{PDOC50092}
{PS50092; TSP1}
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* Thrombospondin type-1 (TSP1) repeat profile *
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The thrombospondin  type-1  repeat (TSP1)  was first identified as an about 55
amino acids  long  module  present  in  thrombospondin  1  and  2  and  in the
circumsporozoite (CS)  protein  of Plasmodium [1]. Since, a number of proteins
involved in  the  complement pathway (properdin, C6, C7, C8A, C8B, C9) as well
as extracellular  matrix  proteins  like  ADAMTS (see <PDOC50215>), mindin, F-
spondin or  SCO-spondin  and  TRAP  proteins  of Plasmodium have been found to
contain one  to  seven  TSP1s.  Within these TSP1 modules, the WSXW and CSVTCG
motifs are  highly  conserved  although  not  ubiquitous.  TSP1s may bind both
protein and glycoconjugate ligands [2].

Averaged secondary  structure  predictions  suggested  that  the  TSP1 has  an
elongated structure   and  contains  two  amphipathic  turn  regions  and  one
hydrophilic beta-strand  region  [3].  The  six  cysteines  of the second TSP1
module of  human thrombospondin 1 have been shown to be connected in a 1-5, 2-
6, 3-4 disulfide-bond pattern. It is noteworthy that there are some members of
the TSP1  module-family  which  lack  certain  pairs  of  cysteines  that form
disulfide-bonds [4].

Some proteins known to contain TSP1s are listed below:

 - Mammalian ADAMTS, extracellular matrix proteases containing metalloprotease
   (see <PDOC50215>  and disintegrin (see <PDOC00351>) domains and one or more
   TSP1s.
 - Vertebrate  C6 (3 TSP1s), C7 (2 TSP1s), C8A (2 TSP1s), C8B (2 TSP1s) and C9
   (1 or 2 TSP1s), components of the membrane attack complex of the complement
   system.
 - Vertebrate F-spondin, may contribute to the growth and guidance of axons in
   both the spinal cord and the PNS. It contains six TSP1s.
 - Mammalian  properdin, a glycoprotein involved in the positive regulation of
   the alternative  pathway  of  the  complement  system  of immune defense by
   binding to   and  stabilizing  the  C3/C5-convertase  complexes.  Properdin
   contains six TSP1s.
 - Mammalian semaphorins 5A and 5B which may act as positive axonal cues. They
   contain seven TSP1s.
 - Vertebrate   thrombospondin  1  and  2.  Thrombospondins  are  a  class  of
   extracellular adhesive  proteins  that  mediate  cell-to-cell  and cell-to-
   matrix interactions.  They  contain six TSP1s. The anti-angiogenic activity
   of TSPs has been localized to the second and third TSP1s [5].
 - Vertebrate NOV protein homolog. It is likely to play a role in cell growth
   regulation.
 - Mammalian connective tissue growth factor (CTGF). It promotes proliferation
   and differentiation of chondrocytes.
 - Mammalian connective tissue growth factor-like protein (CTGFL).
 - Mammalian CYR61 protein. It promotes proliferation, migration and adhesion.
 - Chicken  CEF-10  protein, a probable secreted regulatory protein induced by
   v-src.
 - Plasmodium   circumsporozoite  (CS)  protein,  the  immunodominant  surface
   antigen on the sporozoite. The CS protein contains one TSP1.
 - Plasmodium  thrombospondin-related  anonymous protein (TRAP), implicated in
   the recognition and invasion of salivary glands by the sporozoite [6]. TRAP
   contains one TSP1.

The profile we developed covers the entire TSP1 domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: October 2002 / Profile and text revised.

[ 1] Lawler J., Hynes R.O.
     "The structure of human thrombospondin, an adhesive glycoprotein with
     multiple calcium-binding sites and homologies with several different
     proteins."
     J. Cell Biol. 103:1635-1648(1986).
     PubMed=2430973
[ 2] Adams J.C., Tucker R.P.
     "The thrombospondin type 1 repeat (TSR) superfamily: diverse proteins
     with related roles in neuronal development."
     Dev. Dyn. 218:280-299(2000).
     PubMed=10842357
[ 3] Smith K.F., Nolan K.F., Reid K.B., Perkins S.J.
     "Neutron and X-ray scattering studies on the human complement protein
     properdin provide an analysis of the thrombospondin repeat."
     Biochemistry 30:8000-8008(1991).
     PubMed=1868073
[ 4] Roszmusz E., Patthy A., Trexler M., Patthy L.
     "Structural characterization of the second TSP1-module of human
     thrombospondin."
     Biochem. Biophys. Res. Commun. 296:156-160(2002).
     PubMed=12147243
[ 5] Iruela-Arispe M.L., Lombardo M., Krutzsch H.C., Lawler J.,
     Roberts D.D.
     Circulation 100:1423-1431(1999).
[ 6] Wengelnik K., Spaccapelo R., Naitza S., Robson K.J., Janse C.J.,
     Bistoni F., Waters A.P., Crisanti A.
     "The A-domain and the thrombospondin-related motif of Plasmodium
     falciparum TRAP are implicated in the invasion process of mosquito
     salivary glands."
     EMBO J. 18:5195-5204(1999).
     PubMed=10508153; DOI=10.1093/emboj/18.19.5195

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