Identifying property based sequence motifs in protein families and superfamilies: application to DNase-1 related endonucleases.
BACKGROUND
Identification of short conserved sequence motifs common to a protein family or superfamily can be more useful than overall sequence similarity in suggesting the function of novel gene products. Locating motifs still requires expert knowledge, as automated methods using stringent criteria may not differentiate subtle similarities from statistical noise.


RESULTS
We have developed a novel automatic method, based on patterns of conservation of 237 physical-chemical properties of amino acids in aligned protein sequences, to find related motifs in proteins with little or no overall sequence similarity. As an application, our web-server MASIA identified 12 property-based motifs in the apurinic/apyrimidinic endonuclease (APE) family of DNA-repair enzymes of the DNase-I superfamily. Searching with these motifs located distantly related representatives of the DNase-I superfamily, such as Inositol 5'-polyphosphate phosphatases in the ASTRAL40 database, using a Bayesian scoring function. Other proteins containing APE motifs had no overall sequence or structural similarity. However, all were phosphatases and/or had a metal ion binding active site. Thus our automated method can identify discrete elements in distantly related proteins that define local structure and aspects of function. We anticipate that our method will complement existing ones to functionally annotate novel protein sequences from genomic projects.


BACKGROUND
MASIA WEB site: http://www.scsb.utmb.edu/masia/masia.html


BACKGROUND
The dendrogram of 42 APE sequences used to derive motifs is available on http://www.scsb.utmb.edu/comp_biol.html/DNA_repair/publication.html
Mathura
Venkatarajan S
VS
Sealy Center for Structural Biology, Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX 77555-1157, USA.
Schein
Catherine H
CH
Braun
Werner
W
D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D030562:Databases, Protein; D015253:Deoxyribonucleases, Type I Site-Specific / Q000737:chemistry*; D004720:Endonucleases / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software
D011506:Proteins; D004720:Endonucleases; D015253:Deoxyribonucleases, Type I Site-Specific