GPC1

GPC1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	4ACR, 4AD7, 4BWE, 4YWT
Identifikatori
Aliasi	GPC1
Vanjski ID-jevi	OMIM: 600395 MGI: 1194891 HomoloGene: 20477 GeneCards: GPC1
Lokacija gena (čovjek)
Hrom.	Hromosom 2 (čovjek)
Kraj	240,468,076 bp
Lokacija gena (miš)
Hrom.	Hromosom 1 (miš)
Kraj	92,788,501 bp
Ontologija gena
Molekularna funkcija	• fibroblast growth factor binding; • heparan sulfate proteoglycan binding; • copper ion binding; • laminin binding;
Ćelijska komponenta	• endozom; • membrana; • integral component of plasma membrane; • lysosomal lumen; • Golgi lumen; • Lipidni splav; • anchored component of membrane; • Egzosom; • Vanćelijsko; • nukleoplazma; • citosol; • ćelijska membrana; • GO:0005578 Vanćelijski matriks; • extracellular region; • intrinsic component of plasma membrane; • sinapsa; • anchored component of plasma membrane; • collagen-containing extracellular matrix; • cell surface;
Biološki proces	• 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; • Ćelijska migracija; • regulation of protein localization to membrane;
	Izvori:Amigo / QuickGO
Ortolozi
	2817
	14733
	ENSG00000063660
	ENSMUSG00000034220
	P35052
	Q9QZF2
	NM_002081
	NM_016696
	NP_002072
	NP_057905
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Glipikan-1 (GPC1) jest protein koji je kod ljudi kodiran genom GPC1 sa hromosoma 2, sekvenca q37.3.^[5]^[6]^[7] GPC1 sadrži 558 aminokiselina sa tri predviđena lanca heparan-sulfata.^[7]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 558 aminokiselina, a molekulska težina 61.680 Da.^[6]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MELRARGWWL	LCAAAALVAC	ARGDPASKSR	SCGEVRQIYG	AKGFSLSDVP
QAEISGEHLR	ICPQGYTCCT	SEMEENLANR	SHAELETALR	DSSRVLQAML
ATQLRSFDDH	FQHLLNDSER	TLQATFPGAF	GELYTQNARA	FRDLYSELRL
YYRGANLHLE	ETLAEFWARL	LERLFKQLHP	QLLLPDDYLD	CLGKQAEALR
PFGEAPRELR	LRATRAFVAA	RSFVQGLGVA	SDVVRKVAQV	PLGPECSRAV
MKLVYCAHCL	GVPGARPCPD	YCRNVLKGCL	ANQADLDAEW	RNLLDSMVLI
TDKFWGTSGV	ESVIGSVHTW	LAEAINALQD	NRDTLTAKVI	QGCGNPKVNP
QGPGPEEKRR	RGKLAPRERP	PSGTLEKLVS	EAKAQLRDVQ	DFWISLPGTL
CSEKMALSTA	SDDRCWNGMA	RGRYLPEVMG	DGLANQINNP	EVEVDITKPD
MTIRQQIMQL	KIMTNRLRSA	YNGNDVDFQD	ASDDGSGSGS	GDGCLDDLCS
RKVSRKSSSS	RTPLTHALPG	LSEQEGQKTS	AASCPQPPTF	LLPLLLFLAL
TVARPRWR

Funkcija[uredi | uredi izvor]

Površinski [[heparan-sulfat[]]ni proteoglikani sastoje se od proteinskog jezgra povezanog s membranom supstituiranog s tri lanca heparan-sulfata.^[7] Članovi porodice integralnih membranskih proteoglikana povezanih s glipikanom ( GRIPS) sadrže jezgarne proteine usidrene za citoplazmatsku membranu preko glikozil-fosfatidilinozitolne veze. Ovi proteini mogu imati ulogu u kontroli ćelijske diobe i regulaciji rasta.^[6]

Interakcije[uredi | uredi izvor]

Pokazalo se da glipikan 1 reaguje sa SLIT2.^[8]

Klinički značaj[uredi | uredi izvor]

Ovaj protein je uključen u pogrešno savijanje normalnih prionskih proteina u ćelijskoj membrani u infektivni prionski oblik.^[9]

2015. godine objavljeno je da prisustvo ovog proteina u egzozomima u krvi pacijenata može rano otkriti rak gušterače sa apsolutnom specifičnošću i osjetljivošću.^[10] Međutim, ovaj zaključak je sporan.^[11] and in more recent overviews of potential markers for pancreatic cancer, Glypican 1 is not mentioned.^[12]^[13]

GPC1 je ocijenjen kao potencijalna meta za terapiju raka,^[7] uključujući konjugate antitijela i lijekova,^[14] CAR-T ćelijsku terapiju,^[15]^[16]^[17] radioterapiju,^[18] bispecifični uključivač T-ćelija ^[19] o imunotoksine^[20] u pretkliničkim studijama.

Također pogledajte[uredi | uredi izvor]

Glipikan

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000063660 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000034220 - Ensembl, maj 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 (januar 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 ^c "Entrez Gene: GPC1 glypican 1".
^ ^a ^b ^c ^d Pan J, Ho M (septembar 2021). "The Role of Glypican-1 in Regulating Multiple Cellular Signaling Pathways". American Journal of Physiology. Cell Physiology. 321 (5): C846–C858. doi:10.1152/ajpcell.00290.2021. PMC 8616591 Provjerite vrijednost parametra |pmc= (pomoć). PMID 34550795 Provjerite vrijednost parametra |pmid= (pomoć).
^ 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 (novembar 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. (juli 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 (mart 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. (mart 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 (1. 7. 2019). "Abstract 2309: Chimeric antigen receptor T-cell therapy targeting glypican-1 in pancreatic cancer". Immunology. American Association for Cancer Research. 79 (13_Supplement): 2309. doi:10.1158/1538-7445.am2019-2309. S2CID 216597566.
^ Kato D, Yaguchi T, Iwata T, Katoh Y, Morii K, Tsubota K, et al. (mart 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, ured. (5. 9. 2019). "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. journal zahtijeva |journal= (pomoć)
^ Yeh MC, Tse BW, Fletcher NL, Houston ZH, Lund M, Volpert M, et al. (maj 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 (decembar 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.
^ Pan, Jiajia; Li, Nan; Renn, Alex; Zhu, Hu; Chen, Lu; Shen, Min; Hall, Matthew D.; Qian, Min; Pastan, Ira; Ho, Mitchell (1. 6. 2022). "GPC1-Targeted Immunotoxins Inhibit Pancreatic Tumor Growth in Mice via Depletion of Short-lived GPC1 and Downregulation of Wnt Signaling". Molecular Cancer Therapeutics. 21 (6): 960–973. doi:10.1158/1535-7163.MCT-21-0778. ISSN 1538-8514. PMC 9167738 Provjerite vrijednost parametra |pmc= (pomoć). PMID 35312769 Provjerite vrijednost parametra |pmid= (pomoć).

Dopunska literatura[uredi | uredi izvor]

Karthikeyan L, Maurel P, Rauch U, Margolis RK, Margolis RU (oktobar 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 (decembar 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 (januar 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 (oktobar 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 (novembar 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 (juni 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 (novembar 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. S2CID 43358048.
Matsuda K, Maruyama H, Guo F, Kleeff J, Itakura J, Matsumoto Y, et al. (juli 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 (septembar 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. (novembar 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 (juni 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, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000034220 - Ensembl, maj 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 (januar 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 (septembar 2021). "The Role of Glypican-1 in Regulating Multiple Cellular Signaling Pathways". American Journal of Physiology. Cell Physiology. 321 (5): C846–C858. doi:10.1152/ajpcell.00290.2021. PMC 8616591 Provjerite vrijednost parametra |pmc= (pomoć). PMID 34550795 Provjerite vrijednost parametra |pmid= (pomoć).

[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 (novembar 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. (juli 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 (mart 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. (mart 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 (1. 7. 2019). "Abstract 2309: Chimeric antigen receptor T-cell therapy targeting glypican-1 in pancreatic cancer". Immunology. American Association for Cancer Research. 79 (13_Supplement): 2309. doi:10.1158/1538-7445.am2019-2309. S2CID 216597566.

[pmid32228854-16] Kato D, Yaguchi T, Iwata T, Katoh Y, Morii K, Tsubota K, et al. (mart 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, ured. (5. 9. 2019). "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. journal zahtijeva |journal= (pomoć)

[18] Yeh MC, Tse BW, Fletcher NL, Houston ZH, Lund M, Volpert M, et al. (maj 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 (decembar 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.

[20] Pan, Jiajia; Li, Nan; Renn, Alex; Zhu, Hu; Chen, Lu; Shen, Min; Hall, Matthew D.; Qian, Min; Pastan, Ira; Ho, Mitchell (1. 6. 2022). "GPC1-Targeted Immunotoxins Inhibit Pancreatic Tumor Growth in Mice via Depletion of Short-lived GPC1 and Downregulation of Wnt Signaling". Molecular Cancer Therapeutics. 21 (6): 960–973. doi:10.1158/1535-7163.MCT-21-0778. ISSN 1538-8514. PMC 9167738 Provjerite vrijednost parametra |pmc= (pomoć). PMID 35312769 Provjerite vrijednost parametra |pmid= (pomoć).

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