Description: Homo sapiens heparan sulfate proteoglycan 2 (HSPG2), mRNA. RefSeq Summary (NM_005529): This gene encodes the perlecan protein, which consists of a core protein to which three long chains of glycosaminoglycans (heparan sulfate or chondroitin sulfate) are attached. The perlecan protein is a large multidomain proteoglycan that binds to and cross-links many extracellular matrix components and cell-surface molecules. It has been shown that this protein interacts with laminin, prolargin, collagen type IV, FGFBP1, FBLN2, FGF7 and transthyretin, etc., and it plays essential roles in multiple biological activities. Perlecan is a key component of the vascular extracellular matrix, where it helps to maintain the endothelial barrier function. It is a potent inhibitor of smooth muscle cell proliferation and is thus thought to help maintain vascular homeostasis. It can also promote growth factor (e.g., FGF2) activity and thus stimulate endothelial growth and re-generation. It is a major component of basement membranes, where it is involved in the stabilization of other molecules as well as being involved with glomerular permeability to macromolecules and cell adhesion. Mutations in this gene cause Schwartz-Jampel syndrome type 1, Silverman-Handmaker type of dyssegmental dysplasia, and tardive dyskinesia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]. Transcript (Including UTRs) Position: hg19 chr1:22,148,737-22,263,750 Size: 115,014 Total Exon Count: 97 Strand: - Coding Region Position: hg19 chr1:22,149,809-22,263,710 Size: 113,902 Coding Exon Count: 97
ID:PGBM_HUMAN DESCRIPTION: RecName: Full=Basement membrane-specific heparan sulfate proteoglycan core protein; Short=HSPG; AltName: Full=Perlecan; Short=PLC; Contains: RecName: Full=Endorepellin; Contains: RecName: Full=LG3 peptide; Flags: Precursor; FUNCTION: Integral component of basement membranes. Component of the glomerular basement membrane (GBM), responsible for the fixed negative electrostatic membrane charge, and which provides a barrier which is both size- and charge-selective. It serves as an attachment substrate for cells. Plays essential roles in vascularization. Critical for normal heart development and for regulating the vascular response to injury. Also required for avascular cartilage development. FUNCTION: Endorepellin in an anti-angiogenic and anti-tumor peptide that inhibits endothelial cell migration, collagen-induced endothelial tube morphogenesis and blood vessel growth in the chorioallantoic membrane. Blocks endothelial cell adhesion to fibronectin and type I collagen. Anti-tumor agent in neovascularization. Interaction with its ligand, integrin alpha2/beta1, is required for the anti-angiogenic properties. Evokes a reduction in phosphorylation of receptor tyrosine kinases via alpha2/beta1 integrin-mediated activation of the tyrosine phosphatase, PTPN6. FUNCTION: The LG3 peptide has anti-angiogenic properties that require binding of calcium ions for full activity. SUBUNIT: Purified perlecan has a strong tendency to aggregate in dimers or stellate structures. It interacts with other basement membrane components such as laminin, prolargin and collagen type IV. Interacts with COL13A1, FGFBP1 and VWA1. Interacts (via C- terminus) with ECM1 (via C-terminus). SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix, basement membrane. TISSUE SPECIFICITY: Found in the basement membranes. PTM: Proteolytic processing produces the C-terminal angiogenic peptide, endorepellin. This peptide can be further processed to produce the LG3 peptide. PTM: N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. Perlecan contains three heparan sulfate chains. The LG3 peptide contains at least three and up to five potential O-glycosylation sites but no N-glycosylation. DISEASE: Defects in HSPG2 are the cause of Schwartz-Jampel syndrome (SJS1) [MIM:255800]; a rare autosomal recessive disorder characterized by permanent myotonia (prolonged failure of muscle relaxation) and skeletal dysplasia, resulting in reduced stature, kyphoscoliosis, bowing of the diaphyses and irregular epiphyses. DISEASE: Defects in HSPG2 are the cause of dyssegmental dysplasia Silverman-Handmaker type (DDSH) [MIM:224410]. The dyssegmental dysplasias are rare, autosomal recessive skeletal dysplasias with anisospondyly and micromelia. There are two recognized types: the severe, lethal DDSH and the milder Rolland-Desbuquois form. Individuals with DDSH also have a flat face, micrognathia, cleft palate and reduced joint mobility, and frequently have an encephalocoele. The endochondral growth plate is short, the calcospherites (which are spherical calcium-phosphorus crystals produced by hypertrophic chondrocytes) are unfused, and there is mucoid degeneration of the resting cartilage. MISCELLANEOUS: The LG3 peptide has been found in the urine of patients with end-stage renal disease and in the amniotic fluid of pregnant women with premature rupture of fetal membranes. SIMILARITY: Contains 4 EGF-like domains. SIMILARITY: Contains 22 Ig-like C2-type (immunoglobulin-like) domains. SIMILARITY: Contains 11 laminin EGF-like domains. SIMILARITY: Contains 3 laminin G-like domains. SIMILARITY: Contains 3 laminin IV type A domains. SIMILARITY: Contains 4 LDL-receptor class A domains. SIMILARITY: Contains 1 SEA domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org//Genes/HSPG2ID40890ch1p36.html"; WEB RESOURCE: Name=Wikipedia; Note=Perlecan entry; URL="http://en.wikipedia.org/wiki/Perlecan"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HSPG2";
To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): HSPG2 CDC HuGE Published Literature: HSPG2 Positive Disease Associations: periodontitis Related Studies:
periodontitis Suzuki A 2004, Single nucleotide polymorphisms associated with aggressive periodontitis and severe chronic periodontitis in Japanese., Biochemical and biophysical research communications. 2004 May;317(3):887-92.
[PubMed 15081423]
These appear to be good candidates as genetic factors for future study.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P98160
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001523 retinoid metabolic process GO:0001525 angiogenesis GO:0006024 glycosaminoglycan biosynthetic process GO:0006027 glycosaminoglycan catabolic process GO:0006629 lipid metabolic process GO:0006898 receptor-mediated endocytosis GO:0006954 inflammatory response GO:0007420 brain development GO:0016525 negative regulation of angiogenesis GO:0030154 cell differentiation GO:0030198 extracellular matrix organization GO:0044267 cellular protein metabolic process GO:0060548 negative regulation of cell death GO:0072358 cardiovascular system development
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