Glypican 1

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
Gene location (Human)
Chr.	Chromosome 2 (human)
End	240,468,076 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	92,860,779 bp
RNA expression pattern
	Top expressed in
	left ventricle; ; tibia; ; tibial nerve;
	More reference expression data
	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; GO:0005578 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
	2817
	14733
	ENSG00000063660
	ENSMUSG00000034220
	P35052
	Q9QZF2
	NM_002081
	NM_016696
	NP_002072
	NP_057905
	Wikidata
View/Edit Human	View/Edit Mouse

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]

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]

GPC1 has been evaluated as a potential target for cancer therapy,^[7] including antibody-drug conjugates,^[14] CAR-T cell therapy,^[15]^[16]^[17] radiotherapy^[18] and bispecific T cell engager^[19] in preclinical studies.

References[]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000063660 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000034220 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Vermeesch JR, Mertens G, David G, Marynen P (January 1995). "Assignment of the human glypican gene (GPC1) to 2q35-q37 by fluorescence in situ hybridization". Genomics. 25 (1): 327–9. doi:10.1016/0888-7543(95)80152-C. PMID 7774946.
^ ^a ^b "Entrez Gene: GPC1 glypican 1".
^ ^a ^b ^c ^d Pan J, Ho M (September 2021). "The Role of Glypican-1 in Regulating Multiple Cellular Signaling Pathways". American Journal of Physiology. Cell Physiology. doi:10.1152/ajpcell.00290.2021. PMID 34550795.
^ Ronca F, Andersen JS, Paech V, Margolis RU (August 2001). "Characterization of Slit protein interactions with glypican-1". The Journal of Biological Chemistry. 276 (31): 29141–7. doi:10.1074/jbc.M100240200. PMID 11375980.
^ Taylor DR, Whitehouse IJ, Hooper NM (November 2009). "Glypican-1 mediates both prion protein lipid raft association and disease isoform formation". PLoS Pathogens. 5 (11): e1000666. doi:10.1371/journal.ppat.1000666. PMC 2773931. PMID 19936054.
^ Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, et al. (July 2015). "Glypican-1 identifies cancer exosomes and detects early pancreatic cancer". Nature. 523 (7559): 177–82. Bibcode:2015Natur.523..177M. doi:10.1038/nature14581. PMC 4825698. PMID 26106858.
^ Discussions at www.pubpeer.com; https://pubpeer.com/publications/70714D8ACB8F13164A2752B4335F38#fb119888
^ Balasenthil S, Huang Y, Liu S, Marsh T, Chen J, Stass SA, et al. (August 2017). "A Plasma Biomarker Panel to Identify Surgically Resectable Early-Stage Pancreatic Cancer". Journal of the National Cancer Institute. 109 (8). doi:10.1093/jnci/djw341. PMC 6059209. PMID 28376184.
^ Chang JC, Kundranda M (March 2017). "Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma". International Journal of Molecular Sciences. 18 (3): 667. doi:10.3390/ijms18030667. PMC 5372679. PMID 28335509.
^ Matsuzaki S, Serada S, Hiramatsu K, Nojima S, Matsuzaki S, Ueda Y, et al. (March 2018). "Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer". International Journal of Cancer. 142 (5): 1056–1066. doi:10.1002/ijc.31124. PMID 29055044.
^ Li N, Li D, Ren H, Torres M, Ho M (2019-07-01). "Abstract 2309: Chimeric antigen receptor T-cell therapy targeting glypican-1 in pancreatic cancer". Immunology. American Association for Cancer Research. doi:10.1158/1538-7445.am2019-2309.
^ Kato D, Yaguchi T, Iwata T, Katoh Y, Morii K, Tsubota K, et al. (March 2020). "GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 Ab". eLife. 9. doi:10.7554/eLife.49392. PMC 7108862. PMID 32228854.
^ Honjo T, Settleman J, eds. (2019-09-05). "Decision letter: GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 Ab". doi:10.7554/elife.49392.sa1. {{cite journal}}: Cite journal requires |journal= (help)
^ Yeh MC, Tse BW, Fletcher NL, Houston ZH, Lund M, Volpert M, et al. (May 2020). "Targeted beta therapy of prostate cancer with ¹⁷⁷Lu-labelled Miltuximab® antibody against glypican-1 (GPC-1)". EJNMMI Research. 10 (1): 46. doi:10.1186/s13550-020-00637-x. PMC 7206480. PMID 32382920.
^ Lund ME, Howard CB, Thurecht KJ, Campbell DH, Mahler SM, Walsh BJ (December 2020). "A bispecific T cell engager targeting Glypican-1 redirects T cell cytolytic activity to kill prostate cancer cells". BMC Cancer. 20 (1): 1214. doi:10.1186/s12885-020-07562-1. PMC 7727117. PMID 33302918.

Further reading[]

Karthikeyan L, Maurel P, Rauch U, Margolis RK, Margolis RU (October 1992). "Cloning of a major heparan sulfate proteoglycan from brain and identification as the rat form of glypican". Biochemical and Biophysical Research Communications. 188 (1): 395–401. doi:10.1016/0006-291X(92)92398-H. PMID 1417860.
David G, Lories V, Decock B, Marynen P, Cassiman JJ, Van den Berghe H (December 1990). "Molecular cloning of a phosphatidylinositol-anchored membrane heparan sulfate proteoglycan from human lung fibroblasts". The Journal of Cell Biology. 111 (6 Pt 2): 3165–76. doi:10.1083/jcb.111.6.3165. PMC 2116352. PMID 2148568.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Kleeff J, Ishiwata T, Kumbasar A, Friess H, Büchler MW, Lander AD, Korc M (November 1998). "The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer". The Journal of Clinical Investigation. 102 (9): 1662–73. doi:10.1172/JCI4105. PMC 509114. PMID 9802880.
Gengrinovitch S, Berman B, David G, Witte L, Neufeld G, Ron D (April 1999). "Glypican-1 is a VEGF165 binding proteoglycan that acts as an extracellular chaperone for VEGF165". The Journal of Biological Chemistry. 274 (16): 10816–22. doi:10.1074/jbc.274.16.10816. PMID 10196157.
Liang Y, Annan RS, Carr SA, Popp S, Mevissen M, Margolis RK, Margolis RU (June 1999). "Mammalian homologues of the Drosophila slit protein are ligands of the heparan sulfate proteoglycan glypican-1 in brain". The Journal of Biological Chemistry. 274 (25): 17885–92. doi:10.1074/jbc.274.25.17885. PMID 10364234.
Schofield KP, Gallagher JT, David G (November 1999). "Expression of proteoglycan core proteins in human bone marrow stroma". The Biochemical Journal. 343 (3): 663–8. doi:10.1042/0264-6021:3430663. PMC 1220599. PMID 10527946.
Karumanchi SA, Jha V, Ramchandran R, Karihaloo A, Tsiokas L, Chan B, et al. (April 2001). "Cell surface glypicans are low-affinity endostatin receptors". Molecular Cell. 7 (4): 811–22. doi:10.1016/S1097-2765(01)00225-8. PMID 11336704.
Matsuda K, Maruyama H, Guo F, Kleeff J, Itakura J, Matsumoto Y, et al. (July 2001). "Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells". Cancer Research. 61 (14): 5562–9. PMID 11454708.
Alvarez K, Fadic R, Brandan E (2002). "Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy". Journal of Cellular Biochemistry. 85 (4): 703–13. doi:10.1002/jcb.10184. hdl:10533/173369. PMID 11968010. S2CID 20243469.
Ding K, Mani K, Cheng F, Belting M, Fransson LA (September 2002). "Copper-dependent autocleavage of glypican-1 heparan sulfate by nitric oxide derived from intrinsic nitrosothiols". The Journal of Biological Chemistry. 277 (36): 33353–60. doi:10.1074/jbc.M203383200. PMID 12084716.
Belting M, Mani K, Jönsson M, Cheng F, Sandgren S, Jonsson S, et al. (November 2003). "Glypican-1 is a vehicle for polyamine uptake in mammalian cells: a pivital role for nitrosothiol-derived nitric oxide". The Journal of Biological Chemistry. 278 (47): 47181–9. doi:10.1074/jbc.M308325200. PMID 12972423.
Watanabe N, Araki W, Chui DH, Makifuchi T, Ihara Y, Tabira T (June 2004). "Glypican-1 as an Abeta binding HSPG in the human brain: its localization in DIG domains and possible roles in the pathogenesis of Alzheimer's disease". FASEB Journal. 18 (9): 1013–5. doi:10.1096/fj.03-1040fje. PMID 15084524. S2CID 83560098.
Li J, Kleeff J, Kayed H, Felix K, Penzel R, Büchler MW, et al. (August 2004). "Glypican-1 antisense transfection modulates TGF-beta-dependent signaling in Colo-357 pancreatic cancer cells". Biochemical and Biophysical Research Communications. 320 (4): 1148–55. doi:10.1016/j.bbrc.2004.06.063. PMID 15249209.
Davies EJ, Blackhall FH, Shanks JH, David G, McGown AT, Swindell R, et al. (August 2004). "Distribution and clinical significance of heparan sulfate proteoglycans in ovarian cancer". Clinical Cancer Research. 10 (15): 5178–86. doi:10.1158/1078-0432.CCR-03-0103. PMID 15297422.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000063660 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000034220 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Vermeesch_1995-5] Vermeesch JR, Mertens G, David G, Marynen P (January 1995). "Assignment of the human glypican gene (GPC1) to 2q35-q37 by fluorescence in situ hybridization". Genomics. 25 (1): 327–9. doi:10.1016/0888-7543(95)80152-C. PMID 7774946.

[entrez-6] "Entrez Gene: GPC1 glypican 1".

[Pan_2021-7] Pan J, Ho M (September 2021). "The Role of Glypican-1 in Regulating Multiple Cellular Signaling Pathways". American Journal of Physiology. Cell Physiology. doi:10.1152/ajpcell.00290.2021. PMID 34550795.

[pmid11375980-8] Ronca F, Andersen JS, Paech V, Margolis RU (August 2001). "Characterization of Slit protein interactions with glypican-1". The Journal of Biological Chemistry. 276 (31): 29141–7. doi:10.1074/jbc.M100240200. PMID 11375980.

[Taylor_2009-9] Taylor DR, Whitehouse IJ, Hooper NM (November 2009). "Glypican-1 mediates both prion protein lipid raft association and disease isoform formation". PLoS Pathogens. 5 (11): e1000666. doi:10.1371/journal.ppat.1000666. PMC 2773931. PMID 19936054.

[Melo_2015-10] Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, et al. (July 2015). "Glypican-1 identifies cancer exosomes and detects early pancreatic cancer". Nature. 523 (7559): 177–82. Bibcode:2015Natur.523..177M. doi:10.1038/nature14581. PMC 4825698. PMID 26106858.

[11] Discussions at www.pubpeer.com; https://pubpeer.com/publications/70714D8ACB8F13164A2752B4335F38#fb119888

[pmid28376184-12] Balasenthil S, Huang Y, Liu S, Marsh T, Chen J, Stass SA, et al. (August 2017). "A Plasma Biomarker Panel to Identify Surgically Resectable Early-Stage Pancreatic Cancer". Journal of the National Cancer Institute. 109 (8). doi:10.1093/jnci/djw341. PMC 6059209. PMID 28376184.

[pmid28335509-13] Chang JC, Kundranda M (March 2017). "Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma". International Journal of Molecular Sciences. 18 (3): 667. doi:10.3390/ijms18030667. PMC 5372679. PMID 28335509.

[14] Matsuzaki S, Serada S, Hiramatsu K, Nojima S, Matsuzaki S, Ueda Y, et al. (March 2018). "Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor activity against glypican-1 positive uterine cervical cancer". International Journal of Cancer. 142 (5): 1056–1066. doi:10.1002/ijc.31124. PMID 29055044.

[15] Li N, Li D, Ren H, Torres M, Ho M (2019-07-01). "Abstract 2309: Chimeric antigen receptor T-cell therapy targeting glypican-1 in pancreatic cancer". Immunology. American Association for Cancer Research. doi:10.1158/1538-7445.am2019-2309.

[pmid32228854-16] Kato D, Yaguchi T, Iwata T, Katoh Y, Morii K, Tsubota K, et al. (March 2020). "GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 Ab". eLife. 9. doi:10.7554/eLife.49392. PMC 7108862. PMID 32228854.

[17] Honjo T, Settleman J, eds. (2019-09-05). "Decision letter: GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 Ab". doi:10.7554/elife.49392.sa1. {{cite journal}}: Cite journal requires |journal= (help)

[18] Yeh MC, Tse BW, Fletcher NL, Houston ZH, Lund M, Volpert M, et al. (May 2020). "Targeted beta therapy of prostate cancer with ¹⁷⁷Lu-labelled Miltuximab® antibody against glypican-1 (GPC-1)". EJNMMI Research. 10 (1): 46. doi:10.1186/s13550-020-00637-x. PMC 7206480. PMID 32382920.

[19] Lund ME, Howard CB, Thurecht KJ, Campbell DH, Mahler SM, Walsh BJ (December 2020). "A bispecific T cell engager targeting Glypican-1 redirects T cell cytolytic activity to kill prostate cancer cells". BMC Cancer. 20 (1): 1214. doi:10.1186/s12885-020-07562-1. PMC 7727117. PMID 33302918.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]