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Biology of reproduction1999; 60(5); 1069-1077; doi: 10.1095/biolreprod60.5.1069

Identification of a new aspartic proteinase expressed by the outer chorionic cell layer of the equine placenta.

Abstract: The pregnancy-associated glycoproteins (PAGs) are placental antigens that were initially characterized as pregnancy markers in the maternal circulation of domestic ruminant species. They are members of the aspartic proteinase gene family, having greatest sequence identity with pepsinogens. However, some are not capable of functioning as enzymes. The PAGs are associated with a large gene family within the Artiodactyla order (cattle, camels, pigs). So far, no members of this family have been characterized in species outside this order. This report describes the cloning and initial characterization of a PAG-like protein (equine PAG or ePAG) expressed in the placenta of the horse and zebra (order Perrisodactyla). Equine PAG is a proteinase capable of degrading 14C-hemoglobin and catalyzing the removal of its own pro-peptide. The ePAG mRNA is restricted to the chorion both prior to implantation and in the term placenta. Equine PAG is secreted from cultured placental tissue as both a processed (mature) and unprocessed (zymogen) form. Equine PAG shares similar identity with the PAGs and pepsinogens and probably arose from a pepsinogen-like precursor that gained the ability to be expressed in the placenta. The promoter of the ePAG gene shares sequence identity with the promoter from a bovine PAG gene but not with promoters of other aspartic proteinases. Therefore, we hypothesize that ePAG is a remnant of the pepsinogen-like progenitor gene that was expanded within the Artiodactyla to create the large and highly diverse PAG family.
Publication Date: 1999-04-20 PubMed ID: 10208966DOI: 10.1095/biolreprod60.5.1069Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

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The researchers discovered a new kind of proteinase in the perrisodactyl order (e.g. horses and zebras), which they’ve labeled ePAG. This proteinase, derived from a predecessor similar to pepsinogen, is found in the placenta and plays a role in the breakdown of hemoglobin protein as well as autolysis.

Introduction

  • The paper discusses the identification of a new protein called ‘equine PAG’ or ‘ePAG’, which is a placental antigen (PAG).
  • PAGs were initially known as pregnancy indicators within the maternal circulation of certain species, primarily in the Artiodactyla order which includes animals like cattle, camels, and pigs.
  • No members of this family have previously been characterized in species outside the Artiodactyla order. This study does so by describing the cloning and initial characterization of ePAG in the placenta of horses and zebras, members of the Perrisodactyla order.

Methodology and Results

  • The ePAG is a proteinase or enzyme that can degrade 14C-hemoglobin and can catalyze the removal of its own pro-peptide. This indicates the protein’s activity in protein breakdown processes during pregnancy.
  • The ePAG mRNA, the molecule that carries the code to make the ePAG protein, is found only in the chorion, both prior to implantation and in the term placenta.
  • The ePAG protein is expelled from cultured placental tissue in both processed and unprocessed forms.

Characteristics and Hypotheses

  • The ePAG shows a similar identification pattern with both PAGs and pepsinogens, suggesting that it probably evolved from a predecessor similar to pepsinogen which developed the capability for expression in the placenta.
  • The promoter of the ePAG gene – a region of DNA that initiates transcription of a particular gene – shares sequence similarities with the promoter from a bovine PAG gene but not with promoters of other aspartic proteinases.
  • Based on their findings, the researchers hypothesize that ePAG is a leftover from the pepsinogen-like progenitor gene that expanded in the Artiodactyla order to create the large and diverse family of PAGs.

Cite This Article

APA
Green JA, Xie S, Szafranska B, Gan X, Newman AG, McDowell K, Roberts RM. (1999). Identification of a new aspartic proteinase expressed by the outer chorionic cell layer of the equine placenta. Biol Reprod, 60(5), 1069-1077. https://doi.org/10.1095/biolreprod60.5.1069

Publication

ISSN: 0006-3363
NlmUniqueID: 0207224
Country: United States
Language: English
Volume: 60
Issue: 5
Pages: 1069-1077

Researcher Affiliations

Green, J A
  • Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri 65211, USA.
Xie, S
    Szafranska, B
      Gan, X
        Newman, A G
          McDowell, K
            Roberts, R M

              MeSH Terms

              • Amino Acid Sequence
              • Animals
              • Aspartic Acid Endopeptidases / analysis
              • Aspartic Acid Endopeptidases / biosynthesis
              • Aspartic Acid Endopeptidases / metabolism
              • Base Sequence
              • Blotting, Northern
              • Blotting, Western
              • Chorion / enzymology
              • Cloning, Molecular
              • Culture Techniques
              • Female
              • Hemoglobins / metabolism
              • Horses / metabolism
              • In Situ Hybridization
              • Molecular Sequence Data
              • Placenta / enzymology
              • Pregnancy
              • RNA, Messenger / biosynthesis
              • Recombinant Proteins / analysis
              • Recombinant Proteins / biosynthesis

              Grant Funding

              • HD29483 / NICHD NIH HHS

              Citations

              This article has been cited 5 times.
              1. Lipka A, Panasiewicz G, Majewska M, Paukszto L, Bieniek-Kobuszewska M, Szafranska B. Identification of Placental Aspartic Proteinase in the Eurasian Beaver (Castor fiber L.).. Int J Mol Sci 2018 Apr 18;19(4).
                doi: 10.3390/ijms19041229pubmed: 29670018google scholar: lookup
              2. Majewska M, Lipka A, Panasiewicz G, Gowkielewicz M, Jozwik M, Majewski MK, Szafranska B. Identification of Novel Placentally Expressed Aspartic Proteinase in Humans.. Int J Mol Sci 2017 Jun 8;18(6).
                doi: 10.3390/ijms18061227pubmed: 28594357google scholar: lookup
              3. Bieniek-Kobuszewska M, Panasiewicz G, Lipka A, Majewska M, Szafranska B. Novel SNPs and InDels discovered in two promoter regions of porcine pregnancy-associated glycoprotein 2-like subfamily (pPAG2-Ls) in crossbreed pigs.. Funct Integr Genomics 2016 Nov;16(6):705-715.
                doi: 10.1007/s10142-016-0522-zpubmed: 27709373google scholar: lookup
              4. Mason RW, Bergman CA, Lu G, Frenck Holbrook J, Sol-Church K. Expression and characterization of cathepsin P.. Biochem J 2004 Mar 1;378(Pt 2):657-63.
                doi: 10.1042/BJ20031548pubmed: 14629193google scholar: lookup
              5. Hughes AL, Green JA, Garbayo JM, Roberts RM. Adaptive diversification within a large family of recently duplicated, placentally expressed genes.. Proc Natl Acad Sci U S A 2000 Mar 28;97(7):3319-23.
                doi: 10.1073/pnas.97.7.3319pubmed: 10725351google scholar: lookup