| Literature References | 1. WERB, Z.
ECM and cell surface proteolysis: regulating cellular ecology.
CELL 91 439-442 (1997).
2. KUNO, K., KANADA, N., NAKASHIMA, E., FUJIKI, F., ICHIMURA, F. AND
MATSUSHIMA, K.
Molecular cloning of a gene encoding a new type of metalloproteinase-
disintegrin family protein with thrombospondin motifs as an inflammation
associated gene.
J.BIOL.CHEM. 272 556-562 (1997).
3. HURSKAINEN, T., HIROHATA, S., SELDIN, M. AND APTE, S.
ADAM-TS5, ADAM-TS6 and ADAM-TS7, novel members of a new family of zinc
metalloproteases (ADAM-TS, A disintegrin and metalloprotease domain with
thrombospondin type I motifs). General features and genomic distribution of
the ADAM-TS family.
J.BIOL.CHEM. 274 25555-25563 (1999).
4. COLIGE, A., SIERON, A., LI, S., SCHWARZE, U., PETTY, E., WERTELECKI, W.,
WILCOX, W., KRAKOV, D., COHN, D., REARDON, W., BYERS, P., LAPIERE, C.,
PROCKOP,, D. AND NUSGENS, B.
Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are
caused by mutations in the procollagen I N-proteinase gene.
AM.J.HUM.GENET. 65 308-317 (1999).
5. TORTORELLA, M., BURN, T., PRATTA, M., ABBASZADE, I., HOLLIS, J., LIU, R.,
ROSENFELD, S., COPELAND, R., DECICCO, C., WYNN, R., ROCKWELL, A., YANG, F.,
DUKE, J., SOLOMON, K., GEORGE, H., BRUCKNER, R., NAGASE, H., ITOH, Y.,
ELLIS, D., ROSS, H., WISWALL, B., MURPHY, K., HILLMAN, M., HOLLIS, G.,
NEWTON, R., MAGOLDA, R., TRZASKOS, J. AND ARNER, E.
Purification and cloning of aggrecanase-1: a member of the ADAMTS family of
proteins.
SCIENCE 284 1664-1666 (1999).
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| Documentation | Proteolysis of the extracellular matrix plays a critical role in
establishing tissue architecture during development, and in tissue
degradation in diseases such as cancer, arthritis, Alzheimer's disease
and a variety of inflammatory conditions [1]. The proteolytic enzymes
responsible for this process are members of diverse protease families,
including the secreted zinc metalloproteases (MPs) [1]. Recently, a new
MP family, ADAM-TS (a disintegrin-like and metalloprotease domain with
thrombospondin type I modules) has been identified. The family consists
of at least 20 members that share a high degree of sequence similarity
and conserved domain organisation [2,3].
The defining domains of the ADAM-TS family are (from N- to C-termini) a
pre-pro metalloprotease domain of the reprolysin type, a snake venom
disintegrin-like domain, a thrombospondin type-I (TS) module, a cysteine-
rich region, and a cysteine-free (spacer) domain [3]. Domain organisation
following the spacer domain C-terminus shows some variability in certain
ADAM-TS members, principally in the number of additional TS domains.
Members of the ADAM-TS family have been implicated in a range of diseases.
ADAM-TS1, for example, is reported to be involved in inflammation and cancer
cachexia [2], whilst recessively inherited ADAM-TS2 mutations cause
Ehlers-Danlos syndrome type VIIC, a disorder characterised clinically by
severe skin fragility [4]. ADAM-TS4 is an aggrecanase involved in arthritic
destruction of cartilage [5].
ADAMTSFAMILY is a 3-element fingerprint that provides a signature for the
ADAM-TS family. The fingerprint was derived from an initial alignment of
9 sequences: the motifs were drawn from conserved regions spanning the
N-terminal two thirds of the alignment - motif 1 lies in the first TS
module; and motifs 2 and 3 reside in the cysteine-rich region between the
first TS module and the spacer domain. Two iterations on SPTR40_22f were
required to reach convergence, at which point a true set comprising 49
sequences was identified. A single partial match was also found, Q8MSF8, an
uncharacterised translated Drosophila cDNA that matches motifs 1 and 2.
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