Syndecan 1

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Lua error in Module:Infobox_gene at line 33: attempt to index field 'wikibase' (a nil value). 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

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  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
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Further reading

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External links