title: Human CLEC18 Gene Cluster Contains C-type Lectins with Differential Glycan-binding Specificity.
abstract: The human C-type lectin 18 (clec18) gene cluster, which contains three clec18a, clec18b, and clec18c loci, is located in human chromosome 16q22. Although the amino acid sequences of CLEC18A, CLEC18B, and CLEC18C are almost identical, several amino acid residues located in the C-type lectin-like domain (CTLD) and the sperm-coating protein/Tpx-1/Ag5/PR-1/Sc7 (SCP/TAPS) domain, also known as the cysteine-rich secretory proteins/antigen 5/pathogenesis-related 1 proteins (CAP) domain, are distinct from each other. Genotyping by real-time PCR and sequencing further shows the presence of multiple alleles in clec18a/b/c loci. Flow cytometry analysis demonstrates that CLEC18 (CLEC18A, -B, and -C) are expressed abundantly in human peripheral blood cells. Moreover, CLEC18 expression is further up-regulated when monocytes differentiate into macrophages and dendritic cells. Immunofluorescence staining reveals that CLEC18 are localized in the endoplasmic reticulum, Golgi apparatus, and endosome. Interestingly, CLEC18 are also detectable in human sera and culture supernatants from primary cells and 293T cells overexpressing CLEC18. Moreover, CLEC18 bind polysaccharide in Ca(2+)-independent manner, and amino acid residues Ser/Arg(339) and Asp/Asn(421) in CTLD domain contribute to their differential binding abilities to polysaccharides isolated from Ganoderma lucidum (GLPS-F3). The Ser(339) (CLEC18A) → Arg(339) (CLEC18A-1) mutation completely abolishes CLEC18A-1 binding to GLPS-F3, and a sugar competition assay shows that CLEC18 preferentially binds to fucoidan, β-glucans, and galactans. Because proteins with the SCP/TAPS/CAP domain are able to bind sterol and acidic glycolipid, and are involved in sterol transport and β-amyloid aggregation, it would be interesting to investigate whether CLEC18 modulates host immunity via binding to glycolipids, and are also involved in glycolipid transportation and protein aggregation in the future.
authors.affiliation: From the Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ya-Lang
authors.initials: YL
authors.lastname: Huang
authors.affiliation: the Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei.
authors.forename: Feng-Shuo
authors.initials: FS
authors.lastname: Pai
authors.affiliation: From the Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yun-Ting
authors.initials: YT
authors.lastname: Tsou
authors.affiliation: National Yang-Ming University School of Medicine, Taipei.
authors.forename: Hsien-Chen
authors.initials: HC
authors.lastname: Mon
authors.affiliation: the Genomics Research Center, Academia Sinica, Taipei.
authors.forename: Tsui-Ling
authors.initials: TL
authors.lastname: Hsu
authors.affiliation: the Genomics Research Center, Academia Sinica, Taipei.
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Wu
authors.affiliation: the Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei.
authors.forename: Teh-Ying
authors.initials: TY
authors.lastname: Chou
authors.affiliation: the Genomics Research Center, Academia Sinica, Taipei.
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Yang
authors.affiliation: the Genomics Research Center, Academia Sinica, Taipei.
authors.forename: Chung-Hsuan
authors.initials: CH
authors.lastname: Chen
authors.affiliation: the Genomics Research Center, Academia Sinica, Taipei.
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.affiliation: From the Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan, the Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, the Genomics Research Center, Academia Sinica, Taipei, the Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, and the Institute for Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan slhsieh@gate.sinica.edu.tw slhsieh@ym.edu.tw.
authors.forename: Shie-Liang
authors.initials: SL
authors.lastname: Hsieh
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D037181:Lectins, C-Type / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D011134:Polysaccharides / Q000378:metabolism*; D011485:Protein Binding; D016415:Sequence Alignment
chemical_list: C000603316:CLEC18A protein, human; C000603317:CLEC18B protein, human; C000603318:CLEC18C protein, human; D037181:Lectins, C-Type; D011134:Polysaccharides
keywords: carbohydrate-binding protein; glycobiology; glycoconjugate; glycolipid; glycoprotein; lectin