Ovalbumin Serpins

Abstract

Ovalbumin serpins (ov‐serpins) are a clade of intracellular protease inhibitors belonging to the serpin superfamily. They are involved in tumor progression, cell growth and differentiation, and the control of cell death. The genes are clustered at 6p25 and 18q21–23 and have almost identical structures.

Keywords: serpin; ov‐serpin; gene; gene localization; gene structure

Figure 1.

Serpin structure. This shows the arrangement of structural elements of the prototypical serpin, α1 antitrypsin, as deduced by X‐ray crystallography. Nine α‐helices (hA–hF) and three β‐sheets (A–C) make up the core structure. The reactive center loop (RCL) extrudes from the top of the molecule and contains the peptide bond (P1–P1′) cleaved by the cognate protease. When the model is viewed from this perspective, the RCL inserts between the second and third strands of the A‐sheet after cleavage. (Prepared by J. Irving.)

Figure 2.

Relationships between ovalbumin (ov) serpins shown as a 1000‐bootstrap maximum parsimony tree based on amino acid sequence using antithrombin as the outgroup. MNEI: monocyte/neutrophil elastase inhibitor; PAI: plasminogen activator inhibitor; PI: proteinase inhibitor; SCCA: squamous cell carcinoma antigen. (Prepared by J. Irving after Scott et al., 1999.)

Figure 3.

Ovalbumin (ov‐) serpin genes. The upper panel shows the clustering and order of ov‐serpin genes at 18q21 (over approximately 800 kb) and 6p25 (over approximately 200 kb). The lower panel shows aligned ov‐serpin coding regions exemplified by PAI‐2 (class I) and PI‐6 (class II). Open arrowheads indicate the position of introns. The region encoding the interhelical CD loop is indicated by the shaded box. Figure is not to scale. MNEI: monocyte/neutrophil elastase inhibitor; PAI: plasminogen activator inhibitor; PI: proteinase inhibitor; SCCA: squamous cell carcinoma antigen.

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References

Askew YS, Pak SC, Luke CJ, et al. (2001) SERPINB12 is a novel member of the human ov‐serpin family that is widely expressed and inhibits trypsin‐like serine proteinases. Journal of Biological Chemistry 276: 49320–49330.

Bird CH, Sutton VR, Sun J, et al. (1998) Selective regulation of apoptosis: the cytotoxic lymphocyte serpin proteinase inhibitor 9 protects against granzyme B‐mediated apoptosis without perturbing the Fas cell death pathway. Molecular Cell Biology 18: 6387–6398.

Dougherty KM, Pearson JM, Yang AY, et al. (1999) The plasminogen activator inhibitor‐2 gene is not required for normal murine development or survival. Proceedings of the National Academy of Sciences of the United States of America 96: 686–691.

Duggan C, Kennedy S, Kramer MD, et al. (1997) Plasminogen activator inhibitor type 2 in breast cancer. British Journal of Cancer 76: 622–627.

Huntington JA, Read RA and Carrell RW (2000) Structure of a serpin–protease complex shows inhibition by deformation. Nature 407: 923–926.

Jin L, Abrahams JP, Skinner R, et al. (1998) The anticoagulant activation of antithrombin by heparin. Proceedings of the National Academy of Sciences of the United States of America 94: 14683–14688.

Keijer J, Ehrlich HJ, Linders M, Preissner KT and Pannekoek H (1991) Vitronectin governs the interaction between plasminogen activator inhibitor 1 and tissue‐type plasminogen activator. Journal of Biological Chemistry 266: 10700–10707.

Rees DD, Rogers RA, Cooley J, et al. (1999) Recombinant human monocyte/neutrophil elastase inhibitor protects rat lungs against injury from cystic fibrosis airway secretions. American Journal of Respiratory Cell and Molecular Biology 20: 69–78.

Remold‐O'Donnell E (1993) The ovalbumin family of serpin proteins. FEBS Letters 315: 105–108.

Riewald M and Schleef RR (1996) Human cytoplasmic antiproteinase neutralizes rapidly and efficiently chymotrypsin and trypsin‐like proteinases utilizing distinct reactive site residues. Journal of Biological Chemistry 271: 14526–14532.

Scott FL, Eyre HJ, Lioumi M, et al. (1999) Human ovalbumin serpin evolution: phylogenic analysis, gene organization, and identification of new PI‐8‐related genes suggest that two interchromosomal and several intrachromosomal duplications generated the gene clusters at 18q21–q23 and 6p25. Genomics 62: 490–499.

Zhang M, Volpert O, Shi YH and Bouck N (2000) Maspin is an angiogenesis inhibitor. Nature Medicine 6: 196–199.

Further Reading

Antalis TM, La Linn M, Donnan K, et al. (1998) The serine proteinase inhibitor (serpin) plasminogen activation inhibitor type 2 protects against viral cytopathic effects by constitutive interferon alpha/beta priming. Journal of Experimental Medicine 187: 1799–1811.

Belin D (1993) Biology and facultative secretion of plasminogen activator inhibitor‐2. Thrombosis and Haemostasis 70: 144–147.

Bird PI (1999) Regulation of pro‐apoptotic leucocyte granule serine proteinases by intracellular serpins. Immunology and Cell Biology 77: 47–57.

Grigoryev SA, Bednar J and Woodcock CL (1999) MENT, a heterochromatin protein that mediates higher order chromatin folding, is a new serpin family member. Journal of Biological Chemistry 274: 5626–5636.

Silverman GS, Bird PI, Carrell RW, et al. (2001) The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Journal of Biological Chemistry 276: 33293–33296.

Stein PE and Carrell RW (1995) What do dysfunctional serpins tell us about molecular mobility and disease? Structural Biology 2: 96–113.

Zou Z, Anisowicz A, Hendrix MJC, et al. (1994) Maspin, a serpin with tumour‐supressing activity in human mammary epithelial cells. Science 263: 526–529.

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How to Cite close
Bird, Phillip I, and Silverman, Gary A(Jan 2006) Ovalbumin Serpins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005903]