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FLASH GENE

Symbol

VCAN

contributors: shn - updated : 04-03-2019

HGNC name	versican
HGNC id	2464

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal globular domain with two putative GAG, hyaluronic acid-binding domains,
	a lectin-like sequence
	middle region of the versican core protein is encoded by two large exons that encode for the GAG attachment regions (subdomains GAG- alpha and GAG-beta
	a G1 domain, which contains two Link modules that bind to hyaluronan (HA), may be central to role in impacting proliferation, adhesion, pericellular matrix composition, and elastogenesis
	a complement regulatory-like domain (sushi structure), in the C terminal region

isoforms

Precursor

a 3376 amino acids mature peptide (370,5 kDa)

HOMOLOGY

interspecies	ortholog to VCAN, Pan troglodytes
	homolog to Vcan, Rattus norvegicus
	ortholog to Vcan, Mus musculus

Homologene

FAMILY	aggrecan/versican proteoglycan family
	lectican family

CATEGORY

adhesion , protooncogene

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,lumen
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,lysosome

basic FUNCTION	a modular proteoglycan involved in the control of cellular growth and differentiation
	chondroitin sulfate proteoglycan, likely playing an essential role both in mesenchymal condensation and in hair induction
	intercellular signaling and connecting cells with the extracellular matrix
	large chondroitin sulfate proteoglycan, which, in vitreous, binds to hyaluronan and link protein and forms large aggregates that are important for maintaining structural integrity
	amy be playing a role in regulating aqueous humor outflow and intraocular pressure via the trabecular meshwork (HTM) of the eye
	mediates mesenchymal-epithelial transition
	connects microfibrils to the hyaluronan-rich matrix for viscoelasticity
	large chondroitin sulfate proteoglycan of the extracellular matrix that is involved in a variety of cellular processes
	plays a role in cell adhesion, migration, proliferation, epithelial-mesenchymal transition, differentiation, invasiveness, angiogenesis, and apoptosis
	facilitates chondrogenesis and joint morphogenesis, by localizing TGF-beta in the extracellular matrix and regulating its signaling
	DSPP, MEPE, VCAN, OGN play complementary roles during odontogenesis
	regulates the development of peritoneal metastasis originating from cells and spheroids
	potential intracellular function for VCAN in vascular cells where it appears to play a role in mitotic spindle organization during cell division
	possible role of VCAN in modulating hepatic fibrogenesis
	possible role of VCAN in ovulatory dysfunction and in the pathogenesis of PCOS (polycystic ovary syndrome)
	macrophage-derived VCAN is likely an immunomodulatory molecule with anti-inflammatory properties in acute pulmonary inflammation
	is a key regulator in human colon cancer development and progression involved in cell adhesion, proliferation, migration and angiogenesis and plays a central role in tissue morphogenesis and maintenance

CELLULAR PROCESS	cell life
	cell communication

PHYSIOLOGICAL PROCESS

development

text	control of cell proliferation and differentiation

PATHWAY

metabolism

signaling

a component	extracellular matrix compoment
	major hyaluronan-binding component in the dermis

INTERACTION

DNA

RNA

small molecule

protein	fibulin 1, FBLN1
	fibulin 2, FBLN2
	L-selectin, P-selectin, and CD44
	CXC chemokines gamma interferon-inducible protein 10 (IP-10), platelet factor 4, and SDF-1beta, the C chemokine lymphotactin, and the CC chemokines MCP-1, MCP-2, RANTES, liver and activation-regulated chemokine (LARC), and SLC
	fibrillin 1, FBN1
	integrin beta 1, ITGB1
	hyaluronan, HA and link protein, LP
	P-selectin glycoprotein ligand-1, PSGL-1
	FBLN1 regulates VCAN-dependent events in ventricular morphogenesis by promoting ADAMTS1 cleavage of VCAN leading to suppression of trabecular cardiomyocyte proliferation mediated by the ERBB2-Map kinase pathway
	enhanced PAPSS2/VCAN sulfation axis is essential for SNAI1-mediated breast cancer cell migration and metastasis

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

WGN1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   overexpressed in medulloblastomas, gliomas, schwannomas, neurofibromas mennigiomas constitutional somatic mutation       Wagner disease and erosive vitreoretinopathy (ERVR) are caused by mRNA isoform balance shifts. Representing a novel disease mechanism. constitutional       loss of function loss of the Hyaluronan (HA)-binding ability of versican followed by HA exclusion may be responsible for the pathological and phenotypical changes observed in solar elastosis tumoral     --over   overexpressed in cutaneous melanomas as well as in premalignant lesions, contributes to melanoma progression, favoring the detachment of cells and the metastatic dissemination tumoral     --over   in cervical carcinoma (expression can serve as an indicator of poor prognosis in patients with cervical cancer) tumoral     --over   in colon cancer and increased expression of VCAN was associated with the progression of colon cancer constitutional     --low   in patients with PCOS (polycystic ovary syndrome) tumoral     --over   in leiomyosarcoma

Susceptibility

to intracranial aneurysms

Variant & Polymorphism SNP	increasing the risk of intracranial aneurysms

Candidate gene
Marker	may be as biomarker for identification of the pathological grade of colon cancer
	has biomarker potential for renal cell cancer
Therapy target
	System Type Disorder Pubmed cancer urinary   has therapeutic potential for renal cell cancer cancer muscle   role for using VCAN as a point of control in the management and treatment of leiomyosarcoma

ANIMAL & CELL MODELS