Update of the human and mouse SERPIN gene superfamily

Abstract

The serpin family comprises a structurally similar, yet functionally diverse, set of proteins. Named originally for their function as serine proteinase inhibitors, many of its members are not inhibitors but rather chaperones, involved in storage, transport, and other roles. Serpins are found in genomes of all kingdoms, with 36 human protein-coding genes and five pseudogenes. The mouse has 60 Serpin functional genes, many of which are orthologous to human SERPIN genes and some of which have expanded into multiple paralogous genes. Serpins are found in tissues throughout the body; whereas most are extracellular, there is a class of intracellular serpins. Serpins appear to have roles in inflammation, immune function, tumorigenesis, blood clotting, dementia, and cancer metastasis. Further characterization of these proteins will likely reveal potential biomarkers and therapeutic targets for disease.

Figure 1

Native SERPINA1. Native SERPINA1 with labeled structural elements: β sheet a and reactive center loop (RCL); α helices in red, β sheets in turquoise, turns in green. (Adapted from PDB 1HP7).

Figure 2

SERPIN phylogenetic tree. Phylogenetic tree of human and mouse serpin proteins. Protein sequences were aligned using TCOFFEE and analysed using neighbour-joining methods with 10,000 bootstrap replicates in the Phylip package.