PROSITE documentation PDOC00599

AP endonucleases family 2 signatures and profile

Description

Cellular DNA is spontaneously and continuously damaged by environmental and internal factors such as X-rays, UV light and agents such as the antitumor drugs bleomycin and neocarzinostatin or those that generate oxygen radicals. Apurinic/apyrimidinic (AP) sites form both spontaneously and as highly cytotoxic intermediates in the removal of the damaged base by the base excision repair (BER) pathway. DNA repair at the AP sites is initiated by specific endonuclease cleavage of the phosphodiester backbone. Such endonucleases are also generally capable of removing blocking groups from the 3'terminus of DNA strand breaks.

AP endonucleases can be classified into two families on the basis of sequence similarity and structure (cf. family 1 <PDOC00598>). What we call family 2 groups the enzymes listed below [1,2].

  • Bacterial endonuclease IV (gene nfo) (EC 3.1.21.2).
  • Fungal and Caenorhabditis elegans apurinic endonuclase APN1 (EC 4.2.99.18).
  • Dictyostelium endonuclease 4 homolog (EC 3.1.21.2).
  • Archaeal probable endonuclease 4 homologs (EC 3.1.21.2).
  • Mimivirus putative endonuclease 4 (EC 3.1.21.2).

APN1 and nfo have been shown to be transition metalloproteins that bind three zinc ions [3,4]. The metal-binding sites have been determined from the 3D-structure of Escherichia coli nfo [4,6,7], which shows an α/β-barrel fold (see <PDB:1QTW; A>) similar to that of other divalent metal-dependent TIM barrel enzymes (see <PDOC00155>), such as xylose isomerase (see <PDOC00156>).

We developed three signature patterns for this family of enzymes. The patterns are based on regions that contain conserved residues involved in zinc-binding. We also developed a profile that covers the entire AP endonuclease family 2 structure.

Last update:

February 2009 / Text revised; profile added.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

AP_NUCLEASE_F2_4, PS51432; AP endonucleases family 2 profile  (MATRIX)
Sequences known to belong to this class detected by the profile: ALL
Other sequence(s) detected in Swiss-Prot: NONE.
• Domain architecture view of Swiss-Prot proteins matching PS51432
PS51432
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS51432
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS51432
• Scan Swiss-Prot/TrEMBL entries against PS51432
• view ligand binding statistics
Matching PDB structures: 1QTW 1QUM 1XP3 2NQ9 ... [ALL]
AP_NUCLEASE_F2_1, PS00729; AP endonucleases family 2 signature 1  (PATTERN)
Consensus pattern: H-[GSAD]-x-Y-[LIF]-[LIMN]-N-[LIVMFCAP]-[AGC]
The H is a zinc ligand
Sequences known to belong to this class detected by the pattern: ALL
Other sequence(s) detected in Swiss-Prot: NONE.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00729
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00729
• Scan Swiss-Prot/TrEMBL entries against PS00729
• view ligand binding statistics
Matching PDB structures: 1QTW 1QUM 1XP3 2NQH ... [ALL]
AP_NUCLEASE_F2_2, PS00730; AP endonucleases family 2 signature 2  (PATTERN)
Consensus pattern: [GSARY]-[LIVMF]-[CT]-[LIVMFY]-D-T-C-H
The D and the H are zinc ligands
Sequences known to belong to this class detected by the pattern: ALL
Other sequence(s) detected in Swiss-Prot: NONE.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00730
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00730
• Scan Swiss-Prot/TrEMBL entries against PS00730
• view ligand binding statistics
Matching PDB structures: 1QTW 1QUM 1XP3 2NQ9 ... [ALL]
AP_NUCLEASE_F2_3, PS00731; AP endonucleases family 2 signature 3  (PATTERN)
Consensus pattern: [LIVMFW]-H-x-N-[DEG]-[SA]-x(4)-[GNAQ]-x(3)-D-x-H
The 2 H's and the D are zinc ligands
Sequences known to belong to this class detected by the pattern: ALL
Other sequence(s) detected in Swiss-Prot: NONE.
• Retrieve an alignment of Swiss-Prot true positive hits:
  Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00731
• Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00731
• Scan Swiss-Prot/TrEMBL entries against PS00731
• view ligand binding statistics
Matching PDB structures: 1QTW 1QUM 1XP3 2NQ9 ... [ALL]

References

1 Authors Popoff S.C., Spira A.I., Johnson A.W., Demple B.
Title Yeast structural gene (APN1) for the major apurinic endonuclease: homology to Escherichia coli endonuclease IV.
Source Proc. Natl. Acad. Sci. U.S.A. 87:4193-4197(1990).
PubMed ID 1693433
2 Authors Barzilay G., Hickson I.D.
Title Structure and function of apurinic/apyrimidinic endonucleases.
Source BioEssays 17:713-719(1995).
PubMed ID 7661852
3 Authors Levin J.D., Shapiro R., Demple B.
Title Metalloenzymes in DNA repair. Escherichia coli endonuclease IV and Saccharomyces cerevisiae Apn1.
Source J. Biol. Chem. 266:22893-22898(1991).
PubMed ID 1720775
4 Authors Hosfield D.J., Guan Y., Haas B.J., Cunningham R.P., Tainer J.A.
Title Structure of the DNA repair enzyme endonuclease IV and its DNA complex: double-nucleotide flipping at abasic sites and three-metal-ion catalysis.
Source Cell 98:397-408(1999).
PubMed ID 10458614
5 Authors Ishchenko A.A., Sanz G., Privezentzev C.V., Maksimenko A.V., Saparbaev M.
Title Characterisation of new substrate specificities of Escherichia coli and Saccharomyces cerevisiae AP endonucleases.
Source Nucleic Acids Res. 31:6344-6353(2003).
PubMed ID 14576322
6 Authors Ivanov I., Tainer J.A., McCammon J.A.
Title Unraveling the three-metal-ion catalytic mechanism of the DNA repair enzyme endonuclease IV.
Source Proc. Natl. Acad. Sci. U.S.A. 104:1465-1470(2007).
PubMed ID 17242363
DOI 10.1073/pnas.0603468104
7 Authors Garcin E.D., Hosfield D.J., Desai S.A., Haas B.J., Bjoras M., Cunningham R.P., Tainer J.A.
Title DNA apurinic-apyrimidinic site binding and excision by endonuclease IV.
Source Nat. Struct. Mol. Biol. 15:515-522(2008).
PubMed ID 18408731
DOI 10.1038/nsmb.1414

Copyright

PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)