P-selectin glycoprotein ligand-1

SELPLG
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1G1S
Identifiers
Aliases	SELPLG, CD162, CLA, PSGL-1, PSGL1, selectin P ligand
External IDs	OMIM: 600738 MGI: 106689 HomoloGene: 2261 GeneCards: SELPLG
Gene location (Human) Chr. Chromosome 12 (human) Band 12q24.11 Start 108,621,895 bp End 108,633,894 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5 F|5 55.59 cM Start 113,956,597 bp End 113,970,705 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in blood monocyte spleen lymph node inferior ganglion of vagus nerve periodontal fiber appendix bone marrow cells vena cava right lung Top expressed in thymus bone marrow spleen blood ankle joint entorhinal cortex superior frontal gyrus subcutaneous adipose tissue right lung lobe substantia nigra More reference expression data BioGPS More reference expression data
Gene ontology Molecular function signaling receptor binding protein binding virus receptor activity Cellular component uropod integral component of plasma membrane integral component of membrane membrane plasma membrane plasma membrane raft Biological process cellular response to interleukin-6 leukocyte adhesive activation viral entry into host cell viral process cell adhesion leukocyte migration leukocyte tethering or rolling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6404 20345 Ensembl ENSG00000110876 ENSMUSG00000048163 UniProt Q14242 Q62170 RefSeq (mRNA) NM_001206609 NM_003006 NM_009151 RefSeq (protein) NP_001193538 NP_002997 n/a Location (UCSC) Chr 12: 108.62 – 108.63 Mb Chr 5: 113.96 – 113.97 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Selectin P ligand, also known as SELPLG or CD162 (cluster of differentiation 162), is a human gene.

SELPLG codes for PSGL-1, the high affinity counter-receptor for P-selectin on myeloid cells and stimulated T lymphocytes. As such, it plays a critical role in the tethering of these cells to activated platelets or endothelia expressing P-selectin.

The organization of the SELPLG gene closely resembles that of CD43 and the human platelet glycoprotein GpIb-alpha both of which have an intron in the 5-prime-noncoding region, a long second exon containing the complete coding region, and TATA-less promoters.

P-selectin glycoprotein ligand-1 (PSGL-1) is a glycoprotein found on white blood cells and endothelial cells that binds to P-selectin (P stands for platelet), which is one of a family of selectins that includes E-selectin (endothelial) and L-selectin (leukocyte). Selectins are part of the broader family of cell adhesion molecules. PSGL-1 can bind to all three members of the family but binds best (with the highest affinity) to P-selectin.

Posttranslational modification

PSGL-1 protein requires two distinct posttranslational modifications to gain its selectin binding activity:

• sulfation of tyrosines
• the addition of the sialyl Lewis x tetrasaccharide (sLex) to its O-linked glycans

Function

PSGL-1 is expressed on all white blood cells and plays an important role in the recruitment of white blood cells into inflamed tissue: White blood cells normally do not interact with the endothelium of blood vessels. However, inflammation causes the expression of cell adhesion molecules (CAM) such as P-selectin on the surface of the blood vessel wall. White blood cells present in flowing blood can interact with CAM. The first step in this interaction process is carried out by PSGL-1 interacting with P-selectin and/or E-selectin on endothelial cells and adherent platelets. This interaction results in "rolling" of the white blood cell on the endothelial cell surface followed by stable adhesion and transmigration of the white blood cell into the inflamed tissue.

In cancer

In mice it seems to be an immune factor regulating T-cell checkpoints, and it could be a target for future checkpoint inhibitor anti-cancer drugs.

PSGL-1 has been shown to bind to VISTA (V-domain Ig suppressor of T cell activation) but this binding only occurs under acidic pH conditions (pH < 6.5) such as can be found in tumor microenvironments (TME).

In mice, PSGL-1 seems to facilitate T cell exhaustion in tumors.

Further reading

• Furie B, Furie BC (2004). "Role of platelet P-selectin and microparticle PSGL-1 in thrombus formation". Trends in Molecular Medicine. 10 (4): 171–8. doi:10.1016/j.molmed.2004.02.008. PMID 15059608.
• Sako D, Chang XJ, Barone KM, et al. (1993). "Expression cloning of a functional glycoprotein ligand for P-selectin". Cell. 75 (6): 1179–86. doi:10.1016/0092-8674(93)90327-M. PMID 7505206. S2CID 23786141.
• Moore KL, Eaton SF, Lyons DE, et al. (1994). "The P-selectin glycoprotein ligand from human neutrophils displays sialylated, fucosylated, O-linked poly-N-acetyllactosamine". J. Biol. Chem. 269 (37): 23318–27. doi:10.1016/S0021-9258(17)31656-3. PMID 7521878.
• Veldman GM, Bean KM, Cumming DA, et al. (1995). "Genomic organization and chromosomal localization of the gene encoding human P-selectin glycoprotein ligand". J. Biol. Chem. 270 (27): 16470–5. doi:10.1074/jbc.270.27.16470. PMID 7541799.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Guyer DA, Moore KL, Lynam EB, et al. (1996). "P-selectin glycoprotein ligand-1 (PSGL-1) is a ligand for L-selectin in neutrophil aggregation". Blood. 88 (7): 2415–21. doi:10.1182/blood.V88.7.2415.bloodjournal8872415. PMID 8839831.
• Goetz DJ, Greif DM, Ding H, et al. (1997). "Isolated P-selectin glycoprotein ligand-1 dynamic adhesion to P- and E-selectin". J. Cell Biol. 137 (2): 509–19. doi:10.1083/jcb.137.2.509. PMC 2139768. PMID 9128259.
• Fuhlbrigge RC, Kieffer JD, Armerding D, Kupper TS (1997). "Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells". Nature. 389 (6654): 978–81. Bibcode:1997Natur.389..978F. doi:10.1038/40166. PMID 9353122. S2CID 4376296.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Snapp KR, Ding H, Atkins K, et al. (1998). "A novel P-selectin glycoprotein ligand-1 monoclonal antibody recognizes an epitope within the tyrosine sulfate motif of human PSGL-1 and blocks recognition of both P- and L-selectin". Blood. 91 (1): 154–64. doi:10.1182/blood.V91.1.154. PMID 9414280.
• Bennett EP, Hassan H, Mandel U, et al. (1998). "Cloning of a human UDP-N-acetyl-alpha-D-Galactosamine:polypeptide N-acetylgalactosaminyltransferase that complements other GalNAc-transferases in complete O-glycosylation of the MUC1 tandem repeat". J. Biol. Chem. 273 (46): 30472–81. doi:10.1074/jbc.273.46.30472. hdl:2066/216411. PMID 9804815.
• Wimazal F, Ghannadan M, Müller MR, et al. (2000). "Expression of homing receptors and related molecules on human mast cells and basophils: a comparative analysis using multi-color flow cytometry and toluidine blue/immunofluorescence staining techniques". Tissue Antigens. 54 (5): 499–507. doi:10.1034/j.1399-0039.1999.540507.x. PMID 10599889.
• Epperson TK, Patel KD, McEver RP, Cummings RD (2000). "Noncovalent association of P-selectin glycoprotein ligand-1 and minimal determinants for binding to P-selectin". J. Biol. Chem. 275 (11): 7839–53. doi:10.1074/jbc.275.11.7839. PMID 10713099.
• André P, Spertini O, Guia S, et al. (2000). "Modification of P-selectin glycoprotein ligand-1 with a natural killer cell-restricted sulfated lactosamine creates an alternate ligand for L-selectin". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3400–5. doi:10.1073/pnas.040569797. PMC 16251. PMID 10725346.
• Frenette PS, Denis CV, Weiss L, et al. (2000). "P-Selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo". J. Exp. Med. 191 (8): 1413–22. doi:10.1084/jem.191.8.1413. PMC 2193129. PMID 10770806.
• Woltmann G, McNulty CA, Dewson G, et al. (2000). "Interleukin-13 induces PSGL-1/P-selectin-dependent adhesion of eosinophils, but not neutrophils, to human umbilical vein endothelial cells under flow". Blood. 95 (10): 3146–52. doi:10.1182/blood.V95.10.3146. PMID 10807781.
• Tsuchihashi S, Fondevila C, Shaw GD, et al. (2006). "Molecular characterization of rat leukocyte P-selectin glycoprotein ligand-1 and effect of its blockade: protection from ischemia-reperfusion injury in liver transplantation". J Immunol. 176 (1): 616–24. doi:10.4049/jimmunol.176.1.616. PMID 16365457.

External links

• P-selectin+glycoprotein+ligand-1 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.