Glypican 1

Glypican-1 (GPC1) is a protein that in humans is encoded by the GPC1 gene.^[5][6] GPC1 is encoded by human GPC1 gene located at 2q37.3.^[7] GPC1 contains 558 amino acids with three predicted heparan sulfate chains.^[7]

GPC1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4ACR, 4AD7, 4BWE, 4YWT
Identifiers
Aliases	GPC1, glypican, Glypican 1
External IDs	OMIM: 600395; MGI: 1194891; HomoloGene: 20477; GeneCards: GPC1; OMA:GPC1 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q37.3 Start 240,435,663 bp[1] End 240,468,076 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 D Start 92,759,367 bp[2] End 92,788,501 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone apex of heart right hemisphere of cerebellum skin of abdomen stromal cell of endometrium right frontal lobe tibial nerve skin of leg left ventricle periodontal fiber Top expressed in calvaria renal corpuscle ankle ventricular zone muscle of thigh myocardium of ventricle temporal muscle interventricular septum sternum triceps brachii muscle More reference expression data BioGPS n/a
Gene ontology Molecular function fibroblast growth factor binding heparan sulfate proteoglycan binding copper ion binding laminin binding Cellular component endosome membrane integral component of plasma membrane lysosomal lumen Golgi lumen membrane raft anchored component of membrane extracellular exosome extracellular space nucleoplasm cytosol plasma membrane extracellular matrix extracellular region intrinsic component of plasma membrane synapse anchored component of plasma membrane collagen-containing extracellular matrix cell surface Biological process glycosaminoglycan metabolic process myelin assembly heparan sulfate proteoglycan catabolic process retinoid metabolic process axon guidance negative regulation of fibroblast growth factor receptor signaling pathway positive regulation of skeletal muscle cell differentiation glycosaminoglycan catabolic process glycosaminoglycan biosynthetic process Schwann cell differentiation leukocyte migration regulation of signal transduction cell migration regulation of protein localization to membrane Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2817 14733 Ensembl ENSG00000063660 ENSMUSG00000034220 UniProt P35052 Q9QZF2 RefSeq (mRNA) NM_002081 NM_016696 RefSeq (protein) NP_002072 NP_057905 Location (UCSC) Chr 2: 240.44 – 240.47 Mb Chr 1: 92.76 – 92.79 Mb PubMed search [3] [4]
Wikidata
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Function

Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with three heparan sulfate chains.^[7] Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation.^[6]

Interactions

Glypican 1 has been shown to interact with SLIT2.^[8]

Clinical significance

This protein is involved in the misfolding of normal prion proteins in the cell membrane to the infectious prion form.^[9]

In 2015 it was reported that the presence of this protein in exosomes in patients' blood is able to detect early pancreatic cancer with absolute specificity and sensitivity.^[10] However this conclusion is disputed.^[11] and in more recent overviews of potential markers for pancreatic cancer, Glypican 1 is not mentioned.^[12][13]

Therapeutic antibodies against GPC1 have been developed.^{[14][15][16][17]} GPC1 has been evaluated as a potential target for cancer therapy,^[7] including antibody-drug conjugates,^[18] CAR-T cell therapy,^[16][15][17] radiotherapy,^[19] bispecific T cell engager^[20] and immunotoxins^[14] 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 (Bethesda, US).^[17] The Ho lab also produced a dromedary camel V_HH nanobody called D4 specific for GPC1.^[17]The D4 V_HH nanobody-based CAR-T cells^[17] and immunotoxins^[14] were active against pancreatic cancer in mice. Miltuximab, a chimeric antibody against GPC1, was tested in radioimmunotherapy models of prostate cancer.^[21]

See also

• Glypican