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Versican: Wikis


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Symbols VCAN; CSPG2; DKFZp686K06110; ERVR; PG-M; WGN; WGN1
External IDs OMIM118661 MGI102889 HomoloGene3228 GeneCards: VCAN Gene
RNA expression pattern
PBB GE VCAN 204620 s at tn.png
PBB GE VCAN 204619 s at tn.png
PBB GE VCAN 211571 s at tn.png
More reference expression data
Species Human Mouse
Entrez 1462 13003
Ensembl ENSG00000038427 ENSMUSG00000021614
UniProt P13611 P70267
RefSeq (mRNA) NM_004385 XM_488510
RefSeq (protein) NP_004376 XP_488510
Location (UCSC) Chr 5:
82.8 - 82.91 Mb
Chr 13:
90.13 - 90.22 Mb
PubMed search [1] [2]

Versican, also known as VCAN, is a large extracellular matrix proteoglycan that is present in a variety of human tissues. It is encoded by the VCAN gene.[1][2]

Versican is a large chondroitin sulfate proteoglycan with an apparent molecular mass of more than 1000kDa. In 1989, Zimmermann and Ruoslahti cloned and sequenced the core protein of fibroblast chondroitin sulfate proteoglycan.[3] They designated it versican in recognition of its versatile modular structure. Versican belongs to the lectican protein family, with Aggrecan (abundant in Cartilage), Brevican and Neurocan (nervous system proteoglycans) as other members. Versican is also known as Chondroitin sulfate proteoglycan core protein 2 (CSPG-2), PG-M, and Chondroitin sulfate proteoglycan 2.



These proteoglycans share a homologous globular N-terminal, C-terminal, and glycosaminoglycan (GAG) binding regions.

The N-terminal (G1) globular domain consists of Ig-like loop and two link modules, and has Hyaluronan (HA) binding properties.

Versican occurs in 4 isoforms : V0, V1, V2, V3. The central domain of versican V0 contains both the GAG-α and GAG-β domains. V1 isoforms has the GAG-β domain, V2 has the GAG-α domain, and V3 is void of any GAG attachment domains. The GAGs, being composed of repeating disaccharide units, contribute to the negative charge and many other properties of proteoglycans.

The C-terminal (G3) globular domain consists of one or two Epidermal growth factor (EGF) repeats, a C-type lectin domain and complement regulatory protein (CRP)-like domain. The C-terminal domain binds a variety of ligands in ECM which contribute significantly to the functions of lecticans.


The role of versican in cell adhesion, migration, and proliferation is extensively studied. Versican is often considered an anti-adhesive molecule. Considering the large size (>1000 kDa) and hydration capability of versican, it is possible that the interaction of integrins (large family of cell adhesion molecules) with their cell surface receptors is sterically hindered.



The N-terminal of Versican has an important role in maintaining the integrity of the ECM by interacting with hyaluronan. Its interactions with link protein has also been studied.

Glycosaminoglycan binding region

The central domain of Versican is decorated with glycosaminoglycans. The structural and functional diversity of Versican is increased by variations in GAG sulfation patterns and the type of GAG chains bound to the core protein. There is a single versican gene, however alternative splicing of its mRNA produces 4 distinct versican isoforms that differ in their potential number of GAG chains. All isoforms have homologous N-terminal (HA binding) and C-terminal (lectin-like) domains. The central domain of versican V0 contains both the GAG-α and GAG-β domains. V1 isoforms has the GAG-β domain, V2 has the GAG-α domain, and V3 is void of any GAG attachment domains, and only consists of the N-terminal and C-terminal globular domains. It is known that the isoforms are differentially expressed in different tissue types. The biological significance of alternative splicing is yet to be determined.

Because of their negatively charged sulfates or carboxyl groups, chondroitin sulfate chains are attracted to various positively charged molecules such as certain growth factors, cytokines, and chemokines. This interaction in the extracellular matrix or on the cell surface is important in the formation of immobilized gradients of these factors, their protection from proteolytic cleavage, and their presentation to specific cell-surface receptors. The binding of versican with leukocyte adhesion molecules L-selectin, P-selectin, and CD44 is also mediated by the interaction of CS chains of versican with the carbohydrate-binding domain of these molecules. Both CD44 and L-selectin have been implicated in leukocyte trafficking. The ability of versican to bind a large panel of chemokines and the biological consequences of such binding has also been examined. Versican can bind specific chemokines through its CS chains and this interaction down-regulates the chemokines function. Recently, in light of results that V1 and V2 isoforms of versican have opposite effects on cell proliferation, glycosaminoglycan domain GAG-β has been implicated in versican-enhanced cell proliferation and versican-induced reduction of cell apoptosis.


The C-terminal of Versican interacts with a variety of molecules in the matrix. One important family of ligands is the tenascin family. For example, The C-lectin domain of versican interacts with Tenascin R through its fibronectin type III (FnIII) repeat 3-5 domain in a calcium dependent manner, in vivo. Different tenascin domains interact with a wide range of cellular receptors, including integrins, cell adhesion molecules and members of the syndecan and glypican proteoglycan families. Versican’s C-terminal domain interacts with Fibulin-2, a protein whose expression is associated with that of versican in the developing heart. The EGF domain of the C-terminal of versican also binds the EGF-receptor molecule, in vivo.

Tissue expression

Expression of versican is observed in various adult tissues such as blood vessels, skin, and developing heart. Smooth muscle cells of blood vessels, epithelial cells of skin, and the cells of central and peripheral nervous system are a few examples of cell types that express versican physiologically. Versican is involved in development, guiding embryonic cell migration important in the formation of the heart and outlining the path for neural crest cell migration.

Versican is a key factor in inflammation through interactions with adhesion molecules on the surfaces of inflammatory leukocytes and interactions with chemokines that are involved in recruiting inflammatory cells.

In the adult central nervous system, versican is found in perineuronal nets, where it may stabilize synaptic connections. Versican can also inhibit nervous system regeneration and axonal growth following an injury to the central nervous system.

Role in cancer and metastasis

Increased versican expression is often observed in tumor growth in tissues such as breast, brain, ovary, gastrointestinal tract, prostate, and melanoma, Sarcoma, and mesothelioma.

Versican is required for Lewis lung carcinoma in mice to metastasize to lung, liver and adrenal glands, acting via TLR2 to activate myeloid cells and produce TNF-alpha.[4]


Versican has been shown to interact with HAPLN1[5] and Aggrecan.[5]


  1. ^ "Entrez Gene: VCAN versican".  
  2. ^ Iozzo RV, Naso MF, Cannizzaro LA, Wasmuth JJ, McPherson JD (December 1992). "Mapping of the versican proteoglycan gene (CSPG2) to the long arm of human chromosome 5 (5q12-5q14)". Genomics 14 (4): 845–51. PMID 1478664.  
  3. ^ Zimmermann DR, Ruoslahti E (October 1989). "Multiple domains of the large fibroblast proteoglycan, versican". EMBO J. 8 (10): 2975–81. PMID 2583089.  
  4. ^ Nature V457 1 Jan 2009, p102-106
  5. ^ a b Matsumoto, Kazu; Shionyu Masafumi, Go Mitiko, Shimizu Katsuji, Shinomura Tamayuki, Kimata Koji, Watanabe Hideto (Oct. 2003). "Distinct interaction of versican/PG-M with hyaluronan and link protein". J. Biol. Chem. (United States) 278 (42): 41205–12. doi:10.1074/jbc.M305060200. ISSN 0021-9258. PMID 12888576.  

Further reading

  • Wight TN, Merrilees MJ (2004). "Proteoglycans in atherosclerosis and restenosis: key roles for versican.". Circ. Res. 94 (9): 1158–67. doi:10.1161/01.RES.0000126921.29919.51. PMID 15142969.  
  • Kenagy RD, Plaas AH, Wight TN (2006). "Versican degradation and vascular disease.". Trends Cardiovasc. Med. 16 (6): 209–15. doi:10.1016/j.tcm.2006.03.011. PMID 16839865.  
  • Perides G, Rahemtulla F, Lane WS, et al. (1992). "Isolation of a large aggregating proteoglycan from human brain.". J. Biol. Chem. 267 (33): 23883–7. PMID 1429726.  
  • Iozzo RV, Naso MF, Cannizzaro LA, et al. (1993). "Mapping of the versican proteoglycan gene (CSPG2) to the long arm of human chromosome 5 (5q12-5q14).". Genomics 14 (4): 845–51. PMID 1478664.  
  • Perides G, Lane WS, Andrews D, et al. (1989). "Isolation and partial characterization of a glial hyaluronate-binding protein.". J. Biol. Chem. 264 (10): 5981–7. PMID 2466833.  
  • Bignami A, Lane WS, Andrews D, Dahl D (1989). "Structural similarity of hyaluronate binding proteins in brain and cartilage.". Brain Res. Bull. 22 (1): 67–70. PMID 2469524.  
  • Zimmermann DR, Ruoslahti E (1990). "Multiple domains of the large fibroblast proteoglycan, versican.". EMBO J. 8 (10): 2975–81. PMID 2583089.  
  • Krusius T, Gehlsen KR, Ruoslahti E (1987). "A fibroblast chondroitin sulfate proteoglycan core protein contains lectin-like and growth factor-like sequences.". J. Biol. Chem. 262 (27): 13120–5. PMID 2820964.  
  • Naso MF, Zimmermann DR, Iozzo RV (1995). "Characterization of the complete genomic structure of the human versican gene and functional analysis of its promoter.". J. Biol. Chem. 269 (52): 32999–3008. PMID 7528742.  
  • Brown DM, Graemiger RA, Hergersberg M, et al. (1995). "Genetic linkage of Wagner disease and erosive vitreoretinopathy to chromosome 5q13-14.". Arch. Ophthalmol. 113 (5): 671–5. PMID 7748141.  
  • Dours-Zimmermann MT, Zimmermann DR (1995). "A novel glycosaminoglycan attachment domain identified in two alternative splice variants of human versican.". J. Biol. Chem. 269 (52): 32992–8. PMID 7806529.  
  • Zako M, Shinomura T, Ujita M, et al. (1995). "Expression of PG-M(V3), an alternatively spliced form of PG-M without a chondroitin sulfate attachment in region in mouse and human tissues.". J. Biol. Chem. 270 (8): 3914–8. PMID 7876137.  
  • Yao LY, Moody C, Schönherr E, et al. (1994). "Identification of the proteoglycan versican in aorta and smooth muscle cells by DNA sequence analysis, in situ hybridization and immunohistochemistry.". Matrix Biol. 14 (3): 213–25. PMID 7921538.  
  • Bode-Lesniewska B, Dours-Zimmermann MT, Odermatt BF, et al. (1996). "Distribution of the large aggregating proteoglycan versican in adult human tissues.". J. Histochem. Cytochem. 44 (4): 303–12. PMID 8601689.  
  • Paulus W, Baur I, Dours-Zimmermann MT, Zimmermann DR (1996). "Differential expression of versican isoforms in brain tumors.". J. Neuropathol. Exp. Neurol. 55 (5): 528–33. PMID 8627343.  
  • Sartipy P, Johansen B, Camejo G, et al. (1996). "Binding of human phospholipase A2 type II to proteoglycans. Differential effect of glycosaminoglycans on enzyme activity.". J. Biol. Chem. 271 (42): 26307–14. PMID 8824283.  
  • Aspberg A, Miura R, Bourdoulous S, et al. (1997). "The C-type lectin domains of lecticans, a family of aggregating chondroitin sulfate proteoglycans, bind tenascin-R by protein-protein interactions independent of carbohydrate moiety.". Proc. Natl. Acad. Sci. U.S.A. 94 (19): 10116–21. PMID 9294172.  
  • Sartipy P, Bondjers G, Hurt-Camejo E (1999). "Phospholipase A2 type II binds to extracellular matrix biglycan: modulation of its activity on LDL by colocalization in glycosaminoglycan matrixes.". Arterioscler. Thromb. Vasc. Biol. 18 (12): 1934–41. PMID 9848887.  
  • Perveen R, Hart-Holden N, Dixon MJ, et al. (1999). "Refined genetic and physical localization of the Wagner disease (WGN1) locus and the genes CRTL1 and CSPG2 to a 2- to 2.5-cM region of chromosome 5q14.3.". Genomics 57 (2): 219–26. doi:10.1006/geno.1999.5766. PMID 10198161.  
  • Lemire JM, Braun KR, Maurel P, et al. (1999). "Versican/PG-M isoforms in vascular smooth muscle cells.". Arterioscler. Thromb. Vasc. Biol. 19 (7): 1630–9. PMID 10397680.  

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