FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Biochem Genet / The equine major plasma serpin multigene family: partial cha...
Biochemical genetics1991; 29(9-10); 477-499; doi: 10.1007/BF02399689

The equine major plasma serpin multigene family: partial characterization including sequence of the reactive-site regions.

Abstract: The equine Pi system, which is highly polymorphic and was considered to be controlled by a single locus, has been shown to be controlled by four loci (named Spi 1-4). This system is the equine equivalent of the major human plasma serpin (serine protease inhibitor), human alpha 1 PI. Twenty-two haplotypes of the equine Pi system have been characterized by two-dimensional electrophoresis, resulting in the assignment of pI, Mr, and bovine trypsin and chymotrypsin inhibition characteristics to 109 proteins. These proteins have been analyzed further to determine their relatedness to each other as well as to human alpha 1 PI using immunochemical, structural, and functional criteria. The amino acid sequences of the N termini and reactive-site regions have been determined on proteins from each of the four equine Spi loci. This allowed the designation of the proteins from the Spi 1 locus as being METserpins and the functional equivalents of human alpha 1 PI. The Spi 4 proteins are ARGserpins, and by alignment the Spi 2 proteins are ILEserpins, the first so far described. The P1 residue for the Spi 3 proteins was unable to be determined. The limited peptide and immunopeptide mapping revealed that proteins from all four loci were closely related, but within the four there were two pairs (Spi 1 and 2 and Spi 3 and 4) which were more related. All were probably derived from the same gene that gave rise to human alpha 1 PI.
Get Full Text
Publication Date: 1991-10-01 PubMed ID: 1772402DOI: 10.1007/BF02399689Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research explores the equine Pi system, specifically identifying it to be controlled by four loci (Spi 1-4). It includes detailed findings on the characterization of the system’s proteins and their relationship to human alpha 1 PI.

Exploration of Equine Pi System

  • The research primarily explores the equine Pi system, previously assumed to be controlled by a singular locus, but now shown to be controlled by four loci labelled Spi 1-4.
  • Defining the exact workings of this system is crucial as it is the equine equivalent of the human plasma serpin or human alpha 1 PI, a significant element within the human immune system.

Characterization of the Pi System

  • The team managed to identify twenty-two haplotypes within the equine Pi system using two-dimensional electrophoresis.
  • This allowed assignment of pI, Mr, and bovine trypsin and chymotrypsin inhibition characteristics to 109 proteins.
  • The functional, structural, and immunochemical similarities between these proteins and human alpha 1 PI were established as well.

Sequencing the Spi Loci

  • The researchers also sequenced the N termini and reactive-site regions of each of the protein samples derived from the four equine Spi loci.
  • This led to the designation of Spi 1 derived proteins as METserpins, operationally equivalent to human alpha 1 PI.
  • The proteins from the Spi 4 locus were labelled as ARGserpins, and, by alignment, the Spi 2 proteins were ILEserpins.

Peptide and Immunopeptide Mapping

  • The research further involved the limited peptide and immunopeptide mapping of proteins.
  • This mapping showed that proteins from all four loci are closely related, but pairs of loci, specifically Spi 1 and 2, and Spi 3 and 4, displayed more similarities.
  • This indicated to the researchers that all the proteins were probably derived from the same gene that also gave rise to human alpha 1 PI.

Cite This Article

APA
Patterson SD, Bell K, Shaw DC. (1991). The equine major plasma serpin multigene family: partial characterization including sequence of the reactive-site regions. Biochem Genet, 29(9-10), 477-499. https://doi.org/10.1007/BF02399689

Publication

Biochemical genetics
ISSN: 0006-2928
NlmUniqueID: 0126611
Country: United States
Language: English
Volume: 29
Issue: 9-10
Pages: 477-499

Researcher Affiliations

Patterson, S D
  • Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
Bell, K
    Shaw, D C

      MeSH Terms

      • Amino Acid Sequence
      • Animals
      • Binding Sites
      • Haplotypes
      • Horses / genetics
      • Molecular Sequence Data
      • Multigene Family
      • N-Acetylneuraminic Acid
      • Oxidation-Reduction
      • Peptide Mapping
      • Polymorphism, Genetic
      • Serpins / blood
      • Serpins / chemistry
      • Serpins / genetics
      • Serpins / metabolism
      • Sialic Acids / analysis

      References

      This article includes 57 references
      1. Patterson SD, Bell K, Manton VJ. Equus przewalskii plasma protease inhibitor (Pi) system.. Anim Genet 1990;21(2):129-39.
        pubmed: 2386311doi: 10.1111/j.1365-2052.1990.tb03217.xgoogle scholar: lookup
      2. Jeppsson JO, Laurell CB, Fagerhol M. Properties of isolated human alpha1-antitrypsins of Pi types M, S and Z.. Eur J Biochem 1978 Feb 1;83(1):143-53.
        pubmed: 304805doi: 10.1111/j.1432-1033.1978.tb12078.xgoogle scholar: lookup
      3. Patterson SD, Bell K, Poole WE. Tammar wallaby plasma protease inhibitory (Pi) proteins.. Aust J Biol Sci 1987;40(4):355-64.
        pubmed: 3453036doi: 10.1071/bi9870355google scholar: lookup
      4. Pellegrini A, Zweifel HR, von Fellenberg R. Horse alpha-1 protease inhibitors: relationship between the slow (S) and fast (F) isoforms.. Int J Biochem 1985;17(4):463-9.
        pubmed: 3891451doi: 10.1016/0020-711x(85)90141-7google scholar: lookup
      5. Carrell RW, Pemberton PA, Boswell DR. The serpins: evolution and adaptation in a family of protease inhibitors.. Cold Spring Harb Symp Quant Biol 1987;52:527-35.
        pubmed: 3502621doi: 10.1101/sqb.1987.052.01.060google scholar: lookup
      6. Patterson SD, Bell K. Application of an affinity electrophoretic and in situ oxidation method to the study of the equine protease inhibitory proteins.. Electrophoresis 1989 Jan;10(1):40-5.
        pubmed: 2714237doi: 10.1002/elps.1150100110google scholar: lookup
      7. Carrell R. Therapy by instant evolution.. Nature 1984 Nov 1-7;312(5989):14.
        pubmed: 6333640doi: 10.1038/312014a0google scholar: lookup
      8. Hill RE, Hastie ND. Accelerated evolution in the reactive centre regions of serine protease inhibitors.. Nature 1987 Mar 5-11;326(6108):96-9.
        pubmed: 3493437doi: 10.1038/326096a0google scholar: lookup
      9. Potempa J, Wunderlich JK, Travis J. Comparative properties of three functionally different but structurally related serpin variants from horse plasma.. Biochem J 1991 Mar 1;274 ( Pt 2)(Pt 2):465-71.
        pubmed: 2006910doi: 10.1042/bj2740465google scholar: lookup
      10. Juneja RK, Gahne B, Sandberg K. Genetic polymorphism and close linkage of two alpha 1-protease inhibitors in horse serum.. Anim Blood Groups Biochem Genet 1979;10(4):235-51.
        pubmed: 94978doi: 10.1111/j.1365-2052.1979.tb01031.xgoogle scholar: lookup
      11. Pemberton PA, Harrison RA, Lachmann PJ, Carrell RW. The structural basis for neutrophil inactivation of C1 inhibitor.. Biochem J 1989 Feb 15;258(1):193-8.
        pubmed: 2930506doi: 10.1042/bj2580193google scholar: lookup
      12. Jallat S, Carvallo D, Tessier LH, Roecklin D, Roitsch C, Ogushi F, Crystal RG, Courtney M. Altered specificities of genetically engineered alpha 1 antitrypsin variants.. Protein Eng 1986 Oct-Nov;1(1):29-35.
        pubmed: 3509863doi: 10.1093/protein/1.1.29google scholar: lookup
      13. Patterson SD, Bell K, Shaw DC. The tammar wallaby major plasma serpin: partial characterization including the sequence of the reactive site region.. Comp Biochem Physiol C Comp Pharmacol Toxicol 1991;98(2-3):359-67.
        pubmed: 1676950doi: 10.1016/0742-8413(91)90217-hgoogle scholar: lookup
      14. Carrell RW, Owen MC. Plakalbumin, alpha 1-antitrypsin, antithrombin and the mechanism of inflammatory thrombosis.. Nature 1985 Oct 24-30;317(6039):730-2.
        pubmed: 3877243doi: 10.1038/317730a0google scholar: lookup
      15. Patterson SD, Bell K. ISO-DALT characterization of 12 'new' equine plasma protease inhibitor (Pi) alleles.. Anim Genet 1987;18(2):167-80.
        pubmed: 3662116doi: 10.1111/j.1365-2052.1987.tb00756.xgoogle scholar: lookup
      16. Pellegrini A, Hägeli G, von Fellenberg R. Resistance of horse alpha 1-proteinase inhibitor to perchloric acid denaturation and a simplified purification procedure resulting therefrom.. Biochim Biophys Acta 1986 Nov 21;874(2):144-9.
        pubmed: 3022814doi: 10.1016/0167-4838(86)90111-1google scholar: lookup
      17. Carrell RW, Jeppsson JO, Laurell CB, Brennan SO, Owen MC, Vaughan L, Boswell DR. Structure and variation of human alpha 1-antitrypsin.. Nature 1982 Jul 22;298(5872):329-34.
        pubmed: 7045697doi: 10.1038/298329a0google scholar: lookup
      18. Potempa J, Watorek W, Travis J. The inactivation of human plasma alpha 1-proteinase inhibitor by proteinases from Staphylococcus aureus.. J Biol Chem 1986 Oct 25;261(30):14330-4.
        pubmed: 3533918
      19. Patterson SD, Bell K, Shaw DC. Donkey and horse alpha 1 B-glycoprotein: partial characterization and new alleles.. Comp Biochem Physiol B 1991;98(4):523-8.
        pubmed: 1868686doi: 10.1016/0305-0491(91)90247-bgoogle scholar: lookup
      20. Pellegrini A, von Fellenberg R. Fractionation and partial characterization of alpha-1-protease isoinhibitors of horse.. Biochim Biophys Acta 1980 Dec 4;616(2):351-61.
        pubmed: 6971123doi: 10.1016/0005-2744(80)90152-7google scholar: lookup
      21. Braend M. Genetics of horse acidic prealbumins.. Genetics 1970 Jul;65(3):495-503.
        pubmed: 5519647doi: 10.1093/genetics/65.3.495google scholar: lookup
      22. Board PG, Suzuki T, Shaw DC. Human muscle glutathione S-transferase (GST-4) shows close homology to human liver GST-1.. Biochim Biophys Acta 1988 Apr 14;953(3):214-7.
        pubmed: 3281712doi: 10.1016/0167-4838(88)90027-1google scholar: lookup
      23. Pollitt CC, Bell K. Protease inhibitor system in horses: classification and detection of a new allele.. Anim Blood Groups Biochem Genet 1980;11(4):235-44.
        pubmed: 7247075doi: 10.1111/j.1365-2052.1980.tb01514.xgoogle scholar: lookup
      24. Laegreid WW, Breeze RG, Counts DF. Isolation and some properties of equine alpha 1-antitrypsin.. Int J Biochem 1982;14(4):327-34.
        pubmed: 6978269doi: 10.1016/0020-711x(82)90094-5google scholar: lookup
      25. Pollitt CC, Bell K. Characterisation of the alpha 1-protease inhibitor system in Thoroughbred horse plasma by horizontal two-dimensional (ISO-DALT) electrophoresis. 1. Protein staining.. Anim Blood Groups Biochem Genet 1983;14(2):83-105.
        pubmed: 6193745doi: 10.1111/j.1365-2052.1983.tb01065.xgoogle scholar: lookup
      26. Laskowski M Jr, Kato I, Kohr WJ, Park SJ, Tashiro M, Whatley HE. Positive darwinian selection in evolution of protein inhibitors of serine proteinases.. Cold Spring Harb Symp Quant Biol 1987;52:545-53.
        pubmed: 3502622doi: 10.1101/sqb.1987.052.01.062google scholar: lookup
      27. Pollitt CC, Bell K. Characterisation of the alpha 1-protease inhibitor system in Thoroughbred horse plasma by horizontal two-dimensional (ISO-DALT) electrophoresis. 2. Protease inhibition.. Anim Blood Groups Biochem Genet 1983;14(2):107-18.
        pubmed: 6604473doi: 10.1111/j.1365-2052.1983.tb01066.xgoogle scholar: lookup
      28. Kelsey GD, Parkar M, Povey S. The human alpha-1-antitrypsin-related sequence gene: isolation and investigation of its expression.. Ann Hum Genet 1988 May;52(2):151-60.
        pubmed: 2470331doi: 10.1111/j.1469-1809.1988.tb01091.xgoogle scholar: lookup
      29. Krauter KS, Citron BA, Hsu MT, Powell D, Darnell JE Jr. Isolation and characterization of the alpha 1-antitrypsin gene of mice.. DNA 1986 Feb;5(1):29-36.
        pubmed: 3007061doi: 10.1089/dna.1986.5.29google scholar: lookup
      30. Papamokos E, Weber E, Bode W, Huber R, Empie MW, Kato I, Laskowski M Jr. Crystallographic refinement of Japanese quail ovomucoid, a Kazal-type inhibitor, and model building studies of complexes with serine proteases.. J Mol Biol 1982 Jul 5;158(3):515-37.
        pubmed: 6752426doi: 10.1016/0022-2836(82)90212-1google scholar: lookup
      31. Hill RE, Shaw PH, Barth RK, Hastie ND. A genetic locus closely linked to a protease inhibitor gene complex controls the level of multiple RNA transcripts.. Mol Cell Biol 1985 Aug;5(8):2114-22.
        pubmed: 2427931doi: 10.1128/mcb.5.8.2114-2122.1985google scholar: lookup
      32. Okayama H, Holmes MD, Brantly ML, Crystal RG. Characterization of the coding sequence of the normal M4 alpha 1-antitrypsin gene.. Biochem Biophys Res Commun 1989 Aug 15;162(3):1560-70.
        pubmed: 2788414doi: 10.1016/0006-291x(89)90853-xgoogle scholar: lookup
      33. Patterson SD, Bell K. Frequencies of plasma protease inhibitor alleles in Australian horse breeds and the recognition of two new alleles.. Anim Genet 1987;18(2):181-6.
        pubmed: 3662117doi: 10.1111/j.1365-2052.1987.tb00757.xgoogle scholar: lookup
      34. Brennan SO, Borg JY, George PM, Soria C, Soria J, Caen J, Carrell RW. New carbohydrate site in mutant antithrombin (7 Ile----Asn) with decreased heparin affinity.. FEBS Lett 1988 Sep 12;237(1-2):118-22.
        pubmed: 3169232doi: 10.1016/0014-5793(88)80183-2google scholar: lookup
      35. Holmes WE, Lijnen HR, Collen D. Characterization of recombinant human alpha 2-antiplasmin and of mutants obtained by site-directed mutagenesis of the reactive site.. Biochemistry 1987 Aug 11;26(16):5133-40.
        pubmed: 2444252doi: 10.1021/bi00390a036google scholar: lookup
      36. Diven WF, Vietmeier B, Hempel J, Chambers J. Purification and N-terminal characterization of Chinchilla villidera alpha-1-antitrypsin.. Comp Biochem Physiol B 1990;95(1):39-44.
        pubmed: 2184987doi: 10.1016/0305-0491(90)90245-ogoogle scholar: lookup
      37. Patterson SD, Bell K. The equine protease inhibitory system (Pi): abnormal expressions of PiF, PiL, and PiS1.. Biochem Genet 1986 Aug;24(7-8):529-43.
        pubmed: 3753429doi: 10.1007/BF00504333google scholar: lookup
      38. Stephens AW, Siddiqui A, Hirs CH. Site-directed mutagenesis of the reactive center (serine 394) of antithrombin III.. J Biol Chem 1988 Nov 5;263(31):15849-52.
        pubmed: 3141397
      39. Saito A, Sinohara H. Differential interactions of rabbit plasma alpha-1-antiproteinases S and F with porcine trypsin.. J Biochem 1988 Feb;103(2):247-53.
        pubmed: 3259574doi: 10.1093/oxfordjournals.jbchem.a122255google scholar: lookup
      40. Nukiwa T, Brantly ML, Ogushi F, Fells GA, Crystal RG. Characterization of the gene and protein of the common alpha 1-antitrypsin normal M2 allele.. Am J Hum Genet 1988 Sep;43(3):322-30.
        pubmed: 2901226
      41. Putt W, Whitehouse DB. Genetics of four plasma protein loci in Equus przewalskii: new alleles at the prealbumin, postalbumin and transferrin loci.. Anim Blood Groups Biochem Genet 1983;14(1):7-16.
        pubmed: 6614596doi: 10.1111/j.1365-2052.1983.tb01055.xgoogle scholar: lookup
      42. Loebermann H, Tokuoka R, Deisenhofer J, Huber R. Human alpha 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function.. J Mol Biol 1984 Aug 15;177(3):531-57.
        pubmed: 6332197
      43. Kress LF. Inactivation of human plasma serine proteinase inhibitors (serpins) by limited proteolysis of the reactive site loop with snake venom and bacterial metalloproteinases.. J Cell Biochem 1986;32(1):51-8.
        pubmed: 2429973doi: 10.1002/jcb.240320106google scholar: lookup
      44. Stein PE, Leslie AG, Finch JT, Turnell WG, McLaughlin PJ, Carrell RW. Crystal structure of ovalbumin as a model for the reactive centre of serpins.. Nature 1990 Sep 6;347(6288):99-102.
        pubmed: 2395463doi: 10.1038/347099a0google scholar: lookup
      45. Ek N, Braend M. Quantitative comparisons of acidic prealbumin (PR) phenotypes in horses.. Acta Vet Scand 1980;21(3):380-8.
        pubmed: 7446321doi: 10.1186/BF03546870google scholar: lookup
      46. Saito A, Sinohara H. Amino acid sequence at the reactive site of rabbit alpha-1-antiproteinases.. J Biochem 1990 Jul;108(1):80-5.
        pubmed: 2229014doi: 10.1093/oxfordjournals.jbchem.a123167google scholar: lookup
      47. Chandra T, Stackhouse R, Kidd VJ, Robson KJ, Woo SL. Sequence homology between human alpha 1-antichymotrypsin, alpha 1-antitrypsin, and antithrombin III.. Biochemistry 1983 Oct 25;22(22):5055-61.
        pubmed: 6606438doi: 10.1021/bi00291a001google scholar: lookup
      48. Chao S, Chai KX, Chao L, Chao J. Molecular cloning and primary structure of rat alpha 1-antitrypsin.. Biochemistry 1990 Jan 16;29(2):323-9.
        pubmed: 2302382doi: 10.1021/bi00454a004google scholar: lookup
      49. Bell K, Patterson S, Pollitt CC. The plasma protease inhibitor system (Pi) of Standardbred horses.. Anim Blood Groups Biochem Genet 1984;15(3):191-206.
        pubmed: 6517392doi: 10.1111/j.1365-2052.1984.tb01116.xgoogle scholar: lookup
      50. Hofker MH, Nelen M, Klasen EC, Nukiwa T, Curiel D, Crystal RG, Frants RR. Cloning and characterization of an alpha 1-antitrypsin like gene 12 KB downstream of the genuine alpha 1-antitrypsin gene.. Biochem Biophys Res Commun 1988 Sep 15;155(2):634-42.
        pubmed: 2901833doi: 10.1016/s0006-291x(88)80542-4google scholar: lookup
      51. Beatty K, Bieth J, Travis J. Kinetics of association of serine proteinases with native and oxidized alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin.. J Biol Chem 1980 May 10;255(9):3931-4.
        pubmed: 6989830
      52. Borriello F, Krauter KS. Reactive site polymorphism in the murine protease inhibitor gene family is delineated using a modification of the PCR reaction (PCR + 1).. Nucleic Acids Res 1990 Sep 25;18(18):5481-7.
        pubmed: 2216721doi: 10.1093/nar/18.18.5481google scholar: lookup
      53. Laskowski M Jr. An algorithmic approach to sequence leads to reactivity of proteins. Specificity of protein inhibitors of serine proteinases.. Biochem Pharmacol 1980 Aug 1;29(15):2089-94.
        pubmed: 6996686doi: 10.1016/0006-2952(80)90177-xgoogle scholar: lookup
      54. Patterson SD, Bell K. The carbohydrate side chains of the major plasma serpins of horse and wallaby: analyses of enzymatic and chemically treated (including 'Smith degradation') protein blots by lectin binding.. Biochem Int 1990;20(3):429-36.
        pubmed: 2111994
      55. Lindmark B, Lilja H, Alm R, Eriksson S. The microheterogeneity of desialylated alpha 1-antichymotrypsin: the occurrence of two amino-terminal isoforms, one lacking a His-Pro dipeptide.. Biochim Biophys Acta 1989 Jul 27;997(1-2):90-5.
        pubmed: 2787670doi: 10.1016/0167-4838(89)90139-8google scholar: lookup
      56. Koide T, Foster D, Odani S. The heparin-binding site(s) of histidine-rich glycoprotein as suggested by sequence homology with antithrombin III.. FEBS Lett 1986 Jan 6;194(2):242-4.
        pubmed: 3000827doi: 10.1016/0014-5793(86)80092-8google scholar: lookup
      57. Kurachi K, Chandra T, Degen SJ, White TT, Marchioro TL, Woo SL, Davie EW. Cloning and sequence of cDNA coding for alpha 1-antitrypsin.. Proc Natl Acad Sci U S A 1981 Nov;78(11):6826-30.
        pubmed: 7031661doi: 10.1073/pnas.78.11.6826google scholar: lookup

      Citations

      This article has been cited 2 times.
      1. Arthur H, Bell K, VandeBerg JL, van Oorschot RA. Plasma protease inhibitor (PI) system in the laboratory opossum, Monodelphis domestica. Biochem Genet 1996 Oct;34(9-10):389-99.
        doi: 10.1007/BF00554414pubmed: 8978911google scholar: lookup
      2. Billingsley GD, Walter MA, Hammond GL, Cox DW. Physical mapping of four serpin genes: alpha 1-antitrypsin, alpha 1-antichymotrypsin, corticosteroid-binding globulin, and protein C inhibitor, within a 280-kb region on chromosome I4q32.1. Am J Hum Genet 1993 Feb;52(2):343-53.
        pubmed: 8381582
      Subscribe to our newsletter
      Join 99,001 horse owners like you who receive our email updates on horse health and nutrition.