ArticleProceedings of the National Academy of Sciences of the United States of America1997
The diversity and evolutionary relationships of the pregnancy-associated glycoproteins, an aspartic proteinase subfamily consisting of many trophoblast-expressed genes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 185 citations in OpenAlex.
- Pregnancy-Associated Glycoproteins Identification in Skopelos Goat Milk by Means of Mass Spectrometry.Veterinary sciences · 2025Article
- Early pregnancy detection in ruminants: challenges and innovations.The Journal of reproduction and development · 2025Review
- Article
- Using Pregnancy-Associated Glycoproteins (PAGs) to Improve Reproductive Management: From Dairy Cows to Other Dairy Livestock.Animals : an open access journal from MDPI · 2022Review
- Short Communication: Influence of estrus activity and reproductive tract size and position scores on fertility in Bos indicus and Bos taurus suckled beef cows.Journal of animal science · 2022Article
- Article
- Evolution of Placental Hormones: Implications for Animal Models.Frontiers in endocrinology · 2022Review
- Approaches to Identify Pregnancy Failure in Buffalo Cows.Animals : an open access journal from MDPI · 2021Article
- Plasmatic Profile of Pregnancy-Associated Glycoprotein (PAG) during Gestation and Postpartum in Sarda and Lacaune Sheep Determined with Two Radioimmunoassay Systems.Animals : an open access journal from MDPI · 2020Article
- Evolution of placentation in cattle and antelopes.Animal reproduction · 2020Article
- Cattle adapted to tropical and subtropical environments: genetic and reproductive considerations.Journal of animal science · 2020Review
- Buffalo early pregnancy biomarker coding sequence cloning and partial length expression inHeliyon · 2019Article
- mRNA expression profiling in cotyledons reveals significant up-regulation of the two bovine pregnancy-associated glycoprotein genes boPAG-8 and boPAG-11 in early gestation.Veterinary medicine and science · 2018Article
- Identification of Placental Aspartic Proteinase in the Eurasian Beaver (International journal of molecular sciences · 2018Article
- Article
- Identification of Novel Placentally Expressed Aspartic Proteinase in Humans.International journal of molecular sciences · 2017Article
- Novel SNPs and InDels discovered in two promoter regions of porcine pregnancy-associated glycoprotein 2-like subfamily (pPAG2-Ls) in crossbreed pigs.Functional & integrative genomics · 2016Article
- Purification of pregnancy-associated glycoproteins from late-pregnancy Bubalus bubalis placentas and development of a radioimmunoassay for pregnancy diagnosis in water buffalo females.BMC veterinary research · 2013Article
- Crystal structure of a putative aspartic proteinase domain of the Mycobacterium tuberculosis cell surface antigen PE_PGRS16.FEBS open bio · 2013Article
- Transcriptional regulation of two conceptus interferon tau genes expressed in Japanese black cattle during peri-implantation period.PloS one · 2013Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The pregnancy-associated glycoproteins (PAGs) are structurally related to the pepsins, thought to be restricted to the hooved (ungulate) mammals and characterized by being expressed specifically in the outer epithelial cell layer (chorion/trophectoderm) of the placenta. At least some PAGs are catalytically inactive as proteinases, although each appears to possess a cleft capable of binding peptides. By cloning expressed genes from ovine and bovine placental cDNA libraries, by Southern genomic blotting, by screening genomic libraries, and by using PCR to amplify portions of PAG genes from genomic DNA, we estimate that cattle, sheep, and most probably all ruminant Artiodactyla possess many, possibly 100 or more, PAG genes, many of which are placentally expressed. The PAGs are highly diverse in sequence, with regions of hypervariability confined largely to surface-exposed loops. Nonsynonymous (replacement) mutations in the regions of the genes coding for these hypervariable loop segments have accumulated at a higher rate than synonymous (silent) mutations. Construction of distance phylograms, based on comparisons of PAG and related aspartic proteinase amino acid sequences, suggests that much diversification of the PAG genes occurred after the divergence of the Artiodactyla and Perissodactyla, but that at least one gene is represented outside the hooved species. The results also suggest that positive selection of duplicated genes has acted to provide considerable functional diversity among the PAGs, whose presence at the interface between the placenta and endometrium and in the maternal circulation indicates involvement in fetal-maternal interactions.
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