CD244

CD244 (CD244 Molecule) is a Protein Coding gene. Diseases associated with CD244 include Rheumatoid Arthritis and Lymphoproliferative Syndrome, X-Linked, 1. Among its related pathways are Response to elevated platelet cytosolic Ca2+ and Hematopoietic Stem Cell Differentiation Pathways and Lineage-specific Markers. Gene Ontology (GO) annotations related to this gene include receptor activity.

Full Name

CD244 Molecule

Function

Heterophilic receptor of the signaling lymphocytic activation molecule (SLAM) family; its ligand is CD48. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Acts as activating natural killer (NK) cell receptor (PubMed:10359122, PubMed:8376943, PubMed:11714776).
Activating function implicates association with SH2D1A and FYN (PubMed:15713798).
Downstreaming signaling involves predominantly VAV1, and, to a lesser degree, INPP5D/SHIP1 and CBL. Signal attenuation in the absence of SH2D1A is proposed to be dependent on INPP5D and to a lesser extent PTPN6/SHP-1 and PTPN11/SHP-2 (PubMed:10934222, PubMed:15713798).
Stimulates NK cell cytotoxicity, production of IFN-gamma and granule exocytosis (PubMed:8376943, PubMed:11714776).
Optimal expansion and activation of NK cells seems to be dependent on the engagement of CD244 with CD48 expressed on neighboring NK cells (By similarity).
Acts as costimulator in NK activation by enhancing signals by other NK receptors such as NCR3 and NCR1 (PubMed:10741393).
At early stages of NK cell differentiation may function as an inhibitory receptor possibly ensuring the self-tolerance of developing NK cells (PubMed:11917118).
Involved in the regulation of CD8+ T-cell proliferation; expression on activated T-cells and binding to CD488 provides costimulatory-like function for neighboring T-cells (By similarity).
Inhibits inflammatory responses in dendritic cells (DCs) (By similarity).

Biological Process

Adaptive immune response Source: UniProtKB-KW
Innate immune response Source: UniProtKB-KW
Leukocyte migration Source: Reactome
Natural killer cell activation involved in immune response Source: UniProtKB
Positive regulation of granzyme B production Source: UniProtKB
Positive regulation of inositol phosphate biosynthetic process Source: UniProtKB
Positive regulation of interferon-gamma production Source: UniProtKB
Positive regulation of interleukin-8 production Source: UniProtKB
Signal transduction Source: ProtInc

Cellular Location

Cell membrane; Membrane. Receptor engagement results in a recruitment to lipid drafts essential for the subsequent tyrosine phosphorylation of the ITSMs.

Topology

Extracellular: 22-229
Helical: 230-250
Cytoplasmic: 251-370

PTM

N-linked glycosylation is essential for the binding to its ligand CD48. Also O-glycosylated, in contrast, O-linked sialylation has a negative impact on ligand binding.
Phosphorylated by FYN and CSK on tyrosine residues following activation. Coligation with inhibitory receptors such as KIR2DL1 inhibits phosphorylation upon contact of NK cells with sensitive target cells.