ArticleProceedings of the National Academy of Sciences of the United States of America2002
Inference of functional regions in proteins by quantification of evolutionary constraints.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Predicting Pathogenicity ofInternational journal of molecular sciences · 2026Article
- In Silico Analysis Identified Putative Pathogenic Missense Single Nucleotide Polymorphisms (SNPs) in the HumanInternational journal of molecular sciences · 2025Article
- CONSTRUCT: an algorithmic tool for identifying functional or structurally important regions in protein tertiary structure.Bioinformatics (Oxford, England) · 2025Article
- CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis.Nature cell biology · 2018Article
- Aminode: Identification of Evolutionary Constraints in the Human Proteome.Scientific reports · 2018Article
- Article
- Phylogenetic Gaussian process model for the inference of functionally important regions in protein tertiary structures.PLoS computational biology · 2014Article
- Duplication and maintenance of the Myb genes of vertebrate animals.Biology open · 2013Article
- Evolutionary Analysis of Functional Divergence among Chemokine Receptors, Decoy Receptors, and Viral Receptors.Frontiers in microbiology · 2012Article
- The non-random clustering of non-synonymous substitutions and its relationship to evolutionary rate.BMC genomics · 2011Article
- ProPhylER: a curated online resource for protein function and structure based on evolutionary constraint analyses.Genome research · 2010Article
- Physical and functional characterization of the genetic locus of IBtk, an inhibitor of Bruton's tyrosine kinase: evidence for three protein isoforms of IBtk.Nucleic acids research · 2008Article
- Identification of the Otopetrin Domain, a conserved domain in vertebrate otopetrins and invertebrate otopetrin-like family members.BMC evolutionary biology · 2008Article
- Article
- APRIN is a unique Pds5 paralog with features of a chromatin regulator in hormonal differentiation.The Journal of steroid biochemistry and molecular biology · 2008Article
- Structural and molecular evolutionary analysis of Agouti and Agouti-related proteins.Chemistry & biology · 2006Article
- Physicochemical constraint violation by missense substitutions mediates impairment of protein function and disease severity.Genome research · 2005Article
- Phenotype-genotype correlation in Hirschsprung disease is illuminated by comparative analysis of the RET protein sequence.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- Using multiple alignments to improve seeded local alignment algorithms.Nucleic acids research · 2005Article
- Functional evolution of the vertebrate Myb gene family: B-Myb, but neither A-Myb nor c-Myb, complements Drosophila Myb in hemocytes.Genetics · 2005Article
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3 authors.
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Abstract
Likelihood estimates of local rates of evolution within proteins reveal that selective constraints on structure and function are quantitatively stable over billions of years of divergence. The stability of constraints produces an intramolecular clock that gives each protein a characteristic pattern of evolutionary rates along its sequence. This pattern allows the identification of constrained regions and, because the rate of evolution is a quantitative measure of the strength of the constraint, of their functional importance. We show that results from such analyses, which require only sequence alignments, are consistent with experimental and mutational data. The methodology has significant predictive power and may be used to guide structure--function studies for any protein represented by a modest number of homologs in sequence databases.
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