Glypican-1 (GPC1) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''GPC1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. GPC1 is encoded by human ''GPC1'' gene located at 2q37.3. GPC1 contains 558 amino acids with three predicted

heparan sulfate Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs in 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 ma ...

chains.

Function

Cell surface heparan sulfate

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 ...

s are composed of a membrane-associated protein core substituted with three heparan sulfate chains. Members of the

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 glypica ...

-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a

glycosyl phosphatidylinositol Glycosylphosphatidylinositol () or glycophosphatidylinositol (GPI) 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 in a wide varie ...

linkage. These proteins may play a role in the control of cell division and growth regulation.

Interactions

Glypican 1 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with SLIT2.

Clinical significance

This protein is involved in the misfolding of normal

prion A prion () is a Proteinopathy, misfolded protein that induces misfolding in normal variants of the same protein, leading to cellular death. Prions are responsible for prion diseases, known as transmissible spongiform encephalopathy (TSEs), w ...

proteins in the cell membrane to the infectious prion form. In 2015 it was reported that the presence of this protein in

exosome Exosome may refer to: * Exosome complex, an intracellular macromolecular protein complex involved in RNA degradation * Exosome (vesicle) Exosomes, ranging in size from 30 to 150 nanometers, are membrane-bound extracellular vesicles (EVs) th ...

s in patients' blood is able to detect early

pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...

with absolute specificity and sensitivity. However this conclusion is disputed. and in more recent overviews of potential markers for pancreatic cancer, Glypican 1 is not mentioned. Therapeutic antibodies against GPC1 have been developed. GPC1 has been evaluated as a potential target for cancer therapy, including antibody-drug conjugates, CAR-T cell therapy, radiotherapy, bispecific T cell engager and immunotoxins in preclinical studies. HM2 is a mouse monoclonal antibody targeting the C-terminal end of GPC1 developed by the laboratory of Mitchell Ho at the NCI,

NIH The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...

(Bethesda, US). The Ho lab also produced a dromedary camel V_HH nanobody called D4 specific for GPC1.The D4 V_HH nanobody-based CAR-T cells and immunotoxins were active against pancreatic cancer in mice. Miltuximab, a chimeric antibody against GPC1, was tested in radioimmunotherapy models of prostate cancer.

Function

Interactions

Clinical significance

See also

References

Further reading