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GPC5 (glypican 5)

Written2010-11Khin Thway, Joanna Selfe, Janet Shipley
Molecular Cytogenetics, Section of Molecular Carcinogenesis, the Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, United Kingdom

(Note : for Links provided by Atlas : click)

Identity

Other alias
HGNC (Hugo) GPC5
LocusID (NCBI) 2262
Atlas_Id 45705
Location 13q31.3  [Link to chromosome band 13q31]
Location_base_pair Starts at 92050873 and ends at 93519487 bp from pter ( according to hg19-Feb_2009)  [Mapping GPC5.png]
Local_order Centromere - MIR17HG - GPC5 - GPC6 - DCT - TGDS - GPR180 - SOX21 - telomere.
Fusion genes
(updated 2016)
GAS6 (13q34) / GPC5 (13q31.3)GPC5 (13q31.3) / CDYL (6p25.1)GPC5 (13q31.3) / GPC5 (13q31.3)
GPC6 (13q31.3) / GPC5 (13q31.3)MYO10 (5p15.1) / GPC5 (13q31.3)

DNA/RNA

Note The gene spans 1.47 Mb of DNA, comprising 8 exons.
Transcription 2.904 kb mRNA. 1718 bp open reading frame.

Protein

Description 572 amino acids; 64 kDa protein (core protein). GPC5 is a heparan sulfate proteoglycan (HSPG), that is bound to the cell surface by a glycosyl-phosphatidylinositol (GPI) anchor.
Expression GPC5 is expressed mainly in fetal tissues, including brain, lung and liver. In the adult, expression is primarily in brain tissue.
Localisation Attached to the cell membrane by a GPI anchor.
 
  Schematic of glypican protein structure at the cell surface. The protein is held in the plasma membrane by a GPI anchor at the carboxyl terminus. Numerous glycosoaminoglycan (GAG) attachment sites close to the membrane surface allow heparin and chondroitin sulphate chains to be attached to the core protein (shown in green). The amino terminal end of the protein is a globular structure held together by a conserved set of cysteine residues forming disulphide bridges. (Picture reproduced from Filmus and Selleck, 2001).
Function The precise functions of GPC5 have yet to be fully established. HSPGs are common constituents of cell surfaces and the extracellular matrix (ECM), with essential functions in cell growth and development (Burgess and Macaig, 1989; Andres et al., 1992). Glypicans appear to be expressed predominantly during development, with expression levels changing in a stage- and tissue-specific manner, suggesting their involvement in morphogenesis (Sing and Filmus, 2002). As they can bind numerous ligands and be associated with a variety of receptors, they act as co-receptors for a number of heparin-binding growth factors, modulating their activity. The heparan sulfate modifications of glypicans can mediate interactions with growth factors or ECM proteins, but ligands and ECM proteins can also bind through motifs in the core proteins (Mythreye and Blobe, 2009). Glypicans can be secreted from the cell surface, such soluble forms can also bind growth factors. Evidence to date suggests that glypicans can regulate Wnt, hedgehog, fibroblast growth factor and bone morphogenetic protein pathways. The effect on these pathways may be stimulatory or inhibitory depending on cellular context (Gallet et al., 2008; Capurro et al., 2008; Kreuger et al., 2004; Yan and Lin, 2007; Grisaru et al., 2001; Yan et al., 2010).
GPC5 expression has been shown in the developing central nervous system, limbs and kidneys of mice, and its expression in mammalian fetal tissues suggests roles in growth and differentiation during development (Veugelers et al., 1997; Saunders et al., 1997; Luxardi et al., 2007). Its almost exclusive expression in adult brain tissue suggests a possible role in controlling neurotropic factors and maintaining neural function.
Homology GPC5 is a member of the glypican family of HSPGs, of which six members (GPC1, GPC2, GPC3, GPC4, GPC5, GPC6) have been identified in mammals. GPC3 is the most homologous member to GPC5 in humans. There is approximately 20-60% sequence homology between family members, including conservation of a pattern of 14 cysteine residues. Homolog glypican-like genes are also present in Drosophila (dally and dally-like).

Implicated in

Note
  
Entity Tumourigenesis
Note Amplification of 13q31-32 has been shown in poor prognosis liposarcomas, breast cancers and neurologic tumours (Reardon et al., 2000; Ojopi et al., 2001; Ullmann et al., 2001; Schmidt et al., 2005). Amplification of 13q31-32 has also been shown in approximately 20% of alveolar rhabdomyosarcoma, as well as gain of GPC5 copies in both alveolar and embryonal rhabdomyosarcoma (Gordon et al., 2000). GPC5 is overexpressed in the majority of rhabdomyosarcomas compared with normal skeletal muscle and has been shown to modulate responses to FGF2 in rhabdomyosarcoma cells (Williamson et al., 2007). GPC5 may also potentiate hedgehog signalling in these cells as it can bind to both Hedgehog and the Patched receptor (Li et al., 2010a). A recent genome wide association study has linked polymorphisms in GPC5 to risk of lung cancer in never-smokers (Li et al., 2010b). The high-risk allele was coincident with lower expression of GPC5, suggesting that the role of GPC5 is likely to be tumour type-specific in an analogous manner to GPC3, the closest family member to GPC5.
  
  
Entity Developmental disorders
Note Studies on the role of GPC5 in disease are still relatively limited. In humans, deletions of the 13q31-32 region are associated with the 13q deletion syndrome, a developmental disorder with a wide phenotypic spectrum including mental and growth retardation, congenital defects and craniofacial dysmorphy, and GPC5 is suggested as a candidate gene for digital malformations in this syndrome (Quelin et al., 2009). Correspondingly, GPC5 is also a candidate gene for postaxial polydactyly type A2, which is associated with duplication of 13q31-32 (van der Zwaag et al., 2010).
  
  
Entity Multiple sclerosis
Note Several genome wide association studies have identified GPC5 as having a potential role in Multiple Sclerosis (MS) (Baranzini et al., 2009; Lorentzen et al., 2010). Several different GPC5 polymorphisms were also highlighted in an independent study designed to determine which genes are associated with efficacy of interferon beta therapy in MS (Byun et al., 2008), this finding has subsequently been confirmed in a separate study (Cenit et al., 2009). HSPGs are found in dense networks in active MS plaques, where they may sequester pro-inflammatory cytokines.
  

Bibliography

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Andres JL, DeFalcis D, Noda M, Massague J.
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PMID 1556106
 
Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis.
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The heparin-binding (fibroblast) growth factor family of proteins.
Burgess WH, Maciag T.
Annu Rev Biochem. 1989;58:575-606. (REVIEW)
PMID 2549857
 
Genome-wide pharmacogenomic analysis of the response to interferon beta therapy in multiple sclerosis.
Byun E, Caillier SJ, Montalban X, Villoslada P, Fernandez O, Brassat D, Comabella M, Wang J, Barcellos LF, Baranzini SE, Oksenberg JR.
Arch Neurol. 2008 Mar;65(3):337-44. Epub 2008 Jan 14.
PMID 18195134
 
Glypican-3 inhibits Hedgehog signaling during development by competing with patched for Hedgehog binding.
Capurro MI, Xu P, Shi W, Li F, Jia A, Filmus J.
Dev Cell. 2008 May;14(5):700-11.
PMID 18477453
 
Glypican 5 is an interferon-beta response gene: a replication study.
Cenit MD, Blanco-Kelly F, de las Heras V, Bartolome M, de la Concha EG, Urcelay E, Arroyo R, Martinez A.
Mult Scler. 2009 Aug;15(8):913-7. Epub 2009 Jun 25.
PMID 19556317
 
Glypicans: proteoglycans with a surprise.
Filmus J, Selleck SB.
J Clin Invest. 2001 Aug;108(4):497-501. (REVIEW)
PMID 11518720
 
Cellular trafficking of the glypican Dally-like is required for full-strength Hedgehog signaling and wingless transcytosis.
Gallet A, Staccini-Lavenant L, Therond PP.
Dev Cell. 2008 May;14(5):712-25.
PMID 18477454
 
A novel and consistent amplicon at 13q31 associated with alveolar rhabdomyosarcoma.
Gordon AT, Brinkschmidt C, Anderson J, Coleman N, Dockhorn-Dworniczak B, Pritchard-Jones K, Shipley J.
Genes Chromosomes Cancer. 2000 Jun;28(2):220-6.
PMID 10825007
 
Glypican-3 modulates BMP- and FGF-mediated effects during renal branching morphogenesis.
Grisaru S, Cano-Gauci D, Tee J, Filmus J, Rosenblum ND.
Dev Biol. 2001 Mar 1;231(1):31-46.
PMID 11180950
 
Opposing activities of Dally-like glypican at high and low levels of Wingless morphogen activity.
Kreuger J, Perez L, Giraldez AJ, Cohen SM.
Dev Cell. 2004 Oct;7(4):503-12.
PMID 15469839
 
Glypican-5 stimulates rhabdomyosarcoma cell proliferation by activating hedgehog signaling.
Li FE, Shi W, Capurro M, Filmus J.
Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; 2010a. Abstract no. 3191.
 
Genetic variants and risk of lung cancer in never smokers: a genome-wide association study.
Li Y, Sheu CC, Ye Y, de Andrade M, Wang L, Chang SC, Aubry MC, Aakre JA, Allen MS, Chen F, Cunningham JM, Deschamps C, Jiang R, Lin J, Marks RS, Pankratz VS, Su L, Li Y, Sun Z, Tang H, Vasmatzis G, Harris CC, Spitz MR, Jen J, Wang R, Zhang ZF, Christiani DC, Wu X, Yang P.
Lancet Oncol. 2010b Apr;11(4):321-30. Epub 2010 Mar 19.
PMID 20304703
 
Association to the Glypican-5 gene in multiple sclerosis.
Lorentzen AR, Melum E, Ellinghaus E, Smestad C, Mero IL, Aarseth JH, Myhr KM, Celius EG, Lie BA, Karlsen TH, Franke A, Harbo HF.
J Neuroimmunol. 2010 Sep 14;226(1-2):194-7. Epub 2010 Aug 6.
PMID 20692050
 
Glypicans are differentially expressed during patterning and neurogenesis of early mouse brain.
Luxardi G, Galli A, Forlani S, Lawson K, Maina F, Dono R.
Biochem Biophys Res Commun. 2007 Jan 5;352(1):55-60. Epub 2006 Nov 10.
PMID 17107664
 
Proteoglycan signaling co-receptors: roles in cell adhesion, migration and invasion.
Mythreye K, Blobe GC.
Cell Signal. 2009 Nov;21(11):1548-58. Epub 2009 May 8. (REVIEW)
PMID 19427900
 
Comparative genomic hybridization detects novel amplifications in fibroadenomas of the breast.
Ojopi EP, Rogatto SR, Caldeira JR, Barbieri-Neto J, Squire JA.
Genes Chromosomes Cancer. 2001 Jan;30(1):25-31.
PMID 11107172
 
Twelve new patients with 13q deletion syndrome: genotype-phenotype analyses in progress.
Quelin C, Bendavid C, Dubourg C, de la Rochebrochard C, Lucas J, Henry C, Jaillard S, Loget P, Loeuillet L, Lacombe D, Rival JM, David V, Odent S, Pasquier L.
Eur J Med Genet. 2009 Jan-Feb;52(1):41-6. Epub 2008 Oct 31.
PMID 19022413
 
Multiple genomic alterations including N-myc amplification in a primary large cell medulloblastoma.
Reardon DA, Jenkins JJ, Sublett JE, Burger PC, Kun LK.
Pediatr Neurosurg. 2000 Apr;32(4):187-91.
PMID 10940769
 
Expression of the cell surface proteoglycan glypican-5 is developmentally regulated in kidney, limb, and brain.
Saunders S, Paine-Saunders S, Lander AD.
Dev Biol. 1997 Oct 1;190(1):78-93.
PMID 9331333
 
Gains of 13q are correlated with a poor prognosis in liposarcoma.
Schmidt H, Bartel F, Kappler M, Wurl P, Lange H, Bache M, Holzhausen HJ, Taubert H.
Mod Pathol. 2005 May;18(5):638-44.
PMID 15540119
 
The role of glypicans in mammalian development.
Song HH, Filmus J.
Biochim Biophys Acta. 2002 Dec 19;1573(3):241-6. (REVIEW)
PMID 12417406
 
Chromosomal aberrations in a series of large-cell neuroendocrine carcinomas: unexpected divergence from small-cell carcinoma of the lung.
Ullmann R, Petzmann S, Sharma A, Cagle PT, Popper HH.
Hum Pathol. 2001 Oct;32(10):1059-63.
PMID 11679939
 
Characterization of glypican-5 and chromosomal localization of human GPC5, a new member of the glypican gene family.
Veugelers M, Vermeesch J, Reekmans G, Steinfeld R, Marynen P, David G.
Genomics. 1997 Feb 15;40(1):24-30.
PMID 9070915
 
Role for amplification and expression of glypican-5 in rhabdomyosarcoma.
Williamson D, Selfe J, Gordon T, Lu YJ, Pritchard-Jones K, Murai K, Jones P, Workman P, Shipley J.
Cancer Res. 2007 Jan 1;67(1):57-65.
PMID 17210683
 
Drosophila glypican Dally-like acts in FGF-receiving cells to modulate FGF signaling during tracheal morphogenesis.
Yan D, Lin X.
Dev Biol. 2007 Dec 1;312(1):203-16. Epub 2007 Sep 20.
PMID 17959166
 
The cell-surface proteins Dally-like and Ihog differentially regulate Hedgehog signaling strength and range during development.
Yan D, Wu Y, Yang Y, Belenkaya TY, Tang X, Lin X.
Development. 2010 Jun;137(12):2033-44.
PMID 20501592
 
An interstitial duplication of chromosome 13q31.3q32.1 further delineates the critical region for postaxial polydactyly type A2.
van der Zwaag PA, Dijkhuizen T, Gerssen-Schoorl KB, Colijn AW, Broens PM, Flapper BC, van Ravenswaaij-Arts CM.
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PMID 19941983
 

Citation

This paper should be referenced as such :
Thway, K ; Selfe, J ; Shipley, J
GPC5 (glypican 5)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(7):557-559.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/GPC5ID45705ch13q31.html


External links

Nomenclature
HGNC (Hugo)GPC5   4453
Cards
AtlasGPC5ID45705ch13q31
Entrez_Gene (NCBI)GPC5  2262  glypican 5
Aliases
GeneCards (Weizmann)GPC5
Ensembl hg19 (Hinxton)ENSG00000179399 [Gene_View]  chr13:92050873-93519487 [Contig_View]  GPC5 [Vega]
Ensembl hg38 (Hinxton)ENSG00000179399 [Gene_View]  chr13:92050873-93519487 [Contig_View]  GPC5 [Vega]
ICGC DataPortalENSG00000179399
TCGA cBioPortalGPC5
AceView (NCBI)GPC5
Genatlas (Paris)GPC5
WikiGenes2262
SOURCE (Princeton)GPC5
Genetics Home Reference (NIH)GPC5
Genomic and cartography
GoldenPath hg19 (UCSC)GPC5  -     chr13:92050873-93519487 +  13q32   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)GPC5  -     13q32   [Description]    (hg38-Dec_2013)
EnsemblGPC5 - 13q32 [CytoView hg19]  GPC5 - 13q32 [CytoView hg38]
Mapping of homologs : NCBIGPC5 [Mapview hg19]  GPC5 [Mapview hg38]
OMIM602446   
Gene and transcription
Genbank (Entrez)AF001462 AK312815 BC030584 BC039730 DB100549
RefSeq transcript (Entrez)NM_004466
RefSeq genomic (Entrez)NC_000013 NC_018924 NG_009370 NT_009952 NW_004929389
Consensus coding sequences : CCDS (NCBI)GPC5
Cluster EST : UnigeneHs.655675 [ NCBI ]
CGAP (NCI)Hs.655675
Alternative Splicing GalleryENSG00000179399
Gene ExpressionGPC5 [ NCBI-GEO ]   GPC5 [ EBI - ARRAY_EXPRESS ]   GPC5 [ SEEK ]   GPC5 [ MEM ]
Gene Expression Viewer (FireBrowse)GPC5 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2262
GTEX Portal (Tissue expression)GPC5
Protein : pattern, domain, 3D structure
UniProt/SwissProtP78333   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP78333  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP78333
Splice isoforms : SwissVarP78333
PhosPhoSitePlusP78333
Domaine pattern : Prosite (Expaxy)GLYPICAN (PS01207)   
Domains : Interpro (EBI)Glypican    Glypican-5    Glypican_CS   
Domain families : Pfam (Sanger)Glypican (PF01153)   
Domain families : Pfam (NCBI)pfam01153   
Conserved Domain (NCBI)GPC5
DMDM Disease mutations2262
Blocks (Seattle)GPC5
SuperfamilyP78333
Human Protein AtlasENSG00000179399
Peptide AtlasP78333
HPRD03902
IPIIPI00019180   
Protein Interaction databases
DIP (DOE-UCLA)P78333
IntAct (EBI)P78333
FunCoupENSG00000179399
BioGRIDGPC5
STRING (EMBL)GPC5
ZODIACGPC5
Ontologies - Pathways
QuickGOP78333
Ontology : AmiGOretinoid metabolic process  extracellular region  proteinaceous extracellular matrix  extracellular space  Golgi lumen  plasma membrane  integral component of plasma membrane  glycosaminoglycan biosynthetic process  glycosaminoglycan catabolic process  glycosaminoglycan metabolic process  anchored component of membrane  lysosomal lumen  heparan sulfate proteoglycan binding  
Ontology : EGO-EBIretinoid metabolic process  extracellular region  proteinaceous extracellular matrix  extracellular space  Golgi lumen  plasma membrane  integral component of plasma membrane  glycosaminoglycan biosynthetic process  glycosaminoglycan catabolic process  glycosaminoglycan metabolic process  anchored component of membrane  lysosomal lumen  heparan sulfate proteoglycan binding  
REACTOMEP78333 [protein]
REACTOME Pathways1971475 [pathway]   2022928 [pathway]   2024096 [pathway]   3560783 [pathway]   3560801 [pathway]   3656237 [pathway]   3656253 [pathway]   4420332 [pathway]   5362798 [pathway]   975634 [pathway]   
NDEx NetworkGPC5
Atlas of Cancer Signalling NetworkGPC5
Wikipedia pathwaysGPC5
Orthology - Evolution
OrthoDB2262
GeneTree (enSembl)ENSG00000179399
Phylogenetic Trees/Animal Genes : TreeFamGPC5
HOVERGENP78333
HOGENOMP78333
Homologs : HomoloGeneGPC5
Homology/Alignments : Family Browser (UCSC)GPC5
Gene fusions - Rearrangements
Fusion : MitelmanGAS6/GPC5 [13q34/13q31.3]  [t(13;13)(q31;q34)]  
Fusion : MitelmanGPC6/GPC5 [13q31.3/13q31.3]  [t(13;13)(q31;q31)]  
Fusion: TCGAGAS6 13q34 GPC5 13q31.3 LUAD
Fusion: TCGAGPC6 13q31.3 GPC5 13q31.3 HNSC KIRC PRAD
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerGPC5 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)GPC5
dbVarGPC5
ClinVarGPC5
1000_GenomesGPC5 
Exome Variant ServerGPC5
ExAC (Exome Aggregation Consortium)GPC5 (select the gene name)
Genetic variants : HAPMAP2262
Genomic Variants (DGV)GPC5 [DGVbeta]
DECIPHER (Syndromes)13:92050873-93519487  ENSG00000179399
CONAN: Copy Number AnalysisGPC5 
Mutations
ICGC Data PortalGPC5 
TCGA Data PortalGPC5 
Broad Tumor PortalGPC5
OASIS PortalGPC5 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICGPC5  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDGPC5
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch GPC5
DgiDB (Drug Gene Interaction Database)GPC5
DoCM (Curated mutations)GPC5 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)GPC5 (select a term)
intoGenGPC5
NCG5 (London)GPC5
Cancer3DGPC5(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602446   
Orphanet
MedgenGPC5
Genetic Testing Registry GPC5
NextProtP78333 [Medical]
TSGene2262
GENETestsGPC5
Huge Navigator GPC5 [HugePedia]
snp3D : Map Gene to Disease2262
BioCentury BCIQGPC5
ClinGenGPC5 (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD2262
Chemical/Pharm GKB GenePA28834
Clinical trialGPC5
Miscellaneous
canSAR (ICR)GPC5 (select the gene name)
Probes
Litterature
PubMed52 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineGPC5
EVEXGPC5
GoPubMedGPC5
iHOPGPC5
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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