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Q68G58 (APEX2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length516 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 516516DNA-(apurinic or apyrimidinic site) lyase 2
PRO_0000200015

Regions

Region389 – 3968Required for the colocalization with PCNA in nuclear foci in presence of oxidative-induced DNA damaging agents By similarity

Sites

Active site1551 By similarity
Active site1961Proton donor/acceptor By similarity
Metal binding81Magnesium 1 By similarity
Metal binding471Magnesium 1 By similarity
Metal binding1961Magnesium 2 By similarity
Metal binding1981Magnesium 2 By similarity
Metal binding3021Magnesium 1 By similarity
Site1981Transition state stabilizer By similarity
Site2761Important for catalytic activity By similarity
Site3031Interaction with DNA substrate By similarity

Natural variations

Alternative sequence791S → SECSCPSP in isoform 2.
VSP_015346
Alternative sequence213 – 26654ECFEE…VVSGA → LPVAACGHTNLVPEWEAGPV WERTMREIMEGFCDLLHSVR IFHHHTASLLRPSY in isoform 4.
VSP_015347
Alternative sequence213 – 26048ECFEE…AFTCW → LPVAACGHTNLVPEWEAGPV WERTMREIMEVKTRFCSRPL KFTESPCL in isoform 5.
VSP_015348
Alternative sequence213 – 24634ECFEE…FMDSY → VRFPLNHRPQFCSVHPASQN WEFGTRGSFFYGKK in isoform 3.
VSP_015349
Alternative sequence247 – 516270Missing in isoform 3.
VSP_015350
Alternative sequence261 – 516256Missing in isoform 5.
VSP_015351
Alternative sequence267 – 516250Missing in isoform 4.
VSP_015352

Experimental info

Sequence conflict1101G → S in BAC38077. Ref.2
Sequence conflict1831A → P in BAB32346. Ref.2
Sequence conflict3721C → F in AAH78633. Ref.3
Sequence conflict4331V → M in AAH78633. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: ED32A88D9CEABB85

FASTA51657,340
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 50712632B2D818F7
Show »

FASTA52358,043
Isoform 3 [UniParc].

Checksum: 194A612EF3CB1D8F
Show »

FASTA24627,389
Isoform 4 [UniParc].

Checksum: 7EBE161284108FD5
Show »

FASTA26629,575
Isoform 5 [UniParc].

Checksum: 0186A39DE091BA93
Show »

FASTA26028,880

References

« Hide '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. expand/collapse author list , 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.
CCDSCCDS30463.1. [Q68G58-1]
RefSeqNP_084219.1. NM_029943.1.
UniGeneMm.440275.

3D structure databases

ProteinModelPortalQ68G58.
SMRQ68G58. Positions 1-307.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ68G58.

Proteomic databases

PaxDbQ68G58.
PRIDEQ68G58.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000112725; ENSMUSP00000108345; ENSMUSG00000025269. [Q68G58-5]
ENSMUST00000112727; ENSMUSP00000108347; ENSMUSG00000025269. [Q68G58-4]
GeneID77622.
KEGGmmu:77622.

Organism-specific databases

CTD27301.
MGIMGI:1924872. Apex2.

Phylogenomic databases

eggNOGCOG0708.
GeneTreeENSGT00530000063540.
HOVERGENHBG054715.
KOK10772.
OMAREIMEGF.
OrthoDBEOG7NKKJZ.

Gene expression databases

BgeeQ68G58.
CleanExMM_APEX2.
GenevestigatorQ68G58.

Family and domain databases

Gene3D3.60.10.10. 1 hit.
InterProIPR004808. AP_endonuc_1.
IPR020847. AP_endonuclease_F1_BS.
IPR005135. Endo/exonuclease/phosphatase.
IPR010666. Znf_GRF.
[Graphical view]
PANTHERPTHR22748. PTHR22748. 1 hit.
PfamPF03372. Exo_endo_phos. 1 hit.
PF06839. zf-GRF. 1 hit.
[Graphical view]
SUPFAMSSF56219. SSF56219. 1 hit.
TIGRFAMsTIGR00633. xth. 1 hit.
PROSITEPS00726. AP_NUCLEASE_F1_1. 1 hit.
PS51435. AP_NUCLEASE_F1_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio347242.
PROQ68G58.
SOURCESearch...

Entry information

Entry nameAPEX2_MOUSE
AccessionPrimary (citable) accession number: Q68G58
Secondary accession number(s): Q8BJP7 expand/collapse secondary AC list , Q8BTR7, Q8BUZ2, Q8BYE9, Q8R018, Q8R328, Q9CS12
Entry history
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: October 11, 2004
Last modified: July 9, 2014
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot