DP00007: DNA-(apurinic or apyrimidinic site) lyaseFASTA viewXML view

General information
DisProt:DP00007
Name:DNA-(apurinic or apyrimidinic site) lyase
Synonym(s):APEX1_HUMAN
Apurinic-apyrimidinic endonuclease 1
AP endonuclease 1
APEX nuclease
APEN
APE nuclease
HAP1
Apurinic/apyrimidinic endonuclease
Protein REF-1
EC=4.2.99.18
First appeared in release:Release 2.0 (02/14/2005)
UniProt:P27695
UniGene:Hs.73722
SwissProt: APEX1_HUMAN
TrEMBL:  
NCBI (GI): 113984
Source organism:Homo sapiens (Human)
Sequence length:318
Percent disordered:19%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MPKRGKKGAV AEDGDELRTE PEAKKSKTAA KKNDKEAAGE GPALYEDPPD QKTSPSGKPA - 60
TLKICSWNVD GLRAWIKKKG LDWVKEEAPD ILCLQETKCS ENKLPAELQE LPGLSHQYWS - 120
APSDKEGYSG VGLLSRQCPL KVSYGIGDEE HDQEGRVIVA EFDSFVLVTA YVPNAGRGLV - 180
RLEYRQRWDE AFRKFLKGLA SRKPLVLCGD LNVAHEEIDL RNPKGNKKNA GFTPQERQGF - 240
GELLQAVPLA DSFRHLYPNT PYAYTFWTYM MNARSKNVGW RLDYFLLSHS LLPALCDSKI - 300
RSKALGSDHC PITLYLAL



Functional narrative    

DNA-(apurinic or apyrimidinic site) lyase is a member of the AP endonuclease family and part of the base excision DNA repair pathway. DNA-(apurinic or apyrimidinic site) lyase protein has several functions, two of which are to clip DNA 5’ to AP sites by hydrolyzing the backbone of the DNA and Ref-1 activity. It regulates the sequence-specific DNA-binding affinity of p52 via a redox method (Robson, 1992). DNA-(apurinic or apyrimidinic site) lyase has interactions with at least two metal ions in its active sites.

Region 6: 1-42 Region 1: 1-43 Region 2: 36-43 Region 5: 100-104 Region 3: 102-112 Region 4: 123-127

Map of ordered and disordered regions







Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.


Region 1
Type:Disordered - Extended
Name: 
Location:1 - 43
Length:43
Region sequence:

MPKRGKKGAVAEDGDELRTEPEAKKSKTAAKKNDKEAAGEGPA

Modification type: Complex
Native
PDB: 1HD7:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Disordered region is not essential for protein function
Unknown
Detection methods:
  1. X-ray crystallography (pH: 4.6; lead (II) acetate 1 mM; polyethylene glycol 4000 (25% (w/v)); sodium acetate (pH 4.6) 0.1 M)
References:
  1. Beernink PT, Segelke BW, Hadi MZ, Erzberger JP, Wilson DM 3rd, Rupp B. "Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism." J Mol Biol. 2001; 307(4): 1023-34. PubMed: 11286553
Comments:
This structure is refered to as 'form II' in Beernink (2001).


Region 2
Type:Disordered - Extended
Name: 
Location:36 - 43
Length:8
Region sequence:

EAAGEGPA

Modification type: Complex
Engineered
Fragment
PDB: 1BIX:_
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Disordered region is not essential for protein function
Unknown
Detection methods:
  1. X-ray crystallography (pH: 6.2; 1,4- Dioxane (5 percent w/v); calcium acetate (292 Kelvin) 200 mM; crystals flash cooled (110 Kelvin); HEPES (pH 7.4) 10 mM; MES (pH 6.2) 100 mM; PEG 8000 (16 to 20 percent w/v); samarium acetate (7.5-30 mM); well solution 3 ml)
References:
  1. Gorman MA, Morera S, Rothwell DG, de La Fortelle E, Mol CD, Tainer JA, Hickson ID, Freemont PS. "The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites." Embo J. 1997; 16(21): 6548-58. PubMed: 9351835
Comments:
This structure is refered to as 'form I' in Beernink (2001).

The experimental sequence did not contain the N-terminal residues 1-35.


Region 3
Type:Disordered - Extended
Name: 
Location:102 - 112
Length:11
Region sequence:

NKLPAELQELP

Modification type: Complex
Native
PDB: 1HD7:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography (pH: 4.6; lead (II) acetate 1 mM; polyethylene glycol 4000 (25% (w/v)); sodium acetate (pH 4.6) 0.1 M)
References:
  1. Beernink PT, Segelke BW, Hadi MZ, Erzberger JP, Wilson DM 3rd, Rupp B. "Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism." J Mol Biol. 2001; 307(4): 1023-34. PubMed: 11286553
Comments:
This structure is refered to as 'form II' in Beernink (2001).


Region 4
Type:Disordered - Extended
Name: 
Location:123 - 127
Length:5
Region sequence:

SDKEG

Modification type: Complex
Native
PDB: 1HD7:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography (pH: 4.6; lead (II) acetate 1 mM; polyethylene glycol 4000 (25% (w/v)); sodium acetate (pH 4.6) 0.1 M)
References:
  1. Beernink PT, Segelke BW, Hadi MZ, Erzberger JP, Wilson DM 3rd, Rupp B. "Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism." J Mol Biol. 2001; 307(4): 1023-34. PubMed: 11286553
Comments:
This structure is refered to as 'form II' in Beernink (2001).


Region 5
Type:Disordered
Name: 
Location:100 - 104
Length:5
Region sequence:

SENKL

Modification type: Complex
Engineered
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography (pH: 6.2; 1,4- Dioxane (5 percent w/v); calcium acetate (292 Kelvin) 200 mM; crystals flash cooled (110 Kelvin); HEPES (pH 7.4) 10 mM; MES (pH 6.2) 100 mM; PEG 8000 (16 to 20 percent w/v); samarium acetate (7.5-30 mM); well solution 3 ml)
References:
  1. Beernink PT, Segelke BW, Hadi MZ, Erzberger JP, Wilson DM 3rd, Rupp B. "Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism." J Mol Biol. 2001; 307(4): 1023-34. PubMed: 11286553
Comments:
This structure is refered to as 'form I' in Beernink (2001).

The experimental sequence did not contain the N-terminal residues 1-35.


Region 6
Type:Disordered - Extended
Name: 
Location:1 - 42
Length:42
Region sequence:

MPKRGKKGAVAEDGDELRTEPEAKKSKTAAKKNDKEAAGEGP

Modification type: Complex
Native
PDB: 1E9N:A, 1E9N:B
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Disordered region is not essential for protein function
Unknown
Detection methods:
  1. X-ray crystallography (pH: 7.5; HECAMEG 19.5 mM; lead (II) acetate 1 mM; polyethylene glycol 4000 (25% (w/v)); sodium acetate 0.2 M; Tris-HCl (pH 7.5) 0.1 M)
References:
  1. Gorman MA, Morera S, Rothwell DG, de La Fortelle E, Mol CD, Tainer JA, Hickson ID, Freemont PS. "The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites." Embo J. 1997; 16(21): 6548-58. PubMed: 9351835
Comments:
This region is not essential for function (Gorman 1997).

This structure is refered to as 'form III' in Beernink (2001)


References

  1. Barzilay G, Hickson ID. "Structure and function of apurinic/apyrimidinic endonucleases." Bioessays. 1995; 17(8): 713-9. PubMed: 7661852

  2. Robson CN, Hickson ID. "Isolation of cDNA clones encoding a human apurinic/apyrimidinic endonuclease that corrects DNA repair and mutagenesis defects in E. coli xth (exonuclease III) mutants." Nucleic Acids Res. 1991; 19(20): 5519-5523. PubMed: 1719477

  3. Robson CN, Hochhauser D, Craig R, Rack K, Buckle VJ, Hickson ID. "Structure of the human DNA repair gene HAP1 and its localisation to chromosome 14q 11.2-12." Nucleic Acids Res. 1992; 20(17): 4417-4421. PubMed: 1383925



Comments


For forms I, II and III of this protein referenced in Beernick (2001) , there is relatively high thermal motion in the areas of residues 100-110, 145, 200 and 270. These areas also show large root-mean-square fluctuations.


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