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| | Domain structure of ADAM23. Its deduced amino acid sequence lacks essential residues conserved in metalloproteinases (Cal S. et al., 2000). |
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| Description | 832amino acid protein including a hydrophobic transmembrane domain and eight potential N-linked glycosylation sites. This protein has multiple domain structures including a pro-, a metalloproteinase-like, a desintegrin-like, a cysteine-rich, an epidermal growth factor-like, a transmembrane and a cytoplasmatic domain. Within the metalloproteinase-like domain, ADAM23 lacks HEXXHXXGXXH active-site amino acids for zinc-binding, which is critical for the proteinase activity. So, the metalloproteinase domain is inactive, suggesting that it is exclusively involved in cell adhesion processes rather than in protease-mediated events. |
| Expression | Highly expressed in the brain and weakly expressed in the heart. In the brain, expressed prominently in the amygdala, caudate nucleus, hypothalamus, thalamus, cerebral cortex and occipital pole. |
| Localisation | Cell membrane; single-pass type I membrane protein (Potential). Isoform Gamma: Secreted protein. |
| Function | May play a role in cell-cell and cell-matrix interactions. This is a non-catalytic metalloprotease-like protein. |
| Homology | H. sapiens: ADAM23
P.troglodytes: ADAM23
C.lupus: LOC607871
M.musculus: ADAM23
R.novergicus: ADAM23
G.gallus: LOC424099 |
| Entity | gastric tumors. |
| Note | Hypermethylation of the promoter region of ADAM 23 gene, along with decreased expression, occurs in primary gastric tumors compared with noncancerous gastric tissue. |
| Prognosis | Not determined. |
| Cytogenetics | Not determined. |
| Hybrid/Mutated Gene | Not determined. |
| Oncogenesis | Loss of ADAM23, which is likely to play an important role regard to cell-cell and cell- extracellular matrix interactions in gastric tissue as well, might be essential for the progression of gastric cancer. |
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| Entity | breast tumors. |
| Note | Hypermethylation of the promoter region of ADAM23 gene, along with decreased expression, occurs in primary breast tumors and primary breast tumors with a more advanced grade have higher degree of methylation. |
| Cytogenetics | Not determined. |
| Hybrid/Mutated Gene | Not determined. |
| Oncogenesis | Primary breast tumors with a more advanced grade have a higher degree of methylation, suggesting that the adhesion molecule ADAM23 may be downregulated during the progression of breast cancer. |
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| Entity | Head and neck cancer. |
| Note | Hypermethylation of the promoter region of ADAM23 gene, along with decreased expression, occurs in Head and neck cancer and the frequency of hypermethylation of ADAM23 gene is higher in primary head and neck tumors with a more advanced grade |
| Cytogenetics | Not determined. |
| Hybrid/Mutated Gene | Not determined. |
| Oncogenesis | Hypermethylation of the ADAM23 gene could lead to tumor progression, because the neoplastic cells would lose the contact inhibition. As a consequence, these cells would proliferate in an uncontrolled manner; once the proliferation of most cancer cells is no longer sensitive to density-dependent inhibition, a permissive environment for cell proliferation is created. |
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| Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2 and MDC3: novel human cellular disintegrins highly expressed in the brain. |
| Sagane K, Ohya Y, Hasegawa Y, Tanaka I |
| The Biochemical journal. 1998 ; 334 ( Pt 1) : 93-98. |
| PMID 9693107 |
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| The identification of seven metalloproteinase-disintegrin (ADAM) genes from genomic libraries. |
| Poindexter K, Nelson N, DuBose RF, Black RA, Cerretti DP |
| Gene. 1999 ; 237 (1) : 61-70. |
| PMID 10524237 |
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| ADAM 23/MDC3, a human disintegrin that promotes cell adhesion via interaction with the alphavbeta3 integrin through an RGD-independent mechanism. |
| Cal S, Freije JM, Lˆ„pez JM, Takada Y, Lˆ„pez-Otˆ‚n C |
| Molecular biology of the cell. 2000 ; 11 (4) : 1457-1469. |
| PMID 10749942 |
| |
| Epigenetic silencing of the adhesion molecule ADAM23 is highly frequent in breast tumors. |
| Costa FF, Verbisck NV, Salim AC, Ierardi DF, Pires LC, Sasahara RM, Sogayar MC, Zanata SM, Mackay A, O'Hare M, Soares F, Simpson AJ, Camargo AA |
| Oncogene. 2004 ; 23 (7) : 1481-1488. |
| PMID 14661055 |
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| Two novel isoforms of Adam23 expressed in the developmental process of mouse and human brains. |
| Sun YP, Deng KJ, Wang F, Zhang J, Huang X, Qiao S, Zhao S |
| Gene. 2004 ; 325 : 171-178. |
| PMID 14697522 |
| |
| ADAM23, a possible tumor suppressor gene, is frequently silenced in gastric cancers by homozygous deletion or aberrant promoter hypermethylation. |
| Takada H, Imoto I, Tsuda H, Nakanishi Y, Ichikura T, Mochizuki H, Mitsufuji S, Hosoda F, Hirohashi S, Ohki M, Inazawa J |
| Oncogene. 2005 ; 24 (54) : 8051-8060. |
| PMID 16103878 |
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| Methylation profile of genes CDKN2A (p14 and p16), DAPK1, CDH1, and ADAM23 in head and neck cancer. |
| Calmon MF, Colombo J, Carvalho F, Souza FP, Filho JF, Fukuyama EE, Camargo AA, Caballero OL, Tajara EH, Cordeiro JA, Rahal P |
| Cancer genetics and cytogenetics. 2007 ; 173 (1) : 31-37. |
| PMID 17284367 |
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