Versican (also known as PG-M), encoded by the VCAN/CSPG2 gene, is a large extracellular matrix chondroitin sulfate proteoglycan ubiquitously expressed in interstitial matrices of the human body, including brain ECM. It was first described in the bovine aorta by the research groups of Dick Heinegard and Anders Malmstrom’s groups (1982) and shortly after isolated from the chick embryo by Koji Kimata’s group. Cloning of the human VCAN/CSPG2 gene was accomplished in 1989 by Zimmermann and Ruoslahti, who also named the protein as versican in recognition of its versatile modular structure. Versican belongs to the lectican proteoglycan subgroup, to which aggrecan, brevican and neurocan also belong and share the N-terminal (G1) globular domain. This consists of Ig-like loops and two link modules and is responsible for the binding to hyaluronan, which may or may not be further stabilized by link proteins. At least 4 different alternatively spliced versican isoforms are known in higher vertebrates (denoted V0, V1, V2 and V3) while lower vertebrates may have additional ones in part by duplication of the gene. These isoforms are generated through differential utilization of the central core protein regions denoted GAG-α and GAG-β and encompass glycosaminoglycan (chondroitin sulfate) attachment sites. The V0 isoform is the parental one containing both the above “GAG-attachment” exons; the V1 isoform has only the GAG-β domain; the V2 isoform has only the GAG-α domain; and the V3 isoform is void of any GAG attachment domains, and is therefore a GAG-free proteoglycan. This implies that the versican isoform core proteins have a molecular mass range of 50-550 kDa and, when taking also into consideration the extensive glycosylation of the versican core protein, the molecular weights of the different isoforms vary from about 60 kDa to 1,500-2,000 kDa. The C-terminal (G3) globular domain consists of one or two EGF repeats, a C-type lectin module and complement regulatory protein (CRP)-like domain. The C-terminal domain binds a variety of ligands in the ECM and thereby contributes to the macromolecular organization of versican. The role of versican in ECM assembly of elastic matrices, cell adhesion, cell migration, and cell proliferation has been extensively described and its essential role during embryonic development is confirmed by early lethality of murine embryos homozygous for CSPG2 gene deletion. Like other large proteoglycans, versican is processed by multiple MMPs and ADAMTSs and its matrix deposition may be strongly down- or up-regulated in degenerative diseases and cancer. In some tumors its expression pattern has been proposed to have a prognostic value.

References:
1) Wight TN., Curr Opin Cell Biol.2002 Oct;14(5):617-23. PMID:12231358
2) Wu YJ, et all., Cell Res. 2005 Jul;15(7):483-94. PMID:16045811.
3) Cattaruzza S, et all., J Biol Chem. 2002 Dec 6;277(49):47626-35..PMID:12221092
4) Garusi E, et all., Cell Mol Life Sci. 2012 Feb;69(4):553-79. PMID:21964924
5) Heinegard D, et all., Biochem J. 1985 Aug 15;230(1):181-94. PMID:4052035
6) Kimata K, et all., J Biol Chem.1986 Oct 15;261(29):13517-25. PMID:3759975
7) Morgelin M., et all., J Biol Chem.1989 Jul 15;264(20):12080-90. PMID:2745430
8) Zimmermann DR, et all., EMBO J. 1989 Oct;8(10):2975-81. PMID:2583089

Versican (also known as PG-M), encoded by the VCAN/CSPG2 gene, is a large extracellular matrix chondroitin sulfate proteoglycan ubiquitously expressed in interstitial matrices of the human body, including brain ECM. It was first described in the bovine aorta by the research groups of Dick Heinegard and Anders Malmstrom’s groups (1982) and shortly after isolated from the chick embryo by Koji Kimata’s group. Cloning of the human VCAN/CSPG2 gene was accomplished in 1989 by Zimmermann and Ruoslahti, who also named the protein as versican in recognition of its versatile modular structure. Versican belongs to the lectican proteoglycan subgroup, to which aggrecan, brevican and neurocan also belong and share the N-terminal (G1) globular domain. This consists of Ig-like loops and two link modules and is responsible for the binding to hyaluronan, which may or may not be further stabilized by link proteins. At least 4 different alternatively spliced versican isoforms are known in higher vertebrates (denoted V0, V1, V2 and V3) while lower vertebrates may have additional ones in part by duplication of the gene. These isoforms are generated through differential utilization of the central core protein regions denoted GAG-α and GAG-β and encompass glycosaminoglycan (chondroitin sulfate) attachment sites. The V0 isoform is the parental one containing both the above “GAG-attachment” exons; the V1 isoform has only the GAG-β domain; the V2 isoform has only the GAG-α domain; and the V3 isoform is void of any GAG attachment domains, and is therefore a GAG-free proteoglycan. This implies that the versican isoform core proteins have a molecular mass range of 50-550 kDa and, when taking also into consideration the extensive glycosylation of the versican core protein, the molecular weights of the different isoforms vary from about 60 kDa to 1,500-2,000 kDa. The C-terminal (G3) globular domain consists of one or two EGF repeats, a C-type lectin module and complement regulatory protein (CRP)-like domain. The C-terminal domain binds a variety of ligands in the ECM and thereby contributes to the macromolecular organization of versican. The role of versican in ECM assembly of elastic matrices, cell adhesion, cell migration, and cell proliferation has been extensively described and its essential role during embryonic development is confirmed by early lethality of murine embryos homozygous for CSPG2 gene deletion. Like other large proteoglycans, versican is processed by multiple MMPs and ADAMTSs and its matrix deposition may be strongly down- or up-regulated in degenerative diseases and cancer. In some tumors its expression pattern has been proposed to have a prognostic value.

References:
1) Wight TN., Curr Opin Cell Biol.2002 Oct;14(5):617-23. PMID:12231358
2) Wu YJ, et all., Cell Res. 2005 Jul;15(7):483-94. PMID:16045811.
3) Cattaruzza S, et all., J Biol Chem. 2002 Dec 6;277(49):47626-35..PMID:12221092
4) Garusi E, et all., Cell Mol Life Sci. 2012 Feb;69(4):553-79. PMID:21964924
5) Heinegard D, et all., Biochem J. 1985 Aug 15;230(1):181-94. PMID:4052035
6) Kimata K, et all., J Biol Chem.1986 Oct 15;261(29):13517-25. PMID:3759975
7) Morgelin M., et all., J Biol Chem.1989 Jul 15;264(20):12080-90. PMID:2745430
8) Zimmermann DR, et all., EMBO J. 1989 Oct;8(10):2975-81. PMID:2583089