CD300a

Target id: 2918

Nomenclature: CD300a

Family: CD molecules

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     CD300a has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 299 17q25.1 CD300A CD300a molecule 10
Mouse 1 318 11 E2; 11 80.54 cM Cd300a CD300A molecule
Rat 1 310 10q32.1 Cd300a Cd300a molecule
Gene and Protein Information Comments
The human RefSeq links here refer to IRC1a (the longest transcript giving rise to protein isoform 1). A shorter isoform 2 (IRC1c) has also been identified.
Previous and Unofficial Names
CMRF-35-H9 | Irp60 | LMIR1 (mouse) | CLM-8 | IGSF12
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Immunopharmacology Comments
CD300a is a member of the CD300 family of leucocyte surface receptors [6], a family known to regulate a diverse array of immune cell processes. Expression of CD300a is found in cells of myeloid lineage. CD300a contains ITIMs (immunoreceptor tyrosine-based inhibitory motifs) in its cytoplasmic tail which facilitate inhibitory signalling [8]. CD300a binds phosphatidylserine and phosphatidylethanolamine (aminophospholipids exposed on the outer leaflet of dead and activated cells). The family relationship, expression pattern and ligand binding profile suggest roles for CD300a in modulation of immune functions and participation in host responses to a number disease states, including infectious diseases, cancer, allergy, and chronic inflammatory diseases [15].

Some CD300a functions include:
Inhibition of IgE-induced mast cell degranulation [5]
Inhibition of eotaxin-dependent transmigration of eosinophils
Reduced TNFα and increased IFNα secretion by human plasmacytoid dendritic cells [1]
CD300a also activates SH2-containing tyrosine phosphatase 1 (SHP-1) involved in TLR9/MyD88-mediated signalling [12].

Despite its disease relevance [15], no progress has been made in developing clinical candidates directly targeting CD300a, but in vitro studies have shown that cross-linking CD300a to KIT [3] or IgE [4] (using bispecific antibodies/antibody fragments) abrogates KIT signalling and allergic reaction (mast cell degranulation) respectively.
Cell Type Associations
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)
Comment:  Functional CD300a is expressed on human mast cells.
References:  5
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   plasmacytoid dendritic cell (CL:0000784)
References:  11
Immuno Cell Type:  T cells
Cell Ontology Term:   CD4-positive, alpha-beta T cell (CL:0000624)
T-helper 1 cell (CL:0000545)
References:  9,14
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   eosinophil (CL:0000771)
neutrophil (CL:0000775)
References:  2,13
Immuno Cell Type:  Natural killer cells
Cell Ontology Term:   natural killer cell (CL:0000623)
Comment:  CD300a (IRp60) was originally identified in NK cells.
References:  7
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 8 GO processes
GO:0033007 negative regulation of mast cell activation involved in immune response IDA
GO:0034125 negative regulation of MyD88-dependent toll-like receptor signaling pathway IMP
GO:0043305 negative regulation of mast cell degranulation IDA
GO:0043312 neutrophil degranulation TAS
GO:0060101 negative regulation of phagocytosis, engulfment IMP
GO:1902564 negative regulation of neutrophil activation IDA
GO:1902567 negative regulation of eosinophil activation IDA
GO:2000417 negative regulation of eosinophil migration IDA
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes
GO:0060101 negative regulation of phagocytosis, engulfment IMP
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0051134 negative regulation of NK T cell activation IDA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0030889 negative regulation of B cell proliferation IMP
Immuno Process:  Immune regulation
GO Annotations:  Associated to 11 GO processes
GO:0030889 negative regulation of B cell proliferation IMP
GO:0033007 negative regulation of mast cell activation involved in immune response IDA
GO:0034125 negative regulation of MyD88-dependent toll-like receptor signaling pathway IMP
GO:0043305 negative regulation of mast cell degranulation IDA
GO:0050776 regulation of immune response TAS
GO:0050856 regulation of T cell receptor signaling pathway IDA
GO:0050859 negative regulation of B cell receptor signaling pathway IDA
GO:0051134 negative regulation of NK T cell activation IDA
GO:1902564 negative regulation of neutrophil activation IDA
GO:1902567 negative regulation of eosinophil activation IDA
GO:2000417 negative regulation of eosinophil migration IDA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 2 GO processes
GO:0051134 negative regulation of NK T cell activation IDA
GO:2000417 negative regulation of eosinophil migration IDA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 10 GO processes
GO:0030889 negative regulation of B cell proliferation IMP
GO:0033007 negative regulation of mast cell activation involved in immune response IDA
GO:0034125 negative regulation of MyD88-dependent toll-like receptor signaling pathway IMP
GO:0043305 negative regulation of mast cell degranulation IDA
GO:0043312 neutrophil degranulation TAS
GO:0050856 regulation of T cell receptor signaling pathway IDA
GO:0050859 negative regulation of B cell receptor signaling pathway IDA
GO:0051134 negative regulation of NK T cell activation IDA
GO:1902564 negative regulation of neutrophil activation IDA
GO:1902567 negative regulation of eosinophil activation IDA

References

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1. A-González N, Castrillo A. (2011) Liver X receptors as regulators of macrophage inflammatory and metabolic pathways. Biochim. Biophys. Acta, 1812 (8): 982-94. [PMID:21193033]

2. Alvarez Y, Tang X, Coligan JE, Borrego F. (2008) The CD300a (IRp60) inhibitory receptor is rapidly up-regulated on human neutrophils in response to inflammatory stimuli and modulates CD32a (FcgammaRIIa) mediated signaling. Mol. Immunol., 45 (1): 253-8. [PMID:17588661]

3. Bachelet I, Munitz A, Berent-Maoz B, Mankuta D, Levi-Schaffer F. (2008) Suppression of normal and malignant kit signaling by a bispecific antibody linking kit with CD300a. J. Immunol., 180 (9): 6064-9. [PMID:18424727]

4. Bachelet I, Munitz A, Levi-Schaffer F. (2006) Abrogation of allergic reactions by a bispecific antibody fragment linking IgE to CD300a. J. Allergy Clin. Immunol., 117 (6): 1314-20. [PMID:16750992]

5. Bachelet I, Munitz A, Moretta A, Moretta L, Levi-Schaffer F. (2005) The inhibitory receptor IRp60 (CD300a) is expressed and functional on human mast cells. J. Immunol., 175 (12): 7989-95. [PMID:16339535]

6. Borrego F. (2013) The CD300 molecules: an emerging family of regulators of the immune system. Blood, 121 (11): 1951-60. [PMID:23293083]

7. Cantoni C, Bottino C, Augugliaro R, Morelli L, Marcenaro E, Castriconi R, Vitale M, Pende D, Sivori S, Millo R et al.. (1999) Molecular and functional characterization of IRp60, a member of the immunoglobulin superfamily that functions as an inhibitory receptor in human NK cells. Eur. J. Immunol., 29 (10): 3148-59. [PMID:10540326]

8. Clark GJ, Green BJ, Hart DN. (2000) 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 (2): 101-9. [PMID:10746781]

9. Clark GJ, Rao M, Ju X, Hart DN. (2007) Novel human CD4+ T lymphocyte subpopulations defined by CD300a/c molecule expression. J. Leukoc. Biol., 82 (5): 1126-35. [PMID:17702825]

10. Green BJ, Clark GJ, Hart DN. (1998) The CMRF-35 mAb recognizes a second leukocyte membrane molecule with a domain similar to the poly Ig receptor. Int. Immunol., 10 (7): 891-9. [PMID:9701027]

11. Ju X, Zenke M, Hart DN, Clark GJ. (2008) CD300a/c regulate type I interferon and TNF-alpha secretion by human plasmacytoid dendritic cells stimulated with TLR7 and TLR9 ligands. Blood, 112 (4): 1184-94. [PMID:18535206]

12. Kim EJ, Lee SM, Suk K, Lee WH. (2012) CD300a and CD300f differentially regulate the MyD88 and TRIF-mediated TLR signalling pathways through activation of SHP-1 and/or SHP-2 in human monocytic cell lines. Immunology, 135 (3): 226-35. [PMID:22043923]

13. Munitz A, Bachelet I, Eliashar R, Moretta A, Moretta L, Levi-Schaffer F. (2006) The inhibitory receptor IRp60 (CD300a) suppresses the effects of IL-5, GM-CSF, and eotaxin on human peripheral blood eosinophils. Blood, 107 (5): 1996-2003. [PMID:16254138]

14. Narayanan S, Silva R, Peruzzi G, Alvarez Y, Simhadri VR, Debell K, Coligan JE, Borrego F. (2010) Human Th1 cells that express CD300a are polyfunctional and after stimulation up-regulate the T-box transcription factor eomesodermin. PLoS ONE, 5 (5): e10636. [PMID:20498708]

15. Zenarruzabeitia O, Vitallé J, Eguizabal C, Simhadri VR, Borrego F. (2015) The Biology and Disease Relevance of CD300a, an Inhibitory Receptor for Phosphatidylserine and Phosphatidylethanolamine. J. Immunol., 194 (11): 5053-60. [PMID:25980030]

How to cite this page

CD molecules: CD300a. Last modified on 16/05/2017. Accessed on 24/06/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2918.