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EXT2 exostoses (multiple) 2

Identity

HGNC (Hugo) EXT2
LocusID (NCBI) 2132
Location 11p11.2
Location_base_pair Starts at 44117747 and ends at 44266980 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  EXT2 (11p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

DNA/RNA

 
Description Sixteen exons across the EXT2 locus were identified, two of which (1a and 1b) are alternatively spliced; spans approximately 108 kb of genomic DNA
Transcription 3.5 and 3.7 kb

Protein

Description 718 amino acids; 82.2 kDa
Expression mRNA is ubiquitously expressed. In mouse embryo's, a high level of expression of Ext2 mRNA has been found in developing limb buds and expression was demonstrated to be confined to the proliferating and prehypertrophic chondrocytes of the growth plate.
Localisation endoplasmic reticulum
Function
  • a tumour suppressor function is suggested; exostosin-2 (EXT2) is an endoplasmic reticulum localized type II transmembrane glycoprotein which together with exostosin-1 (EXT1) forms a Golgi-localized hetero-oligomeric complex that catalyzes heparan sulphate (HS) polymerization.
  • It is thus hypothesized that EXT controls HSPG synthesis and display at the cell surface, which in turn is involved in FGF and IHh/PTHrP signalling within the normal growth plate.
    • Homology human EXT1, EXTL1, EXTL2 and EXTL3, mouse Ext2

    Mutations

    Germinal germline mutations in EXT2 are causative for hereditary multiple exostoses, a heterogeneous autosomal dominant disorder; mutations include nucleotide substitutions (57%), small deletions (19%) and small insertions (24%), of which the majority is predicted to result in a truncated or non-functional protein
    Somatic no somatic mutations were found in 34 sporadic and hereditary osteochondromas and secondary peripheral chondrosarcomas tested

    Implicated in

    Entity hereditary multiple exostoses
    Prognosis the main complication in hereditary multiple exostoses is malignant transformation of an osteochondroma (exostosis) into chondrosarcoma, which is estimated to occur in 1-3% of the HME cases
    Cytogenetics 11p rearrangement was found in 1 sporadic osteochondroma (exostosis) using cytogenetic analysis; loss of heterozygosity at the EXT2 locus was absent in 14 osteochondromas
      

    External links

    Nomenclature
    HGNC (Hugo)EXT2   3513
    Cards
    AtlasEXT2ID213
    Entrez_Gene (NCBI)EXT2  2132  exostosin glycosyltransferase 2
    GeneCards (Weizmann)EXT2
    Ensembl (Hinxton)ENSG00000151348 [Gene_View]  chr11:44117747-44266980 [Contig_View]  EXT2 [Vega]
    AceView (NCBI)EXT2
    Genatlas (Paris)EXT2
    WikiGenes2132
    SOURCE (Princeton)NM_000401 NM_001178083 NM_207122
    Genomic and cartography
    GoldenPath (UCSC)EXT2  -  11p11.2   chr11:44117747-44266980 +  11p12-p11   [Description]    (hg19-Feb_2009)
    EnsemblEXT2 - 11p12-p11 [CytoView]
    Mapping of homologs : NCBIEXT2 [Mapview]
    OMIM133701   608210   
    Gene and transcription
    Genbank (Entrez)AK296713 AK309459 AK312375 BC010058 BC013050
    RefSeq transcript (Entrez)NM_000401 NM_001178083 NM_207122
    RefSeq genomic (Entrez)AC_000143 NC_000011 NC_018922 NG_007560 NT_009237 NW_001838022 NW_004929378
    Consensus coding sequences : CCDS (NCBI)EXT2
    Cluster EST : UnigeneHs.368404 [ NCBI ]
    CGAP (NCI)Hs.368404
    Alternative Splicing : Fast-db (Paris)GSHG0004777
    Alternative Splicing GalleryENSG00000151348
    Gene ExpressionEXT2 [ NCBI-GEO ]     EXT2 [ SEEK ]   EXT2 [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ93063 (Uniprot)
    NextProtQ93063  [Medical]
    With graphics : InterProQ93063
    Splice isoforms : SwissVarQ93063 (Swissvar)
    Catalytic activity : Enzyme2.4.1.224 [ Enzyme-Expasy ]   2.4.1.2242.4.1.224 [ IntEnz-EBI ]   2.4.1.224 [ BRENDA ]   2.4.1.224 [ KEGG ]   
    Domains : Interpro (EBI)Exostosin    Exostosin-2    HexNAc_Trfase_a   
    Related proteins : CluSTrQ93063
    Domain families : Pfam (Sanger)Exostosin (PF03016)    Glyco_transf_64 (PF09258)   
    Domain families : Pfam (NCBI)pfam03016    pfam09258   
    DMDM Disease mutations2132
    Blocks (Seattle)Q93063
    Human Protein AtlasENSG00000151348
    Peptide AtlasQ93063
    HPRD00599
    IPIIPI00004047   IPI00922132   IPI00942173   IPI00976549   IPI00953659   
    Protein Interaction databases
    DIP (DOE-UCLA)Q93063
    IntAct (EBI)Q93063
    FunCoupENSG00000151348
    BioGRIDEXT2
    InParanoidQ93063
    Interologous Interaction database Q93063
    IntegromeDBEXT2
    STRING (EMBL)EXT2
    Ontologies - Pathways
    Ontology : AmiGOGolgi membrane  ossification  mesoderm formation  endoplasmic reticulum  endoplasmic reticulum membrane  Golgi apparatus  carbohydrate metabolic process  glycosaminoglycan biosynthetic process  glycosaminoglycan biosynthetic process  protein glycosylation  signal transduction  acetylglucosaminyltransferase activity  heparan sulfate proteoglycan biosynthetic process  heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process  glucuronosyltransferase activity  integral to membrane  transferase activity, transferring glycosyl groups  cell differentiation  glycosaminoglycan metabolic process  intrinsic to endoplasmic reticulum membrane  cellular polysaccharide biosynthetic process  heparan sulfate N-acetylglucosaminyltransferase activity  protein homodimerization activity  small molecule metabolic process  protein heterodimerization activity  glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity  
    Ontology : EGO-EBIGolgi membrane  ossification  mesoderm formation  endoplasmic reticulum  endoplasmic reticulum membrane  Golgi apparatus  carbohydrate metabolic process  glycosaminoglycan biosynthetic process  glycosaminoglycan biosynthetic process  protein glycosylation  signal transduction  acetylglucosaminyltransferase activity  heparan sulfate proteoglycan biosynthetic process  heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process  glucuronosyltransferase activity  integral to membrane  transferase activity, transferring glycosyl groups  cell differentiation  glycosaminoglycan metabolic process  intrinsic to endoplasmic reticulum membrane  cellular polysaccharide biosynthetic process  heparan sulfate N-acetylglucosaminyltransferase activity  protein homodimerization activity  small molecule metabolic process  protein heterodimerization activity  glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity  
    Pathways : KEGGGlycosaminoglycan biosynthesis - heparan sulfate / heparin   
    REACTOMEEXT2
    Protein Interaction DatabaseEXT2
    Wikipedia pathwaysEXT2
    Gene fusion - rearrangments
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)EXT2
    SNP (GeneSNP Utah)EXT2
    SNP : HGBaseEXT2
    Genetic variants : HAPMAPEXT2
    1000_GenomesEXT2 
    ICGC programENSG00000151348 
    Cancer Gene: CensusEXT2 
    Somatic Mutations in Cancer : COSMICEXT2 
    CONAN: Copy Number AnalysisEXT2 
    Mutations and Diseases : HGMDEXT2
    OMIM133701    608210   
    GENETestsEXT2
    Disease Genetic AssociationEXT2
    Huge Navigator EXT2 [HugePedia]  EXT2 [HugeCancerGEM]
    Genomic VariantsEXT2  EXT2 [DGVbeta]
    Exome VariantEXT2
    dbVarEXT2
    ClinVarEXT2
    snp3D : Map Gene to Disease2132
    General knowledge
    Homologs : HomoloGeneEXT2
    Homology/Alignments : Family Browser (UCSC)EXT2
    Phylogenetic Trees/Animal Genes : TreeFamEXT2
    Chemical/Protein Interactions : CTD2132
    Chemical/Pharm GKB GenePA27925
    Clinical trialEXT2
    Cancer Resource (Charite)ENSG00000151348
    Other databases
    Probes
    ProbeCancer Cytogenetics (Bari)
    Litterature
    PubMed87 Pubmed reference(s) in Entrez
    CoreMineEXT2
    iHOPEXT2

    Bibliography

    Genetic heterogeneity in families with hereditary multiple exostoses.
    Cook A, Raskind W, Blanton SH, Pauli RM, Gregg RG, Francomano CA, Puffenberger E, Conrad EU, Schmale G, Schellenberg G
    American journal of human genetics. 1993 ; 53 (1) : 71-79.
    PMID 8317501
     
    Assignment of a second locus for multiple exostoses to the pericentromeric region of chromosome 11.
    Wu YQ, Heutink P, de Vries BB, Sandkuijl LA, van den Ouweland AM, Niermeijer MF, Galjaard H, Reyniers E, Willems PJ, Halley DJ
    Human molecular genetics. 1994 ; 3 (1) : 167-171.
    PMID 8162019
     
    Hereditary multiple exostosis and chondrosarcoma: linkage to chromosome II and loss of heterozygosity for EXT-linked markers on chromosomes II and 8.
    Hecht JT, Hogue D, Strong LC, Hansen MF, Blanton SH, Wagner M
    American journal of human genetics. 1995 ; 56 (5) : 1125-1131.
    PMID 7726168
     
    Loss of heterozygosity in chondrosarcomas for markers linked to hereditary multiple exostoses loci on chromosomes 8 and 11.
    Raskind WH, Conrad EU, Chansky H, Matsushita M
    American journal of human genetics. 1995 ; 56 (5) : 1132-1139.
    PMID 7726169
     
    Refinement of the multiple exostoses locus (EXT2) to a 3-cM interval on chromosome 11.
    Wuyts W, Ramlakhan S, Van Hul W, Hecht JT, van den Ouweland AM, Raskind WH, Hofstede FC, Reyniers E, Wells DE, de Vries B
    American journal of human genetics. 1995 ; 57 (2) : 382-387.
    PMID 7668264
     
    The EXT2 multiple exostoses gene defines a family of putative tumour suppressor genes.
    Stickens D, Clines G, Burbee D, Ramos P, Thomas S, Hogue D, Hecht JT, Lovett M, Evans GA
    Nature genetics. 1996 ; 14 (1) : 25-32.
    PMID 8782816
     
    Positional cloning of a gene involved in hereditary multiple exostoses.
    Wuyts W, Van Hul W, Wauters J, Nemtsova M, Reyniers E, Van Hul EV, De Boulle K, de Vries BB, Hendrickx J, Herrygers I, Bossuyt P, Balemans W, Fransen E, Vits L, Coucke P, Nowak NJ, Shows TB, Mallet L, van den Ouweland AM, McGaughran J, Halley DJ, Willems PJ
    Human molecular genetics. 1996 ; 5 (10) : 1547-1557.
    PMID 8894688
     
    The structure of the human multiple exostoses 2 gene and characterization of homologs in mouse and Caenorhabditis elegans.
    Clines GA, Ashley JA, Shah S, Lovett M
    Genome research. 1997 ; 7 (4) : 359-367.
    PMID 9110175
     
    Isolation and characterization of the murine homolog of the human EXT2 multiple exostoses gene.
    Stickens D, Evans GA
    Biochemical and molecular medicine. 1997 ; 61 (1) : 16-21.
    PMID 9232192
     
    Clonal karyotypic abnormalities of the hereditary multiple exostoses chromosomal loci 8q24.1 (EXT1) and 11p11-12 (EXT2) in patients with sporadic and hereditary osteochondromas.
    Bridge JA, Nelson M, Orndal C, Bhatia P, Neff JR
    Cancer. 1998 ; 82 (9) : 1657-1663.
    PMID 9576285
     
    The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate.
    Lind T, Tufaro F, McCormick C, Lindahl U, Lidholt K
    The Journal of biological chemistry. 1998 ; 273 (41) : 26265-26268.
    PMID 9756849
     
    Loss of heterozygosity and DNA ploidy point to a diverging genetic mechanism in the origin of peripheral and central chondrosarcoma.
    Bovˆ©e JV, Cleton-Jansen AM, Kuipers-Dijkshoorn NJ, van den Broek LJ, Taminiau AH, Cornelisse CJ, Hogendoorn PC
    Genes, chromosomes & cancer. 1999 ; 26 (3) : 237-246.
    PMID 10502322
     
    EXT-mutation analysis and loss of heterozygosity in sporadic and hereditary osteochondromas and secondary chondrosarcomas.
    Bovˆ©e JV, Cleton-Jansen AM, Wuyts W, Caethoven G, Taminiau AH, Bakker E, Van Hul W, Cornelisse CJ, Hogendoorn PC
    American journal of human genetics. 1999 ; 65 (3) : 689-698.
    PMID 10441575
     
    The tumor suppressor EXT-like gene EXTL2 encodes an alpha1, 4-N-acetylhexosaminyltransferase that transfers N-acetylgalactosamine and N-acetylglucosamine to the common glycosaminoglycan-protein linkage region. The key enzyme for the chain initiation of heparan sulfate.
    Kitagawa H, Shimakawa H, Sugahara K
    The Journal of biological chemistry. 1999 ; 274 (20) : 13933-13937.
    PMID 10318803
     
    New perspectives on the molecular basis of hereditary bone tumours.
    McCormick C, Duncan G, Tufaro F
    Molecular medicine today. 1999 ; 5 (11) : 481-486.
    PMID 10529789
     
    A direct interaction between EXT proteins and glycosyltransferases is defective in hereditary multiple exostoses.
    Simmons AD, Musy MM, Lopes CS, Hwang LY, Yang YP, Lovett M
    Human molecular genetics. 1999 ; 8 (12) : 2155-2164.
    PMID 10545594
     
    A direct interaction between EXT proteins and glycosyltransferases is defective in hereditary multiple exostoses.
    Simmons AD, Musy MM, Lopes CS, Hwang LY, Yang YP, Lovett M
    Human molecular genetics. 1999 ; 8 (12) : 2155-2164.
    PMID 10545594
     
    EXT genes are differentially expressed in bone and cartilage during mouse embryogenesis.
    Stickens D, Brown D, Evans GA
    Developmental dynamics : an official publication of the American Association of Anatomists. 2000 ; 218 (3) : 452-464.
    PMID 10878610
     
    Molecular basis of multiple exostoses: mutations in the EXT1 and EXT2 genes.
    Wuyts W, Van Hul W
    Human mutation. 2000 ; 15 (3) : 220-227.
    PMID 10679937
     
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    Contributor(s)

    Written01-2000Judith VMG Bovée
    Updated03-2002Judith VMG Bovée

    Citation

    This paper should be referenced as such :
    Bovée JVMG . EXT2 exostoses (multiple) 2. Atlas Genet Cytogenet Oncol Haematol. January 2000 .
    Bovée JVMG . EXT2 exostoses (multiple) 2. Atlas Genet Cytogenet Oncol Haematol. March 2002 .
    URL : http://AtlasGeneticsOncology.org/Genes/EXT2ID213.html

    The various updated versions of this paper are referenced and archived by INIST as such :
    http://documents.irevues.inist.fr/bitstream/2042/37576/1/01-2000-EXT2ID213.pdf   [ Bibliographic record ]
    http://documents.irevues.inist.fr/bitstream/2042/37861/1/03-2002-EXT2ID213.pdf   [ Bibliographic record ]

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    indexed on : Fri Apr 18 17:36:33 CEST 2014
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