• Leu-19
• NKH1
• neural cell adhesion molecule, NCAM

MAJOR LINKS FOR CD56  

• NCBI LocusLink Record: 4684
• Mendelian Inheritance in Man (OMIM): 116930
• SwissProt annotated protein record: P13592
• SwissProt annotated protein record: P13591
• SwissProt annotated protein record: P13593

CELLULAR FUNCTION OF CD56  

• In the nervous system, there is evidence for both homophilic and heterophilic adhesion by NCAM. It is implicated in neural development
• This has not been convincingly demonstrated with hematopoietic cells
• No consensus has emerged on the role of N-CAM in T or NK cell function, although there have been reports for involvement in homophilic adhesion

DISEASE RELEVANCE OF CD56 AND FUNCTION OF CD56 IN INTACT ANIMAL   - No information

• Families in which CD56 is a member
  • CD56-->neural cell adhesion molecule-->immunoglobulin supergene family

MOLECULAR STRUCTURE OF CD56  

• NK and T cells predominantly express the 140 kDa isoform of N-CAM
• The extracellular domain of the 140 kDa N-CAM glycoprotein contains 689
• amino acids, composed of 5 C2-set Ig superfamily domains and two fibronectin
• type III domains
• There are 6 potential sites for N-linked glycosylation
• The cytoplasmic domain is 119 amino acids

MOLECULAR MASS OF CD56  

POST-TRANSCRIPTIONAL MODIFICATION OF CD56  

• Single gene that generates multiple isoforms by alternative splicing
• Soluble, transmembrane-anchored, and glycosylphosphatidylinositol (GPI)-anchored glycoproteins have been identified in different tissues
• The predominant isoform in NK and T cells is the transmembrane-anchored 140 kDa glycoprotein

POST-TRANSLATIONAL MODIFICATION OF CD56  

• There are 6 potential sites for N-linked glycosylation
• N-CAM on NK and T cells is extensively modified with polysialic acid and migrates as a diffuse band of high molecular weight on SDS-PAGE gels
• After treatment with neuraminidase to remove sialic acid, the predominant glycoprotein is ~140 kDa

SUBSTRATES FOR CD56   - No information

ENZYMES WHICH MODIFY CD56   - No information

LIGANDS FOR CD56 AND MOLECULES ASSOCIATED WITH CD56  

• CD56 is the prototypic marker of human NK cells that is also present on a subset of CD4+ and CD8+ T cells in peripheral blood, and is variably expressed on in vitro cultured T cell clones
• CD56 is also present on brain in the cerebellum and cortex and at neuromuscular junctions
• CD56 is also present on certain LGL leukemias, small cell lung carcinomas, neural-derived tumors, myelomas, and myeloid leukemias

• While N-CAM is expressed in the brain of humans and rodents, N-CAM is present on human NK cells, but is not found on mouse or rat NK cells
• T and NK cell development and function appear normal in mice with disrupted N-CAM genes**
• NCAM is a single gene on chromosome 11q23-q24

SELECTION OF OTHER CD56-SPECIFIC REFERENCE MAB  

REVIEWS

PRIMARY CITATIONS

1. Thiery JP,Duband JL,Rutishauser U,Edelman GM Cell adhesion molecules in early chicken embryogenesis. Proc Natl Acad Sci U S A 1982 79:6737 PubMed

2. Rutishauser U,Grumet M,Edelman GM Neural cell adhesion molecule mediates initial interactions between spinal cord neurons and muscle cells in culture. J Cell Biol 1983 97:145 PubMed

3. Lanier LL,Testi R,Bindl J,Phillips JH Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med 1989 169:2233 PubMed

4. Hercend T,Griffin JD,Bensussan A,Schmidt RE,Edson MA,Brennan A,Murray C,Daley JF,Schlossman SF,Ritz J Generation of monoclonal antibodies to a human natural killer clone. Characterization of two natural killer-associated antigens, NKH1A and NKH2, expressed on subsets of large granular lymphocytes. J Clin Invest 1985 75:932 PubMed

5. Cunningham BA,Hemperly JJ,Murray BA,Prediger EA,Brackenbury R,Edelman GM Neural cell adhesion molecule: structure, immunoglobulin-like domains, cell surface modulation, and alternative RNA splicing. Science 1987 236:799 PubMed

6. Barton CH,Dickson G,Gower HJ,Rowett LH,Putt W,Elsom V,Moore SE,Goridis C,Walsh FS Complete sequence and in vitro expression of a tissue-specific phosphatidylinositol-linked N-CAM isoform from skeletal muscle. Development 1988 104:165 PubMed

7. Lanier LL,Chang C,Azuma M,Ruitenberg JJ,Hemperly JJ,Phillips JH Molecular and functional analysis of human natural killer cell- associated neural cell adhesion molecule (N-CAM/CD56). J Immunol 1991 146:4421 PubMed

8. Hemperly JJ,DeGuglielmo JK,Reid RA Characterization of cDNA clones defining variant forms of human neural cell adhesion molecule N-CAM. J Mol Neurosci 1990 2:71 PubMed

9. Cremer H,Lange R,Christoph A,Plomann M,Vopper G,Roes J,Brown R,Baldwin S,Kraemer P,Scheff S,et al Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning. Nature 1994 367:455 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov