Somatomedin B Explained

Somatomedin B is a serum factor of unknown function, is a small cysteine-rich peptide, derived proteolytically from the N-terminus of the cell-substrate adhesion protein vitronectin.^[1] Cys-rich somatomedin B-like domains are found in a number of proteins,^[2] including plasma-cell membrane glycoprotein (which has nucleotide pyrophosphate and alkaline phosphodiesterase I activities)^[3] 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 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.^[4] 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 centre of the domain forming a covalently bonded core.^[5] 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.^[6]

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'C': conserved cysteine probably involved in a disulfide bond.'

• '

position of the pattern.

Human proteins containing this domain

ENPP1

ENPP2; ENPP3; PRG4; SUSD2; VTN;

Notes and References

1. Jenne D, Stanley KK . 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 . 21 . 6735–6742 . 1987 . 2447940 . 10.1021/bi00395a024.
2. Jenne D . Homology of placental protein 11 and pea seed albumin 2 with vitronectin . Biochem. Biophys. Res. Commun. . 176 . 3 . 1000–1006 . 1991 . 1710108 . 10.1016/0006-291X(91)90381-G.
3. Rebbe NF, Tong BD, Finley EM, Hickman S . Identification of nucleotide pyrophosphatase/alkaline phosphodiesterase I activity associated with the mouse plasma cell differentiation antigen PC-1 . Proc. Natl. Acad. Sci. U.S.A. . 88 . 12 . 5192–5196 . 1991 . 1647027 . 10.1073/pnas.88.12.5192 . 51838. 1991PNAS...88.5192R . free .
4. Gijsbers R, Ceulemans H, Bollen M . Functional characterization of the non-catalytic ectodomains of the nucleotide pyrophosphatase/phosphodiesterase NPP1 . Biochem. J. . 371 . Pt 2. 321–330 . 2003 . 12533192 . 10.1042/BJ20021943 . 1223305.
5. Jane Dyson . Dyson HJ, Kamikubo Y, Kroon G, Curriden S, Neels JG, Churchill MJ, Dawson P, Jagielska A, Scheraga HA, Loskutoff DJ, De Guzman R, OBdziej S . Disulfide bonding arrangements in active forms of the somatomedin B domain of human vitronectin . Biochemistry . 43 . 21 . 6519–6534 . 2004 . 15157085 . 10.1021/bi049647c.
6. Carrell RW, Zhou A, Read RJ, Huntington JA, Pannu NS . How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration . Nat. Struct. Biol. . 10 . 7 . 541–544 . 2003 . 12808446 . 10.1038/nsb943. 26086796 .