Protein family

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A protein family is a group of evolutionarily related proteins, and is often nearly synonymous with gene family. The term protein family should not be confused with family as it is used in taxonomy.

Proteins in a family descend from a common ancestor (see homology) and typically have similar three-dimensional structures, functions, and significant sequence similarity. While it is difficult to evaluate the significance of functional or structural similarity, there is a fairly well developed framework for evaluating the significance of similarity between a group of sequences using sequence alignment methods. Proteins that do not share a common ancestor are very unlikely to show statistically significant sequence similarity, making sequence alignment a powerful tool for identifying the members of protein families.

Currently, over 60,000 protein families have been defined,[1], although ambiguity in the definition of protein family leads different researchers to wildly varying numbers. (list of major families coming soon).

Terminology and Usage

As with many biological terms, the use of protein family is somewhat context dependent; it may indicate large groups of proteins with the lowest possible level of detectable sequence similarity, or very narrow groups of proteins with almost identical sequence, function, and three-dimensional structure, or any kind of group in-between. To distinguish between these situations, Dayhoff introduced the concept of a protein superfamily.[2][3][4] Other terms such as protein class, protein group, and protein sub-family have been coined over the years, but all suffer similar ambiguities of usage. A common usage is superfamily > family > sub-family. In the end, caveat emptor, it is up to a reader to discern exactly how these terms are being used in a particular context.

Protein Domains and Motifs

The concept of protein family was conceived at a time when very few protein structures or sequences were known; at that time, primarily small, single-domain proteins such as myoglobin, hemoglobin, and cytochrome c. Since that time, we have discovered that many proteins comprise multiple, independently folding regions (functional units) or domains. Due to evolutionary shuffling, domains in a protein may not have a common history (i.e., have evolved along different paths). This has led, in recent years, to a focus on families of protein domains. A number of online resources are devoted to identifying and cataloging such domains (see list of links at the end of this article).

Regions of each protein have differing functional constraints (features critical to the structure and function of the protein). For example, the active site of an enzyme requires certain amino acid residues to be precisely oriented in three-dimensions. On the other hand, a protein-protein binding interface may consist of a large surface with constraints on the hydrophobicity or polarity of the amino acid residues. Functionally constrained regions of proteins evolve more slowly than unconstrained regions such as surface loops, giving rise to discernable blocks of conserved sequence when the sequences of a protein family are compared (see multiple sequence alignment). These blocks are mot commonly referred to as motifs, although many other terms are used (blocks,signatures,fingerprints, etc.). Again, a large number of online resources are devoted to identifying and cataloging protein motifs (see list at end of article).

Evolution of protein families

According to current dogma, protein families arise in two ways. Firstly, the separation of a parent species into two genetically isolated descendent species allows a gene/protein to independently accumulate variations (mutations in these two lineages. This results in a family of orthologous proteins, usually with conserved sequence motifs. Many times these families are the result of gene duplication events. Secondly, a gene duplication may create a second copy of a gene (termed a paralog). Because the original gene is still able to perform its function, the duplicated gene is free to diverge and may acquire new functions (by random mutation). Certain gene/protein families, especially in eukaryotes, undergo extreme expansions and contractions in the course of evolution, sometimes in concert with whole genome duplications. This expansion and contraction of protein families is one of the salient features of genome evolution, but its importance and ramifications are currently unclear.

Use and Importance of Protein Families

As the total number of sequenced proteins increases and interest expands in proteome analysis, there is an ongoing effort to organize proteins into families and to describe their component domains and motifs. Reliable identification of protein families is key to phylogenetic analysis, functional annotation and the exploration of diversity of protein function in a given phylogenetic branch.

Methods for Identifying Protein Familes & Assigning Proteins to Families

The algorithmic means for establishing protein families on large scale are based on a notion of similarity. Most of the time the only similarity we have access to is sequence similarity.

See also

Related Articles

Protein Structure Resources

Protein Families

()s contain a highly abbreviated hint of the function of the family

External links

  • Pfam - Protein families database of alignments and HMMs
  • PROSITE - Database of protein domains, families and functional sites
  • PIRSF - SuperFamily Classification System
  • PASS2 - Protein Alignment as Structural Superfamilies v2 - PASS2@NCBS

References

  1. V.Kunin, I. Cases, A.J. Enrigh, V. de Lorenzo, C.A. Ouzounis, 'Myriads of protein families, and still counting', Genome Biology 4, 401, 2003.[1]
  2. Dayhoff, M.O., Computer analysis of protein sequences, Fed. Proc. 33, 2314-2316, 1974.
  3. Dayhoff, M.O., McLaughlin, P.J., Barker, W.C., and Hunt, L.T., Evolution of sequences within protein superfamilies,Naturwissenschaften 62, 154-161, 1975.
  4. Dayhoff, M.O., The origin and evolution of protein superfamilies, Fed. Proc. 35, 2132-2138, 1976.

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| group5 = Clinical Trials Involving Protein family | list5 = Ongoing Trials on Protein family at Clinical Trials.govTrial results on Protein familyClinical Trials on Protein family at Google


| group6 = Guidelines / Policies / Government Resources (FDA/CDC) Regarding Protein family | list6 = US National Guidelines Clearinghouse on Protein familyNICE Guidance on Protein familyNHS PRODIGY GuidanceFDA on Protein familyCDC on Protein family


| group7 = Textbook Information on Protein family | list7 = Books and Textbook Information on Protein family


| group8 = Pharmacology Resources on Protein family | list8 = AND (Dose)}} Dosing of Protein familyAND (drug interactions)}} Drug interactions with Protein familyAND (side effects)}} Side effects of Protein familyAND (Allergy)}} Allergic reactions to Protein familyAND (overdose)}} Overdose information on Protein familyAND (carcinogenicity)}} Carcinogenicity information on Protein familyAND (pregnancy)}} Protein family in pregnancyAND (pharmacokinetics)}} Pharmacokinetics of Protein family


| group9 = Genetics, Pharmacogenomics, and Proteinomics of Protein family | list9 = AND (pharmacogenomics)}} Genetics of Protein familyAND (pharmacogenomics)}} Pharmacogenomics of Protein familyAND (proteomics)}} Proteomics of Protein family


| group10 = Newstories on Protein family | list10 = Protein family in the newsBe alerted to news on Protein familyNews trends on Protein family


| group11 = Commentary on Protein family | list11 = Blogs on Protein family

| group12 = Patient Resources on Protein family | list12 = Patient resources on Protein familyDiscussion groups on Protein familyPatient Handouts on Protein familyDirections to Hospitals Treating Protein familyRisk calculators and risk factors for Protein family


| group13 = Healthcare Provider Resources on Protein family | list13 = Symptoms of Protein familyCauses & Risk Factors for Protein familyDiagnostic studies for Protein familyTreatment of Protein family

| group14 = Continuing Medical Education (CME) Programs on Protein family | list14 = CME Programs on Protein family

| group15 = International Resources on Protein family | list15 = Protein family en EspanolProtein family en Francais

| group16 = Business Resources on Protein family | list16 = Protein family in the MarketplacePatents on Protein family

| group17 = Informatics Resources on Protein family | list17 = List of terms related to Protein family


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