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PR01860

Identifier
ADAMTS5  [View Relations]  [View Alignment]  
Accession
PR01860
No. of Motifs
4
Creation Date
14-MAR-2003
Title
ADAM-TS5 protein signature
Database References
PRINTS; PR01857 ADAMTSFAMILY
MIM; 605007
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).
 
6. TORTORELLA, M., LIU, R., BURN, T., NEWTON, R. AND ARNER, E.
Characterization of human aggrecanase 2 (ADAM-TS5): substrate specificity
studies and comparison with aggrecanase 1 (ADAM-TS4).
MATRIX BIOL. 21 499-511 (2002).

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].
 
ADAM-TS5, also termed aggrecanase 2, was identified through expressed 
sequence tag database searching, pursuing sequences similar to 
ADAM-TS1-4 [4]. In vitro studies have shown that ADAM-TS5, like ADAM-TS4,
is an aggrecanase, able to cleave cartilage aggrecan [6].
 
ADAMTS5 is a 4-element fingerprint that provides a signature for the
ADAM-TS5 proteins. The fingerprint was derived from an initial alignment
of 2 sequences: the motifs were drawn from conserved regions in the 
N-terminal quarter of the alignment, focusing on those sections that 
characterise ADAM-TS5 proteins and distinguish them from other family
members - all motifs lie in the N-terminal region preceding the metallo-
protease domain. A single iteration on SPTR40_22f was required to reach
convergence, no further sequences being identified beyond the starting set.
Summary Information
2 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
42222
30000
20000
1234
True Positives
ATS5_HUMAN    ATS5_MOUSE    
Sequence Titles
ATS5_HUMAN  ADAMTS-5 precursor (EC 3.4.24.-) (A disintegrin and metalloproteinase with thrombospondin motifs 5) (ADAM-TS 5) (ADAM-TS5) (Aggrecanase-2) (ADMP-2) (ADAM-TS 11) - Homo sapiens (Human). 
ATS5_MOUSE ADAMTS-5 precursor (EC 3.4.24.-) (A disintegrin and metalloproteinase with thrombospondin motifs 5) (ADAM-TS 5) (ADAM-TS5) (Aggrecanase-2) (ADMP-2) (Implantin) - Mus musculus (Mouse).
Scan History
SPTR40_22f 1  200  NSINGLE    
Initial Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
AVGPAATPAQDK ATS5_HUMAN 19 19 -
ADSPAAAPAQDK ATS5_MOUSE 24 24 -

Motif 2 width=13
Element Seqn Id St Int Rpt
RSKGLVQNIDQLY ATS5_HUMAN 69 38 -
RSGGLVHNIDQLY ATS5_MOUSE 70 34 -

Motif 3 width=14
Element Seqn Id St Int Rpt
GFFAVKHARYTLKP ATS5_HUMAN 154 72 -
GFFAVKHARYTLKP ATS5_MOUSE 156 73 -

Motif 4 width=29
Element Seqn Id St Int Rpt
YGDGSARILHVYTREGFSFEALPPRASCE ATS5_HUMAN 182 14 -
YGDGSSRILHVYNREGFSFEALPPRASCE ATS5_MOUSE 182 12 -
Final Motifs
Motif 1  width=12
Element Seqn Id St Int Rpt
AVGPAATPAQDK ATS5_HUMAN 19 19 -
ADSPAAAPAQDK ATS5_MOUSE 24 24 -

Motif 2 width=13
Element Seqn Id St Int Rpt
RSKGLVQNIDQLY ATS5_HUMAN 69 38 -
RSGGLVHNIDQLY ATS5_MOUSE 70 34 -

Motif 3 width=14
Element Seqn Id St Int Rpt
GFFAVKHARYTLKP ATS5_HUMAN 154 72 -
GFFAVKHARYTLKP ATS5_MOUSE 156 73 -

Motif 4 width=29
Element Seqn Id St Int Rpt
YGDGSARILHVYTREGFSFEALPPRASCE ATS5_HUMAN 182 14 -
YGDGSSRILHVYNREGFSFEALPPRASCE ATS5_MOUSE 182 12 -