Somatomedin B is a
serum factor of unknown function, is a small
cysteine-rich
peptide
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides.
...
, derived
proteolytically from the
N-terminus of the
cell-substrate adhesion protein
vitronectin
Vitronectin (VTN or VN) is a glycoprotein of the hemopexin family which is abundantly found in serum, the extracellular matrix and bone. In humans it is encoded by the ''VTN'' gene.
Vitronectin binds to integrin alpha-V beta-3 and thus promotes ...
.
Cys-rich somatomedin B-like domains are found in a number of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s,
including plasma-cell membrane
glycoprotein (which has nucleotide
pyrophosphate
In chemistry, pyrophosphates are phosphorus oxyanions that contain two phosphorus atoms in a P–O–P linkage. A number of pyrophosphate salts exist, such as disodium pyrophosphate (Na2H2P2O7) and tetrasodium pyrophosphate (Na4P2O7), among othe ...
and alkaline
phosphodiesterase
A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, ''phosphodiesterase'' refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many ot ...
I activities)
and placental protein 11 (which appears to possess
amidolytic activity).
The SMB domain of vitronectin has been demonstrated to interact with both the
urokinase receptor
The Urokinase receptor, also known as urokinase plasminogen activator surface receptor (uPAR) or CD87 (Cluster of Differentiation 87), is a protein encoded in humans by the PLAUR gene. It is a multidomain glycoprotein tethered to the cell membra ...
and the
plasminogen activator inhibitor-1
Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor or serpin E1 is a protein that in humans is encoded by the ''SERPINE1'' gene. Elevated PAI-1 is a risk factor for thrombosis and atherosclerosis
P ...
(PAI-1) and the conserved cysteines of the NPP1 somatomedin B-like domain have been shown to mediate
homodimerization
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...
.
As shown in the following schematic representation below the SMB domain contains eight Cys residues, arranged into four
disulfide bond
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In ...
s. 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 centre of the domain forming a covalently bonded core.
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.
********************
'C': conserved cysteine probably involved in a disulfide bond.
'*': position of the pattern.
Human proteins containing this domain
ENPP1;
ENPP2;
ENPP3;
PRG4;
SUSD2;
VTN;
References
{{InterPro content, IPR001212
Protein domains
Protein families
Single-pass transmembrane proteins