 210 220 230 240 AEALLAAGSH VIILGDLNTA HRPIDHCDAS SLLPVAACGH TNLVPEWEAG PVWERTMREI 250 260 MEVKTRFCSR PLKFTESPCL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the genomic structure and expression of the mouse Apex2 gene." Ide Y., Tsuchimoto D., Tominaga Y., Iwamoto Y., Nakabeppu Y. Genomics 81:47-57(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH PCNA, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Strain: 129/Sv and C57BL/6. Tissue: B-cell.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1/2/4/5). Strain: NOD. Tissue: Adipose tissue, Head and Thymus.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Strain: FVB/N-3. Tissue: Mammary tumor.
[4]	"Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice." Ide Y., Tsuchimoto D., Tominaga Y., Nakashima M., Watanabe T., Sakumi K., Ohno M., Nakabeppu Y. Blood 104:4097-4103(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
[5]	"APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination." Guikema J.E., Linehan E.K., Tsuchimoto D., Nakabeppu Y., Strauss P.R., Stavnezer J., Schrader C.E. J. Exp. Med. 204:3017-3026(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION.
[6]	"Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes." Sabouri Z., Okazaki I.M., Shinkura R., Begum N., Nagaoka H., Tsuchimoto D., Nakabeppu Y., Honjo T. Int. Immunol. 21:947-955(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB072498 mRNA. Translation: BAB88654.1. AB085235 Genomic DNA. Translation: BAC11807.1. AK021248 mRNA. Translation: BAB32346.1. AK040145 mRNA. Translation: BAC30522.1. AK050858 mRNA. Translation: BAC34436.1. AK080916 mRNA. Translation: BAC38077.1. AK081677 mRNA. Translation: BAC38287.1. AK088918 mRNA. Translation: BAC40652.1. BC026769 mRNA. Translation: AAH26769.1. BC078633 mRNA. Translation: AAH78633.1.
IPI	IPI00225176. IPI00473955. IPI00473962. IPI00474999. IPI00828973.
RefSeq	NP_084219.1. NM_029943.1.
UniGene	Mm.440275.
3D structure databases
ProteinModelPortal	Q68G58.
SMR	Q68G58. Positions 1-307.
ModBase	Search...
PTM databases
PhosphoSite	Q68G58.
Proteomic databases
PaxDb	Q68G58.
PRIDE	Q68G58.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000112725; ENSMUSP00000108345; ENSMUSG00000025269. ENSMUST00000112727; ENSMUSP00000108347; ENSMUSG00000025269.
GeneID	77622.
KEGG	mmu:77622.
Organism-specific databases
CTD	27301.
MGI	MGI:1924872. Apex2.
Phylogenomic databases
eggNOG	COG0708.
GeneTree	ENSGT00530000063540.
HOVERGEN	HBG054715.
KO	K10772.
OrthoDB	EOG4NS3BQ.
Gene expression databases
ArrayExpress	Q68G58.
Bgee	Q68G58.
CleanEx	MM_APEX2.
Genevestigator	Q68G58.
GermOnline	ENSMUSG00000025269. Mus musculus.
Family and domain databases
Gene3D	3.60.10.10. 1 hit.
InterPro	IPR020847. AP_endonuclease_F1_BS. IPR005135. Endo/exonuclease/phosphatase. IPR004808. ExoDNase_III. IPR010666. Znf_GRF. [Graphical view]
PANTHER	PTHR22748. PTHR22748. 1 hit.
Pfam	PF03372. Exo_endo_phos. 1 hit. PF06839. zf-GRF. 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. False negative. PS51435. AP_NUCLEASE_F1_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	347242.
SOURCE	Search...

Entry information

Entry name

APEX2_MOUSE

Accession

Primary (citable) accession number: Q68G58
Secondary accession number(s): Q8BJP7 , Q8BTR7, Q8BUZ2, Q8BYE9, Q8R018, Q8R328, Q9CS12

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 30, 2005
Last sequence update:	October 11, 2004
Last modified:	May 29, 2013
This is version 75 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program