Syndecan 1

Syndecan 1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SDC1 ; CD138; SDC; SYND1; syndecan
External IDs OMIM: 186355 MGI: 1349162 HomoloGene: 2252 GeneCards: SDC1 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 6382 20969
Ensembl ENSG00000115884 ENSMUSG00000020592
UniProt P18827 P18828
RefSeq (mRNA) NM_001006946 NM_011519
RefSeq (protein) NP_001006947 NP_035649
Location (UCSC) Chr 2:
20.2 – 20.23 Mb		 Chr 12:
8.77 – 8.79 Mb
PubMed search

Syndecan 1 is a protein which in humans is encoded by the SDC1 gene.[1][2]

Function

The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan 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-1 tat 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.

It is a specific antigen on multiple myeloma cells.[6]

Indatuximab ravtansine targets this protein.

Application

It is a useful marker for plasma cells,[7] but only if the cells tested are already known to be derived from blood.[8]

References

  1. ↑ 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. PMID 2324102.
  2. ↑ 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. PMID 2173154.
  3. 1 2 Ma P, Beck SL, Raab RW, McKown RL, Coffman GL, Utani A, Chirico WJ, Rapraeger AC, Laurie GW (Sep 2006). "Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin". The Journal of Cell Biology 174 (7): 1097–106. doi:10.1083/jcb.200511134. PMC 1666580. PMID 16982797.
  4. 1 2 3 Zhang Y, Wang N, Raab RW, McKown RL, Irwin JA, Kwon I, van Kuppevelt TH, Laurie GW (Apr 2013). "Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity". The Journal of Biological Chemistry 288 (17): 12090–101. doi:10.1074/jbc.M112.422717. PMC 3636894. PMID 23504321.
  5. ↑ "Entrez Gene: SDC1 syndecan 1".
  6. ↑ Indatuximab Ravtansine (BT062) In Combination With Lenalidomide and Low-Dose Dexamethasone In Patients With Relapsed and/Or Refractory Multiple Myeloma: Clinical Activity In Len/Dex-Refractory Patients
  7. ↑ Rawstron AC (May 2006). "Immunophenotyping of plasma cells". Current Protocols in Cytometry / Editorial Board, J. Paul Robinson, Managing Editor ... [Et Al.] Chapter 6: Unit6.23. doi:10.1002/0471142956.cy0623s36. ISBN 0-471-14295-6. PMID 18770841.
  8. ↑ O'Connell FP, Pinkus JL, Pinkus GS (Feb 2004). "CD138 (syndecan-1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms". American Journal of Clinical Pathology 121 (2): 254–63. doi:10.1309/617D-WB5G-NFWX-HW4L. PMID 14983940.

Further reading

  • 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. PMID 1442271. 
  • 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. ISBN 978-0-12-540063-3. PMID 10506830. 
  • Wijdenes J, Dore JM, Clement C, Vermot-Desroches C (2003). "CD138". Journal of Biological Regulators and Homeostatic Agents 16 (2): 152–5. PMID 12144130. 
  • 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. PMID 1339431. 
  • 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. PMID 1644217. 
  • 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. PMID 1664683. 
  • 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. PMID 2173154. 
  • 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. PMID 2324102. 
  • Sanderson RD, Lalor P, Bernfield M (Nov 1989). "B lymphocytes express and lose syndecan at specific stages of differentiation". Cell Regulation 1 (1): 27–35. PMC 361422. PMID 2519615. 
  • 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. PMID 7592855. 
  • 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. PMID 7592967. 
  • Barillari G, Gendelman R, Gallo RC, Ensoli B (Sep 1993). "The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence". Proceedings of the National Academy of Sciences of the United States of America 90 (17): 7941–5. doi:10.1073/pnas.90.17.7941. PMC 47263. PMID 7690138. 
  • 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. PMID 7959737. 
  • 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. PMID 8118875. 
  • 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. PMID 8125298. 
  • 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. PMID 8163535. 
  • 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. PMID 8570206. 
  • 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. PMID 8889548. 
  • 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. PMID 9050911. 

External links

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