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]

GPC1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

4ACR, 4AD7, 4BWE, 4YWT

Identifikatori
AliasiGPC1
Vanjski ID-jeviOMIM: 600395 MGI: 1194891 HomoloGene: 20477 GeneCards: GPC1
Lokacija gena (čovjek)
Hromosom 2 (čovjek)
Hrom.Hromosom 2 (čovjek)[1]
Hromosom 2 (čovjek)
Genomska lokacija za GPC1
Genomska lokacija za GPC1
Bend2q37.3Početak240,435,663 bp[1]
Kraj240,468,076 bp[1]
Lokacija gena (miš)
Hromosom 1 (miš)
Hrom.Hromosom 1 (miš)[2]
Hromosom 1 (miš)
Genomska lokacija za GPC1
Genomska lokacija za GPC1
Bend1|1 DPočetak92,759,367 bp[2]
Kraj92,788,501 bp[2]
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
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_002081

NM_016696

RefSeq (bjelančevina)

NP_002072

NP_057905

Lokacija (UCSC)Chr 2: 240.44 – 240.47 MbChr 1: 92.76 – 92.79 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Aminokiselinska sekvenca

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

1020304050
MELRARGWWLLCAAAALVACARGDPASKSRSCGEVRQIYGAKGFSLSDVP
QAEISGEHLRICPQGYTCCTSEMEENLANRSHAELETALRDSSRVLQAML
ATQLRSFDDHFQHLLNDSERTLQATFPGAFGELYTQNARAFRDLYSELRL
YYRGANLHLEETLAEFWARLLERLFKQLHPQLLLPDDYLDCLGKQAEALR
PFGEAPRELRLRATRAFVAARSFVQGLGVASDVVRKVAQVPLGPECSRAV
MKLVYCAHCLGVPGARPCPDYCRNVLKGCLANQADLDAEWRNLLDSMVLI
TDKFWGTSGVESVIGSVHTWLAEAINALQDNRDTLTAKVIQGCGNPKVNP
QGPGPEEKRRRGKLAPRERPPSGTLEKLVSEAKAQLRDVQDFWISLPGTL
CSEKMALSTASDDRCWNGMARGRYLPEVMGDGLANQINNPEVEVDITKPD
MTIRQQIMQLKIMTNRLRSAYNGNDVDFQDASDDGSGSGSGDGCLDDLCS
RKVSRKSSSSRTPLTHALPGLSEQEGQKTSAASCPQPPTFLLPLLLFLAL
TVARPRWR

Funkcija

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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

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

Klinički značaj

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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

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Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000063660 - Ensembl, maj 2017
  2. ^ a b c 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.
  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.
  6. ^ a b c "Entrez Gene: GPC1 glypican 1".
  7. ^ 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).
  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.
  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.
  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
  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.
  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.
  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).

Dopunska literatura

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