NCAM1/CD56 (human, recombinant)

CD56, also known as neural cell adhesion molecule 1 (NCAM1), is a cell surface glycoprotein and member of the immunoglobulin superfamily that is involved in cellular adhesion and neural development.^1,2,3 Alternative splicing of the NCAM1 pre-mRNA produces several isoforms, including two transmembrane isoforms of 180 and 140 kDa, NCAM-180 and NCAM-140, respectively, that differ in size of the cytoplasmic domain, and a 120 kDa isoform, NCAM-120, that lacks the cytoplasmic domain and is linked to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor.¹ CD56 is composed of an extracellular N-terminal domain containing five immunoglobulin-like (Ig-like) domains and two fibronectin type III domains that mediate homophilic and heterophilic interactions, a transmembrane domain, and an intracellular C-terminal signaling domain.^2,4 It is used as a marker for neural and natural killer (NK) cells, but is also expressed by other immune cells, including monocytes, T cells, and dendritic cells (DCs), as well as tumor cells, in an isoform-dependent manner.^1,2,4 CD56 is increased on NK cells by stimulation with IL-15 or IL-2 and correlates with upregulation of the NK cell activating receptors NKG2D, NKp30, and NKp46 and NK cell-mediated cytotoxicity.^1,4 Homophilic CD56 interactions induce neurite outgrowth of cerebellar neurons and promote NK cell-mediated tumor cell lysis in vitro.^1,2,3,4 The frequency of peripheral blood CD56^bright NK cells is increased in patients with melanoma and associated with reduced overall survival.⁵ Cayman’s NCAM1/CD56 (human, recombinant) protein consists of 591 amino acids, has a calculated molecular weight of 66.1 kDa, and a predicted N-terminus of Leu20 after signal peptide cleavage. By SDS-PAGE, under reducing conditions, the apparent molecular mass of the protein is approximately 80-110 kDa due to glycosylation.

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1. Van Acker, H.H., Capsomidis, A., Smits, E.L., et al. CD56 in the immune system: More than a marker for cytotoxicity? Front. Immunol. 8, 892 (2017).

2. Kitlevsen, D.K., Povlsen, G.K., Berezin, V., et al. NCAM-induced intracellular signaling revisited. J. Neurosci. Res. 86(4), 727-743 (2008).

3. Williams, E.J., Furness, J., Walsh, F.S., et al. Activation of the FGF receptor underlies neurite outgrowth stimulated by L1, N-CAM, and N-cadherin. Neuron. 13(3), 583-594 (1994).

4. Van Acker, H.H., Van Acker, Z.P., Versteven, M., et al. CD56 homodimerization and participation in anti-tumor immune effector cell functioning: A role for interleukin-15. Cancers (Basel) 11(7), 1029 (2019).

5. de Jonge, K., Ebering, A., Nassiri, S., et al. Circulating CD56 bright NK cells inversely correlate with survival of melanoma patients. Sci. Rep. 9(1), 4487 (2019).