title: Phylogeny of the serpin superfamily: implications of patterns of amino acid conservation for structure and function.
abstract: We present a comprehensive alignment and phylogenetic analysis of the serpins, a superfamily of proteins with known members in higher animals, nematodes, insects, plants, and viruses. We analyze, compare, and classify 219 proteins representative of eight major and eight minor subfamilies, using a novel technique of consensus analysis. Patterns of sequence conservation characterize the family as a whole, with a clear relationship to the mechanism of function. Variations of these patterns within phylogenetically distinct groups can be correlated with the divergence of structure and function. The goals of this work are to provide a carefully curated alignment of serpin sequences, to describe patterns of conservation and divergence, and to derive a phylogenetic tree expressing the relationships among the members of this family. We extend earlier studies by Huber and Carrell as well as by Marshall, after whose publication the serpin family has grown functionally, taxonomically, and structurally. We used gene and protein sequence data, crystal structures, and chromosomal location where available. The results illuminate structure-function relationships in serpins, suggesting roles for conserved residues in the mechanism of conformational change. The phylogeny provides a rational evolutionary framework to classify serpins and enables identification of conserved amino acids. Patterns of conservation also provide an initial point of comparison for genes identified by the various genome projects. New homologs emerging from sequencing projects can either take their place within the current classification or, if necessary, extend it.
authors: Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne, Victoria 3168, Australia.
authors: J A
authors: JA
authors: Irving
authors: R N
authors: RN
authors: Pike
authors: A M
authors: AM
authors: Lesk
authors: J C
authors: JC
authors: Whisstock
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D005110:Extracellular Space / Q000737:chemistry / Q000502:physiology; D015801:Helminth Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology; D007424:Intracellular Fluid / Q000737:chemistry / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D010940:Plant Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology; D011487:Protein Conformation; D016415:Sequence Alignment; D015843:Serpins / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000502:physiology
chemical_list: D015801:Helminth Proteins; D019476:Insect Proteins; D010940:Plant Proteins; D015843:Serpins; D014764:Viral Proteins