• Purity

  >90%, by SDS-PAGE under reducing conditions and visualized by silver stain

• Endotoxin Level

  <0.10 EU per 1 μg of the protein by the LAL method.  

• Activity

  Measured by the ability of the immobilized protein to support the adhesion of BCE C/D?1b bovine corneal endothelial cells. The ED    ₅₀ for this effect is 20-100 ng/mL.

• Source

  Chinese Hamster Ovary cell line, CHO-derived Gly26-His528 (Leu78Val), with a C-terminal 8-His tag

• Accession #

• N-terminal Sequence    
  Analysis

  Gly26 & Asn233

• Structure / Form

  Mixture of pro and mature forms

• Predicted Molecular Mass

  58 kDa (pro) & 34 kDa (mature)

• SDS-PAGE

  40-45 kDa & 69-80 kDa, reducing conditions

Background: ADAM22

A disintegrin and metalloproteinase 22 (ADAM22), also known as MDC2, is an 85-90 kDa transmembrane member of the M12B family of peptidases (1). Human ADAM22 contains an N-terminal 197 amino acid (aa) cleavable proregion and a 514 aa extracellular domain (ECD). The ECD contains a nonfunctional metalloprotease domain, an integrin?binding disintegrin domain, a cysteine?rich region, and one EGF-like domain (2). The cytoplasmic portion contains two phosphorylation motifs which bind to 14-3-3 proteins to mediate cell adhesion (3, 4). Alternative splicing generates multiple isoforms with a variety of insertions, deletions, and substitutions in the cytoplasmic region (2, 5, 6). Within the peptidase-like and disintegrin domains, human ADAM22 shares 96% sequence identity with mouse and rat ADAM22. ADAM22 is expressed on neurons, astrocytes, and Schwann cells in the cerebral cortex, hippocampus, and cerebellum and also on some low-grade gliomas (5, 7-9). It can be up-regulated in endocrine therapy-resistant breast cancer, and it contributes to tumor cell migration (10). It mediates cell adhesion through binding to Integrins alpha 6, alpha 9, and beta 3 (7). ADAM22 is localized to post-synaptic densities (11). It binds the secreted protein LGI1 which functions as a bridge to link ADAM22 with pre-synaptically expressed ADAM23 (9). The interaction of LGI1 with ADAM22 promotes AMPA receptor expression in hippocampal neurons and strengthens excitatory synapses (9). In axonal juxtaparanodes, ADAM22 is a component of the voltage-gated Kv1 potassium channel that responds to LGI1 (12). It also colocalizes with Kv1 channels in basket cell interneuron terminals of the cerebellum (12). ADAM22 additionally binds to Schwann cell derived LGI4 and is required for LGI4 to promote axon myelination (8). Mice lacking ADAM22 expression exhibit hypomyelination and profound ataxia (13).

• References:

1. Edwards, D.R. et al. (2008) Mol. Aspects Med. 29:258.

2. Sagane, K. et al. (1998) Biochem. J. 334:93.

3. Godde, N.J. et al. (2006) J. Cell Sci. 119:3296.

4. Zhu, P. et al. (2005) Biochem. Biophys. Res. Commun. 331:938.

5. Harada, T. et al. (2000) Jpn. J. Cancer Res. 91:1001.

6. Godde, N.J. et al. (2007) Gene 403:80.

7. D’Abaco, G.M. et al. (2006) Neurosurgery 58:179.

8. Ozkaynak, E. et al. (2010) J. Neurosci. 30:3857.

9. Fukata, Y. et al. (2006) Science 313:1792.

10. McCartan, D. et al. (2012) Cancer Res. 72:220.

11. Fukata, Y. et al. (2010) Proc. Natl. Acad. Sci. USA 107:3799.

12. Ogawa, Y. et al. (2010) J. Neurosci. 30:1038.

13. Sagane, K. et al. (2005) BMC Neurosci. 6:33.

• Long Name:

  A Disintegrin and Metalloproteinase Domain 22

• Entrez Gene IDs:

  53616 (Human); 11496 (Mouse); 57033 (Rat)

• Alternate Names:

  ADAM 22; ADAM metallopeptidase domain 22; ADAM22; MDC2; metalloproteinase-disintegrin ADAM22-3; metalloproteinase-like, disintegrin-like, and cysteine-rich protein 2; MGC149832