PILRA explained

Paired immunoglobin like type 2 receptor alpha is a protein that in humans is encoded by the PILRA gene.^[1]

Function

Cell signaling pathways rely on a dynamic interaction between activating and inhibiting processes. SHP-1-mediated dephosphorylation of protein tyrosine residues is central to the regulation of several cell signaling pathways. Two types of inhibitory receptor superfamily members are immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing receptors and their non-ITIM-bearing, activating counterparts.

Control of cell signaling via SHP-1 is thought to occur through a balance between PILRalpha-mediated inhibition and PILRbeta-mediated activation. These paired immunoglobulin-like receptor genes are located in a tandem head-to-tail orientation on chromosome 7. This particular gene encodes the ITIM-bearing member of the receptor pair, which functions in the inhibitory role. Alternative splicing has been observed at this locus, and three variants, each encoding a distinct isoform, are described.

In contrast to PILRbeta, which has only one known natural ligand, PILRalpha has many known protein-protein interactions.^[2] PILRalpha recruits PTPN6 and PTPN1 via interactions of its ITIM motifs. PILRalpha is also used by some viruses, notably HSV-1, for cell entry.^[3]

Structure

As with other paired receptors, PILRalpha has a longer cytoplasmic tail compared to PILRbeta and features two intracellular ITIM motifs.^{[4] [5]} PILRalpha has an extracellular domain with a siglec-like immunoglobulin fold that substitutes hydrophobic interactions for the siglec fold's characteristic disulfide bond. The structure of this domain is very similar to that of PILRbeta, but the two proteins nevertheless have different binding affinities for sialic acid.

Further reading

• Tabata S, Kuroki K, Maita N, Wang J, Shiratori I, Arase H, Kohda D, Maenaka K . 6 . Expression, crystallization and preliminary X-ray diffraction analysis of human paired Ig-like type 2 receptor alpha (PILRalpha) . Acta Crystallographica. Section F, Structural Biology and Crystallization Communications . 64 . Pt 1 . 44–6 . January 2008 . 18097101 . 2373998 . 10.1107/S1744309107065384 .
• Satoh T, Arii J, Suenaga T, Wang J, Kogure A, Uehori J, Arase N, Shiratori I, Tanaka S, Kawaguchi Y, Spear PG, Lanier LL, Arase H . 6 . PILRalpha is a herpes simplex virus-1 entry coreceptor that associates with glycoprotein B . Cell . 132 . 6 . 935–44 . March 2008 . 18358807 . 2394663 . 10.1016/j.cell.2008.01.043 .
• Arii J, Uema M, Morimoto T, Sagara H, Akashi H, Ono E, Arase H, Kawaguchi Y . 6 . Entry of herpes simplex virus 1 and other alphaherpesviruses via the paired immunoglobulin-like type 2 receptor alpha . Journal of Virology . 83 . 9 . 4520–7 . May 2009 . 19244335 . 2668467 . 10.1128/JVI.02601-08 .
• Fan Q, Lin E, Satoh T, Arase H, Spear PG . Differential effects on cell fusion activity of mutations in herpes simplex virus 1 glycoprotein B (gB) dependent on whether a gD receptor or a gB receptor is overexpressed . Journal of Virology . 83 . 15 . 7384–90 . August 2009 . 19457990 . 2708615 . 10.1128/JVI.00087-09 .
• Kogure A, Shiratori I, Wang J, Lanier LL, Arase H . PANP is a novel O-glycosylated PILRα ligand expressed in neural tissues . Biochemical and Biophysical Research Communications . 405 . 3 . 428–33 . February 2011 . 21241660 . 4089865 . 10.1016/j.bbrc.2011.01.047 .
• Sun Y, Senger K, Baginski TK, Mazloom A, Chinn Y, Pantua H, Hamidzadeh K, Ramani SR, Luis E, Tom I, Sebrell A, Quinones G, Ma Y, Mukhyala K, Sai T, Ding J, Haley B, Shadnia H, Kapadia SB, Gonzalez LC, Hass PE, Zarrin AA . 6 . Evolutionarily conserved paired immunoglobulin-like receptor α (PILRα) domain mediates its interaction with diverse sialylated ligands . The Journal of Biological Chemistry . 287 . 19 . 15837–50 . May 2012 . 22396535 . 3346071 . 10.1074/jbc.M111.286633 . free .
• Chowdhury S, Naderi M, Chouljenko VN, Walker JD, Kousoulas KG . Amino acid differences in glycoproteins B (gB), C (gC), H (gH) and L (gL) are associated with enhanced herpes simplex virus type-1 (McKrae) entry via the paired immunoglobulin-like type-2 receptor α . Virology Journal . 9 . 112 . June 2012 . 22695228 . 3402990 . 10.1186/1743-422X-9-112 . free .
• Chowdhury S, Chouljenko VN, Naderi M, Kousoulas KG . The amino terminus of herpes simplex virus 1 glycoprotein K is required for virion entry via the paired immunoglobulin-like type-2 receptor alpha . Journal of Virology . 87 . 6 . 3305–13 . March 2013 . 23302878 . 3592154 . 10.1128/JVI.02982-12 .
• Lun YZ, Chi Q, Wang XL, Wang F, Sui W . Identification of paired immunoglobulin-like type 2 receptor α as hepatitis B virus DNA polymerase transactivated protein 1 interacting proteins . Molecular Medicine Reports . 9 . 2 . 720–4 . February 2014 . 24253495 . 10.3892/mmr.2013.1813 . free .

Notes and References

1. Web site: Entrez Gene: Paired immunoglobin like type 2 receptor alpha. 2017-01-10.
2. Lu Q, Lu G, Qi J, Wang H, Xuan Y, Wang Q, Li Y, Zhang Y, Zheng C, Fan Z, Yan J, Gao GF . 6 . PILRα and PILRβ have a siglec fold and provide the basis of binding to sialic acid . Proceedings of the National Academy of Sciences of the United States of America . 111 . 22 . 8221–6 . June 2014 . 24843130 . 10.1073/pnas.1320716111 . 4050567 . 2014PNAS..111.8221L . free .
3. Furukawa A, Kakita K, Yamada T, Ishizuka M, Sakamoto J, Hatori N, Maeda N, Ohsaka F, Saitoh T, Nomura T, Kuroki K, Nambu H, Arase H, Matsunaga S, Anada M, Ose T, Hashimoto S, Maenaka K . 6 . Structural and thermodynamic analyses reveal critical features of glycopeptide recognition by the human PILRα immune cell receptor . The Journal of Biological Chemistry . 292 . 51 . 21128–21136 . December 2017 . 29046357 . 10.1074/jbc.M117.799239 . 5743085 . free .
4. Mousseau DD, Banville D, L'Abbé D, Bouchard P, Shen SH . PILRalpha, a novel immunoreceptor tyrosine-based inhibitory motif-bearing protein, recruits SHP-1 upon tyrosine phosphorylation and is paired with the truncated counterpart PILRbeta . The Journal of Biological Chemistry . 275 . 6 . 4467–74 . February 2000 . 10660620 . 10.1074/jbc.275.6.4467 . free .
5. Wilson MD, Cheung J, Martindale DW, Scherer SW, Koop BF . Comparative analysis of the paired immunoglobulin-like receptor (PILR) locus in six mammalian genomes: duplication, conversion, and the birth of new genes . Physiological Genomics . 27 . 3 . 201–18 . November 2006 . 16926269 . 10.1152/physiolgenomics.00284.2005 .