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PR01861

Identifier
ADAMTS8  [View Relations]  [View Alignment]  
Accession
PR01861
No. of Motifs
7
Creation Date
14-MAR-2003
Title
ADAM-TS8 protein signature
Database References
PRINTS; PR01857 ADAMTSFAMILY
MIM; 605175
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. VAZQUEZ, F., HASTINGS, G., ORTEGA, M., LANE, T., OIKEMUS, S, LOMBARDO, M.
AND TRUELA-ARISPE, M.
METH-1, a human ortholog of ADAMTS-1, and METH-2 are members of a new family
of proteins with angio-inhibitory activity.
J.BIOL.CHEM. 274 23349-23357 (1999).

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-TS8, also termed METH2, was identified by searching expressed sequence
tag databases for sequences that contained TS modules [6]. In vitro studies
have shown recombinant ADAM-TS8 to be effective in blocking angiogenesis,
and to inhibit endothelial cell growth [6].
 
ADAMTS8 is a 7-element fingerprint that provides a signature for the
ADAM-TS8 proteins. The fingerprint was derived from an initial alignment of
2 sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise
ADAM-TS8 proteins and distinguish them from other family members - motifs 1 
and 2 lie in the N-terminal region preceding the metalloprotease domain;
motifs 3 and 4 reside in the metalloprotease domain; motif 5 lies in the
cysteine-rich region; motif 6 lies in the spacer domain; and motif 7 resides 
between the spacer domain and the second TS module. 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  7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
72222222
60000000
50000000
40000000
30000000
20000000
1234567
True Positives
ATS8_HUMAN    ATS8_MOUSE    
Sequence Titles
ATS8_HUMAN  ADAMTS-8 precursor (EC 3.4.24.-) (A disintegrin and metalloproteinase with thrombospondin motifs 8) (ADAM-TS 8) (ADAM-TS8) (METH-2) (METH-8) - Homo sapiens (Human). 
ATS8_MOUSE ADAMTS-8 precursor (EC 3.4.24.-) (A disintegrin and metalloproteinase with thrombospondin motifs 8) (ADAM-TS 8) (ADAM-TS8) (METH-2) - Mus musculus (Mouse).
Scan History
SPTR40_22f 1  150  NSINGLE    
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
ELVVPTRLPGSAGELALHLS ATS8_HUMAN 40 40 -
ELVVPTRLPGSASELAFHLS ATS8_MOUSE 41 41 -

Motif 2 width=21
Element Seqn Id St Int Rpt
GPEWEVETGEGQRQERGDHQE ATS8_HUMAN 165 105 -
GLEWEVEMGNGQGQERSDNEE ATS8_MOUSE 177 116 -

Motif 3 width=15
Element Seqn Id St Int Rpt
EKWGPEVSDNGGLTL ATS8_HUMAN 277 91 -
ERWGPEVSDNGGLTL ATS8_MOUSE 291 93 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PLFVHLNQTLPW ATS8_HUMAN 395 103 -
PFFIHVNKTLPW ATS8_MOUSE 409 103 -

Motif 5 width=13
Element Seqn Id St Int Rpt
NAYNYTDMDGNLL ATS8_HUMAN 597 190 -
NAYNHTDLDGNFL ATS8_MOUSE 612 191 -

Motif 6 width=12
Element Seqn Id St Int Rpt
RSHPGVQNDGNY ATS8_HUMAN 722 112 -
RSHPGVRNDGSY ATS8_MOUSE 737 112 -

Motif 7 width=26
Element Seqn Id St Int Rpt
TVPGEVFPPKVKYTFFVPNDVDFSMQ ATS8_HUMAN 793 59 -
TVSGEVFPPKVRYTFFVPNDMDFSVQ ATS8_MOUSE 808 59 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
ELVVPTRLPGSAGELALHLS ATS8_HUMAN 40 40 -
ELVVPTRLPGSASELAFHLS ATS8_MOUSE 41 41 -

Motif 2 width=21
Element Seqn Id St Int Rpt
GPEWEVETGEGQRQERGDHQE ATS8_HUMAN 165 105 -
GLEWEVEMGNGQGQERSDNEE ATS8_MOUSE 177 116 -

Motif 3 width=15
Element Seqn Id St Int Rpt
EKWGPEVSDNGGLTL ATS8_HUMAN 277 91 -
ERWGPEVSDNGGLTL ATS8_MOUSE 291 93 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PLFVHLNQTLPW ATS8_HUMAN 395 103 -
PFFIHVNKTLPW ATS8_MOUSE 409 103 -

Motif 5 width=13
Element Seqn Id St Int Rpt
NAYNYTDMDGNLL ATS8_HUMAN 597 190 -
NAYNHTDLDGNFL ATS8_MOUSE 612 191 -

Motif 6 width=12
Element Seqn Id St Int Rpt
RSHPGVQNDGNY ATS8_HUMAN 722 112 -
RSHPGVRNDGSY ATS8_MOUSE 737 112 -

Motif 7 width=26
Element Seqn Id St Int Rpt
TVPGEVFPPKVKYTFFVPNDVDFSMQ ATS8_HUMAN 793 59 -
TVSGEVFPPKVRYTFFVPNDMDFSVQ ATS8_MOUSE 808 59 -