Identification and characterization of a novel human myeloid inhibitory C-type lectin-like receptor (MICL) that is predominantly expressed on granulocytes and monocytes

J Biol Chem. 2004 Apr 9;279(15):14792-802. doi: 10.1074/jbc.M313127200. Epub 2004 Jan 22.


Inhibitory and activatory C-type lectin-like receptors play an important role in immunity through the regulation of leukocytes. Here, we report the identification and characterization of a novel myeloid inhibitory C-type lectin-like receptor (MICL) whose expression is primarily restricted to granulocytes and monocytes. This receptor, which contains a single C-type lectin-like domain and a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, is related to LOX-1 (lectin-like receptor for oxidized low density lipoprotein-1) and the beta-glucan receptor (Dectin-1) and is variably spliced and highly N-glycosylated. We demonstrate that it preferentially associates with the signaling phosphatases SHP-1 and SHP-2, but not with SHIP. Novel chimeric analyses with a construct combining MICL and the beta-glucan receptor show that MICL can inhibit cellular activation through its cytoplasmic immunoreceptor tyrosine-based inhibitory motif. These data suggest that MICL is a negative regulator of granulocyte and monocyte function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • CHO Cells
  • Cell Line
  • Cloning, Molecular
  • Cricetinae
  • Cytoplasm / metabolism
  • Glycosylation
  • Granulocytes / metabolism*
  • Humans
  • Lectins, C-Type
  • Mice
  • Models, Biological
  • Molecular Sequence Data
  • Monocytes / metabolism*
  • NIH 3T3 Cells
  • Phylogeny
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA / chemistry
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, LDL / chemistry
  • Receptors, Mitogen / chemistry*
  • Receptors, Mitogen / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Spectrometry, Fluorescence
  • Tissue Distribution
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism


  • CLEC12A protein, human
  • Lectins, C-Type
  • RNA, Messenger
  • Receptors, LDL
  • Receptors, Mitogen
  • Tumor Necrosis Factor-alpha
  • RNA

Associated data

  • GENBANK/AY498550
  • GENBANK/AY498551
  • GENBANK/AY498552