Glypican 2 (GPC2), also known cerebroglycan, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
which in humans is encoded by the ''GPC2''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
The ''GPC2'' gene is at locus 7q22.1 and encodes for a 579 amino acid protein. The C-terminus of GPC2 has the GPI attachment site, at G554, and the
N-terminus
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
encodes a signal peptide, from M1 to S24. Multiple GPC2 mRNA transcripts have been identified.
''GPC2-201'' is the isoform overexpressed in pediatric cancers. Tumor-associated exon 3 of GPC2 shows the lowest expression in normal tissues compared with other exons.
Function
Cerebroglycan is a
glycophosphatidylinositol
Glycosylphosphatidylinositol (), or glycophosphatidylinositol, or GPI in short, is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles i ...
-linked integral membrane
heparan sulfate
Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (HSPG, i.e. Heparan Sulfate ProteoGlycan) in which two or three HS chains are attached in close proximity to cell surface or extracellular m ...
proteoglycan
Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to w ...
found in the
developing
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Arts
*Development hell, when a project is stuck in development
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*Development (music), the process thematic material is reshaped
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nervous system. Cerebroglycan participates in
cell adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as cell junctions or indir ...
and is thought to regulate the growth and
guidance of
axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action ...
s.
Cerebroglycan has especially high affinity for
laminin-1.
Implications in cancer
GPC2 has been suggested as a therapeutic target in neuroblastoma.
GPC2 is highly expressed in about half of neuroblastoma cases and that high GPC2 expression correlates with poor overall survival.
GPC2 silencing inactivates Wnt/β-catenin signaling and reduces the expression of N-Myc, an oncogenic driver of neuroblastoma tumorigenesis.
Chimeric antigen receptor (CAR) T cells and Immunotoxins (antibody-cytotoxin fusion proteins) targeting GPC2 inhibit neuroblastoma growth in mouse models.
A GPC2 specific antibody drug conjugate (ADC) can also inhibit neuroblastoma cell proliferation.
The CT3 monoclonal antibody specific for tumor-associated exons has been reported.
Immunohistochemistry using the CT3 antibody shows its high tumor specificity. CT3-derived CAR T cells regress neuroblastoma in mice.
See also
*
Glypican
Glypicans constitute one of the two major families of heparan sulfate proteoglycans, with the other major family being syndecans. Six glypicans have been identified in mammals, and are referred to as GPC1 through GPC6. In ''Drosophila'' two glyp ...
References
External links
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