Quantitative sequence-function relationships in proteins based on gene ontology

Abstract

Background:The relationship between divergence of amino-acid sequence and divergence of function among homologous proteins is complex. The assumption that homologs share functionthe basis of transfer of annotations in databases -must therefore be regarded with caution. Here, we present a quantitative study of sequence and function divergence, based on the Gene Ontology classification of function. We determined the relationship between sequence divergence and function divergence in 6828 protein families from the PFAM database. Within families there is a broad range of sequence similarity from very closely related proteins -for instance, orthologs in different mammals -to very distantly-related proteins at the limit of reliable recognition of homology.

Domain-Based and Family-Specific Sequence Identity Thresholds Increase the Levels of Reliable Protein Function Transfer

“…13 Both report a general correlation between increasing sequence identity and the conservation of GO annotations between sequences. 14,15 However, these analyses also show that intrinsic features of the GO hierarchy impede its use for sequence annotation comparison in a fashion similar to the EC system. This is particularly the structure of the directed acyclic graph underlying GO, where branch lengths (the number of levels of annotational detail) vary greatly.…”

A Computational Biology Approach in Function Annotation to Enzymes

“…(Sangar et al, 2007). 721 suf 3210 sf 3210 enzyme functional subfamilies identified in 721 CATH-Gene3D enzyme superfamilies.…”

Bioinformatics of Protein Function

“…Sangar, Blankenberg, Altman and Lesk 64 have extended these studies by determining how sequence divergence is related to functional divergence as measured using the GO functional classification. They find a threshold at about 50% sequence identity beyond which the divergence of function is accelerated.…”