HGNC Approved Gene Symbol: ADAM33
Cytogenetic location: 20p13 Genomic coordinates (GRCh38) : 20:3,667,975-3,682,010 (from NCBI)
ADAM33 is a member of the 'a disintegrin and metalloprotease domain' family of proteins.
Yoshinaka et al. (2002) isolated mouse and human cDNAs encoding ADAM33. The 813-amino acid human protein shares 70% identity with the mouse protein. ADAM33 has a domain organization identical to that of previously reported members of the ADAM family, and contains the typical zinc-binding consensus sequence in the metalloprotease domain and a pattern of cysteine localization in the EGF-like domain that is typical of an EGF-like motif. The human protein shows 44% identity with Xenopus ADAM13, 40% with human ADAM19 (603640), and 39% with human ADAM12 (602714).
Yoshinaka et al. (2002) showed that the ADAM33 gene consists of 22 exons and is over 14 kb long.
Yoshinaka et al. (2002) mapped the human ADAM33 gene to chromosome 20p13.
Van Eerdewegh et al. (2002) performed a genomewide scan of 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (600807) with a lod score of 2.94 and to bronchial hyperresponsiveness with a lod score of 3.93. A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene as being significantly associated with asthma using case-control, transmission disequilibrium, and haplotype analyses (P = 0.04-0.000003). Since ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell surface proteins such as cytokines and cytokine receptors, Van Eerdewegh et al. (2002) suggested that identification of ADAM33 as a gene implicated in asthma susceptibility should provide insights into the pathogenesis and natural history of this common disease.
Shapiro and Owen (2002) reviewed the role of ADAM33 as an 'asthma gene.'
Chae et al. (2003) identified 16 novel polymorphisms in the ADAM33 gene, including 3 in the promoter region and 1 in the 3-prime untranslated region.
In a large study of 612 Caucasian patients with asthma and 473 nonasthmatic Caucasian controls, Kedda et al. (2006) did not find an association between asthma and 10 different SNPs of the ADAM33 gene. However, there was an association between asthma and several rare ADAM33 haplotypes.
Sakagami et al. (2007) found differences in ADAM33 allele and haplotype frequencies between Japanese patients with aspirin-intolerant asthma (AIA), aspirin-tolerant asthma, and controls. They concluded that sequence variations in ADAM33 are likely to correlate with susceptibility to aspirin-intolerant asthma in Japanese.
Chae, S.-C., Yoon, K.-H., Chung, H.-T. Identification of novel polymorphisms in the Adam33 gene. J. Hum. Genet. 48: 278-281, 2003. [PubMed: 12768445] [Full Text: https://doi.org/10.1007/s10038-003-0019-1]
Kedda, M.-A., Duffy, D. L., Bradley, B., O'Hehir, R. E., Thompson, P. J. ADAM33 haplotypes are associated with asthma in a large Australian population. Europ. J. Hum. Genet. 14: 1027-1036, 2006. [PubMed: 16773130] [Full Text: https://doi.org/10.1038/sj.ejhg.5201662]
Sakagami, T., Jinnai, N., Nakajima, T., Sekigawa, T., Hasegawa, T., Suzuki, E., Inoue, I., Gejyo, F. ADAM33 polymorphisms are associated with aspirin-intolerant asthma in the Japanese population. J. Hum. Genet. 52: 66-72, 2007. [PubMed: 17061022] [Full Text: https://doi.org/10.1007/s10038-006-0081-6]
Shapiro, S. D., Owen, C. A. ADAM-33 surfaces as an asthma gene. (Letter) New Eng. J. Med. 347: 936-938, 2002. [PubMed: 12239266] [Full Text: https://doi.org/10.1056/NEJMcibr022144]
Van Eerdewegh, P., Little, R. D., Dupuis, J., Del Mastro, R. G., Falls, K., Simon, J., Torrey, D., Pandit, S., McKenny, J., Braunschweiger, K., Walsh, A., Liu, Z., and 26 others. Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature 418: 426-430, 2002. [PubMed: 12110844] [Full Text: https://doi.org/10.1038/nature00878]
Yoshinaka, T., Nishii, K., Yamada, K., Sawada, H., Nishiwaki, E., Smith, K., Yoshino, K., Ishiguro, H., Higashiyama, S. Identification and characterization of novel mouse and human ADAM33s with potential metalloprotease activity. Gene 282: 227-236, 2002. [PubMed: 11814695] [Full Text: https://doi.org/10.1016/s0378-1119(01)00818-6]