Alternative titles; symbols
HGNC Approved Gene Symbol: CD300A
Cytogenetic location: 17q25.1 Genomic coordinates (GRCh38) : 17:74,466,373-74,484,798 (from NCBI)
The CMRF35 antigen (CMRF35A; 606786), which was identified by reactivity with a monoclonal antibody, is present on monocytes, neutrophils, and some T and B lymphocytes. CMRF35H is recognized by the same antibody and is distinct from CMRF35 (Green et al., 1998).
By screening a cDNA library with a probe to CMRF35, Green et al. (1998) identified a cDNA encoding CMRF35H, which they called CMRF35H9. The deduced 301-amino acid type I transmembrane protein contains a leader sequence; an extracellular region with a single V-like Ig domain and 2 conserved N-linked glycosylation sites; a membrane proximal region with potential O-linked glycosylation sites and a proline-rich, relatively rigid hinge region; a transmembrane domain; and a long cytoplasmic domain containing 4 potential immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and 2 dileucine motifs, which are associated with endocytosis. The extracellular regions of CMRF35H9 and CMRF35A are 89% identical. Flow cytometric analysis showed that cells expressing CMRF35H9 were reactive with the CMRF35 antibody, supporting the conclusion that that antibody recognizes 2 related antigens. FACS analysis demonstrated expression of CMRF35H9 in monocytes and T cells. RT-PCR analysis detected expression of CMRF35H9 in K562 erythroleukemia cells, which do not express CMRF35A, but did not detect expression in U937 or THP1 monocytic cell lines, which do express CMRF35A. Expression was also detected in T cells, granulocytes, natural killer cells, monocytes, and dendritic cells. Green et al. (1998) proposed that CMRF35H9, with its 4 potential ITIMs, may have inhibitory functions, while CMRF35A, which has a charged amino acid in its transmembrane domain, may have an activation function in association with another molecule.
Bachelet et al. (2005) found that IRp60 was constitutively expressed on cord blood mast cells. IRp60 was downregulated in vitro by eosinophil major basic protein (PRG2; 605601) and eosinophil-derived neurotoxin (RNASE2; 131410). Crosslinking of IRp60 with immune complexes inhibited IgE-induced degranulation and stem cell factor (KITLG; 184745)-mediated mast cell survival via a mechanism that involved IRp60 tyrosine phosphorylation, phosphatase recruitment, and termination of Ca(2+) influx. Bachelet et al. (2005) showed that neutralization of the murine IRp60 homolog, Lmir1, using antibodies led to a significantly augmented release of inflammatory mediators and eosinophil infiltration. They proposed that IRp60 may be a target for regulation and treatment of allergic responses.
By genomic sequence analysis, Clark et al. (2000) determined that the CMRF35H9 gene spans 12 kb and contains 7 exons of varying length. Promoter analysis indicated a transcriptional start site 134 bp upstream of the translational start site. There are no TATA or CAAT boxes, but a number of binding motifs for leukocyte-specific transcription factors were identified.
Using somatic cell hybrid analysis and FISH, Clark et al. (2000) mapped the CMRF35H9 gene to chromosome 17q24.
Bachelet, I., Munitz, A., Moretta, A., Moretta, L., Levi-Schaffer, F. The inhibitory receptor IRp60 (CD300a) is expressed and functional on human mast cells. J. Immun. 175: 7989-7995, 2005. [PubMed: 16339535] [Full Text: https://doi.org/10.4049/jimmunol.175.12.7989]
Clark, G. J., Green, B. J., Hart, D. N. J. The CMRF-35H gene structure predicts for an independently expressed member of an ITIM/ITAM pair of molecules localized to human chromosome 17. Tissue Antigens 55: 101-109, 2000. [PubMed: 10746781] [Full Text: https://doi.org/10.1034/j.1399-0039.2000.550201.x]
Green, B. J., Clark, G. J., Hart, D. N. J. The CMRF-35 mAb recognizes a second leukocyte membrane molecule with a domain similar to the poly Ig receptor. Int. Immun. 10: 891-899, 1998. [PubMed: 9701027] [Full Text: https://doi.org/10.1093/intimm/10.7.891]