Syndecan 1

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SDC1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSDC1, CD138, SDC, SYND1, syndecan, syndecan 1
External IDsOMIM: 186355 MGI: 1349162 HomoloGene: 2252 GeneCards: SDC1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001006946
NM_002997

NM_011519

RefSeq (protein)

NP_001006947
NP_002988

NP_035649

Location (UCSC)Chr 2: 20.2 – 20.23 MbChr 12: 8.82 – 8.84 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Syndecan 1 is a protein which in humans is encoded by the SDC1 gene.[5][6]

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 and chemokines[7], with binding largely via heparan sulfate chains.

An exception is the prosecretory mitogen lacritin that binds syndecan-1 only after heparanase modification.[8][9] 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.[8] 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.[9] 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.[9]

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.[10]

Studies in syndecan-1-deficient (knockout ) mice

Role in inflammation. Syndecan-1 deficient mice show increased inflammation, which was attributed to an increased ICAM-1 and heparan sulfate-dependent recruitment of leukocytes (including neutrophils and dendritic cells) [11]to the inflamed endothelium. [12] This increase results in higher inflammatory responses and tissue damage in experimental models of contact dermatitis[13] , inflammation of the kidney [14], myocardial infarction [15], inflammatory bowel disease [16] and experimental autoimmune encephalomyelitis [17] In experimental colitis-induced colon carcinoma, syndecan-1 deficiency promotes tumor growth in an IL-6 / STAT -signaling-dependent manner. [18]

Clinical significance

Altered syndecan-1 expression has been detected in several different tumor types.[19] [20]In breast cancer, syndecan-1 is upregulated and contributes to to the cancer stem cell phenotype, which is linked to increased resistance to chemotherapy and radiation therapy [21][22]

It is a specific antigen on multiple myeloma cells.[23]

Indatuximab ravtansine targets this protein.

Application

It is a useful marker for plasma cells,[24] but only if the cells tested are already known to be derived from blood.[25]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115884Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020592Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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.
  7. ^ Götte, Martin (2003). "Syndecans in inflammation". FASEB Journal. 17 (6): 575–591. doi:10.1096/fj.02-0739rev. PMID 12665470.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ a b 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.
  9. ^ a b c 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ "Entrez Gene: SDC1 syndecan 1".
  11. ^ Averbeck; et al. (2017). "Syndecan-1 regulates dendritic cell migration in cutaneous hypersensitivity to haptens". Experimental Dermatology. 26 (11): 1060–1067. doi:10.1111/exd.13374. PMID 28453867. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  12. ^ Götte, Martin (2002). "Role of syndecan-1 in leukocyte-endothelial interactions in the ocular vasculature". IOVS. 43 (4): 1135–41. PMID 11923257.
  13. ^ Kharabi Masouleh; et al. (2009). "Role of the heparan sulfate proteoglycan syndecan-1 (CD138) in delayed-type hypersensitivity". Journal of Immunology. 182 (8): 4985–93. doi:10.4049/jimmunol.0800574. PMID 19342678. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  14. ^ Rops; et al. (2007). "Syndecan-1 deficiency aggravates anti-glomerular basement membrane nephritis". Kidney International. 72 (10): 1204–15. doi:10.1038/sj.ki.5002514. PMID 17805240. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  15. ^ Vanhoutte; et al. (2007). "Increased expression of syndecan-1 protects against cardiac dilatation and dysfunction after myocardial infarction". Circulation. 115 (4): 475–82. doi:10.1161/CIRCULATIONAHA.106.644609. PMID 17242279. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  16. ^ Floer; et al. (2010). "Enoxaparin improves the course of dextran sodium sulfate-induced colitis in syndecan-1-deficient mice". American Journal of Pathology. 176 (1): 146–57. doi:10.2353/ajpath.2010.080639. PMID 20008145. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  17. ^ Zhang; et al. (2013). "Syndecan-1, a cell surface proteoglycan, negatively regulates initial leukocyte recruitment to the brain across the choroid plexus in murine experimental autoimmune encephalomyelitis". Journal of Immunology. 191 (9): 4551–61. doi:10.4049/jimmunol.1300931. PMID 24078687. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  18. ^ Binder-Gallimidi; et al. (2017). "Syndecan-1 deficiency promotes tumor growth in a murine model of colitis-induced colon carcinoma". PLOS ONE. 12 (3): e0174343. doi:10.1371/journal.pone.0174343. PMID 28350804. {{cite journal}}: Explicit use of et al. in: |first1= (help)CS1 maint: unflagged free DOI (link)
  19. ^ Yip; et al. (2006). "Therapeutic value of glycosaminoglycans in cancer". Molecular Cancer Therapeutics. 5 (9): 2139-48. doi:10.1158/1535-7163.MCT-06-0082. PMID 16985046. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  20. ^ Stepp; et al. (2015). "Syndecan-1 and Its Expanding List of Contacts". Adv Wound Care (New Rochelle). 4 (4): 235–249. doi:10.1089/wound.2014.0555. PMID 25945286. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  21. ^ Hassan, Hebatallah (2013). "Syndecan-1 modulates β-integrin-dependent and interleukin-6-dependent functions in breast cancer cell adhesion, migration, and resistance to irradiation". FEBS Journal. 280 (10): 2216–27. doi:10.1111/febs.12111. PMID 23289672.
  22. ^ Ibrahim, Sherif (March 7, 2017). "Syndecan-1 is a novel molecular marker for triple negative inflammatory breast cancer and modulates the cancer stem cell phenotype via the IL-6/STAT3, Notch and EGFR signaling pathways". Molecular Cancer. 16 (1): 57. doi:10.1186/s12943-017-0621-z. PMC 5341174. PMID 28270211.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  23. ^ 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
  24. ^ Rawstron AC (May 2006). "Immunophenotyping of plasma cells". Current Protocols in Cytometry. Chapter 6: Unit6.23. doi:10.1002/0471142956.cy0623s36. ISBN 0-471-14295-6. PMID 18770841.
  25. ^ 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.[permanent dead link]

[1]== Further reading ==

External links

  1. ^ Götte, Martin (2003). "Syndecans in inflammation". FASEB Journal. 17 (6): 575–91. doi:10.1096/fj.02-0739rev. PMID 12665470.{{cite journal}}: CS1 maint: unflagged free DOI (link)