EXT2

Identity

HGNC	EXT2
Location	11p11-p12
Location_base_pair	Starts at 44073675 and ends at 44223556 bp from pter ( according to hg18-Mar_2006).
	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	EXT2   3513
Entrez_Gene	EXT2  2132  exostoses (multiple) 2
	Cards
Atlas	EXT2ID213
GeneCards	EXT2
Ensembl	ENSG00000151348 [Gene_View]  EXT2 [Vega]
Genatlas	EXT2
	Genomic and cartography
GoldenPath	EXT2  -     chr11:44073675-44223556 +  11p12-p11   [Description]    (hg18-Mar_2006)
Ensembl	EXT2 - 11p12-p11 [CytoView]
NCBI	Mapview
OMIM	133701 Disease map [OMIM]
OMIM	608210 Disease map [OMIM]
HomoloGene	EXT2
	Gene and transcription
Genbank	AK309459 [ ENTREZ ]
Genbank	AK312375 [ ENTREZ ]
Genbank	BC010058 [ ENTREZ ]
Genbank	BC013050 [ ENTREZ ]
Genbank	BC068545 [ ENTREZ ]
RefSeq	NM_000401 [ SRS ]    NM_000401 [ ENTREZ ]
RefSeq	NM_207122 [ SRS ]    NM_207122 [ ENTREZ ]
RefSeq	AC_000054 [ SRS ]    AC_000054 [ ENTREZ ]
RefSeq	AC_000143 [ SRS ]    AC_000143 [ ENTREZ ]
RefSeq	NC_000011 [ SRS ]    NC_000011 [ ENTREZ ]
RefSeq	NG_007560 [ SRS ]    NG_007560 [ ENTREZ ]
RefSeq	NT_009237 [ SRS ]    NT_009237 [ ENTREZ ]
RefSeq	NW_001838022 [ SRS ]    NW_001838022 [ ENTREZ ]
RefSeq	NW_925006 [ SRS ]    NW_925006 [ ENTREZ ]
CCDS	EXT2 CCDS - NCBI
AceView	EXT2 AceView - NCBI
Unigene	Hs.368404 [ SRS ]    Hs.368404 [ NCBI ]
Fast-db	5338 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q6NUL1 [ SRS]    Q6NUL1 [ EXPASY ]     Q6NUL1 [ INTERPRO ]     Q6NUL1 [ UNIPROT ] Q6NUL1 [ VarSplice FASTA ]
Interpro	IPR004263 Exostosin [ SRS ]    IPR004263 Exostosin [ EBI ]
Interpro	IPR015338 HexNAc_Trfase_a [ SRS ]    IPR015338 HexNAc_Trfase_a [ EBI ]
CluSTr	Q6NUL1
Pfam	PF03016 Exostosin [ SRS ]    PF03016 Exostosin [ Sanger ]    pfam03016 [ NCBI-CDD ]
Pfam	PF09258 EXTL2 [ SRS ]    PF09258 EXTL2 [ Sanger ]    pfam09258 [ NCBI-CDD ]
Blocks	Q6NUL1
HPRD	00599
	Protein Interaction databases
DIP	Q6NUL1
IntAct	Q6NUL1
	Polymorphism : SNP, mutations, diseases
OMIM	133701    [ map ]
OMIM	608210    [ map ]
GENETests	133701
GENETests	608210
SNP	EXT2 [dbSNP-NCBI]
SNP	NM_000401 [SNP-NCI]
SNP	NM_207122 [SNP-NCI]
SNP	EXT2 [GeneSNPs - Utah]  EXT2] [HGBASE - SRS]
HAPMAP	EXT2 [HAPMAP]
COSMIC	EXT2 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	EXT2
Genetic Association	EXT2
CDC HuGE	EXT2
	General knowledge
Family Browser	EXT2 [UCSC Family Browser]
SOURCE	NM_000401
SOURCE	NM_207122
SMD	Hs.368404
SAGE	Hs.368404
GO	Golgi membrane [Amigo]  Golgi membrane
GO	ossification [Amigo]  ossification
GO	protein binding [Amigo]  protein binding
GO	endoplasmic reticulum [Amigo]  endoplasmic reticulum
GO	endoplasmic reticulum membrane [Amigo]  endoplasmic reticulum membrane
GO	Golgi apparatus [Amigo]  Golgi apparatus
GO	glycosaminoglycan biosynthetic process [Amigo]  glycosaminoglycan biosynthetic process
GO	signal transduction [Amigo]  signal transduction
GO	heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process [Amigo]  heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process
GO	membrane [Amigo]  membrane
GO	integral to membrane [Amigo]  integral to membrane
GO	transferase activity, transferring glycosyl groups [Amigo]  transferase activity, transferring glycosyl groups
GO	heparan sulfate N-acetylglucosaminyltransferase activity [Amigo]  heparan sulfate N-acetylglucosaminyltransferase activity
GO	protein homodimerization activity [Amigo]  protein homodimerization activity
GO	negative regulation of cell cycle [Amigo]  negative regulation of cell cycle
GO	protein heterodimerization activity [Amigo]  protein heterodimerization activity
GO	glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity [Amigo]  glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity
GO	N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity [Amigo]  N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity
KEGG	Heparan sulfate biosynthesis
KEGG	Glycan structures - biosynthesis 1
PubGene	EXT2
TreeFam	EXT2
CTD	2132 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	Cancer Cytogenetics (Bari)
Probe	EXT2 Related clones (RZPD - Berlin)
	PubMed
PubMed	48 Pubmed reference(s) in Entrez

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)

Written	01-2000	Judith VMG Bovée
Updated	03-2002	Judith 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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Thu Nov 27 13:22:40 2008