Glypican
Encyclopedia
The glypican family of heparan sulfate
Heparan sulfate
Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins...

 proteoglycans are anchored to the cell-surface via a covalent linkage to glycosylphosphatidylinositol (GPI). Six glypican family members have been identified in vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

s, two in Drosophila
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...

and one in C. elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...

.

Glypicans can modify cell signaling pathways and contribute to cellular proliferation and tissue growth. In Drosophila, the glypican dally assists diffusion of the BMP-family growth-promoting morphogen Decapentaplegic
Decapentaplegic
Decapentaplegic is a key morphogen involved in the development of the fruit fly Drosophila melanogaster. It is known to be necessary for the correct patterning of the fifteen imaginal discs, which are tissues that will become limbs and other organs and structures in the adult fly. It has also been...

 in the developing wing, while the developing haltere lacks dally and remains small. Extracellular localization of the other glypican in Drosophila, dally-like, is also required for the proper level of Hedgehog signaling in the developing wing.

In humans, glypican-1 is overexpressed in breast and brain cancers (gliomas), while glypican-3 is overexpressed in liver cancers.

Structure

All glypicans contain an N-terminal signal peptide
Signal peptide
A signal peptide is a short peptide chain that directs the transport of a protein.Signal peptides may also be called targeting signals, signal sequences, transit peptides, or localization signals....

 and a hydrophobic domain in their C-terminal region, required for attachment of the GPI anchor. The amino acid sequences of the six vertebrate glypican family members vary from being 17% to 63% identical.
The location of 14 cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

 amino acids is conserved
Conserved sequence
In biology, conserved sequences are similar or identical sequences that occur within nucleic acid sequences , protein sequences, protein structures or polymeric carbohydrates across species or within different molecules produced by the same organism...

 between the glypicans, suggesting the existence of a highly similar three-dimensional structure. Heparan sulfate
Heparan sulfate
Heparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins...

 glycosaminoglycan
Glycosaminoglycan
Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose or a hexuronic acid, linked to a hexosamine .-Production:Protein cores made in the rough endoplasmic reticulum are posttranslationally...

chains are attached at the 50 amino acids at the C-terminal end of the protein, near the anchor and the cell membrane.
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