Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

HSPG2 (heparan sulfate proteoglycan 2)

Written2008-10Mary C Farach-Carson, Brian Grindel
Department of Biological Sciences, University of Delaware, 209 Hullihen Hall, Newark DE 19716, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesSJS1
Schwartz-Jampel syndrome 1 (chondrodystrophic myotonia)
Alias_symbol (synonym)perlecan
PRCAN
Other aliasHSPG
PLC
Perlecan
SJA
SJS
HGNC (Hugo) HSPG2
LocusID (NCBI) 3339
Atlas_Id 40890
Location 1p36.12  [Link to chromosome band 1p36]
Location_base_pair Starts at 21822232 and ends at 21937297 bp from pter ( according to hg19-Feb_2009)  [Mapping HSPG2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
EIF3B (7p22.3) / HSPG2 (1p36.12)HSPG2 (1p36.12) / HSPG2 (1p36.12)HSPG2 (1p36.12) / MOV10 (1p13.2)
HSPG2 (1p36.12) / NTNG1 (1p13.3)HSPG2 (1p36.12) / SIAE (11q24.2)HSPG2 (1p36.12) / SUSD6 (14q24.1)
LRP8 (1p32.3) / HSPG2 (1p36.12)UBR4 (1p36.13) / HSPG2 (1p36.12)

DNA/RNA

Description The HSPG2 gene consists of 115,014 bases and 97 exons. Evidence suggests that the encoded protein's modular structure is a result of gene duplication and exon shuffling (Cohen et al., 1993). The perlecan gene promoter lacks the TATA and CAAT boxes, but has four GC boxes and three GGGCGG hexanucleotides. The gene also was found to contain multiple start sites (Cohen et al., 1993).
Transcription The transcribed mRNA is 14,294 bp (Cohen et al., 1993). An alternative transcript for unc-52, the homologous gene to perlecan in C. elegans, has been reported (Spike et al., 2002). In addition, a human alternative transcript was submitted to the NCBI (Accession Q8TEU3_HUMAN) as a sequence for a short version variant, miniperl, encoding a 240 amino acid protein of 25.942 kD. Expression of HSPG2 was found to be induced by TGF-beta via NF-1 (Iozzo et al., 1997), and inhibited by NF-gamma via STAT1 (Sharma and Iozzo, 1998).

Protein

 
  Figure1: Perlecan as a Scaffold: Functional Uncoupling by Proteolysis (from Farach-Carson and Carson, 2007).
Description 4,391 amino acids; 468,825 (core protein) to ~850,000 Da (depends upon amount of glycosaminoglycan (GAG) additions). Perlecan is composed of 5 domains. Following a 21 amino acid signal peptide for ER targeting is the N-terminal domain I, spanning amino acids 22-193 (Murdoch et al., 1992). Domain I contains 3 SGD sequences for attachment of heparan sulfate (HS) and/or chondroitin sulfate (CS) GAGs on serine residues, and a 120 amino acid SEA (Sperm protein, Enterokinase, Agrin) module. The SEA module has no definitive function, but deletion studies in domain I suggest it increases HS chain attachment (Dolan et al., 1997). Domain I of this protein is unique to perlecan, as it shares no significant homology with any other protein (Murdoch et al., 1992). The 210 amino acid domain II (amino acids 194-403) contains 4 cysteine-rich low-density lipoprotein (LDL) receptor-like modules. Adjacent to this is one immunoglobulin G (IgG)-like repeat (residues 404-504). Domain III (1,172 amino acids; residues 505-1676) consists of modules homologous to the short arm laminin alpha-chains including 3 laminin domain IV-like modules and eight laminin epidermal growth factor (EGF)-like repeats. Domain IV is the largest domain (2010 amino acids; residues 1677-3686), containing 21 IgG-like repeats (murine perlecan has only 14 IgG-like repeats, missing IgG repeats 5-12) similar to neural cell adhesion molecules (N-CAM). Domain V (705 amino acids; residues 3687-4391) has 3 modules with sequence homology to the globular domain of laminin alpha-chains and agrin. In addition, this domain contains 4 interspersed EGF-like repeats, and another GAG chain attachment site. Domain V of perlecan also is referred to as endorepellin for its angiostatic properties and was shown to be cleaved from perlecan by BMP-1/mTLL (Mongiat et al., 2003; Gonzalez et al., 2005). Several other cleavage sites are predicted for perlecan including sites for thrombin, plasmin, collagenase, and stromelysin, although some sites may be cryptic (Whitelock et al., 1996; d'Ortho et al., 1997).
 
  Figure 2: from Farach-Carson and Carson, 2007.
Expression Perlecan is expressed in the basement membranes of pituitary gland, skin, breast, thymus, prostate, colon, liver, pancreas, spleen, heart, and lung. Vascular basement membranes also express perlecan. In the subendothelial region, perlecan is highly expressed in the liver's perisinusoidal space, spleen, lymph nodes, and pituitary gland (Murdoch et al., 1994). In the kidney, perlecan is found in the mesangium, Bowman's capsule, the tubular basement membrane, but is only slightly expressed in the glomerular basement membrane (Groffen et al., 1997). In bone, marrow but not the mineral compartment, is rich in perlecan (Schofield et al., 1999). In human fetal tissue (12-14 week old), pericellular perlecan expression was detected in the rudiment and growth plate chondrocytes, and was found in the perichondrial capillary networks and cartilage canals (Melrose et al., 2004).
Localisation Perlecan is found in the extracellular matrix (ECM), most commonly in the basement membrane underlying epithelial and endothelial cells. It also is found at high levels in cartilage, bone marrow and in muscle tissue.
Function Perlecan is a multifunctional protein involved in maintaining the basement membrane, growth factor binding and signaling, cell differentiation, angiogenesis, neuromuscular function and bone development. Perlecan is an important component of the basement membrane. It binds several other basement membrane proteins including aminin 1, fibronectin, nidogen, PRELP, and collagen IV via its core protein or HS chains (Sasaki et al., 1998; Hopf et al., 2001; Kvansakul et al., 2001; Bengtsson et al., 2002). Endorepellin (domain V) also interacts with cell surface integrins (alpha2beta1), forming additional complexes linking the ECM with the cell (Bix et al., 2004). The loss of perlecan and the basement membrane architecture is sometimes indicative of carcinomas, as is the case with invasive breast carcinoma (Nerlich et al., 1997). Perlecan has extensive growth factor regulating functions afforded to its ability to bind, sequester, and activate growth factors and growth factor binding proteins. This function connects perlecan to several actions concerning cell differentiation and proliferation. Perlecan has both pro-angiogenic (whole molecule) and anti-angiogenic (endorepellin) properties, linked to its ability regulate factors such as VEGF and FGF2. Consequently, perlecan has been implicated in supporting tumor angiogenesis in several cancers (reviewed in Bix and Iozzo, 2008). In all, perlecan has been shown to bind many growth factors including BMP-2, CTGF, PDGF, several FGFs, and VEGF and modulate several others (reviewed in Bix and Iozzo, 2008; Melrose et al., 2008). Perlecan has important functions in bone development. Perlecan sustains growth plate chondrocyte organization and hypertrophic chondrocytes, greatly assists endochondral ossification, and maintains cartilage stability in general (Arikawa-Hirasawa et al., 1999; Costell et al., 1999). The complex structure and function of perlecan suggest that it acts as an extracellular matrix scaffold. Based upon rotary shadowing of individual domains and atomic force microscopy, intact perlecan is predicted to span 100-200 nm (Chakravarti et al., 1995; Costell et al., 1996; Brown et al., 1997; Dolan et al., 1997; Hopf et al., 1999; Chen and Hansma, 2000). Given that this matches the dimensions of other scaffolding domains and that perlecan has a modular structure capable of binding many partners at once, perlecan may create stable "signalosomes" by clustering transmembrane proteins and stabilizing their interactions. As a result, `erleka. may be essential in directing cell signaling and hence function as an extracellular signaling scaffold (Farach-Carson and Carson, 2007).
 
  Figure 3: Perlecan as a Scaffold: Domains and interactions (from Farach-Carson and Carson, 2007).
Homology Mouse (~85%), Chicken (67%), Zebrafish (62%), Fruitfly (35%), Worm (35%).

Mutations

Note Perlecan has 37 reported mutations. Over 34 mutations are attributed to Schwartz-Jampel Syndrome (SJS) and 3 are attributed to dyssegmental dysplasia, Silverman-Handmaker type (DDHS).
 

Implicated in

Note
  
Entity Prostate Cancer
Note Perlecan expression was correlated with aggressive prostate tumors (high Gleason score). Primary prostate cancer tumors and metastatic prostate cancer to the lung and liver showed increased perlecan expression, but metastasis to the lymph nodes showed decreased perlecan protein expression. Furthermore, perlecan expression was shown to promote survival of tumors in low androgen and/or low growth factor environments. Perlecan may mediate prostate cancer progression through its regulation of the sonic hedgehog signaling pathway, whose activity has been implicated in prostate cancer (Datta et al., 2006). Targeted reduction of perlecan in prostate cancer xenografts growing in mice reduced tumor growth and vascularization (Savorè et al., 2005).
Disease Prostate cancer is an adenocarcimona affecting the gland cells of the prostate. It is a slow growing cancer usually affecting older men. The most common site of metastasis of prostate cancer is the bone.
  
  
Entity Breast Cancer
Note Perlecan mRNA expression was shown to be increased in invasive breast carcinomas, yet immunohistochemical analysis showed a lack of perlecan deposition in the carcinoma (Nerlich et al., 1997; Nerlich et al., 1998). This suggests subsequent proteolytic cleavage of perlecan or translational defects in breast cancer. However, in breast cancer stromal cells, high perlecan deposition was also reported (Iozzo et al., 1994).
Disease Breast cancer refers to the many types of cancer affecting breast tissue including ductal carcinoma and lobular carcinoma. Breast cancers are further defined as in situ or invasive. An especially deadly form is inflammatory breast cancer. The most common target of breast cancer metastasis is the lymphatic system. It is the most common form of cancer for women and the second cause of cancer-related deaths for women.
Prognosis None
  
  
Entity Melanoma
Note In metastatic melanoma, perlecan mRNA expression was increased 15 fold over normal tissue, which correlated with enhanced perlecan deposition in the melanoma's pericellular matrix (Cohen et al., 1994). When perlecan expression was blocked with a perlecan antisense cDNA construct in metastatic melanoma cells, the proliferative and invasive properties were reduced. Perlecan serves as a reservoir for growth factors involved in angiogenesis and proliferation (VEGF, bFGF/FGF-2, FGF-7), and is needed for growth factor signaling. bFGF/FGF-2 was shown to be an important autocrine regulator of metastatic melanoma, and perlecan is needed for bFGF to advance melanoma. Without perlecan, growth factor activity is diminished, abrogating tumor progression (Adatia et al., 1997).
Disease Melanoma is a type of skin cancer originating in the melanocytes.
Prognosis None
  
  
Entity Colon cancer
Note When perlecan was blocked by antisense targeting in xenografts with human colon carcinoma cells and tumor allografts, tumor progression and neovascularization were substantially decreased in a mouse model. Perlecan inhibition is thought to suppress FGF-7 binding and receptor activation, thereby blocking tumor growth and angiogenesis (Sharma et al., 1998). As in other cancers, perlecan is a contributing factor in colon cancer progression.
Disease Colon cancer usually begins as a non-cancerous adenomatous polyp and spreads into the wall of the colon, where it may metastasize through blood vessels or the lymphatic system.
Prognosis None
  
  
Entity Fibrosarcoma
Note In contrast to other cancers, when perlecan was suppressed by antisense cDNA in fibrosarcoma cells, the phenotype became more aggressive in that they had increased migration, invasion, and adhesiveness to type IV collagen substrates. Perlecan action in fibrosarcoma is thought to be independent of the bFGF pathway and possibly prevent mesenchymal tumor invasion (Mathiak et al., 1997).
Disease Fibrosarcoma is a type of malignant tumor originating in the connective tissue, mostly affecting the leg, arm, and jawbone in humans.
Prognosis None
  
  
Entity Adenoid cystic carcinoma (ACC)
Note Perlecan expression was increased in ACC cells forming small stromal pseudocysts, but not in advanced flat ACC cells producing large pseudocysts or already attached to peripheral nerves, which have abundant perlecan. This suggests perlecan is needed for initial ACC cell growth (Kimura et al., 2000).
Disease ACC is a tumor affecting the salivary glands. It is usually slow growing and not as aggressive as other salivary gland cancers.
Prognosis None
  
  
Entity Intrahepatic cholangiocarcinoma (ICC)
Note Perlecan is highly expressed in the tumor specific fibro-myxoid stroma of ICC. In addition, the ICC cells on the invading fronts expressed higher levels of perlecan than other ICC cells, suggesting that perlecan is an important component of ICC tumor invasiveness (Sabit et al., 2001).
Disease ICC is a tumor originating in the biliary system (bile ducts) of the liver. It is associated with the hepatitis C virus and chronic cholangitis.
Prognosis None
  
  
Entity Amyloidosis and related diseases
Note In a murine model of AA amyloidogenesis perlecan expression increased before the deposits of AA amyloids, indicating that perlecan is required for the earliest stages of amyloid fibrillogenesis (Ailles et al., 1993). Perlecan was shown to accelerate beta-amyloid fibril formation and also stabilize the formed fibrils, demonstrating perlecan's role in beta-amyloidogenesis in Alzheimer's disease (Castillo et al., 1997). In addition, during hemodialysis induced beta2-microglobulin (beta2M) amyloidosis, increased amounts of HSPGs, like perlecan, direct where beta2M deposits will occur and assist fibrillogenesis (Ohashi, 2001).
Disease Amyloidosis refers to a wide spectrum of diseases where the abnormal deposition of amyloid species (insoluble proteins in a beta-pleated secondary conformation) occurs in any organ or tissue. Alzheimer's disease is an example of amyloidosis affecting the brain.
Prognosis None
  
  
Entity Schwartz-Jampel Syndrome (SJS)
Note Mutations in the perlecan gene were implicated in SJS in 2000 by (Nicole et al., 2000). Two mutations are found in the C-terminal region of domain III, SJS1-H C1532Y and SJS1-B 4740G→A, resulting in lost disulfide bonds. One mutation was found in domain IV, SJS1-A IVS64+4a→g, leaving a truncated protein missing domain IV Ig-like repeats 13-21 and domain V. (Arikawa-Hirasawa et al., 2002) reported additional mutations resulting in early stop codons. (Stum et al., 2006) reported an additional 22 perlecan mutations. In all of these mutational analyses, no evidence of a founder effect existed. The mutated perlecan proteins are secreted in lower amounts or are more susceptible to proteases and have varying degrees of functionality, resulting in the defects characteristic of SJS. However, (Rodgers et al., 2007) using mice with site specific perlecan mutations suggested that it was not the truncated protein or faulty secretion, but a downregulation of perlecan at the transcriptional level. With respect to myotonia, perlecan was shown to localize acetylcholinesterase (AChE) to the neuromuscular junction. With less functional perlecan, AChE is largely absent at the synapse, resulting in a higher concentration of ACh. This aberrantly stimulates the ACh receptor causing muscle contractions associated with myotonia.
Disease SJS is a rare autosomal recessive disease characterized by skeletal dysplasias and myotonia, a neuromuscular disorder resulting in prolonged muscle contraction. Patients with the disorder have short stature, blepharophimosis (drooping eyelids with reduced size, flat nasal bridge, underdeveloped orbital rim), pursed lips, low-set ears, myopia, and a fixed facial expression. SJS is characterized by several skeletal dysplasias including kyphoscloliosis, platyspondyly (flattened vertebrae), joint contractures, and metaphyseal and epiphyseal dysplasias. Based upon clinical examination, several other disorders including kyphomelic chondrodyplasia, Burton's disease, micromelic chondrodysplasia were suggested by (Spranger et al., 2000) to be reclassified as SJS.
  
  
Entity Dyssegmental dysplasia, Silverman-Handmaker type (DDHS)
Note Functional null mutations of perlecan have been implicated in DDHS. (Arikawa-Hirasawa et al., 2001) reported an 89-bp duplication in exon 34, and a 5' donor site mutation in intron 52 and exon 73, resulting in a truncated perlecan protein core. In contrast to SJS, the truncated perlecan protein is not secreted and deposited, causing a functional null mutation similar to the homozygous perlecan knockout mice. This manifests in more severe defects than SJS, as all DDHS individuals are stillbirths or die shortly thereafter.
Disease DDSH is a rare autosomal recessive lethal disease characterized by severe skeletal dysplasias, anisospondyly and micromelia. DDSH patients also have a flat face, cleft palate, low joint mobility, micrognathia (undersized jaw), and encephalocoele. The endochondral growth plate has shortening defects, the resting cartilage shows mucoid degeneration, and hypertrophic chondrocytes produce calcospherites that fail to fuse.
  
  
Entity Intracranial aneurysms
Note Two SNPs in the perlecan gene were associated with intracranial aneurysms (Ruigrok et al., 2006). A defect in perlecan is thought to contribute to faulty ECM in the arterial wall, increasing the likelihood of an aneurysm.
Disease An aneurysm is the dilation of the arterial wall due to defects in the ECM. A dilated blood vessel may rupture resulting in a subarachnoid hemorrhage.
  

Bibliography

Suppression of invasive behavior of melanoma cells by stable expression of anti-sense perlecan cDNA.
Adatia R, Albini A, Carlone S, Giunciuglio D, Benelli R, Santi L, Noonan DM.
Ann Oncol. 1997 Dec;8(12):1257-61.
PMID 9496392
 
Induction of perlecan gene expression precedes amyloid formation during experimental murine AA amyloidogenesis.
Ailles L, Kisilevsky R, Young ID.
Lab Invest. 1993 Oct;69(4):443-8.
PMID 8231112
 
Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia.
Arikawa-Hirasawa E, Le AH, Nishino I, Nonaka I, Ho NC, Francomano CA, Govindraj P, Hassell JR, Devaney JM, Spranger J, Stevenson RE, Iannaccone S, Dalakas MC, Yamada Y.
Am J Hum Genet. 2002 May;70(5):1368-75.
PMID 11941538
 
The leucine-rich repeat protein PRELP binds perlecan and collagens and may function as a basement membrane anchor.
Bengtsson E, Morgelin M, Sasaki T, Timpl R, Heinegard D, Aspberg A.
J Biol Chem. 2002 Apr 26;277(17):15061-8.
PMID 11847210
 
Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through alpha2beta1 integrin.
Bix G, Fu J, Gonzalez EM, Macro L, Barker A, Campbell S, Zutter MM, Santoro SA, Kim JK, Hook M, Reed CC, Iozzo RV.
J Cell Biol. 2004 Jul 5;166(1):97-109.
PMID 15240572
 
Novel interactions of perlecan: unraveling perlecan's role in angiogenesis.
Bix G, Iozzo RV.
Microsc Res Tech. 2008 May;71(5):339-48. (REVIEW)
PMID 18300285
 
The C-terminal domain V of perlecan promotes beta1 integrin-mediated cell adhesion, binds heparin, nidogen and fibulin-2 and can be modified by glycosaminoglycans.
Brown JC, Sasaki T, Gohring W, Yamada Y, Timpl R.
Eur J Biochem. 1997 Nov 15;250(1):39-46.
PMID 9431988
 
Perlecan binds to the beta-amyloid proteins (A beta) of Alzheimer's disease, accelerates A beta fibril formation, and maintains A beta fibril stability.
Castillo GM, Ngo C, Cummings J, Wight TN, Snow AD.
J Neurochem. 1997 Dec;69(6):2452-65.
PMID 9375678
 
Recombinant domain III of perlecan promotes cell attachment through its RGDS sequence.
Chakravarti S, Horchar T, Jefferson B, Laurie GW, Hassell JR.
J Biol Chem. 1995 Jan 6;270(1):404-9.
PMID 7814401
 
Basement membrane macromolecules: insights from atomic force microscopy.
Chen CH, Hansma HG.
J Struct Biol. 2000 Jul;131(1):44-55.
PMID 10945969
 
Structural characterization of the complete human perlecan gene and its promoter.
Cohen IR, Grassel S, Murdoch AD, Iozzo RV.
Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10404-8.
PMID 8234307
 
Abnormal expression of perlecan proteoglycan in metastatic melanomas.
Cohen IR, Murdoch AD, Naso MF, Marchetti D, Berd D, Iozzo RV.
Cancer Res. 1994 Nov 15;54(22):5771-4.
PMID 7954396
 
Perlecan maintains the integrity of cartilage and some basement membranes.
Costell M, Gustafsson E, Aszodi A, Morgelin M, Bloch W, Hunziker E, Addicks K, Timpl R, Fassler R.
J Cell Biol. 1999 Nov 29;147(5):1109-22.
PMID 10579729
 
Structural characterization of recombinant domain II of the basement membrane proteoglycan perlecan.
Costell M, Sasaki T, Mann K, Yamada Y, Timpl R.
FEBS Lett. 1996 Nov 4;396(2-3):127-31.
PMID 8914972
 
Perlecan, a candidate gene for the CAPB locus, regulates prostate cancer cell growth via the Sonic Hedgehog pathway.
Datta MW, Hernandez AM, Schlicht MJ, Kahler AJ, DeGueme AM, Dhir R, Shah RB, Farach-Carson C, Barrett A, Datta S.
Mol Cancer. 2006 5:9.
PMID 16507112
 
Identification of sites in domain I of perlecan that regulate heparan sulfate synthesis.
Dolan M, Horchar T, Rigatti B, Hassell JR.
J Biol Chem. 1997 Feb 14;272(7):4316-22.
PMID 9020150
 
Perlecan--a multifunctional extracellular proteoglycan scaffold.
Farach-Carson MC, Carson DD.
Glycobiology. 2007 Sep;17(9):897-905. (REVIEW)
PMID 17442708
 
BMP-1/Tolloid-like metalloproteases process endorepellin, the angiostatic C-terminal fragment of perlecan.
Gonzalez EM, Reed CC, Bix G, Fu J, Zhang Y, Gopalakrishnan B, Greenspan DS, Iozzo RV.
J Biol Chem. 2005 Feb 25;280(8):7080-7.
PMID 15591058
 
Evidence for the existence of multiple heparan sulfate proteoglycans in the human glomerular basement membrane and mesangial matrix.
Groffen AJ, Hop FW, Tryggvason K, Dijkman H, Assmann KJ, Veerkamp JH, Monnens LA, Van den Heuvel LP.
Eur J Biochem. 1997 Jul 1;247(1):175-82.
PMID 9249024
 
Mapping of binding sites for nidogens, fibulin-2, fibronectin and heparin to different IG modules of perlecan.
Hopf M, Gohring W, Mann K, Timpl R.
J Mol Biol. 2001 Aug 17;311(3):529-41.
PMID 11493006
 
The biology of perlecan: the multifaceted heparan sulphate proteoglycan of basement membranes and pericellular matrices.
Iozzo RV, Cohen IR, Grassel S, Murdoch AD.
Biochem J. 1994 Sep 15;302 ( Pt 3):625-39. (REVIEW)
PMID 7945186
 
Structural and functional characterization of the human perlecan gene promoter. Transcriptional activation by transforming growth factor-beta via a nuclear factor 1-binding element.
Iozzo RV, Pillarisetti J, Sharma B, Murdoch AD, Danielson KG, Uitto J, Mauviel A.
J Biol Chem. 1997 Feb 21;272(8):5219-28.
PMID 9030592
 
Perlecan (heparan sulfate proteoglycan) gene expression reflected in the characteristic histological architecture of salivary adenoid cystic carcinoma.
Kimura S, Cheng J, Ida H, Hao N, Fujimori Y, Saku T.
Virchows Arch. 2000 Aug;437(2):122-8.
PMID 10993271
 
Structural basis for the high-affinity interaction of nidogen-1 with immunoglobulin-like domain 3 of perlecan.
Kvansakul M, Hopf M, Ries A, Timpl R, Hohenester E.
Embo J. 2001 Oct 1;20(19):5342-6.
PMID 11574465
 
A role for perlecan in the suppression of growth and invasion in fibrosarcoma cells.
Mathiak M, Yenisey C, Grant DS, Sharma B, Iozzo RV.
Cancer Res. 1997 Jun 1;57(11):2130-6.
PMID 9187109
 
Perlecan, the "jack of all trades" proteoglycan of cartilaginous weight-bearing connective tissues.
Melrose J, Hayes AJ, Whitelock JM, Little CB.
Bioessays. 2008 May;30(5):457-69. (REVIEW)
PMID 18404701
 
Perlecan immunolocalizes to perichondrial vessels and canals in human fetal cartilaginous primordia in early vascular and matrix remodeling events associated with diarthrodial joint development.
Melrose J, Smith S, Whitelock J.
J Histochem Cytochem. 2004 Nov;52(11):1405-13.
PMID 15505335
 
Endorepellin, a novel inhibitor of angiogenesis derived from the C terminus of perlecan.
Mongiat M, Sweeney SM, San Antonio JD, Fu J, Iozzo RV.
J Biol Chem. 2003 Feb 7;278(6):4238-49.
PMID 12435733
 
Widespread expression of perlecan proteoglycan in basement membranes and extracellular matrices of human tissues as detected by a novel monoclonal antibody against domain III and by in situ hybridization.
Murdoch AD, Liu B, Schwarting R, Tuan RS, Iozzo RV.
J Histochem Cytochem. 1994 Feb;42(2):239-49.
PMID 7507142
 
Morphological aspects of altered basement membrane metabolism in invasive carcinomas of the breast and the larynx.
Nerlich AG, Lebeau A, Hagedorn HG, Sauer U, Schleicher ED.
Anticancer Res. 1998 Sep-Oct;18(5A):3515-20.
PMID 9858933
 
Perlecan, the major proteoglycan of basement membranes, is altered in patients with Schwartz-Jampel syndrome (chondrodystrophic myotonia).
Nicole S, Davoine CS, Topaloglu H, Cattolico L, Barral D, Beighton P, Hamida CB, Hammouda H, Cruaud C, White PS, Samson D, Urtizberea JA, Lehmann-Horn F, Weissenbach J, Hentati F, Fontaine B.
Nat Genet. 2000 Dec;26(4):480-3.
PMID 11101850
 
Pathogenesis of beta2-microglobulin amyloidosis.
Ohashi K.
Pathol Int. 2001 Jan;51(1):1-10. (REVIEW)
PMID 11148456
 
Reduced perlecan in mice results in chondrodysplasia resembling Schwartz-Jampel syndrome.
Rodgers KD, Sasaki T, Aszodi A, Jacenko O.
Hum Mol Genet. 2007 Mar 1;16(5):515-28.
PMID 17213231
 
Evidence in favor of the contribution of genes involved in the maintenance of the extracellular matrix of the arterial wall to the development of intracranial aneurysms.
Ruigrok YM, Rinkel GJ, van't Slot R, Wolfs M, Tang S, Wijmenga C.
Hum Mol Genet. 2006 Nov 15;15(22):3361-8.
PMID 17038484
 
Enhanced expression of basement-membrane-type heparan sulfate proteoglycan in tumor fibro-myxoid stroma of intrahepatic cholangiocarcinoma.
Sabit H, Tsuneyama K, Shimonishi T, Harada K, Cheng J, Ida H, Saku T, Saito K, Nakanuma Y.
Pathol Int. 2001 Apr;51(4):248-56.
PMID 11350606
 
Inhibition of glycosaminoglycan modification of perlecan domain I by site-directed mutagenesis changes protease sensitivity and laminin-1 binding activity.
Sasaki T, Costell M, Mann K, Timpl R.
FEBS Lett. 1998 Sep 18;435(2-3):169-72.
PMID 9762901
 
Perlecan knockdown in metastatic prostate cancer cells reduces heparin-binding growth factor responses in vitro and tumor growth in vivo.
Savore C, Zhang C, Muir C, Liu R, Wyrwa J, Shu J, Zhau HE, Chung LW, Carson DD, Farach-Carson MC.
Clin Exp Metastasis. 2005;22(5):377-90.
PMID 16283481
 
Expression of proteoglycan core proteins in human bone marrow stroma.
Schofield KP, Gallagher JT, David G.
Biochem J. 1999 Nov 1;343 Pt 3:663-8.
PMID 10527946
 
Antisense targeting of perlecan blocks tumor growth and angiogenesis in vivo.
Sharma B, Handler M, Eichstetter I, Whitelock JM, Nugent MA, Iozzo RV.
J Clin Invest. 1998 Oct 15;102(8):1599-608.
PMID 9788974
 
Transcriptional silencing of perlecan gene expression by interferon-gamma.
Sharma B, Iozzo RV.
J Biol Chem. 1998 Feb 20;273(8):4642-6.
PMID 9468523
 
MEC-8 regulates alternative splicing of unc-52 transcripts in C. elegans hypodermal cells.
Spike CA, Davies AG, Shaw JE, Herman RK.
Development. 2002 Nov;129(21):4999-5008.
PMID 12397108
 
Spectrum of Schwartz-Jampel syndrome includes micromelic chondrodysplasia, kyphomelic dysplasia, and Burton disease.
Spranger J, Hall BD, Hane B, Srivastava A, Stevenson RE.
Am J Med Genet. 2000 Oct 2;94(4):287-95.
PMID 11038441
 
Spectrum of HSPG2 (Perlecan) mutations in patients with Schwartz-Jampel syndrome.
Stum M, Davoine CS, Vicart S, Guillot-Noel L, Topaloglu H, Carod-Artal FJ, Kayserili H, Hentati F, Merlini L, Urtizberea JA, Hammouda el-H, Quan PC, Fontaine B, Nicole S.
Hum Mutat. 2006 Nov;27(11):1082-91.
PMID 16927315
 
The degradation of human endothelial cell-derived perlecan and release of bound basic fibroblast growth factor by stromelysin, collagenase, plasmin, and heparanases.
Whitelock JM, Murdoch AD, Iozzo RV, Underwood PA.
J Biol Chem. 1996 Apr 26;271(17):10079-86.
PMID 8626565
 
Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases.
d'Ortho MP, Will H, Atkinson S, Butler G, Messent A, Gavrilovic J, Smith B, Timpl R, Zardi L, Murphy G.
Eur J Biochem. 1997 Dec 15;250(3):751-7.
PMID 9461298
 

Citation

This paper should be referenced as such :
Farach-Carson, MC ; Grindel, B
HSPG2 (heparan sulfate proteoglycan 2)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(9):626-633.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/HSPG2ID40890ch1p36.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Bone: Osteochondroma


External links

Nomenclature
HGNC (Hugo)HSPG2   5273
Cards
AtlasHSPG2ID40890ch1p36
Entrez_Gene (NCBI)HSPG2  3339  heparan sulfate proteoglycan 2
AliasesHSPG; PLC; PRCAN; SJA; 
SJS; SJS1
GeneCards (Weizmann)HSPG2
Ensembl hg19 (Hinxton)ENSG00000142798 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000142798 [Gene_View]  chr1:21822232-21937297 [Contig_View]  HSPG2 [Vega]
ICGC DataPortalENSG00000142798
TCGA cBioPortalHSPG2
AceView (NCBI)HSPG2
Genatlas (Paris)HSPG2
WikiGenes3339
SOURCE (Princeton)HSPG2
Genetics Home Reference (NIH)HSPG2
Genomic and cartography
GoldenPath hg38 (UCSC)HSPG2  -     chr1:21822232-21937297 -  1p36.12   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)HSPG2  -     1p36.12   [Description]    (hg19-Feb_2009)
EnsemblHSPG2 - 1p36.12 [CytoView hg19]  HSPG2 - 1p36.12 [CytoView hg38]
Mapping of homologs : NCBIHSPG2 [Mapview hg19]  HSPG2 [Mapview hg38]
OMIM142461   224410   255800   
Gene and transcription
Genbank (Entrez)AA450342 AA507437 AB209851 AF479675 AI131329
RefSeq transcript (Entrez)NM_001291860 NM_005529
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)HSPG2
Cluster EST : UnigeneHs.562227 [ NCBI ]
CGAP (NCI)Hs.562227
Alternative Splicing GalleryENSG00000142798
Gene ExpressionHSPG2 [ NCBI-GEO ]   HSPG2 [ EBI - ARRAY_EXPRESS ]   HSPG2 [ SEEK ]   HSPG2 [ MEM ]
Gene Expression Viewer (FireBrowse)HSPG2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3339
GTEX Portal (Tissue expression)HSPG2
Human Protein AtlasENSG00000142798-HSPG2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP98160   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP98160  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP98160
Splice isoforms : SwissVarP98160
PhosPhoSitePlusP98160
Domaine pattern : Prosite (Expaxy)EGF_1 (PS00022)    EGF_2 (PS01186)    EGF_3 (PS50026)    EGF_LAM_1 (PS01248)    EGF_LAM_2 (PS50027)    IG_LIKE (PS50835)    LAM_G_DOMAIN (PS50025)    LAMININ_IVA (PS51115)    LDLRA_1 (PS01209)    LDLRA_2 (PS50068)    SEA (PS50024)   
Domains : Interpro (EBI)ConA-like_dom    EGF-like_Ca-bd_dom    EGF-like_CS    EGF-like_dom    Ig-like_dom    Ig-like_fold    Ig_I-set    Ig_sub    Ig_sub2    Ig_V-set    Laminin_EGF    Laminin_G    Laminin_IV    LDLR_class-A_CS    LDrepeatLR_classA_rpt    SEA_dom   
Domain families : Pfam (Sanger)EGF (PF00008)    I-set (PF07679)    Ig_2 (PF13895)    Laminin_B (PF00052)    Laminin_EGF (PF00053)    Laminin_G_1 (PF00054)    Ldl_recept_a (PF00057)   
Domain families : Pfam (NCBI)pfam00008    pfam07679    pfam13895    pfam00052    pfam00053    pfam00054    pfam00057   
Domain families : Smart (EMBL)EGF (SM00181)  EGF_CA (SM00179)  EGF_Lam (SM00180)  IG (SM00409)  IGc2 (SM00408)  IGv (SM00406)  LamB (SM00281)  LamG (SM00282)  LDLa (SM00192)  SEA (SM00200)  
Conserved Domain (NCBI)HSPG2
DMDM Disease mutations3339
Blocks (Seattle)HSPG2
PDB (SRS)3SH4    3SH5   
PDB (PDBSum)3SH4    3SH5   
PDB (IMB)3SH4    3SH5   
PDB (RSDB)3SH4    3SH5   
Structural Biology KnowledgeBase3SH4    3SH5   
SCOP (Structural Classification of Proteins)3SH4    3SH5   
CATH (Classification of proteins structures)3SH4    3SH5   
SuperfamilyP98160
Human Protein Atlas [tissue]ENSG00000142798-HSPG2 [tissue]
Peptide AtlasP98160
HPRD00804
IPIIPI00024284   IPI00152842   IPI00514578   IPI00513870   IPI00978243   IPI00514485   IPI00647622   IPI00514355   IPI00514690   
Protein Interaction databases
DIP (DOE-UCLA)P98160
IntAct (EBI)P98160
FunCoupENSG00000142798
BioGRIDHSPG2
STRING (EMBL)HSPG2
ZODIACHSPG2
Ontologies - Pathways
QuickGOP98160
Ontology : AmiGOretinoid metabolic process  angiogenesis  calcium ion binding  protein binding  extracellular region  basement membrane  extracellular space  Golgi lumen  plasma membrane  focal adhesion  glycosaminoglycan biosynthetic process  glycosaminoglycan catabolic process  protein C-terminus binding  extracellular matrix disassembly  extracellular matrix organization  glycosaminoglycan metabolic process  extracellular matrix  extracellular matrix  extracellular matrix  lysosomal lumen  cellular protein metabolic process  extracellular exosome  
Ontology : EGO-EBIretinoid metabolic process  angiogenesis  calcium ion binding  protein binding  extracellular region  basement membrane  extracellular space  Golgi lumen  plasma membrane  focal adhesion  glycosaminoglycan biosynthetic process  glycosaminoglycan catabolic process  protein C-terminus binding  extracellular matrix disassembly  extracellular matrix organization  glycosaminoglycan metabolic process  extracellular matrix  extracellular matrix  extracellular matrix  lysosomal lumen  cellular protein metabolic process  extracellular exosome  
Pathways : KEGGECM-receptor interaction    Hepatitis B    Proteoglycans in cancer   
REACTOMEP98160 [protein]
REACTOME PathwaysR-HSA-977225 [pathway]   
NDEx NetworkHSPG2
Atlas of Cancer Signalling NetworkHSPG2
Wikipedia pathwaysHSPG2
Orthology - Evolution
OrthoDB3339
GeneTree (enSembl)ENSG00000142798
Phylogenetic Trees/Animal Genes : TreeFamHSPG2
HOVERGENP98160
HOGENOMP98160
Homologs : HomoloGeneHSPG2
Homology/Alignments : Family Browser (UCSC)HSPG2
Gene fusions - Rearrangements
Fusion : MitelmanHSPG2/NTNG1 [1p36.12/1p13.3]  
Fusion : MitelmanHSPG2/SIAE [1p36.12/11q24.2]  [t(1;11)(p36;q24)]  
Fusion : MitelmanHSPG2/SUSD6 [1p36.12/14q24.1]  [t(1;14)(p36;q24)]  
Fusion : MitelmanUBR4/HSPG2 [1p36.13/1p36.12]  [t(1;1)(p36;p36)]  
Fusion: TCGAHSPG2 1p36.12 KIAA0247 LUAD
Fusion: TCGAHSPG2 1p36.12 NTNG1 1p13.3 LUAD
Fusion: TCGAHSPG2 1p36.12 SIAE 11q24.2 KIRC
Fusion: TCGAUBR4 1p36.13 HSPG2 1p36.12 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerHSPG2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)HSPG2
dbVarHSPG2
ClinVarHSPG2
1000_GenomesHSPG2 
Exome Variant ServerHSPG2
ExAC (Exome Aggregation Consortium)ENSG00000142798
GNOMAD BrowserENSG00000142798
Genetic variants : HAPMAP3339
Genomic Variants (DGV)HSPG2 [DGVbeta]
DECIPHERHSPG2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisHSPG2 
Mutations
ICGC Data PortalHSPG2 
TCGA Data PortalHSPG2 
Broad Tumor PortalHSPG2
OASIS PortalHSPG2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICHSPG2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDHSPG2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch HSPG2
DgiDB (Drug Gene Interaction Database)HSPG2
DoCM (Curated mutations)HSPG2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)HSPG2 (select a term)
intoGenHSPG2
NCG5 (London)HSPG2
Cancer3DHSPG2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM142461    224410    255800   
Orphanet215    1839   
MedgenHSPG2
Genetic Testing Registry HSPG2
NextProtP98160 [Medical]
TSGene3339
GENETestsHSPG2
Target ValidationHSPG2
Huge Navigator HSPG2 [HugePedia]
snp3D : Map Gene to Disease3339
BioCentury BCIQHSPG2
ClinGenHSPG2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3339
Chemical/Pharm GKB GenePA29537
Clinical trialHSPG2
Miscellaneous
canSAR (ICR)HSPG2 (select the gene name)
Probes
Litterature
PubMed141 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineHSPG2
EVEXHSPG2
GoPubMedHSPG2
iHOPHSPG2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Oct 12 16:24:15 CEST 2017

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.