Atlas of Genetics and Cytogenetics in Oncology and Haematology

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EXT2

Identity

HGNC (Hugo) EXT2
Location 11p11-p12
Location_base_pair Starts at 44073675 and ends at 44223556 bp from pter ( according to hg18-Mar_2006)  [Mapping]
 
  EXT2 (11p12) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

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
    Entrez_Gene (NCBI)EXT2  2132  exostoses (multiple) 2
    Cards
    AtlasEXT2ID213
    GeneCards (Weizmann)EXT2
    Ensembl (Hinxton)ENSG00000151348 [Gene_View]  EXT2 [Vega]
    AceView (NCBI)EXT2
    Genatlas (Paris)EXT2
    euGene (Indiana)2132
    SOURCE (Stanford)NM_000401 NM_207122
    Genomic and cartography
    GoldenPath (UCSC)EXT2  -     chr11:44073675-44223556 +  11p12-p11   [Description]    (hg18-Mar_2006)
    EnsemblEXT2 - 11p12-p11 [CytoView]
    Mapping of homologs : NCBIEXT2 [Mapview]
    OMIM133701   608210   
    Gene and transcription
    Gene : Genbank (Entrez)AK296713 AK309459 AK312375 BC010058 BC013050
    Reference sequence (RefSeq transcript) :SRSNM_000401 NM_207122
    Reference transcript : EntrezNM_000401 NM_207122
    RefSeq genomic : SRSAC_000054 AC_000143 NC_000011 NG_007560 NT_009237 NW_001838022 NW_925006
    RefSeq genomic : EntrezAC_000054 AC_000143 NC_000011 NG_007560 NT_009237 NW_001838022 NW_925006
    Consensus coding sequences : CCDS NCBIEXT2
    Cluster EST : UnigeneHs.368404 [ SRS ] Hs.368404 [ NCBI ]
    Alternative Splicing : Fast-db (Paris)5338
    Protein : pattern, domain, 3D structure
    Protein : UniProt/SwissProtQ93063 (SRS) Q93063 (Expasy) Q93063 (Uniprot)
    With graphics : InterProQ93063
    Splice isoforms : VarSplice FASTAQ93063(VarSplice FASTA)
    Domains : Interpro (SRS)Exostosin    HexNAc_Trfase_a   
    Domains : Interpro (EBI)Exostosin    HexNAc_Trfase_a   
    Related proteins : CluSTrQ93063
    Domain families : Pfam SRSExostosin (PF03016)    EXTL2 (PF09258)   
    Domain families : Pfam SangerExostosin (PF03016)    EXTL2 (PF09258)   
    Domain families : Pfam NCBIpfam03016    pfam09258   
    Blocks (Seattle)Q93063
    Crystal structure of protein : PDB SRS
    Crystal structure of protein : PDBSum
    Crystal structure of protein : IMB
    Crystal structure of protein : PDB RSDB
    HPRD00599
    Protein Interaction databases
    DIP (DOE-UCLA)Q93063
    IntAct (EBI)Q93063
    Polymorphism : SNP, mutations, diseases
    Single Nucleotide Polymorphism (SNP) : dbSNP NCBIEXT2
    SNP : GeneSNP UtahEXT2
    SNP : HGBaseEXT2
    Genetic variants : HAPMAPEXT2
    Somatic Mutations in Cancer : COSMICEXT2 
    Mutations and Diseases : HGMDEXT2
    Hereditary diseases : OMIM133701    608210   
    Hereditary diseases : GENETests133701    608210   
    Diseases : Genetic AssociationEXT2
    General knowledge
    Homologs : HomoloGeneEXT2
    Homology/Alignments : Family Browser UCSCEXT2
    Phylogenetic Trees/Animal Genes : TreeFamEXT2
    Catalytic activity : Enzyme2.4.1.224 [ Enzyme-Expasy ]   2.4.1.224 [ Enzyme-SRS ]   2.4.1.224 [ IntEnz-EBI ]   2.4.1.224 [ BRENDA ]   2.4.1.224 [ KEGG ]   
    Chemical/Protein Interactions : CTD2132
    Keywords Ontology : AmiGOGolgi membrane  ossification  mesoderm formation  protein binding  endoplasmic reticulum  Golgi apparatus  glycosaminoglycan biosynthetic process  signal transduction  heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process  membrane  integral to membrane  cell differentiation  intrinsic to endoplasmic reticulum membrane  heparan sulfate N-acetylglucosaminyltransferase activity  protein homodimerization activity  negative regulation of cell cycle  protein heterodimerization activity  glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity  
    Keywords Ontology : EGO-EBIGolgi membrane  ossification  mesoderm formation  protein binding  endoplasmic reticulum  Golgi apparatus  glycosaminoglycan biosynthetic process  signal transduction  heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process  membrane  integral to membrane  cell differentiation  intrinsic to endoplasmic reticulum membrane  heparan sulfate N-acetylglucosaminyltransferase activity  protein homodimerization activity  negative regulation of cell cycle  protein heterodimerization activity  glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity  
    Pathways : BIOCARTA
    Pathways : KEGGHeparan sulfate biosynthesisGlycan structures - biosynthesis 1
    Other databases
    Probes
    ProbeCancer Cytogenetics (Bari)
    Probes : ImagenesEXT2 Related clones (RZPD - Berlin)
    Literature
    PubMed49 Pubmed reference(s) in Entrez
    PubGeneEXT2

    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. Atlas Genet Cytogenet Oncol Haematol. January 2000 .
    URL : http://AtlasGeneticsOncology.org/Genes/EXT2ID213.html
    Bovée JVMG . EXT2. Atlas Genet Cytogenet Oncol Haematol. March 2002 .
    URL : http://AtlasGeneticsOncology.org/Genes/EXT2ID213.html

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    indexed on : Sat Jun 27 16:41:21 CEST 2009
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