CD300a

Immunopharmacology Ligand Target has curated data in GtoImmuPdb

Target id: 2918

Nomenclature: CD300a

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 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

Previous and Unofficial Names

CMRF-35-H9 | Irp60 | LMIR1 (mouse) | CLM-8 | IGSF12

Database Links
Alphafold	Q9UGN4 (Hs), Q6SJQ0 (Mm), A2TGX5 (Rn)
CATH/Gene3D	2.60.40.10
Ensembl Gene	ENSG00000167851 (Hs), ENSMUSG00000034652 (Mm), ENSRNOG00000057058 (Rn)
Entrez Gene	11314 (Hs), 217303 (Mm), 501736 (Rn)
Human Protein Atlas	ENSG00000167851 (Hs)
KEGG Gene	hsa:11314 (Hs), mmu:217303 (Mm), rno:501736 (Rn)
Pharos	Q9UGN4 (Hs)
RefSeq Nucleotide	NM_007261 (Hs), NM_170758 (Mm), NM_001205348 (Rn)
RefSeq Protein	NP_009192 (Hs), NP_739564 (Mm), NP_001192277 (Rn)
UniProtKB	Q9UGN4 (Hs), Q6SJQ0 (Mm), A2TGX5 (Rn)
Wikipedia	CD300A (Hs)

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.

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:	T-helper 1 cell (CL:0000545) CD4-positive, alpha-beta T cell (CL:0000624)
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:

Immuno Process:

Immuno Process:

Immuno Process:

Immuno Process:

Immuno Process:

Chemotaxis & migration

Immuno Process:

Cellular signalling

General Comments
This protein contains an immunoglobulin (Ig)-like domain that resembles the antibody variable domain, that has been coined the 'V-set domain'. The genes for all human V-set domain containing proteins are listed in HGNC gene group 590.

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]