Structure-function analysis of the ADAM family of disintegrin-like and metalloproteinase-containing proteins (review).
The ADAMs belong to a disintegrin-like and metalloproteinase-containing protein family that are zinc-dependent metalloproteinases. These proteins share all or some of the following domain structure: a signal peptide, a propeptide, a metalloproteinase, a disintegrin, a cysteine-rich, and an epidermal growth factor (EGF)-like domains, a transmembrane region, and a cytoplasmic tail. ADAMs are widely distributed in many organs, tissues, and cells, such as brain, testis, epididymis, ovary, breast, placenta, liver, heart, lung, bone, and muscle. These proteins are capable of four potential functions: proteolysis, adhesion, fusion, and intracellular signaling. Because the number of ADAM genes has grown rapidly and the biological functions of most members are unclear, this review analyzes the protein structures and functions, their activation and processing, their known and potential activities, and their evolutionary relationships. A sequence alignment of human ADAMs is compiled and their homology and physical data are calculated. The conceivable functions of ADAMs in reproduction, development, and diseases are also discussed.
Stone
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Department of Chemistry and Institute of Molecular Biophysics, Florida State University, Tallahassee 32306-4390, USA.
Kroeger
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Sang
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QX
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D003545:Cysteine / Q000032:analysis; D019483:Disintegrins / Q000737:chemistry* / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000737:chemistry; D019143:Evolution, Molecular; D005306:Fertilization; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000502:physiology*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011498:Protein Precursors / Q000737:chemistry; D021382:Protein Sorting Signals / Q000737:chemistry; D016415:Sequence Alignment; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D015032:Zinc / Q000494:pharmacology*
D019483:Disintegrins; D011498:Protein Precursors; D021382:Protein Sorting Signals; D004815:Epidermal Growth Factor; D008666:Metalloendopeptidases; D015032:Zinc; D003545:Cysteine