SDC1 (syndecan 1)

	Genomic structure of the two alternative transcript variants of SDC1. Black boxes indicate exons and red boxes indicate untranslated exons.
Description	The SDC1 gene contains 9 exons and spans 24, 6366 bases (start 20,264,039 bp from pter to end 20,288,675) oriented at the minus strand.
Transcription	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. Variant 1 (NM_001006946) represents the longer transcript and variant 2 (NM_002997) differs in the 5' UTR compared to variant 1. Variant 1: exons-6; transcript length-3309 bp and translation length -310 residues. Variant 2: exons-5; transcript length-3217 bp and translation length -310 residues.
Pseudogene	None

	Schematic representation of the core protein structure of SDC1. C1 and C2 represent highly conserved regions and V represents the central variable region. Lines at amino acids 37, 45 and 47 represents heparan sulfate chain attachment sites and lines at amino acids 210 and 220 represents chondroitin sulfate chain attachment sites.
Description	310 amino acids; 32477 Da; charge -19.5; isoelectric point 4.2618. The core protein contains 3 domains, an ectodomain (extracellular domain), transmembrane domain and cytoplasmic domain. The ectodomain contains a cleavable amino terminal single peptide and the glycosaminoglycan attachment sites. There are 3 highly conserved serine-glycine sites for heparan sulfate attachment (amino acids 37,45 and 47) near the N terminal of the core protein and 2 highly conserved serine-glycine sites for chondroitin sulfate attachment ( amino acids 210 and 220), adjacent to the cell membrane. Shedding of the ectodomain occurs via protease sensitive sites near the plasma membrane. The transmembrane domain, which is highly conserved among the syndecan family members, contains an unusual motif of glycine/alanine that aligns on one face of the domain in the outer membrane leaflet. The non-catalytic COOH-terminal, cytoplasmic domain, which is relatively short (30 amino acids) contains 2 highly conserved regions (C1 and C2) which are identical in each of the 4 syndecan family members (the exception being a conservative substitution of arginine for lysine in syndecan 2). These flank a central variable region (V) that is distant for each family member. The sequence for variable domain (V) for SDC1 is SLEEPKQANGGAYQKPTKQE. The cytoplasmic domain of SDC1 is required for linking the molecule to the cytoskeleton and this interaction is dependent on a tyrosine residue that is conserved among all known syndecan family sequences. The cytoplasmic V region plays critical role in lamellipodial spreading, actin bundling and cell migration.
Expression	SDC1 is expressed predominantly on epithelial cells but is also found on distinct stages of differentiation of normal lymphoid cells (pre-B), mesenchymal cells during development and in mature plasma cells.
Localisation	Membrane; Single-pass type I membrane protein.
Function	The syndecan-1 proteoglycan regulates cell proliferation, cell migration, cell signaling, cytoskeletal organization and mediates both cell-cell and cell-extracellular matrix interactions. Additionally, via its heparan sulfate chains, it binds a wide range of bioactive molecules (e.g., growth factors, chemokines) that regulate cell behaviors important in normal and pathological processes. For example, it can function as trans HIV receptors via binding of HIV-1 gp120 to the syndecan heparan sulfate chains and also serves as a primary receptor for natural HPV infection of keratinocytes. SDC1 is required for Wnt-1 - induced mammary tumorigenesis and can function as either tumor suppressor or tumor promoter depending on tumor type and specific location of the proteoglycan (either cell surface or shed into the microenvironment). Core proteins also have functions independent of the heparan sulfate chains. The cytoplasmic domains can transmit signals and they also bind to anchoring molecules including PDZ family members. The extracellular domains bear the attached heparan sulfate chains but also interact with, and regulate, other cell adhesion molecules and cell surface receptors independent of their heparan sulfate chains. It was recently demonstrated that a domain within the syndecan-1 core protein is required for activation of alphaV/beta3 and alphaV/beta5 integrins and mutational analysis of SDC1 has identified a stretch of 5 hydrophobic amino acids, AVAAV (amino acids 222-226), which are critical for the SDC1 mediated inhibition of tumor cell invasion.
Homology	Belongs to the syndecan family; four members, syndecan- 1, syndecan-2, syndecan-3 and syndecan-4 , have been identified in mammalians. SDC1 orthologs are found in mouse, rat, dog, chimpanzee, guinea pig, Chinese hamster, Hedgehog, cat, Pika, Platypus, Bushbaby, Tree Shrew, and chicken. The extracellular domains of human and mouse SDC1 show 70% sequence identity while the transmembrane domain and cytoplasmic domain show 96 % and 100% identity respectively (see MapViewer).

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