Alternative titles; symbols
HGNC Approved Gene Symbol: ADAM23
Cytogenetic location: 2q33.3 Genomic coordinates (GRCh38): 2:206,443,532-206,621,127 (from NCBI)
The cellular disintegrins, also known as ADAM (a disintegrin and metalloproteinase) and MDC (metalloproteinase-like, disintegrin-like, and cysteine-rich) proteins, are a class of potential cell adhesion molecules.
By searching an EST database for sequences related to MDC (155120), Sagane et al. (1998) identified a partial MDC3 cDNA. They screened a human brain cDNA library and used 3-prime RACE to clone additional cDNAs corresponding to the entire MDC3 coding region. The predicted 832-amino acid protein contains the typical cellular disintegrin domains (see MDC2, or ADAM22; 603709). However, the zinc-binding motif, which is critical for proteinase activity, is disrupted in MDC3 as well as the other MDC proteins. MDC3 shares approximately 52% sequence similarity with MDC and MDC2. Northern blot analysis revealed that MDC3 was expressed predominantly in brain as several transcripts ranging in size from 3.5 to 7 kb.
By radiation hybrid analysis, Poindexter et al. (1999) mapped the ADAM23 gene to chromosome 2q33.
Using immunostaining analysis, Hivert et al. (2019) showed that the voltage-gated Kv1 K+ channel (see 176260)-associated protein Lgi1 (604619) was targeted to the axon initial segment (AIS) of cultured rat hippocampal neurons. Lgi1 colocalized with Adam22, but not with Adam23. However, both ADAM proteins appeared to modulate Lgi1 targeting to the AIS. Coexpression analysis in HEK cells revealed that human ADAM22 and ADAM23 were involved in intracellular trafficking of LGI1 and promoted endoplasmic reticulum (ER) exit and N-glycan maturation of LGI1. Missense mutations in the EPTP6 domain of LGI1 reduced its interaction with ADAM22 and impaired its recruitment to the AIS. Moreover, Lgi1 and Adam23 colocalized in transport vesicles of rat hippocampal neurons, and Lgi1 likely required coexpression with Adam22 or Adam23 for proper trafficking and axonal transport. ADAM22 and ADAM23 also selectively associated with several cell adhesion molecules, including TAG1 (CNTN1; 190197) and CASPR2 (CNTNAP2; 604569), that associated with Kv1 channels at discrete regions of the axon. Axonal targeting of ADAM23 was modulated by its coexpression with TAG1 and CASPR2 in hippocampal neurons.
Hivert, B., Marien, L., Agbam, K. N., Faivre-Sarralh, C. ADAM22 and ADAM23 modulate the targeting of the Kv1 channel-associated protein LGI1 to the axon initial segment. J. Cell Sci. 132: jcs219774, 2019. [PubMed: 30598502] [Full Text: https://doi.org/10.1242/jcs.219774]
Poindexter, K., Nelson, N., DuBose, R. F., Black, R. A., Cerretti, D. P. The identification of seven metalloproteinase-disintegrin (ADAM) genes from genomic libraries. Gene 237: 61-70, 1999. [PubMed: 10524237] [Full Text: https://doi.org/10.1016/s0378-1119(99)00302-9]
Sagane, K., Ohya, Y., Hasegawa, Y., Tanaka, I. Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2 and MDC3: novel human cellular disintegrins highly expressed in the brain. Biochem. J. 334: 93-98, 1998. [PubMed: 9693107] [Full Text: https://doi.org/10.1042/bj3340093]