J. Biol. Chem., Vol. 266, Issue 34, 22939-22947, 12, 1991

The complete sequence of perlecan, a basement membrane heparan sulfate proteoglycan, reveals extensive similarity with laminin A chain, low density lipoprotein-receptor, and the neural cell adhesion molecule

DM Noonan, A Fulle, P Valente, S Cai, E Horigan, M Sasaki, Y Yamada and JR Hassell
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.

A heparan sulfate proteoglycan is a component of all basement membranes. This molecule consists of three heparan sulfate side chains linked to a large core protein of approximately 400 kDa. We have isolated seven overlapping murine cDNA clones that encode the entire mRNA sequence of 12.685 kilobases of this molecule. This sequence has a single open reading frame of 3,707 amino acids that encodes for a protein of 396 kDa. Identical or near identical matchups with nine peptide sequences derived from the core protein of the molecule isolated from the Engelbreth-Holm-Swarm tumor were found with the deduced sequence. Sequence analysis and data base comparison of the deduced sequence show the protein to consist of five different domains, most of which contain internal repeats. Domain I contains a start methionine followed by a typical signal transfer sequence and a unique segment of 172 amino acids that contains the three probable sites of heparan sulfate attachment, SGD. Domain II contains four cysteine- and acidic amino acid-rich repeats that are very similar to those found in the LDL receptor and proteins such as GP330. Domain III consists of cysteine-rich and globular regions, both of which show similarity to those in the short arm of the laminin A chain. Domain IV contains 14 repeats of the immunoglobulin superfamily that are most highly similar to the immunoglobulin-like repeats in the neural cell adhesion molecule. Domain V contains three repeats with similarity to the laminin A chain G domain that are separated by epidermal growth factor- like regions not found in the laminin A chain. As the primary structural data agree with the appearance of the molecule in the electron microscope as a series of globules separated by rods, or "beads on a string," we have adopted the name perlecan for this molecule. The variety of domains in perlecan suggest multiple interactions with other molecules.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Tran-Lundmark, P.-K. Tran, G. Paulsson-Berne, V. Friden, R. Soininen, K. Tryggvason, T. N. Wight, M. G. Kinsella, J. Boren, and U. Hedin Heparan Sulfate in Perlecan Promotes Mouse Atherosclerosis: Roles in Lipid Permeability, Lipid Retention, and Smooth Muscle Cell Proliferation Circ. Res., July 3, 2008; 103(1): 43 - 52. [Abstract] [Full Text] [PDF]

				J. Melrose, P. Roughley, S. Knox, S. Smith, M. Lord, and J. Whitelock The Structure, Location, and Function of Perlecan, a Prominent Pericellular Proteoglycan of Fetal, Postnatal, and Mature Hyaline Cartilages J. Biol. Chem., December 1, 2006; 281(48): 36905 - 36914. [Abstract] [Full Text] [PDF]

				Y. M. Ruigrok, G. J.E. Rinkel, R. van't Slot, M. Wolfs, S. Tang, and C. Wijmenga 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 Hum. Mol. Genet., November 15, 2006; 15(22): 3361 - 3368. [Abstract] [Full Text] [PDF]

				A. Hirata and H. Nakamura Localization of Perlecan and Heparanase in Hertwig's Epithelial Root Sheath During Root Formation in Mouse Molars J. Histochem. Cytochem., October 1, 2006; 54(10): 1105 - 1113. [Abstract] [Full Text] [PDF]

				E. Edovitsky, I. Lerner, E. Zcharia, T. Peretz, I. Vlodavsky, and M. Elkin Role of endothelial heparanase in delayed-type hypersensitivity Blood, May 1, 2006; 107(9): 3609 - 3616. [Abstract] [Full Text] [PDF]

				A.A. DeCarlo and J.M. Whitelock The Role of Heparan Sulfate and Perlecan in Bone-regenerative Procedures J. Dent. Res., February 1, 2006; 85(2): 122 - 132. [Abstract] [Full Text] [PDF]

				M. Gronborg, T. Z. Kristiansen, A. Iwahori, R. Chang, R. Reddy, N. Sato, H. Molina, O. N. Jensen, R. H. Hruban, M. G. Goggins, et al. Biomarker Discovery from Pancreatic Cancer Secretome Using a Differential Proteomic Approach Mol. Cell. Proteomics, January 1, 2006; 5(1): 157 - 171. [Abstract] [Full Text] [PDF]

				C. W. Frevert and P. L. Sannes Matrix proteoglycans as effector molecules for epithelial cell function Eur. Respir. Rev., December 1, 2005; 14(97): 137 - 144. [Abstract] [Full Text] [PDF]

				H. Ida-Yonemochi, K. Ohshiro, W. Swelam, H. Metwaly, and T. Saku Perlecan, a Basement Membrane-type Heparan Sulfate Proteoglycan, in the Enamel Organ: Its Intraepithelial Localization in the Stellate Reticulum J. Histochem. Cytochem., June 1, 2005; 53(6): 763 - 772. [Abstract] [Full Text] [PDF]

				K. Tiedemann, T. Sasaki, E. Gustafsson, W. Gohring, B. Batge, H. Notbohm, R. Timpl, T. Wedel, U. Schlotzer-Schrehardt, and D. P. Reinhardt Microfibrils at Basement Membrane Zones Interact with Perlecan via Fibrillin-1 J. Biol. Chem., March 25, 2005; 280(12): 11404 - 11412. [Abstract] [Full Text] [PDF]

				R. Jasuja, B. L. Allen, W. N. Pappano, A. C. Rapraeger, and D. S. Greenspan Cell-surface Heparan Sulfate Proteoglycans Potentiate Chordin Antagonism of Bone Morphogenetic Protein Signaling and Are Necessary for Cellular Uptake of Chordin J. Biol. Chem., December 3, 2004; 279(49): 51289 - 51297. [Abstract] [Full Text] [PDF]

				J. Melrose, S. Smith, and J. Whitelock Perlecan Immunolocalizes to Perichondrial Vessels and Canals in Human Fetal Cartilaginous Primordia in Early Vascular and Matrix Remodeling Events Associated with Diarthrodial Joint Development J. Histochem. Cytochem., November 1, 2004; 52(11): 1405 - 1413. [Abstract] [Full Text] [PDF]

				A. Segev, N. Nili, and B. H Strauss The role of perlecan in arterial injury and angiogenesis Cardiovasc Res, September 1, 2004; 63(4): 603 - 610. [Abstract] [Full Text] [PDF]

				S. Hummel, A. Osanger, T. M. Bajari, M. Balasubramani, W. Halfter, J. Nimpf, and W. J. Schneider Extracellular Matrices of the Avian Ovarian Follicle: MOLECULAR CHARACTERIZATION OF CHICKEN PERLECAN J. Biol. Chem., May 28, 2004; 279(22): 23486 - 23494. [Abstract] [Full Text] [PDF]

				J. Melrose, S. Smith, P. Ghosh, and J. Whitelock Perlecan, the Multidomain Heparan Sulfate Proteoglycan of Basement Membranes, Is also a Prominent Component of the Cartilaginous Primordia in the Developing Human Fetal Spine J. Histochem. Cytochem., October 1, 2003; 51(10): 1331 - 1341. [Abstract] [Full Text] [PDF]

				M. Mongiat, J. Fu, R. Oldershaw, R. Greenhalgh, A. M. Gown, and R. V. Iozzo Perlecan Protein Core Interacts with Extracellular Matrix Protein 1 (ECM1), a Glycoprotein Involved in Bone Formation and Angiogenesis J. Biol. Chem., May 2, 2003; 278(19): 17491 - 17499. [Abstract] [Full Text] [PDF]

				M. Mongiat, S. M. Sweeney, J. D. San Antonio, J. Fu, and R. V. Iozzo Endorepellin, a Novel Inhibitor of Angiogenesis Derived from the C Terminus of Perlecan J. Biol. Chem., January 31, 2003; 278(6): 4238 - 4249. [Abstract] [Full Text] [PDF]

				T. Vincent, M. Hermansson, M. Bolton, R. Wait, and J. Saklatvala Basic FGF mediates an immediate response of articular cartilage to mechanical injury PNAS, June 11, 2002; 99(12): 8259 - 8264. [Abstract] [Full Text] [PDF]

				P. T. Martin Glycobiology of the synapse Glycobiology, January 1, 2002; 12(1): 1R - 7R. [Abstract] [Full Text] [PDF]

				R. Shimizu-Hirota, H. Sasamura, M. Mifune, H. Nakaya, M. Kuroda, M. Hayashi, and T. Saruta Regulation of Vascular Proteoglycan Synthesis by Angiotensin II Type 1 and Type 2 Receptors J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2609 - 2615. [Abstract] [Full Text] [PDF]

				T. M. Rogalski, G. P. Mullen, M. M. Gilbert, B. D. Williams, and D. G. Moerman The UNC-112 Gene in Caenorhabditis elegans Encodes a Novel Component of Cell-Matrix Adhesion Structures Required for Integrin Localization in the Muscle Cell Membrane J. Cell Biol., July 11, 2000; 150(1): 253 - 264. [Abstract] [Full Text] [PDF]

				M. A. Nugent, H. M. Nugent, R. V. Iozzo, K. Sanchack, and E. R. Edelman Perlecan is required to inhibit thrombosis after deep vascular injury and contributes to endothelial cell-mediated inhibition of intimal hyperplasia PNAS, June 6, 2000; 97(12): 6722 - 6727. [Abstract] [Full Text] [PDF]

				G. J. Jenniskens, A. Oosterhof, R. Brandwijk, J. H. Veerkamp, and T. H. van Kuppevelt Heparan Sulfate Heterogeneity in Skeletal Muscle Basal Lamina: Demonstration by Phage Display-Derived Antibodies J. Neurosci., June 1, 2000; 20(11): 4099 - 4111. [Abstract] [Full Text] [PDF]

				H. Itoh, H. Kataoka, M. Tomita, R. Hamasuna, Y. Nawa, N. Kitamura, and M. Koono Upregulation of HGF activator inhibitor type 1 but not type 2 along with regeneration of intestinal mucosa Am J Physiol Gastrointest Liver Physiol, April 1, 2000; 278(4): G635 - G643. [Abstract] [Full Text] [PDF]

				M. M. Verbeek, I. Otte-Holler, J. van den Born, L. P. W. J. van den Heuvel, G. David, P. Wesseling, and R. M. W. de Waal Agrin Is a Major Heparan Sulfate Proteoglycan Accumulating in Alzheimer’s Disease Brain Am. J. Pathol., December 1, 1999; 155(6): 2115 - 2125. [Abstract] [Full Text] [PDF]

				G. P. Mullen, T. M. Rogalski, J. A. Bush, P. R. Gorji, and D. G. Moerman Complex Patterns of Alternative Splicing Mediate the Spatial and Temporal Distribution of Perlecan/UNC-52 in Caenorhabditis elegans Mol. Biol. Cell, October 1, 1999; 10(10): 3205 - 3221. [Abstract] [Full Text]

				A. J. A. Groffen, J. H. Veerkamp, L. A. H. Monnens, and L. P. W. J. van den Heuvel Recent insights into the structure and functions of heparan sulfate proteoglycans in the human glomerular basement membrane Nephrol. Dial. Transplant., September 1, 1999; 14(9): 2119 - 2129. [Abstract] [Full Text] [PDF]

				D. J. Wassenhove-McCarthy and K. J. McCarthy Molecular Characterization of a Novel Basement Membrane-associated Proteoglycan, Leprecan J. Biol. Chem., August 27, 1999; 274(35): 25004 - 25017. [Abstract] [Full Text] [PDF]

				Z. Chang, A. Choon, and A. Friedl Endostatin Binds to Blood Vessels in Situ Independent of Heparan Sulfate and Does Not Compete for Fibroblast Growth Factor-2 Binding Am. J. Pathol., July 1, 1999; 155(1): 71 - 76. [Abstract] [Full Text] [PDF]

				W. Halfter, S. Dong, B. Schurer, and G. J. Cole Collagen XVIII Is a Basement Membrane Heparan Sulfate Proteoglycan J. Biol. Chem., September 25, 1998; 273(39): 25404 - 25412. [Abstract] [Full Text] [PDF]

				N. P. Dantuma, M. A. P. Pijnenburg, J. H. B. Diederen, and D. J. Van der Horst Multiple interactions between insect lipoproteins and fat body cells: extracellular trapping and endocytic trafficking J. Lipid Res., September 1, 1998; 39(9): 1877 - 1888. [Abstract] [Full Text]

				C. J. I. Raats, M. A. H. Bakker, W. Hoch, W. P. M. Tamboer, A. J. A. Groffen, L. P. W. J. van den Heuvel, J. H. M. Berden, and J. van den Born Differential Expression of Agrin in Renal Basement Membranes As Revealed by Domain-specific Antibodies J. Biol. Chem., July 10, 1998; 273(28): 17832 - 17838. [Abstract] [Full Text] [PDF]

				R. Wang, D. Moorer–Hickman, P. L. St. John, and D. R. Abrahamson Binding of Injected Laminin to Developing Kidney Glomerular Mesangial Matrices and Basement Membranes In Vivo J. Histochem. Cytochem., March 1, 1998; 46(3): 291 - 300. [Abstract] [Full Text]

				R. V. Iozzo, J. Pillarisetti, B. Sharma, A. D. Murdoch, K. G. Danielson, J. Uitto, and A. Mauviel Structural and Functional Characterization of the Human Perlecan Gene Promoter. TRANSCRIPTIONAL ACTIVATION BY TRANSFORMING GROWTH FACTOR-beta VIA A NUCLEAR FACTOR 1-BINDING ELEMENT J. Biol. Chem., February 21, 1997; 272(8): 5219 - 5228. [Abstract] [Full Text] [PDF]

				M. Dolan, T. Horchar, B. Rigatti, and J. R. Hassell Identification of Sites in Domain I of Perlecan That Regulate Heparan Sulfate Synthesis J. Biol. Chem., February 14, 1997; 272(7): 4316 - 4322. [Abstract] [Full Text] [PDF]

				R.-R. Wu and J. R. Couchman cDNA Cloning of the Basement Membrane Chondroitin Sulfate Proteoglycan Core Protein, Bamacan: A Five Domain Structure Including Coiled-Coil Motifs J. Cell Biol., January 27, 1997; 136(2): 433 - 444. [Abstract] [Full Text] [PDF]

				H. Yamazaki, H. Bujo, J. Kusunoki, K. Seimiya, T. Kanaki, N. Morisaki, W. J. Schneider, and Y. Saito Elements of Neural Adhesion Molecules and a Yeast Vacuolar Protein Sorting Receptor Are Present in a Novel Mammalian Low Density Lipoprotein Receptor Family Member J. Biol. Chem., October 4, 1996; 271(40): 24761 - 24768. [Abstract] [Full Text] [PDF]

				J. R. Couchman, R. Kapoor, M. Sthanam, and R.-R. Wu Perlecan and Basement Membrane-Chondroitin Sulfate Proteoglycan (Bamacan) Are Two Basement Membrane Chondroitin/Dermatan Sulfate Proteoglycans in the Engelbreth-Holm-Swarm Tumor Matrix J. Biol. Chem., April 19, 1996; 271(16): 9595 - 9602. [Abstract] [Full Text] [PDF]

				M. R. Mark, J. Chen, R. G. Hammonds, M. Sadick, and P. J. Godowsk Characterization of Gas6, a Member of the Superfamily of G Domain-containing Proteins, as a Ligand for Rse and Axl J. Biol. Chem., April 19, 1996; 271(16): 9785 - 9789. [Abstract] [Full Text] [PDF]

				J. B. Ancsin and R. Kisilevsky Laminin Interactions Important for Basement Membrane Assembly Are Promoted by Zinc and Implicate Laminin Zinc Finger-like Sequences J. Biol. Chem., March 22, 1996; 271(12): 6845 - 6851. [Abstract] [Full Text] [PDF]

				S. Joseph, M. Ford, C Barth, S Portbury, P. Bartlett, V Nurcombe, and U Greferath A proteoglycan that activates fibroblast growth factors during early neuronal development is a perlecan variant Development, January 11, 1996; 122(11): 3443 - 3452. [Abstract] [PDF]

				D. Fischer, R. Chiquet-Ehrismann, C. Bernasconi, and M. Chiquet A Single Heparin Binding Region within the Fibrinogen-like Domain Is Functional in Chick Tenascin-C J. Biol. Chem., February 17, 1995; 270(7): 3378 - 3384. [Abstract] [Full Text] [PDF]

				N SundarRaj, D Fite, S Ledbetter, S Chakravarti, and J. Hassell Perlecan is a component of cartilage matrix and promotes chondrocyte attachment J. Cell Sci., January 7, 1995; 108(7): 2663 - 2672. [Abstract] [PDF]

				S. Chakravarti, T. Horchar, B. Jefferson, G. W. Laurie, and J. R. Hassell Recombinant Domain III of Perlecan Promotes Cell Attachment through Its RGDS Sequence J. Biol. Chem., January 6, 1995; 270(1): 404 - 409. [Abstract] [Full Text] [PDF]

				T M Rogalski, B D Williams, G P Mullen, and D G Moerman Products of the unc-52 gene in Caenorhabditis elegans are homologous to the core protein of the mammalian basement membrane heparan sulfate proteoglycan. Genes & Dev., August 1, 1993; 7(8): 1471 - 1484. [Abstract] [PDF]

				H Schnurch and W Risau Expression of tie-2, a member of a novel family of receptor tyrosine kinases, in the endothelial cell lineage Development, January 11, 1993; 119(3): 957 - 968. [Abstract] [PDF]

				M Yamagata, S Saga, M Kato, M Bernfield, and K Kimata Selective distributions of proteoglycans and their ligands in pericellular matrix of cultured fibroblasts. Implications for their roles in cell-substratum adhesion J. Cell Sci., January 9, 1993; 106(1): 55 - 65. [Abstract] [PDF]

				Y. Ushkaryov, A. Petrenko, M Geppert, and T. Sudhof Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin Science, July 3, 1992; 257(5066): 50 - 56. [Abstract] [PDF]

				M. Mongiat, J. Otto, R. Oldershaw, F. Ferrer, J. D. Sato, and R. V. Iozzo Fibroblast Growth Factor-binding Protein Is a Novel Partner for Perlecan Protein Core J. Biol. Chem., March 23, 2001; 276(13): 10263 - 10271. [Abstract] [Full Text] [PDF]

				I. V. Fuki, R. V. Iozzo, and K. J. Williams Perlecan Heparan Sulfate Proteoglycan. A NOVEL RECEPTOR THAT MEDIATES A DISTINCT PATHWAY FOR LIGAND CATABOLISM J. Biol. Chem., August 11, 2000; 275(33): 25742 - 25750. [Abstract] [Full Text] [PDF]

				B. L. Allen, M. S. Filla, and A. C. Rapraeger Role of heparan sulfate as a tissue-specific regulator of FGF-4 and FGF receptor recognition J. Cell Biol., November 26, 2001; 155(5): 845 - 858. [Abstract] [Full Text] [PDF]