CLEC2A: a novel, alternatively spliced and skin-associated member of the NKC-encoded AICL-CD69-LLT1 family.
The human natural killer gene complex (NKC) encodes for numerous C-type lectin-like receptors (CTLR), which are expressed on various immune cells including natural killer (NK) cells and myeloid cells. Certain activation-induced, NKC-encoded CTLR are grouped into the C-type lectin domain family 2 (CLEC2 family) which, in humans, comprises AICL (CLEC2B), CD69 (CLEC2C), and LLT1 (CLEC2D). In this paper, we characterize a novel member of the CLEC2 family, the human orphan gene CLEC2A. The C-type lectin-like domain (CTLD) of CLEC2A is most similar to the CTLD of LLT1 ( approximately 60% similarity). Like mouse CLEC2 family members Clr-b and Clr-g, CLEC2A lacks two highly conserved cysteines (Cys4 and Cys5), which form an intramolecular bond in the CTLD of most CTLR. Alternative splicing of exon 2 and of two distinct terminal exons (exon 5A/B), respectively, gives rise to four CLEC2A variants differing in the usage of the transmembrane domain and/or in the carboxyterminal portion of the CTLD. CLEC2A transcripts were detected primarily in myeloid cell lines, but not in epithelial cell lines. In tissues, CLEC2A is selectively expressed in the skin and, at lower abundance, in hematopoietic and gonadal tissues. Finally, we show that the CLEC2A1 variant is readily expressed at the cell surface, where it may serve as a ligand for NKC-encoded NK receptors.
Department of Immunology, Interfacultary Institute for Cell Biology, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany.
Jessica
J
Spreu
Eike C
EC
Kienle
Birgit
B
Schrage
Alexander
A
Steinle
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D020298:U937 Cells / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D000099192:CD69 Antigens; C526358:CLEC2A protein, human; C104778:CLEC2B protein, human; C400041:CLEC2D protein, human