Alternative titles; symbols
HGNC Approved Gene Symbol: SELL
Cytogenetic location: 1q24.2 Genomic coordinates (GRCh38): 1:169,690,667-169,711,620 (from NCBI)
Lymphocyte adhesion molecule-1 is a cell surface component that is a member of a family of adhesion proteins. The molecule is composed of multiple domains: 1 homologous to lectins, 1 to epidermal growth factor, and 2 to the consensus repeat units found in C3/C4 binding proteins.
This glycoprotein was first identified in the mouse as the Mel-14 antigen, a lymph node homing receptor (Lnhr) also found on neutrophils and monocytes, by Lasky et al. (1989). In addition to lymphocyte homing, this molecule may play a role in neutrophil adhesion to endothelium at sites of inflammation. The human counterpart was referred to as the LEU8/TQ1 antigen. The human homolog of mouse lymph node homing receptor was cloned by Siegelman and Weissman (1989).
Ord et al. (1990) reported that the LAM1 gene spans more than 30 kb and comprises at least 10 exons.
Disteche et al. (1989) and Tedder et al. (1989) mapped the LYAM1 gene to 1q23-q25 by in situ hybridization. The gene for another member of the adhesion molecule family, SELP (173610), is located in this same area. Indeed, Watson et al. (1990) demonstrated that these 2 genes and that for endothelial leukocyte adhesion molecule-1 (SELE; 131210) map to the same 300-kb segment. Furthermore, Watson et al. (1990) found that these 3 genes are closely situated on distal mouse chromosome 1 which is syntenic with human chromosome 1q; in 428 meiotic events, no crossovers were identified among these 3 genes and the gene for coagulation factor V (F5; 612309). Dowbenko et al. (1991) also mapped the gene to a region of mouse chromosome 1, very near a site previously shown to contain the genes for the family of complement regulatory proteins. They found, furthermore, a correspondence between the domains of the protein and the coding exons of the gene. In the course of constructing a physical map of 1q, Oakey et al. (1992) positioned LYAM between ELAM and SELP and gave the location of all 3, as well as of F5, as 1q23-q25.
Iida and Nakamura (2003) constructed a high-resolution SNP map in the 55-kb region of chromosome 1q24-q25 corresponding to the SELE and SELL genes.
Lasky et al. (1992) defined a tissue-specific mucin-like endothelial glycoprotein that appeared to function as a ligand for L-selectin in the role of a scaffold that presents carbohydrates to the L-selectin lectin domain.
Using fluorescence resonance energy transfer and biochemical analysis, Sitrin et al. (2001) demonstrated that PLAUR (173391) is directly associated with the carbohydrate-binding domain of SELL in the membrane of neutrophils, an association analogous to that between PLAUR and beta-2 integrins (see 600065). Spectrofluorometric analysis indicated that PLAUR-mediated calcium mobilization is SELL dependent.
Trophoblast adhesion to the uterine wall is the requisite first step of implantation and, subsequently, placentation. At the maternal-fetal interface, Genbacev et al. (2003) investigated the expression of selectin adhesion systems that enable leukocyte capture from the bloodstream. On the maternal side, human uterine epithelial cells upregulated selectin oligosaccharide-based ligands during the luteal phase. On the fetal side, human trophoblasts expressed L-selectin. This ligand-receptor system was functional, because beads coated with the selectin ligand 6-sulfo sLe(x) bound to trophoblasts, and trophoblasts bound to ligand-expressing uterine luminal epithelium in tissue sections. These results suggested that trophoblast L-selectin mediates interactions with the uterus and that this adhesion mechanism may be critical to establishing human pregnancy.
Endo et al. (2011) examined expression of cell surface markers to identify functionally distinct subpopulations of mouse memory T helper-2 (Th2) cells. FACS analysis demonstrated 4 Th2 subpopulations based on high or low expression levels of Cd62l and Cxcr3 (300574). All 4 subpopulations produced comparable levels of Il4 (147780) and Il13 (147683), but Th2 cells expressing low levels of both Cd62l and Cxcr3 (Cd62l-lo/Cxcr3-lo cells) selectively produced Il5 (147850). Il5 production in Cd62l-lo/Cxcr3-lo cells was accompanied by histone H3-K4 methylation, a marker for the permissive conformation of chromatin, at the IL5 promoter. DNA microarray analysis and quantitative RT-PCR showed that Cd44 (107269)-positive memory Th2 cells expressing Il5 had lower levels of Eomes (604615) and Tbx21 (604895) and higher levels of Rora (600825) and Pparg (601487) than memory Th2 cells lacking Il5 expression. RNA silencing demonstrated that Eomes downregulation was required for Il5 expression and that Eomes had no effect on H3-K4 methylation at the Il5 promoter. Instead Eomes suppressed Gata3 (131320) transcriptional activity by inhibiting Gata3 binding to the Il5 promoter. Depletion of Cd62l-lo/Cxcr3-lo cells ameliorated memory Th2 cell-dependent airway inflammation in mice. Endo et al. (2011) concluded that IL5 production preferentially occurs in the CD62L-lo/CXCR3-lo subpopulation regulated by EOMES expression.
Smigiel et al. (2014) noted that FOXP3 (300292)-positive regulatory T cells (Tregs) depend on IL2 (147680) for maintaining tolerance and preventing autoimmunity. They showed that mouse central Tregs (cTregs), which express low levels of Cd44 and high levels of Cd62l (i.e., Cd44-lo/Cd62l-hi), were quiescent and long-lived. In contrast, mouse effector Tregs (eTregs), which are Cd44-hi/Cd62l-lo, differentiated from cTregs and underwent rapid proliferation that was balanced by a high rate of apoptotic cell death. Although eTregs expressed lower levels of Cd25 (IL2RA; 147730), they responded well to Il2. cTregs gained access to paracrine Il2 through their expression of Ccr7 (600242), whereas eTregs populating nonlymphoid tissues expressed low Ccr7, did not access Il2-prevalent regions in vivo, and were insensitive to Il2 blockade. eTregs were maintained by signaling through Icos (604558). Smigiel et al. (2014) concluded that there is a fundamental homeostatic subdivision in Treg populations based on their localization and signaling mechanisms in different environments.
Associations Pending Confirmation
Takei et al. (2002) found an association between SNPs in the SELE and SELL genes and IgA nephropathy (IGAN; 161950) in a case-control study involving Japanese subjects. In patients with IGAN they found a significant increase in serine alleles at codon 238 of L-selectin and in tyrosine alleles at codon 468 in E-selectin. They concluded that, because of the role of selectins as adhesion molecules, these alleles are likely to increase susceptibility to the IGAN phenotype with interstitial infiltration.
Bevilacqua et al. (1991) recommended that the homologous proteins involved in cell-cell adhesion should be termed selectins to reflect the involvement of carbohydrate recognition in their functions and that individual members of the family should be designated by a prefix capital letter, as has been done for the cadherins (e.g., 114020). Letters would be chosen on the basis of the tissue of original discovery and would not imply cell-type specificity. Lymphocyte adhesion molecule-1 was thus designated L-selectin.
Bevilacqua, M., Butcher, E., Furie, B., Furie, B., Gallatin, M., Gimbrone, M., Harlan, J., Kishimoto, K., Lasky, L., McEver, R., Paulson, J., Rosen, S., Seed, B., Siegelman, M., Springer, T., Stoolman, L., Tedder, T., Varki, A., Wagner, D., Weissman, I., Zimmerman, G. Selectins: a family of adhesion receptors. (Letter) Cell 67: 233 only, 1991. [PubMed: 1717161] [Full Text: https://doi.org/10.1016/0092-8674(91)90174-w]
Disteche, C. M., Adler, D. A., Tedder, T. F., Saito, H. Mapping of the genes for LYAM1, a new lymphocyte adhesion molecule, and for LAR, a new receptor-linked protein tyrosine phosphatase, to human chromosome 1. (Abstract) Cytogenet. Cell Genet. 51: 990 only, 1989.
Dowbenko, D. J., Diep, A., Taylor, B. A., Lusis, A. J., Lasky, L. A. Characterization of the murine homing receptor gene reveals correspondence between protein domains and coding exons. Genomics 9: 270-277, 1991. [PubMed: 2004776] [Full Text: https://doi.org/10.1016/0888-7543(91)90252-a]
Endo, Y., Iwamura, C., Kuwahara, M., Suzuki, A., Sugaya, K., Tumes, D. J., Tokoyoda, K., Hosokawa, H., Yamashita, M., Nakayama, T. Eomesodermin controls interleukin-5 production in memory T helper 2 cells through inhibition of activity of the transcription factor GATA3. Immunity 35: 733-745, 2011. [PubMed: 22118525] [Full Text: https://doi.org/10.1016/j.immuni.2011.08.017]
Genbacev, O. D., Prakobphol, A., Foulk, R. A., Krtolica, A. R., Ilic, D., Singer, M. S., Yang, Z.-Q., Kiessling, L. L., Rosen, S. D., Fisher, S. J. Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface. Science 299: 405-408, 2003. [PubMed: 12532021] [Full Text: https://doi.org/10.1126/science.1079546]
Iida, A., Nakamura, Y. High-resolution SNP map in the 55-kb region containing the selectin gene family on chromosome 1q24-q25. J. Hum. Genet. 48: 150-154, 2003. [PubMed: 12624727] [Full Text: https://doi.org/10.1007/s100380300023]
Lasky, L. A., Singer, M. S., Dowbenko, D., Imai, Y., Henzel, W. J., Grimley, C., Fennie, C., Gillett, N., Watson, S. R., Rosen, S. D. An endothelial ligand for L-selectin is a novel mucin-like molecule. Cell 69: 927-938, 1992. [PubMed: 1376638] [Full Text: https://doi.org/10.1016/0092-8674(92)90612-g]
Lasky, L. A., Singer, M. S., Yednock, T. A., Dowbenko, D., Fennie, C., Rodriguez, H., Nguyen, T., Stachel, S., Rosen, S. D. Cloning of a lymphocyte homing receptor reveals a lectin domain. Cell 56: 1045-1055, 1989. [PubMed: 2647302] [Full Text: https://doi.org/10.1016/0092-8674(89)90637-5]
Oakey, R. J., Watson, M. L., Seldin, M. F. Construction of a physical map on mouse and human chromosome 1: comparison of 13 Mb of mouse and 11 Mb of human DNA. Hum. Molec. Genet. 1: 613-620, 1992. [PubMed: 1301170] [Full Text: https://doi.org/10.1093/hmg/1.8.613]
Ord, D. C., Ernst, T. J., Zhou, L.-J., Rambaldi, A., Spertini, O., Griffin, J., Tedder, T. F. Structure of the gene encoding the human leukocyte adhesion molecule-1 (TQ1, Leu-8) of lymphocytes and neutrophils. J. Biol. Chem. 265: 7760-7767, 1990. [PubMed: 1692315]
Siegelman, M. H., Weissman, I. L. Human homologue of mouse lymph node homing receptor: evolutionary conservation at tandem cell interaction domains. Proc. Nat. Acad. Sci. 86: 5562-5566, 1989. [PubMed: 2664786] [Full Text: https://doi.org/10.1073/pnas.86.14.5562]
Sitrin, R. G., Pan, P. M., Blackwood, R. A., Huang, J., Petty, H. R. Cutting edge: evidence for a signaling partnership between urokinase receptors (CD87) and L-selectin (CD62L) in human polymorphonuclear neutrophils. J. Immun. 166: 4822-4825, 2001. [PubMed: 11290756] [Full Text: https://doi.org/10.4049/jimmunol.166.8.4822]
Smigiel, K. S., Richards, E., Srivastava, S., Thomas, K. R., Dudda, J. C., Klonowski, K. D., Campbell, D. J. CCR7 provides localized access to IL-2 and defines homeostatically distinct regulatory T cell subsets. J. Exp. Med. 211: 121-136, 2014. Note: Erratum: J. Exp. Med. 216: 1965 only, 2019. [PubMed: 24378538] [Full Text: https://doi.org/10.1084/jem.20131142]
Takei, T., Iida, A., Nitta, K., Tanaka, T., Ohnishi, Y., Yamada, R., Maeda, S., Tsunoda, T., Takeoka, S., Ito, K., Honda, K., Uchida, K., and 10 others. Association between single-nucleotide polymorphisms in selectin genes and immunoglobulin A nephropathy. Am. J. Hum. Genet. 70: 781-786, 2002. [PubMed: 11828340] [Full Text: https://doi.org/10.1086/339077]
Tedder, T. F., Isaacs, C. M., Ernst, T. J., Demetri, G. D., Adler, D. A., Disteche, C. M. Isolation and chromosomal localization of cDNAs encoding a novel human lymphocyte cell surface molecule, LAM-1: homology with the mouse lymphocyte homing receptor and other human adhesion proteins. J. Exp. Med. 170: 123-133, 1989. [PubMed: 2473156] [Full Text: https://doi.org/10.1084/jem.170.1.123]
Watson, M. L., Kingsmore, S. F., Johnston, G. I., Siegelman, M. H., Le Beau, M. M., Lemons, R. S., Bora, N. S., Howard, T. A., Weissman, I. L., McEver, R. P., Seldin, M. F. Genomic organization of the selectin family of leukocyte adhesion molecules on human and mouse chromosome 1. J. Exp. Med. 172: 263-272, 1990. [PubMed: 1694218] [Full Text: https://doi.org/10.1084/jem.172.1.263]