Syndecan 1

Syndecan 1 is a protein which in humans is encoded by the SDC1 gene.^[5][6] The protein is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. 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. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein.

SDC1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4GVC, 4GVD
Identifiers
Aliases	SDC1, CD138, SDC, SYND1, syndecan, syndecan 1
External IDs	OMIM: 186355; MGI: 1349162; HomoloGene: 2252; GeneCards: SDC1; OMA:SDC1 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p24.1 Start 20,200,797 bp[1] End 20,225,433 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12 A1.1|12 3.94 cM Start 8,821,323 bp[2] End 8,843,715 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of abdomen mucosa of pharynx right lobe of liver skin of limb skin of leg gums skin of arm skin of thigh gingival epithelium vulva Top expressed in cumulus cell transitional epithelium of urinary bladder molar conjunctival fornix skin of abdomen lip hair follicle external carotid artery condyle skin of external ear More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein C-terminus binding protein binding identical protein binding Cellular component lysosomal lumen extracellular exosome extracellular region integral component of membrane Golgi lumen integral component of plasma membrane membrane cell surface plasma membrane external side of plasma membrane protein-containing complex Biological process glycosaminoglycan catabolic process canonical Wnt signaling pathway wound healing response to calcium ion odontogenesis glycosaminoglycan biosynthetic process ureteric bud development response to cAMP positive regulation of exosomal secretion Sertoli cell development striated muscle cell development positive regulation of extracellular exosome assembly retinoid metabolic process response to glucocorticoid response to toxic substance response to organic substance response to hydrogen peroxide glycosaminoglycan metabolic process inflammatory response myoblast development leukocyte migration cell migration cytokine-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6382 20969 Ensembl ENSG00000115884 ENSMUSG00000020592 UniProt P18827 P18828 RefSeq (mRNA) NM_001006946 NM_002997 NM_011519 RefSeq (protein) NP_001006947 NP_002988 NP_035649 Location (UCSC) Chr 2: 20.2 – 20.23 Mb Chr 12: 8.82 – 8.84 Mb PubMed search [3] [4]
Wikidata
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Altered syndecan-1 expression has been detected in several different tumor types. Syndecan 1 can be a marker for plasma cells.

Structure

The syndecan-1 core protein consists of an extracellular domain which can be substituted with heparan sulfate and chondroitin sulfate glycosaminoglycan chains, a highly conserved transmembrane domain, and a highly conserved cytoplasmic domain, which contains two constant regions that are separated by a variable region.^[8] The extracellular domain can be cleaved (shed) from the cell surface at a juxtamembrane site,^[9] converting the membrane-bound proteoglycan into a paracrine effector molecule with roles in wound repair ^[10] and invasive growth of cancer cells.^[11]

An exception is the prosecretory mitogen lacritin that binds syndecan-1 only after heparanase modification.^[12][13] 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.^[12] 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.^[13] 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.^[13]

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.^[14]

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)^[15] to the inflamed endothelium.^[16] This increase results in higher inflammatory responses and tissue damage in experimental models of contact dermatitis,^[17] inflammation of the kidney,^[18] myocardial infarction,^[19] inflammatory bowel disease^[20] and experimental autoimmune encephalomyelitis^[21] In experimental colitis-induced colon carcinoma, syndecan-1 deficiency promotes tumor growth in an IL-6 / STAT-signaling-dependent manner.^[22]

Clinical significance

Altered syndecan-1 expression has been detected in several different tumor types.^[23][24] In breast cancer, syndecan-1 is up regulated and contributes to the cancer stem cell phenotype, which is linked to increased resistance to chemotherapy and radiation therapy ^[25][26][27]

It is a specific antigen on multiple myeloma cells.^[28] Indatuximab ravtansine targets this protein.

Application

It is a useful marker for plasma cells,^[29] but only if the cells tested are already known to be derived from blood.^[30] For plasma cells, it usually stains intensely membranous, with or without associated diffuse weak cytoplasmic and/or Golgi staining.^[31] Few cases show cytoplasmic granular staining, with or without associated Golgi staining.^[31]