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PR01405

Identifier
TETRPHPHTASE  [View Relations]  [View Alignment]  
Accession
PR01405
No. of Motifs
6
Creation Date
30-APR-2000
Title
Bis(5'-nucleosyl)-tetraphosphatase signature
Database References
PRINTS; PR00502 NUDIXFAMILY
PROSITE; PS00893 ; MUTT
BLOCKS; BL00893
PFAM; PF00293 mutT
INTERPRO; IPR000086
Literature References
1. MICHAELS, M.L. AND MILLER, J.H.
The GO system protects organisms from the mutagenic effect of the
spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine).
J.BACTERIOL. 174(20) 6321-6325 (1992).
 
2. KOONIN, E.V.
A highly conserved sequence motif defining the family of mutT-related
proteins from eubacteria, eukaryotes and viruses.
NUCLEIC ACIDS RES. 21 4847 (1993).
 
3. MEJEAN, V., SALLES, C., BULLIONS, M.J., BESSMAN, M.J. AND CLAVEREYS, J.P.
Characterisation of the mutX gene of Streptococcus pneumoniae as a homolog
of Escherichia coli mutT, and tentative definition of a catalytic domain of
the dGTP pyrophosphohydrolases.
MOL.MICROBIOL. 11(2) 323-330 (1994).
 
4. SAKUMI, K., FURUICHI, M., TSUZUKI, T., KAKUMA, T., KAWABATA, S.,
MAKI, H. AND SEKIGUCHI, M.
Cloning and expression of cDNA for a human enzyme that hydrolses 8-oxo-dGTP,
a mutagenic substrate for DNA synthesis.
J.BIOL.CHEM. 268 23524-23530 (1993).
 
5. MCLENNAN, A.G. 
The MutT motif family of nucleotide phosphohydrolases in man and human
pathogens.
INT.J.MOL.MED. 4(1) 79-89 (1999).
 
6. BESSMAN, M. J., FRICK, D. N., AND O'HANDLEY, S. F. 
The MutT proteins or "Nudix" hydrolases, a family of versatile, widely
distributed, "housecleaning" enzymes.
J.BIOL.CHEM. 271 25059-25062 (1996). 
 
7. THORNE, N.M.H., HANKIN, S., WILKINSON, M.C., NUNEZ, C., BARRACLOUGH, R.
AND MCLENNAN, A.G.
Human diadenosine 5',5''-P1,P4-tetraphosphate pyrophosphohydrolase
is a member of the MutT family of nucleotide pyrophosphatases.
BIOCHEM.J. 311 717-721 (1995).

Documentation
MutT is a small bacterial protein (~12-15kDa) involved in the GO system [1]
responsible for removing an oxidatively damaged form of guanine (8-hydroxy-
guanine or 7,8-dihydro-8-oxoguanine) from the nucleotide pool.
8-oxo-dGTP is inserted opposite dA and dC residues of template DNA with
near equal efficiency, leading to A.T to G.C transversions. MutT
specifically degrades 8-oxo-dGTP to the monophosphate, with the concomitant
release of pyrophosphate. A short conserved N-terminal region of mutT 
(designated the MutT domain) is also found in a variety of other
prokaryotic, viral, and eukaryotic proteins [2-5]. Recently, the generic
name `NUDIX hydrolases' (NUcleoside DIphosphate linked to some other moeity
X) has been coined for this domain family [6].
 
The enzyme diadenosine 5',5''-P1,P4-tetraphosphate pyrophosphohydrolase 
asymmetrically hydrolyses AP4A to yield AMP and ATP. The catalysed reaction
is as follows:
    P(1),P(4)-bis(5'-adenosyl)tetraphosphate + H(2)O = ATP + AMP.
 
The cDNA and derived amino acid sequence of human diadenosine 5',5"'- 
P1,P4-tetraphosphate pyrophosphohydrolase have been determined by means of
EST analysis [7]. The protein possesses a modification of the MutT domain 
found in certain nucleotide pyrophosphatases. 
 
TETRPHPHTASE is a 6-element fingerprint that provides a signature for 
bis(5'-nucleosyl)-tetraphosphatases. The fingerprint was derived from an
initial alignment of 2 sequences: the motifs were drawn from conserved 
regions spanning the N- and C-terminal portions of the alignment - motifs 1
and 2 lie N-terminal to the MutT domain; and motifs 3-6 lie C-terminal to
it. Two iterations on SPTR37_10f were required to reach convergence, at
which point a true set comprising 3 sequences was identified.
Summary Information
3 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6333333
5000000
4000000
3000000
2000000
123456
True Positives
AP4A_HUMAN    AP4A_MOUSE    AP4A_PIG      
Sequence Titles
AP4A_HUMAN  BIS(5'-NUCLEOSYL)-TETRAPHOSPHATASE (ASYMMETRICAL) (EC 3.6.1.17) (DIADENOSINE 5',5'''-P1,P4-TETRAPHOSPHATE ASYMMETRICAL HYDROLASE) (DIADENOSINE TETRAPHOSPHATASE) (AP4A HYDROLASE) (AP4AASE) - HOMO SAPIENS (HUMAN). 
AP4A_MOUSE Bis(5'-nucleosyl)-tetraphosphatase [asymmetrical] - Mus musculus (Mouse).
AP4A_PIG BIS(5'-NUCLEOSYL)-TETRAPHOSPHATASE (ASYMMETRICAL) (EC 3.6.1.17) (DIADENOSINE 5',5'''-P1,P4-TETRAPHOSPHATE ASYMMETRICAL HYDROLASE) (DIADENOSINE TETRAPHOSPHATASE) (AP4A HYDROLASE) (AP4AASE) - SUS SCROFA (PIG).
Scan History
SPTR37_10f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
ALRACGLIIFRRCLIPKVDN AP4A_HUMAN 1 1 -
ALRRCGLIIFRRHLIPKMDN AP4A_MOUSE 1 1 -

Motif 2 width=19
Element Seqn Id St Int Rpt
IEFLLLQASDGIHHWTPPK AP4A_HUMAN 23 2 -
IEFLLLQASDGIHHWTPPK AP4A_MOUSE 23 2 -

Motif 3 width=22
Element Seqn Id St Int Rpt
QLTIIEGFKRELNYVARNKPKT AP4A_HUMAN 68 26 -
QLTIIEGFRRELNYVARQKPKT AP4A_MOUSE 68 26 -

Motif 4 width=19
Element Seqn Id St Int Rpt
TVIYWLAEVKDYDVEIRLS AP4A_HUMAN 89 -1 -
TVIYWLAEVKDYNVEIRLS AP4A_MOUSE 89 -1 -

Motif 5 width=19
Element Seqn Id St Int Rpt
EHQAYRWLGLEEACQLAQF AP4A_HUMAN 109 1 -
EHQAYRWLGLEEACQLAQF AP4A_MOUSE 109 1 -

Motif 6 width=20
Element Seqn Id St Int Rpt
FKEMKAALQEGHQFLCSIEA AP4A_HUMAN 127 -1 -
FKEMKATLQEGHQFLCSTPA AP4A_MOUSE 127 -1 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
ALRACGLIIFRRCLIPKVDN AP4A_HUMAN 1 1 -
ALRRCGLIIFRRHLIPKMDN AP4A_MOUSE 1 1 -
ALRACGLIIFRRRLIPKVDN AP4A_PIG 1 1 -

Motif 2 width=19
Element Seqn Id St Int Rpt
IEFLLLQASDGIHHWTPPK AP4A_HUMAN 23 2 -
IEFLLLQASDGIHHWTPPK AP4A_MOUSE 23 2 -
IEFLLLQASNGIHHWTPPK AP4A_PIG 23 2 -

Motif 3 width=22
Element Seqn Id St Int Rpt
QLTIIEGFKRELNYVARNKPKT AP4A_HUMAN 68 26 -
QLTIIEGFRRELNYVARQKPKT AP4A_MOUSE 68 26 -
QLTIIEGFRKELNYVAWEKPKT AP4A_PIG 68 26 -

Motif 4 width=19
Element Seqn Id St Int Rpt
TVIYWLAEVKDYDVEIRLS AP4A_HUMAN 89 -1 -
TVIYWLAEVKDYNVEIRLS AP4A_MOUSE 89 -1 -
TVIYWLAEVKDYDVEVRLS AP4A_PIG 89 -1 -

Motif 5 width=19
Element Seqn Id St Int Rpt
EHQAYRWLGLEEACQLAQF AP4A_HUMAN 109 1 -
EHQAYRWLGLEEACQLAQF AP4A_MOUSE 109 1 -
EHQAYRWLGLDEACQLAQF AP4A_PIG 109 1 -

Motif 6 width=20
Element Seqn Id St Int Rpt
FKEMKAALQEGHQFLCSIEA AP4A_HUMAN 127 -1 -
FKEMKATLQEGHQFLCSTPA AP4A_MOUSE 127 -1 -
FKDMKAVLQEGHQFLCSMAA AP4A_PIG 127 -1 -