Many other lipocalin genes have similar exon/intron organization.

Maps to chromosome 9: 138453602-138458801 on forward (plus) strand (5200 bases). Gene consists of 7 exons. Promoter region contains, by sequence similarity, 2 forward and two reverse Sp1-like binding sites, four putative glucocorticoid/progesterone response elements (PREs), cAMP responsive element (CRE) and activator protein-1 (AP-1) element.

PAEP mRNA (NM_001018049) has 857 bp. Several alternatively spliced mRNA forms have been described, but for most of these evidence for the corresponding protein lacks. Alternative Splicing and Transcript Diversity database (ASTD) reports 16 different transcripts.

Not known.

Some of the localization studies have employed antibodies, the specificity of which is questionable. Some of the biological studies have utilized short peptides derived from PAEP sequence. It is unclear whether such peptides are present in vivo. Glycosylation plays an important part in modulating/dictating the activity of PAEP. In the literature, PAEP is widely referred to as PP14 and glycodelin.

PAEP (180 amino acids, of which 18 corresponds to signal sequence) is a 28 kDa secreted glycoprotein, belonging to the kernel lipocalin family. Most family members share three conserved sequence motifs. Although sequence similarity between the family members is low, their three dimensional structures are similar. Lipocalins are small extracellular proteins, many of which bind small hydrophobic molecules, such as retinol and steroids. There is no evidence that PAEP exhibits similar binding properties. PAEP is a glycoprotein with three potential glycosylation sites. Two of them are glycosylated. Many differentially glycosylated forms have been characterized in these sites. Glycosylation modulates/dictates the biological activity of PAEP. Some of the alternatively spliced mRNAs lack the sequences encoding glycosylation sites and/or the lipocalin signature sequence.

The expression of PAEP is highly regulated in a spatiotemporal fashion. In the female, PAEP is mainly expressed in secretory/decidualized endometrial glands after progesterone exposure. In secretory endometrium, expression becomes detectable four days after ovulation and reaches maximum at the end of the menstrual cycle unless pregnancy ensues. PAEP is one of the major proteins in endometrial secretions. In the male, the highest expression has been reported in seminal vesicles. PAEP is also expressed in other epithelial cells of reproductive tissues, such as fallopian tubes, ovary and the breast. In addition, other secretory epithelia, such as eccrine sweat glands and the bronchus epithelium express PAEP. It is also expressed in differentiated areas of breast cancer, ovarian tumors, endometrial adenocarcinoma, and synovial sarcoma. In addition to epithelial tissues, PAEP has been found in megakaryocytes and erythroid precursor cells. Experimental evidence suggests that PAEP expression is regulated by progesterone/progestins, relaxin, and histone deacetylase inhibitors.

PAEP is mostly found in exocrine epithelial cells, from which it is secreted into the gland lumen. In breast cancer, PAEP has been found also in paranuclear vacuoles of lobular carcinoma cells.

PAEP/PP14/glycodelin regulates the functions of spermatozoa during fertilization in a glycosylation dependent manner. The various glycoforms of PAEP have different, sometimes even opposite, biological actions at different phases of the fertilization process. Seminal fluid glycodelin-S binds to the sperm head and inhibits premature capacitation. In the female reproductive tract, spermatozoa come into contact with various PAEP glycoforms, that modulate sperm function, e.g., by preventing premature, progesterone-induced acrosome reaction (glycodelin-F). Glycodelin-A inhibits binding of spermatozoa to the zona pellucida, whereas another glycoform (glycodelin-C) stimulates the same. All these actions are glycosylation-dependent.
PAEP also regulates immune cell functions, which too are, at least in part, regulated by glycosylation. Different PAEP glycoforms contain diverse bi-, tri-, and tetra-antennary complex-type glycans with varying levels of fucose and sialic acid substitution. Glycodelin-A and -F are the most heavily sialylated and inhibit cell proliferation, induce cell death, and suppress interleukin-2 secretion of Jurkat cells and peripheral blood mononuclear cells. No such immunosuppressive effect has been observed for glycodelin-C and -S carrying less or no sialic acids, or for desialylated glycodelin-A and -F. By its immunosuppressive properties one of the PAEP glycoforms (glycodelin-A) may contribute to immunotolerance at the fetomaternal interface and prevent rejection of the fetal semi-allograft.
In early pregnancy, glycodelin-A restrains inappropriate invasion of extravillous cytotrophoblasts by suppressing activity of some key metalloproteinases. In breast and endometrial cancer cell lines, PAEP has been found to revert the malignant phenotype in vitro by inducing morphological differentiation and specific gene expression changes. In a preclinical mouse model, transgenic PAEP expression in breast cancer cells has reduced tumor growth.

Most lipocalins do not share high sequence similarity, but they are likely to be homologous.
Functional PAEP gene has been found in higher primates. Beta-lactoglobulins represent orthologs of PAEP, but they are likely to be functionally different from human PAEP, not least because of their differences in glycosylation. No convincing evidence of a PAEP ortholog in mouse or rat has been reported.

NCBI SNP database reports 128 PAEP SNPs (Homo sapiens, 13 September 2010). Also HinfI restriction enzyme polymorphism has been reported in Finnish population with 5% frequency for allele A1 and 95% frequency for allele A2. No disease associations for mutations have been described.