Serpins: Evolution

Gary A Silverman, Harvard Medical School, Boston, Massachusetts, USA
David J Askew, Harvard Medical School, Boston, Massachusetts, USA
James A Irving, Monash University, Melbourne, Victoria, Australia
Cliff J Luke, Harvard Medical School, Boston, Massachusetts, USA
Dion Kaiserman, Monash University, Melbourne, Victoria, Australia
Phillip I Bird, Monash University, Melbourne, Victoria, Australia
James C Whisstock, Monash University, Melbourne, Victoria, Australia

Published online: May 2008

DOI: 10.1002/9780470015902.a0006118.pub2

The serpin superfamily of serine (and cysteine) proteinase inhibitors contains over 750 members represented in Bacteria, Archaea and Eukarya. All members of the serpin family share a unique tertiary structure that is critical to both inhibitory and noninhibitory functions. Serpins are involved in a vast array of biological processes, including the regulation of thrombosis, fibrinolysis and inflammation, and host defense.

Keywords: serpins; serine proteinase inhibitor; cysteine proteinase inhibitor; evolution; genomes

Figure 1. Multifurcating phylogenic tree showing the relationship between 35 human serpins and other members of the serpin superfamily. The tree was constructed using previously described methods (Irving et al., 2000). Conventional bootstrap values derived from maximum parsimony trees are highlighted by ovals. Hexagons indicate clades identified using the strict consensus method, and rectangles highlight clades identified using the comparison method. Each major clade is labeled A–P, consistent with the nomenclature described (Silverman et al., 2001).
Figure 2. Three mouse serpin clusters are expanded in comparison with humans. Clade A serpins on human chromosome 14 and the two clade B clusters on chromosomes 6 and 18 (top maps) are compared with their mouse counterparts (bottom maps). Synteny is well conserved with expansion of the number of mouse genes in certain regions. C-term only refers to gene fragments that encode for the terminal 200 amino acids only. Although these fragments have an RSL, the absence of N-terminal sequences precludes the synthesis of an active inhibitor. aa: amino acids; cM: centimorgans; kb: kilobases; RSL: reactive site loop.
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 References
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    Silverman GA, Bird PI, Carrell RW et al. (2001) The serpins are an expanding superfamily of structurally similar but functionally diverse proteins: evolution, mechanism of inhibition, novel functions, and a revised nomenclature. Journal of Biological Chemistry 276: 33293–33296.
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 Further Reading
    Atchley WR, Lokot T, Wollenberg K, Dress A and Ragg H (2001) Phylogenetic analyses of amino acid variation in the serpin proteins. Molecular Biology and Evolution 18: 1502–1511.
    Davis RL, Shrimpton AE, Holohan PD et al. (1999) Familial dementia caused by polymerization of mutant neuroserpin. Nature 401: 376–379.
    van Gent D, Sharp P, Morgan K and Kalsheker N (2003) Serpins: structure, function and molecular evolution. International Journal of Biochemistry Cell Biology 35: 1536–1547.
    book Gettins PGW, Patston PA and Olson ST (eds.) (1996) Serpins: Structure, Function and Biology. Austin, TX: RG Landes and Chapman & Hall.
    Huber R and Carrell RW (1989) Implications of the three-dimensional structure of 1-antitrypsin for structure and function of serpins. Biochemistry 28: 8951–8966.
    Marshall CJ (1993) Evolutionary relationships among the serpins. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences 342: 101–119.
    Ragg H, Lokot T, Kamp PB, Atchley WR and Dress A (2001) Vertebrate serpins: construction of a conflict-free phylogeny by combining exon–intron and diagnostic site analyses. Molecular Biology and Evolution 18: 577–584.
    Remold-O'Donnell E (1993) The ovalbumin family of serpin proteins. FEBS Letters 315: 105–108.
 Web Links
    ePath serine (or cysteine) proteinase inhibitor, clade A (-1 antiproteinase, antitrypsin), member 1 (SERPINA1); LocusID: 5265. Locus Link: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5265
    ePath serine (or cysteine) proteinase inhibitor, clade C (antithrombin), member 1 (SERPINC1); LocusID: 462. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=462
    ePath serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 (SERPINE1); LocusID: 5054. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5054
    ePath serine (or cysteine) proteinase inhibitor, clade G (C1 inhibitor), member 1 (SERPING1); LocusID: 710. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=710
    ePath serine (or cysteine) proteinase inhibitor, clade I (neuroserpin), member 1 (SERPINI1); LocusID: 5274. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5274
    ePath serine proteinase inhibitor, clade A (SERPINA1); MIM number: 107400. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?107400
    ePath serine (or cysteine) proteinase inhibitor, clade C (antithrombin), member 1 (SERPINC1); MIM number: 107300. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?107300
    ePath serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 (SERPINE1); MIM number: 173360. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?173360
    ePath serine (or cysteine) proteinase inhibitor, clade G (C1 inhibitor), member 1 (SERPING1); MIM number: 606860. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606860
    ePath serine (or cysteine) proteinase inhibitor, clade I (neuroserpin), member 1 (SERPINI1); MIM number: 602445. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602445

Related Sub-Topics:

Molecular Evolution | Protein Evolution
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Article Title: Serpins: Evolution
 
How to Cite close
Silverman, Gary A, Askew, David J, Irving, James A, Luke, Cliff J, Kaiserman, Dion, Bird, Phillip I, and Whisstock, James C(May 2008) Serpins: Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006118.pub2]