title: An original SERPINA3 gene cluster: elucidation of genomic organization and gene expression in the Bos taurus 21q24 region.
abstract: BACKGROUND
  The superfamily of serine proteinase inhibitors (serpins) is involved in numerous fundamental biological processes as inflammation, blood coagulation and apoptosis. Our interest is focused on the SERPINA3 sub-family. The major human plasma protease inhibitor, alpha1-antichymotrypsin, encoded by the SERPINA3 gene, is homologous to genes organized in clusters in several mammalian species. However, although there is a similar genic organization with a high degree of sequence conservation, the reactive-centre-loop domains, which are responsible for the protease specificity, show significant divergences.
  
  
  RESULTS
  We provide additional information by analyzing the situation of SERPINA3 in the bovine genome. A cluster of eight genes and one pseudogene sharing a high degree of identity and the same structural organization was characterized. Bovine SERPINA3 genes were localized by radiation hybrid mapping on 21q24 and only spanned over 235 Kilobases. For all these genes, we propose a new nomenclature from SERPINA3-1 to SERPINA3-8. They share approximately 70% of identity with the human SERPINA3 homologue. In the cluster, we described an original sub-group of six members with an unexpected high degree of conservation for the reactive-centre-loop domain, suggesting a similar peptidase inhibitory pattern. Preliminary expression analyses of these bovSERPINA3s showed different tissue-specific patterns and diverse states of glycosylation and phosphorylation. Finally, in the context of phylogenetic analyses, we improved our knowledge on mammalian SERPINAs evolution.
  
  
  CONCLUSIONS
  Our experimental results update data of the bovine genome sequencing, substantially increase the bovSERPINA3 sub-family and enrich the phylogenetic tree of serpins. We provide new opportunities for future investigations to approach the biological functions of this unusual subset of serine proteinase inhibitors.
authors.affiliation: INRA, UMR 1061 Unité de Génétique Moléculaire Animale, Université de Limoges, IFR 145, Faculté des Sciences et Techniques, 87060 Limoges, France. patrick.pelissier@unilim.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Pelissier
authors.forename: Didier
authors.initials: D
authors.lastname: Delourme
authors.forename: Agnes
authors.initials: A
authors.lastname: Germot
authors.forename: Xavier
authors.initials: X
authors.lastname: Blanchet
authors.forename: Samira
authors.initials: S
authors.lastname: Becila
authors.forename: Abderrahman
authors.initials: A
authors.lastname: Maftah
authors.forename: Hubert
authors.initials: H
authors.lastname: Leveziel
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ouali
authors.forename: Laure
authors.initials: L
authors.lastname: Bremaud
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015139:Blotting, Southern; D002417:Cattle / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics*; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009132:Muscles / Q000378:metabolism; D010802:Phylogeny; D040901:Proteomics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D009626:Terminology as Topic; D000514:alpha 1-Antichymotrypsin / Q000737:chemistry / Q000235:genetics*
chemical_list: D000514:alpha 1-Antichymotrypsin