Tandem duplication of serpin genes yields functional variation and snake venom inhibitors.

Tandem duplication of genes can play a critical role in the evolution of functional novelty, but our understanding is limited concerning gene duplication's role in coevolution between species. Much is known about the evolution and function of tandemly duplicated snake venom genes, however the potential of gene duplication to fuel venom resistance within prey species is poorly understood. In this study, we characterize patterns of gene duplication of the SERPINA subfamily of genes across in vertebrates and experimentally characterize functional variation in the SERPINA3-like paralogs of a wild rodent.

High-throughput amino acid-level characterization of the interactions of plasminogen activator inhibitor-1 with variably divergent proteases.

While members of large paralogous protein families share structural features, their functional niches often diverge significantly. Serine protease inhibitors (SERPINs), whose members typically function as covalent inhibitors of serine proteases, are one such family. Plasminogen activator inhibitor-1 (PAI-1) is a prototypic SERPIN, which canonically inhibits tissue-and urokinase-type plasminogen activators (tPA and uPA) to regulate fibrinolysis.

Functional overlap between the mammalian and paralogs in vivo.

Proteins carrying a signal peptide and/or a transmembrane domain enter the intracellular secretory pathway at the endoplasmic reticulum (ER) and are transported to the Golgi apparatus via COPII vesicles or tubules. SAR1 initiates COPII coat assembly by recruiting other coat proteins to the ER membrane. Mammalian genomes encode two paralogs, and .