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HGNC Approved Gene Symbol: PAEP
Cytogenetic location: 9q34.3 Genomic coordinates (GRCh38): 9:135,561,756-135,566,955 (from NCBI)
Glycodelin plays an immunosuppressive function in embryo implantation and tumor development, and is thought to play an important role in embryogenesis and tumor development by inducing angiogenesis (summary by Song et al., 2001).
Placental protein-14 is synthesized by the human secretory endometrium and decidua. It is abundantly secreted by the human endometrium under the influence of progesterone. Julkunen et al. (1988) isolated cDNA clones corresponding to PP14 from a human decidual cDNA library and deduced its entire amino acid sequence. It contains 180 amino acids, 18 of which correspond to a putative signal peptide. The predicted molecular weight of the pre-PP14 is 20,555 and that of the mature protein is 18,787. PP14 is encoded by a 1-kilobase mRNA that is expressed in secretory endometrium and decidua but not in postmenopausal endometrium, placenta, liver, kidney, and adrenals. The 162-residue-long sequence of PP14 is highly homologous to beta-lactoglobulin, the main component of equine, bovine, and ovine milk whey.
Van Cong et al. (1991) used a genomic PP14 probe for assignment of the gene to chromosome 9 through analysis of somatic hybrid cells. By in situ hybridization, they refined the assignment to 9q34. The localization in the region of the ABO locus is consistent with the linkage described in cattle between beta-lactoglobulin and the J blood group, which is homologous to the human ABO group.
By linkage analyses in an interspecific backcross progeny in the mouse, Chan et al. (1994) mapped the Paep gene to mouse chromosome 2.
Morris et al. (1996) reported that PP14, which they called glycodelin (Gd), exists as 2 gender-specific forms that differ in their glycosylation patterns. GdA, found in amniotic fluid, inhibits sperm-zona pellucida binding in an established sperm-egg binding system; GdS, found in seminal plasma, does not. Both forms suppress responses by a variety of immune effector cell types.
Angiogenesis plays an important role in neovascularization in tumors. Glycodelin, a hormone-responsive protein, has been detected in tumors of reproductive organs and is found at high levels in the plasma of subjects with gynecologic malignancies. It is also found in the endothelial cells of the umbilical cord and in the blood vessels of tumors. Song et al. (2001) found that increased migration and tube formation of human umbilical vein endothelial cells (HUVECs) occurred in the presence of amniotic fluid and glycodelin peptide (Gp), and that this increase was blocked by antibody against Gp and by antibody against vascular endothelial growth factor (VEGF; 192240), suggesting that the angiogenic effects of glycodelin may be mediated by VEGF. VEGF receptor (165070) mRNA expression in HUVECs was also increased in the presence of Gp. These findings, together with the suggestion from the literature that glycodelin may have immunosuppressive properties, suggest that glycodelin may play an important role in neovascularization during embryogenesis and tumor development.
Bell, K., Hopper, K. E., McKenzie, H. A., Murphy, W. H., Shaw, D. C. A comparison of bovine alpha-lactalbumin A and B of Droughtmaster. Biochim. Biophys. Acta 214: 437-444, 1970. [PubMed: 5534301] [Full Text: https://doi.org/10.1016/0005-2795(70)90302-8]
Bell, K., McKenzie, H. A., Murphy, W. H., Shaw, D. C. Beta-lactoglobulin (Droughtmaster): a unique protein variant. Biochim. Biophys. Acta 214: 427-436, 1970. [PubMed: 5509619] [Full Text: https://doi.org/10.1016/0005-2795(70)90301-6]
Chan, P., Simon-Chazottes, D., Mattei, M. G., Guenet, J. L., Salier, J. P. Comparative mapping of lipocalin genes in human and mouse: the four genes for complement C8 gamma chain, prostaglandin-D-synthase, oncogene-24P3, and progestagen-associated endometrial protein map to HSA9 and MMU2. Genomics 23: 145-150, 1994. [PubMed: 7829063] [Full Text: https://doi.org/10.1006/geno.1994.1470]
Julkunen, M., Seppala, M., Janne, O. A. Complete amino acid sequence of human placental protein 14: a progesterone-regulated uterine protein homologous to beta-lactoglobulins. Proc. Nat. Acad. Sci. 85: 8845-8849, 1988. [PubMed: 3194393] [Full Text: https://doi.org/10.1073/pnas.85.23.8845]
Morris, H. R., Dell, A., Easton, R. L., Panico, M., Koistinen, H., Koistinen, R., Oehninger, S., Patankar, M. S., Seppala, M., Clark, G. F. Gender-specific glycosylation of human glycodelin affects its contraceptive activity. J. Biol. Chem. 271: 32159-32167, 1996. [PubMed: 8943270] [Full Text: https://doi.org/10.1074/jbc.271.50.32159]
Song, M., Ramaswamy, S., Ramachandran, S., Flowers, L. C., Horowitz, I. R., Rock, J. A., Parthasarathy, S. Angiogenic role for glycodelin in tumorigenesis. Proc. Nat. Acad. Sci. 98: 9265-9270, 2001. [PubMed: 11459932] [Full Text: https://doi.org/10.1073/pnas.151151198]
Van Cong, N., Vaisse, C., Gross, M.-S., Slim, R., Milgrom, E., Bernheim, A. The human placental protein 14 (PP14) gene is localized on chromosome 9q34. Hum. Genet. 86: 515-518, 1991. [PubMed: 2016092] [Full Text: https://doi.org/10.1007/BF00194645]