HGNC Approved Gene Symbol: PILRA
Cytogenetic location: 7q22.1 Genomic coordinates (GRCh38) : 7:100,371,291-100,400,096 (from NCBI)
Using an SHP1 (176883) mutant as bait in a yeast 2-hybrid screen of a mammary gland cDNA library, followed by 5-prime RACE, Mousseau et al. (2000) identified a cDNA encoding PILRA (paired immunoglobulin-like receptor-alpha). Sequence analysis predicted that the 303-amino acid PILRA protein does not contain an Ig domain per se, but does contain an Ig-like cysteine-based motif involved in intradomain disulfide bonding. PILRA also has a potential N-glycosylation site; numerous O-glycosylation sites; a transmembrane domain; and 3 potential tyrosine phosphorylation sites, 2 of which are within an immunoreceptor tyrosine-based inhibitory motif (ITIM). When expressed in a kidney cell line, immunoblot and BIAcore analysis showed that the approximately 50-kD PILRA glycoprotein was tyrosine-phosphorylated and coprecipitated with SHP1 through a C-terminal tyrosine. Northern blot analysis revealed strong expression of a 1.4-kb transcript in peripheral blood leukocytes, with lower signals in lung, spleen, and placenta as well as in 2 B-cell lines. RT-PCR analysis indicated that PILRA and PILRB (605342) are expressed, or paired, at the mRNA level in various tissues. Mousseau et al. (2000) concluded that PILRA and PILRB represent a novel immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing and non-ITIM-bearing receptor pair.
By random sequencing of an activated monocyte cDNA library, Fournier et al. (2000) cloned PILRA, which they termed FDF03. RT-PCR analysis identified 2 splice variants lacking transmembrane domains and presumably encoding soluble proteins. RT-PCR and flow cytometry analysis demonstrated expression of PILRA in peripheral blood-derived monocytes, granulocytes, and particularly dendritic cells, but not in lymphocytes. Western blot analysis of a monocyte cell line expressing PILRA suggested that PILRA recruits SHP2 (PTPN11; 176876) more efficiently than it recruits SHP1, whereas LAIR1 (602992), which is also an inhibitory molecule, recruits both molecules equivalently. In contrast to LAIR1, crosslinking of PILRA did not inhibit the differentiation of monocytes into dendritic cells in the presence of GMCSF (CSF2; 138960).
Satoh et al. (2008) noted that herpes simplex virus (HSV)-1 infection requires viral glycoprotein B (gB). Using flow cytometric, immunoprecipitation, and fluorescence microscopy analyses, they showed that PILRA associated with gB and that cells transduced with PILRA became susceptible to HSV-1 infection. Infection of cells expressing both PILRA and HVEM (TNFRSF14; 602746), a receptor for HSV-1 gD, could be blocked with antibody to either receptor, indicating that cellular receptors for both gB and gD are required for HSV-1 infection. Satoh et al. (2008) concluded that PILRA is a coreceptor for HSV-1 infection that associates with gB.
Kogure et al. (2011) noted that binding of PILRA to its ligand, CD99 (313470), is involved in immune regulation. By isolating single cell clones from a mouse skin cell line that did not express Cd99 but still interacted with Pilra, they identified Panp (PIANP; 616065) as a Pilra-binding protein. Panp did not bind Pilrb, which also interacts with Cd99. As in mice, human PANP interacted with PILRA. Binding of PILRA to PANP was dependent on the presence of sialylated glycans and an O-glycosylated threonine in PANP. Kogure et al. (2011) proposed that PANP is involved in immune regulation as a ligand of PILRA.
Mousseau et al. (2000) determined that the PILRA gene contains 7 exons and spans approximately 26.7 kb.
By long-range PCR on genomic DNA and comparison to a chromosome 7 segment (GenBank RG161A02), Mousseau et al. (2000) mapped the PILRA gene to chromosome 7, 5.6 kb downstream from PILRB. Using radiation hybrid analysis, Fournier et al. (2000) mapped the PILRA gene to 7q22, a localization distinct from inhibitory receptor gene families such as LIR (e.g., LILRB1; 604811) on chromosome 19 and the natural killer cell receptors (e.g., KLRG1; 604874) on chromosome 12. The localization of PILRA is close, however, to a region associated with chromosomal abnormalities in the myelodysplastic syndrome and acute myeloid leukemia.
Fournier, N., Chalus, L., Durand, I., Garcia, E., Pin, J.-J., Churakova, T., Patel, S., Zlot, C., Gorman, D., Zurawski, S., Abrams, J., Bates, E. E. M., Garrone, P. FDF03, a novel inhibitory receptor of the immunoglobulin superfamily, is expressed by human dendritic and myeloid cells. J. Immun. 165: 1197-1209, 2000. [PubMed: 10903717] [Full Text: https://doi.org/10.4049/jimmunol.165.3.1197]
Kogure, A., Shiratori, I., Wang, J., Lanier, L. L., Arase, H. PANP is a novel O-glycosylated PILR-alpha ligand expressed in neural tissues. Biochem. Biophys. Res. Commun. 405: 428-433, 2011. [PubMed: 21241660] [Full Text: https://doi.org/10.1016/j.bbrc.2011.01.047]
Mousseau, D. D., Banville, D., L'Abbe, D., Bouchard, P., Shen, S.-H. PILR-alpha, a novel immunoreceptor tyrosine-based inhibitory motif-bearing protein, recruits SHP-1 upon tyrosine phosphorylation and is paired with the truncated counterpart PILR-beta. J. Biol. Chem. 275: 4467-4474, 2000. [PubMed: 10660620] [Full Text: https://doi.org/10.1074/jbc.275.6.4467]
Satoh, T., Arii, J., Suenaga, T., Wang, J., Kogure, A., Uehori, J., Arase, N., Shiratori, I., Tanaka, S., Kawaguchi, Y., Spear, P. G., Lanier, L. L., Arase, H. PILR-alpha is a Herpes simplex virus-1 entry coreceptor that associates with glycoprotein B. Cell 132: 935-944, 2008. [PubMed: 18358807] [Full Text: https://doi.org/10.1016/j.cell.2008.01.043]