{PDOC00453}
{PS00524; SMB_1}
{PS50958; SMB_2}
{BEGIN}
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* Somatomedin B (SMB) domain signature and profile *
****************************************************

Somatomedin B, a serum  factor of  unknown  function, is  a  cysteine-rich  44
residues  peptide  which  is  proteolytically   derived  from  the  N-terminal
extremity of  the cell-substrate adhesion protein vitronectin [1]. Somatomedin
B-like (SMB) domains are also found [2,3] in the following proteins:

 - Ubiquitous  nucleotide  pyrophosphatase/phosphodiesterases  NPP1-3.  NPP1-3
   release 5'monophosphorylated  nucleotides from a variety of nucleotides and
   nucleotide derivatives.  In  addition,  NPP1-3  contain  intrinsic alkaline
   phosphatase activity.  They  consist  of  a  short  cytoplasmic  N-terminal
   domain, a  single  transmembrane  domain  and  a  large extracellular part,
   comprising two  somatomedin-B-like domains, a catalytic domain and a poorly
   defined C-terminal domain.
 - Placental protein 11 (PP11) (EC 3.4.21.-). PP11 is a placental protein that
   seems to possess an amidolytic activity. A copy of the somatomedin B domain
   is present at the N-terminal extremity.
 - Secreted proteoglycan known as superficial zone protein.
 - Some amphibian DNases.
 - Drosophila macrophage-specific Scavenger receptor.

The SMB  domain of vitronectin has been demonstrated to interact with both the
urokinase receptor  and  the plasminogen activator inhibitor-1 (PAI-1) and the
conserved cysteines  of  the NPP1 somatomedin B-like domain have been shown to
mediate homodimerization [3].

As shown  in  the  following  schematic  representation  below  the SMB domain
contains eight  Cys  residues, arranged into four disulfide bonds. It has been
suggested that  the  active SMB domain may be permitted considerable disulfide
bond heterogeneity  or  variability,  provided  that the Cys25-Cys31 disulfide
bond is  preserved.  The  three  dimensional  structure  of  the SMB domain is
extremely compact  and  the  disulfide  bonds  are packed in the center of the
domain forming  a  covalently bonded core [4]. The structure of the SMB domain
presents a new protein fold, with the only ordered secondary structure being a
single-turn alpha-helix and a single-turn 3(10)-helix (see <PDB:1OC0>) [5].

         xxCxxxxxxCxxxxxxxxxCxCxxxCxxxxxCCxxxxxCxxxxx
                            ********************

'C': conserved cysteine probably involved in a disulfide bond.
'*': position of the pattern.

The profile we developed covers the entire SMB domain.

-Consensus pattern: C-x-C-x(3)-C-x(5,6)-C-C-x-[DN]-[FY]-x(3)-C
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Expert(s) to contact by email:
           Jenne D.; djenne@ulys.unil.ch

-Last update: December 2004 / Pattern and text revised.

[ 1] Jenne D., Stanley K.K.
     "Nucleotide sequence and organization of the human S-protein gene:
     repeating peptide motifs in the 'pexin' family and a model for their
     evolution."
     Biochemistry 26:6735-6742(1987).
     PubMed=2447940
[ 2] Jenne D.
     "Homology of placental protein 11 and pea seed albumin 2 with
     vitronectin."
     Biochem. Biophys. Res. Commun. 176:1000-1006(1991).
     PubMed=1710108
[ 3] Gijsbers R., Ceulemans H., Bollen M.
     "Functional characterization of the non-catalytic ectodomains of the
     nucleotide pyrophosphatase/phosphodiesterase NPP1."
     Biochem. J. 371:321-330(2003).
     PubMed=12533192; DOI=10.1042/BJ20021943
[ 4] Kamikubo Y., De Guzman R., Kroon G., Curriden S., Neels J.G.,
     Churchill M.J., Dawson P., Oldziej S., Jagielska A., Scheraga H.A.,
     Loskutoff D.J., Dyson H.J.
     "Disulfide bonding arrangements in active forms of the somatomedin B
     domain of human vitronectin."
     Biochemistry 43:6519-6534(2004).
     PubMed=15157085; DOI=10.1021/bi049647c
[ 5] Zhou A., Huntington J.A., Pannu N.S., Carrell R.W., Read R.J.
     "How vitronectin binds PAI-1 to modulate fibrinolysis and cell
     migration."
     Nat. Struct. Biol. 10:541-544(2003).
     PubMed=12808446; DOI=10.1038/nsb943

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