Recombinant Human Natural killer cell receptor 2B4 (CD244), partial

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:11714776, PubMed:8376943). 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:11714776, PubMed:8376943). 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 CD48 provides costimulatory-like function for neighboring T-cells (By similarity). Inhibits inflammatory responses in dendritic cells (DCs) (By similarity)

Subcellular Location

Membrane (Single-pass type I membrane protein); Cell membrane; Membrane raft

Tissue Specificity

Expressed in spleen, PBL, followed by lung, liver, testis and small intestine. Expressed in all natural killer (NK) cells, monocytes and basophils, TCR-gamma/delta+ T-cells, monocytes, basophils, and on a subset of CD8(+) T-cells

Subunit

Interacts with CD48 (PubMed:27249817, PubMed:9841922). Interacts (via phosphorylated ITSM 1-4) with SH2D1A (via SH2 domain); SH2D1A probably mediates association with FYN. Interacts (via phosphorylated ITSM 3) with PTPN11/SHP-2, INPP5D/SHIP1, PTPN6/SHP-1 and CSK; binding of SH2D1A/SAP prevents association with PTPN11, PTPN6 and CSK; conflictingly a similar association has been described for phosphorylated ITSM 1 also including GRB2 and PLCG1. Interacts weakly (via phosphorylated ITSM 2) with PTPN11/SHP-2 and CSK (PubMed:10358138, PubMed:10934222, PubMed:12458214, PubMed:15713798, PubMed:24642916, PubMed:26221972). Interacts with SH2D1B (PubMed:12458214, PubMed:24642916). Interacts with PIK3R1; PI3K recruits SH2D1A (PubMed:11815622). Interacts with MHC class I proteins; the interaction is proposed to prevent self-killing of NK cells

• Nakajima H. et al. Activating interactions in human NK cell recognition: the role of 2B4-CD48. — Eur. J. Immunol. (1999)
• Kubin M.Z. et al. Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48. — Eur. J. Immunol. (1999)
• Tangye S.G. et al. Human 2B4, an activating NK cell receptor, recruits the protein tyrosine phosphatase SHP-2 and the adaptor signaling protein SAP. — J. Immunol. (1999)
• Boles K.S. et al. Molecular characterization of a novel human natural killer cell receptor homologous to mouse 2B4. — Tissue Antigens (1999)
• Kumaresan P.R. et al. Structure of the human natural killer cell receptor 2B4 gene and identification of a novel alternative transcript. — Immunogenetics (2000)
• Parolini S. et al. X-linked lymphoproliferative disease: 2B4 molecules displaying inhibitory rather than activating function are responsible for the inability of natural killer cells to kill Epstein-Barr virus-infected cells. — J. Exp. Med. (2000)
• Biassoni R. et al. Activating NK receptor homolog to the murine 2B4. (JUL-)
• Gregory S.G. et al. The DNA sequence and biological annotation of human chromosome 1. — Nature (2006)