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HAMAP in 2015: updates to the protein family classification and annotation system.

Pedruzzi I, Rivoire C, Auchincloss AH, Coudert E, Keller G, de Castro E, Baratin D, Cuche BA, Bougueleret L, Poux S, Redaschi N, Xenarios I, Bridge A - Nucleic Acids Res. (2014)

Bottom Line: Here we report on the growth of HAMAP and updates to the HAMAP system since our last report in the NAR Database Issue of 2013.We demonstrate how the complex logic of HAMAP rules allows for precise annotation of individual functional variants within large homologous protein families.We also describe improvements to our web-based tool HAMAP-Scan which simplify the classification and annotation of sequences, and the incorporation of an improved sequence-profile search algorithm.

View Article: PubMed Central - PubMed

Affiliation: Swiss-Prot Group, SIB Swiss Institute of Bioinformatics, CMU, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland.

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HAMAP annotation rule MF_01976 for mixed-substrate PFK group III family. The right hand panel shows snippets of the annotation rule MF_01976 including conditions used to specify site-specific annotations propagated to target sequences. If a protein sequence matches the HAMAP family profile MF_01976, then appropriate annotations for all members of that family (such as family membership) are attached to the sequence. For the annotation of sequence features, the target sequence is aligned to the seed alignment and the active site residue from the template sequence mapped to the target sequence. The nature of the residue at the equivalent position in the target sequence determines which of the possible conditional annotations will be attached to the sequence.
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Figure 2: HAMAP annotation rule MF_01976 for mixed-substrate PFK group III family. The right hand panel shows snippets of the annotation rule MF_01976 including conditions used to specify site-specific annotations propagated to target sequences. If a protein sequence matches the HAMAP family profile MF_01976, then appropriate annotations for all members of that family (such as family membership) are attached to the sequence. For the annotation of sequence features, the target sequence is aligned to the seed alignment and the active site residue from the template sequence mapped to the target sequence. The nature of the residue at the equivalent position in the target sequence determines which of the possible conditional annotations will be attached to the sequence.

Mentions: HAMAP defines 8 PFK families in line with the currently accepted classification of PFKs (32,35) (Table 1). Several of the eight HAMAP families include both PPi-dependent and ATP-dependent members, suggesting that phosphoryl-donor specificity may have changed at multiple times during the evolution of the PFK superfamily. Figure 2 illustrates how this functional variation within families is treated by HAMAP using annotation rule MF_01976, which describes members of the mixed substrate PFK group III subfamily. The precise annotation that is applied to members of this family depends on the nature of the active site residue (D104 in the experimentally characterized template of Amycolatopsis methanolica—UniProtKB/Swiss-Prot record Q59126). Case statements within the rule specify the correct protein name, catalytic activity (including EC number), function, keywords, GO terms and other annotations for family members bearing either D or G at their active site. Sequences having neither of these residues are annotated as generic 6-phosphofructokinases of unknown substrate-specificity. The example of PFK illustrates how a single residue may determine substrate specificity and enzyme function, but HAMAP rule syntax also allows conditional annotation based on the combination of multiple residues or sequence motifs. The methylthioadenosine (MTA) phosphorylases are one example, where conserved amino acid substitutions in the substrate binding pocket convert the substrate specificity of this enzyme from 6-aminopurine (EC 2.4.2.28) to 6-oxopurine nucleosides (EC 2.4.2.44 and EC 2.4.2.1) (described in MF_01963).


HAMAP in 2015: updates to the protein family classification and annotation system.

Pedruzzi I, Rivoire C, Auchincloss AH, Coudert E, Keller G, de Castro E, Baratin D, Cuche BA, Bougueleret L, Poux S, Redaschi N, Xenarios I, Bridge A - Nucleic Acids Res. (2014)

HAMAP annotation rule MF_01976 for mixed-substrate PFK group III family. The right hand panel shows snippets of the annotation rule MF_01976 including conditions used to specify site-specific annotations propagated to target sequences. If a protein sequence matches the HAMAP family profile MF_01976, then appropriate annotations for all members of that family (such as family membership) are attached to the sequence. For the annotation of sequence features, the target sequence is aligned to the seed alignment and the active site residue from the template sequence mapped to the target sequence. The nature of the residue at the equivalent position in the target sequence determines which of the possible conditional annotations will be attached to the sequence.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383873&req=5

Figure 2: HAMAP annotation rule MF_01976 for mixed-substrate PFK group III family. The right hand panel shows snippets of the annotation rule MF_01976 including conditions used to specify site-specific annotations propagated to target sequences. If a protein sequence matches the HAMAP family profile MF_01976, then appropriate annotations for all members of that family (such as family membership) are attached to the sequence. For the annotation of sequence features, the target sequence is aligned to the seed alignment and the active site residue from the template sequence mapped to the target sequence. The nature of the residue at the equivalent position in the target sequence determines which of the possible conditional annotations will be attached to the sequence.
Mentions: HAMAP defines 8 PFK families in line with the currently accepted classification of PFKs (32,35) (Table 1). Several of the eight HAMAP families include both PPi-dependent and ATP-dependent members, suggesting that phosphoryl-donor specificity may have changed at multiple times during the evolution of the PFK superfamily. Figure 2 illustrates how this functional variation within families is treated by HAMAP using annotation rule MF_01976, which describes members of the mixed substrate PFK group III subfamily. The precise annotation that is applied to members of this family depends on the nature of the active site residue (D104 in the experimentally characterized template of Amycolatopsis methanolica—UniProtKB/Swiss-Prot record Q59126). Case statements within the rule specify the correct protein name, catalytic activity (including EC number), function, keywords, GO terms and other annotations for family members bearing either D or G at their active site. Sequences having neither of these residues are annotated as generic 6-phosphofructokinases of unknown substrate-specificity. The example of PFK illustrates how a single residue may determine substrate specificity and enzyme function, but HAMAP rule syntax also allows conditional annotation based on the combination of multiple residues or sequence motifs. The methylthioadenosine (MTA) phosphorylases are one example, where conserved amino acid substitutions in the substrate binding pocket convert the substrate specificity of this enzyme from 6-aminopurine (EC 2.4.2.28) to 6-oxopurine nucleosides (EC 2.4.2.44 and EC 2.4.2.1) (described in MF_01963).

Bottom Line: Here we report on the growth of HAMAP and updates to the HAMAP system since our last report in the NAR Database Issue of 2013.We demonstrate how the complex logic of HAMAP rules allows for precise annotation of individual functional variants within large homologous protein families.We also describe improvements to our web-based tool HAMAP-Scan which simplify the classification and annotation of sequences, and the incorporation of an improved sequence-profile search algorithm.

View Article: PubMed Central - PubMed

Affiliation: Swiss-Prot Group, SIB Swiss Institute of Bioinformatics, CMU, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland.

Show MeSH
Related in: MedlinePlus