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Syndecan 1 is a protein which in humans is encoded by the SDC1gene.[1][2]
The protein encoded by this gene is a transmembrane (type I) heparan sulfateproteoglycan and is a member of the syndecan proteoglycan family. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1tat protein. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors, with binding largely via heparan sulfate chains.
An exception is the prosecretory mitogen lacritin that binds syndecan-1 only after heparanase modification.[3][4] Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial heparanase (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein.[3] Three SDC1 elements are required. (1) The heparanase-exposed hydrophobic sequence GAGAL that promotes the alpha helicity of lacritin's C-terminal amphipathic alpha helix form and likely binds to the hydrophobic face. (2) Heparanase-cleaved heparan sulfate that is 3-O sulfated.[4] This likely interacts with the cationic face of lacritin's C-terminal amphipathic alpha helix. (3) An N-terminal chondroitin sulfate chain that also likely binds to the cationic face. Point mutagenesis of lacritin has narrowed the ligation site.[4]
While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein.[5]
Clinical significance
Altered syndecan-1 expression has been detected in several different tumor types.
↑Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J (Sep 1990). "Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2". Somatic Cell and Molecular Genetics. 16 (5): 501–5. doi:10.1007/BF01233200. PMID2173154.
David G (1992). "Structural and functional diversity of the heparan sulfate proteoglycans". Advances in Experimental Medicine and Biology. 313: 69–78. doi:10.1007/978-1-4899-2444-5_7. PMID1442271.
Jaakkola P, Jalkanen M (1999). "Transcriptional regulation of Syndecan-1 expression by growth factors". Progress in Nucleic Acid Research and Molecular Biology. Progress in Nucleic Acid Research and Molecular Biology. 63: 109–38. doi:10.1016/S0079-6603(08)60721-7. ISBN978-0-12-540063-3. PMID10506830.
Wijdenes J, Dore JM, Clement C, Vermot-Desroches C (2003). "CD138". Journal of Biological Regulators and Homeostatic Agents. 16 (2): 152–5. PMID12144130.
Lories V, Cassiman JJ, Van den Berghe H, David G (Jan 1992). "Differential expression of cell surface heparan sulfate proteoglycans in human mammary epithelial cells and lung fibroblasts". The Journal of Biological Chemistry. 267 (2): 1116–22. PMID1339431.
Vainio S, Jalkanen M, Bernfield M, Saxén L (Aug 1992). "Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney". Developmental Biology. 152 (2): 221–32. doi:10.1016/0012-1606(92)90130-9. PMID1644217.
Kiefer MC, Ishihara M, Swiedler SJ, Crawford K, Stephans JC, Barr PJ (1992). "The molecular biology of heparan sulfate fibroblast growth factor receptors". Annals of the New York Academy of Sciences. 638: 167–76. doi:10.1111/j.1749-6632.1991.tb49027.x. PMID1664683.
Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J (Sep 1990). "Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2". Somatic Cell and Molecular Genetics. 16 (5): 501–5. doi:10.1007/BF01233200. PMID2173154.
Mali M, Jaakkola P, Arvilommi AM, Jalkanen M (Apr 1990). "Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans". The Journal of Biological Chemistry. 265 (12): 6884–9. PMID2324102.
Asundi VK, Carey DJ (Nov 1995). "Self-association of N-syndecan (syndecan-3) core protein is mediated by a novel structural motif in the transmembrane domain and ectodomain flanking region". The Journal of Biological Chemistry. 270 (44): 26404–10. doi:10.1074/jbc.270.44.26404. PMID7592855.
Zhang L, David G, Esko JD (Nov 1995). "Repetitive Ser-Gly sequences enhance heparan sulfate assembly in proteoglycans". The Journal of Biological Chemistry. 270 (45): 27127–35. doi:10.1074/jbc.270.45.27127. PMID7592967.
Spring J, Goldberger OA, Jenkins NA, Gilbert DJ, Copeland NG, Bernfield M (Jun 1994). "Mapping of the syndecan genes in the mouse: linkage with members of the myc gene family". Genomics. 21 (3): 597–601. doi:10.1006/geno.1994.1319. PMID7959737.
Sneed TB, Stanley DJ, Young LA, Sanderson RD (Feb 1994). "Interleukin-6 regulates expression of the syndecan-1 proteoglycan on B lymphoid cells". Cellular Immunology. 153 (2): 456–67. doi:10.1006/cimm.1994.1042. PMID8118875.
Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Kokenyesi R, Bernfield M (Apr 1994). "Core protein structure and sequence determine the site and presence of heparan sulfate and chondroitin sulfate on syndecan-1". The Journal of Biological Chemistry. 269 (16): 12304–9. PMID8163535.
Albini A, Benelli R, Presta M, Rusnati M, Ziche M, Rubartelli A, Paglialunga G, Bussolino F, Noonan D (Jan 1996). "HIV-tat protein is a heparin-binding angiogenic growth factor". Oncogene. 12 (2): 289–97. PMID8570206.
Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID8889548.
Kaukonen J, Alanen-Kurki L, Jalkanen M, Palotie A (Mar 1997). "The mapping and visual ordering of the human syndecan-1 and N-myc genes near the telomeric region of chromosome 2p". Human Genetics. 99 (3): 295–7. doi:10.1007/s004390050360. PMID9050911.
