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Protein

Exostosin-1

Gene

EXT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Glycosyltransferase required for the biosynthesis of heparan-sulfate. The EXT1/EXT2 complex possesses substantially higher glycosyltransferase activity than EXT1 or EXT2 alone. Appears to be a tumor suppressor. Required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413).2 Publications

Catalytic activityi

UDP-N-acetyl-D-glucosamine + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan = UDP + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-proteoglycan.
UDP-alpha-D-glucuronate + N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan = UDP + beta-D-glucuronosyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-(1->4)-beta-D-glucuronosyl-proteoglycan.

Cofactori

Mn2+By similarity

Pathwayi: protein glycosylation

This protein is involved in the pathway protein glycosylation, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein glycosylation and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei518SubstrateBy similarity1
Metal bindingi567Manganese; catalyticBy similarity1
Binding sitei595SubstrateBy similarity1
Active sitei654By similarity1

GO - Molecular functioni

  • acetylglucosaminyltransferase activity Source: BHF-UCL
  • glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity Source: UniProtKB
  • glucuronosyltransferase activity Source: BHF-UCL
  • heparan sulfate N-acetylglucosaminyltransferase activity Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity Source: UniProtKB
  • protein heterodimerization activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • transferase activity, transferring glycosyl groups Source: BHF-UCL

GO - Biological processi

  • axon guidance Source: Ensembl
  • cellular polysaccharide biosynthetic process Source: BHF-UCL
  • embryonic skeletal joint development Source: Ensembl
  • endoderm development Source: Ensembl
  • gastrulation Source: Ensembl
  • glycosaminoglycan biosynthetic process Source: BHF-UCL
  • heparan sulfate proteoglycan biosynthetic process Source: UniProtKB
  • heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process Source: BHF-UCL
  • mesoderm development Source: Ensembl
  • olfactory bulb development Source: Ensembl
  • ossification Source: BHF-UCL
  • protein glycosylation Source: UniProtKB-UniPathway
  • signal transduction Source: ProtInc
  • skeletal system development Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Glycosyltransferase, Transferase

Keywords - Ligandi

Manganese, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS00012-MONOMER.
ZFISH:HS00012-MONOMER.
BRENDAi2.4.1.224. 2681.
2.4.1.225. 2681.
ReactomeiR-HSA-2022928. HS-GAG biosynthesis.
SIGNORiQ16394.
UniPathwayiUPA00378.

Protein family/group databases

CAZyiGT47. Glycosyltransferase Family 47.
GT64. Glycosyltransferase Family 64.

Names & Taxonomyi

Protein namesi
Recommended name:
Exostosin-1 (EC:2.4.1.224, EC:2.4.1.225)
Alternative name(s):
Glucuronosyl-N-acetylglucosaminyl-proteoglycan/N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase
Multiple exostoses protein 1
Putative tumor suppressor protein EXT1
Gene namesi
Name:EXT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:3512. EXT1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 7CytoplasmicSequence analysis7
Transmembranei8 – 28Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini29 – 746LumenalSequence analysisAdd BLAST718

GO - Cellular componenti

  • endoplasmic reticulum Source: BHF-UCL
  • endoplasmic reticulum membrane Source: BHF-UCL
  • Golgi apparatus Source: BHF-UCL
  • Golgi membrane Source: BHF-UCL
  • integral component of endoplasmic reticulum membrane Source: UniProtKB
  • integral component of membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Hereditary multiple exostoses 1 (EXT1)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionEXT is a genetically heterogeneous bone disorder caused by genes segregating on human chromosomes 8, 11, and 19 and designated EXT1, EXT2 and EXT3 respectively. EXT is a dominantly inherited skeletal disorder primarily affecting endochondral bone during growth. The disease is characterized by formation of numerous cartilage-capped, benign bone tumors (osteocartilaginous exostoses or osteochondromas) that are often accompanied by skeletal deformities and short stature. In a small percentage of cases exostoses have exhibited malignant transformation resulting in an osteosarcoma or chondrosarcoma. Osteochondromas development can also occur as a sporadic event.
See also OMIM:133700
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01281527Q → K in EXT1; no loss of activity. 1
Natural variantiVAR_012816164D → H in EXT1; loss of activity. 1 Publication1
Natural variantiVAR_012817215 – 221Missing in EXT1. 7
Natural variantiVAR_002370280R → G in EXT1; loss of activity. 3 Publications1
Natural variantiVAR_002371280R → S in EXT1; loss of activity. 1 Publication1
Natural variantiVAR_002372339G → D in EXT1; loss of activity. 1 PublicationCorresponds to variant rs119103288dbSNPEnsembl.1
Natural variantiVAR_002373340R → C in EXT1; loss of activity; still able to form an oligomeric complex. 1 PublicationCorresponds to variant rs119103290dbSNPEnsembl.1
Natural variantiVAR_002374340R → H in EXT1; loss of activity. 2 PublicationsCorresponds to variant rs119103287dbSNPEnsembl.1
Natural variantiVAR_002375340R → L in EXT1; loss of activity. 1 PublicationCorresponds to variant rs119103287dbSNPEnsembl.1
Natural variantiVAR_002376340R → S in EXT1; loss of activity. 1 Publication1
Natural variantiVAR_012821486A → V in EXT1; no loss of activity. 1 PublicationCorresponds to variant rs188859975dbSNPEnsembl.1
Natural variantiVAR_012822496P → L in EXT1; no loss of activity. 1 Publication1
Natural variantiVAR_002377627Missing in EXT1; loss of activity. 1 Publication1
Tricho-rhino-phalangeal syndrome 2 (TRPS2)
The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration resulting in the loss of functional copies of TRPS1 and EXT1 has been found in TRPS2 patients.
Disease descriptionA syndrome that combines the clinical features of tricho-rhino-phalangeal syndrome type 1 and multiple exostoses type 1. Affected individuals manifest multiple dysmorphic facial features including large, laterally protruding ears, a bulbous nose, an elongated upper lip, as well as sparse scalp hair, winged scapulae, multiple cartilaginous exostoses, redundant skin, and mental retardation.
See also OMIM:150230
Chondrosarcoma (CHDSA)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA malignant neoplasm derived from cartilage cells. Chondrosarcomas range from slow-growing non-metastasizing lesions to highly aggressive metastasizing sarcomas.
See also OMIM:215300

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi27Q → A or P: No effect on heparan-sulfate biosynthesis. 1 Publication1
Mutagenesisi27Missing : No effect on heparan-sulfate biosynthesis. 1 Publication1
Mutagenesisi164D → E: Abolishes heparan-sulfate biosynthesis. 1 Publication1
Mutagenesisi164Missing : Abolishes heparan-sulfate biosynthesis. 1 Publication1
Mutagenesisi316N → A: No effect on heparan-sulfate biosynthesis. 1 Publication1
Mutagenesisi316Missing : No effect on heparan-sulfate biosynthesis. 1 Publication1
Mutagenesisi486A → H: No effect on heparan-sulfate biosynthesis. 1 Publication1
Mutagenesisi486Missing : No effect on heparan-sulfate biosynthesis. 1 Publication1
Mutagenesisi496P → H: No effect on heparan-sulfate biosynthesis. 1 Publication1
Mutagenesisi496Missing : No effect on heparan-sulfate biosynthesis. 1 Publication1

Keywords - Diseasei

Disease mutation, Hereditary multiple exostoses, Tumor suppressor

Organism-specific databases

DisGeNETi2131.
MalaCardsiEXT1.
MIMi133700. phenotype.
150230. phenotype.
215300. phenotype.
OpenTargetsiENSG00000182197.
Orphaneti55880. Chondrosarcoma.
502. Langer-Giedion syndrome.
321. Multiple osteochondromas.
PharmGKBiPA27924.

Polymorphism and mutation databases

BioMutaiEXT1.
DMDMi20141422.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001496481 – 746Exostosin-1Add BLAST746

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi89N-linked (GlcNAc...)Sequence analysis1
Glycosylationi330N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi652 ↔ 704By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ16394.
MaxQBiQ16394.
PaxDbiQ16394.
PeptideAtlasiQ16394.
PRIDEiQ16394.

PTM databases

iPTMnetiQ16394.
PhosphoSitePlusiQ16394.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000182197.
CleanExiHS_EXT1.
ExpressionAtlasiQ16394. baseline and differential.
GenevisibleiQ16394. HS.

Organism-specific databases

HPAiHPA044394.

Interactioni

Subunit structurei

Forms a homo/hetero-oligomeric complex with EXT2.1 Publication

GO - Molecular functioni

  • protein heterodimerization activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi108432. 23 interactors.
IntActiQ16394. 2 interactors.
MINTiMINT-120274.
STRINGi9606.ENSP00000367446.

Structurei

3D structure databases

ProteinModelPortaliQ16394.
SMRiQ16394.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni544 – 549Substrate bindingBy similarity6
Regioni565 – 567Substrate bindingBy similarity3
Regioni650 – 654Substrate bindingBy similarity5
Regioni688 – 701Substrate bindingBy similarityAdd BLAST14

Sequence similaritiesi

Belongs to the glycosyltransferase 47 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1021. Eukaryota.
ENOG410XTFH. LUCA.
GeneTreeiENSGT00550000074496.
HOGENOMiHOG000266990.
HOVERGENiHBG003459.
InParanoidiQ16394.
KOiK02366.
OMAiVTTCKHG.
OrthoDBiEOG091G0BDR.
PhylomeDBiQ16394.
TreeFamiTF314231.

Family and domain databases

Gene3Di3.90.550.10. 1 hit.
InterProiIPR004263. Exostosin.
IPR027670. Exostosin-1.
IPR015338. EXT_C.
IPR029044. Nucleotide-diphossugar_trans.
[Graphical view]
PANTHERiPTHR11062:SF97. PTHR11062:SF97. 2 hits.
PfamiPF03016. Exostosin. 1 hit.
PF09258. Glyco_transf_64. 1 hit.
[Graphical view]
SUPFAMiSSF53448. SSF53448. 1 hit.

Sequencei

Sequence statusi: Complete.

Q16394-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQAKKRYFIL LSAGSCLALL FYFGGLQFRA SRSHSRREEH SGRNGLHHPS
60 70 80 90 100
PDHFWPRFPD ALRPFVPWDQ LENEDSSVHI SPRQKRDANS SIYKGKKCRM
110 120 130 140 150
ESCFDFTLCK KNGFKVYVYP QQKGEKIAES YQNILAAIEG SRFYTSDPSQ
160 170 180 190 200
ACLFVLSLDT LDRDQLSPQY VHNLRSKVQS LHLWNNGRNH LIFNLYSGTW
210 220 230 240 250
PDYTEDVGFD IGQAMLAKAS ISTENFRPNF DVSIPLFSKD HPRTGGERGF
260 270 280 290 300
LKFNTIPPLR KYMLVFKGKR YLTGIGSDTR NALYHVHNGE DVVLLTTCKH
310 320 330 340 350
GKDWQKHKDS RCDRDNTEYE KYDYREMLHN ATFCLVPRGR RLGSFRFLEA
360 370 380 390 400
LQAACVPVML SNGWELPFSE VINWNQAAVI GDERLLLQIP STIRSIHQDK
410 420 430 440 450
ILALRQQTQF LWEAYFSSVE KIVLTTLEII QDRIFKHISR NSLIWNKHPG
460 470 480 490 500
GLFVLPQYSS YLGDFPYYYA NLGLKPPSKF TAVIHAVTPL VSQSQPVLKL
510 520 530 540 550
LVAAAKSQYC AQIIVLWNCD KPLPAKHRWP ATAVPVVVIE GESKVMSSRF
560 570 580 590 600
LPYDNIITDA VLSLDEDTVL STTEVDFAFT VWQSFPERIV GYPARSHFWD
610 620 630 640 650
NSKERWGYTS KWTNDYSMVL TGAAIYHKYY HYLYSHYLPA SLKNMVDQLA
660 670 680 690 700
NCEDILMNFL VSAVTKLPPI KVTQKKQYKE TMMGQTSRAS RWADPDHFAQ
710 720 730 740
RQSCMNTFAS WFGYMPLIHS QMRLDPVLFK DQVSILRKKY RDIERL
Length:746
Mass (Da):86,255
Last modified:March 27, 2002 - v2
Checksum:i842CD7E6C1312C1A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti60 – 61DA → EP (PubMed:7550340).Curated2
Sequence conflicti60 – 61DA → EP (Ref. 3) Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01281527Q → K in EXT1; no loss of activity. 1
Natural variantiVAR_012816164D → H in EXT1; loss of activity. 1 Publication1
Natural variantiVAR_012818215 – 222MLAKASIS → I in isolated osteochondroma; somatic mutation. 1 Publication8
Natural variantiVAR_012817215 – 221Missing in EXT1. 7
Natural variantiVAR_012819235 – 239Missing in multiple osteochondromas. 1 Publication5
Natural variantiVAR_002370280R → G in EXT1; loss of activity. 3 Publications1
Natural variantiVAR_002371280R → S in EXT1; loss of activity. 1 Publication1
Natural variantiVAR_012820316N → S in chondrosarcoma; no loss of activity. 1 Publication1
Natural variantiVAR_002372339G → D in EXT1; loss of activity. 1 PublicationCorresponds to variant rs119103288dbSNPEnsembl.1
Natural variantiVAR_002373340R → C in EXT1; loss of activity; still able to form an oligomeric complex. 1 PublicationCorresponds to variant rs119103290dbSNPEnsembl.1
Natural variantiVAR_002374340R → H in EXT1; loss of activity. 2 PublicationsCorresponds to variant rs119103287dbSNPEnsembl.1
Natural variantiVAR_002375340R → L in EXT1; loss of activity. 1 PublicationCorresponds to variant rs119103287dbSNPEnsembl.1
Natural variantiVAR_002376340R → S in EXT1; loss of activity. 1 Publication1
Natural variantiVAR_012821486A → V in EXT1; no loss of activity. 1 PublicationCorresponds to variant rs188859975dbSNPEnsembl.1
Natural variantiVAR_012822496P → L in EXT1; no loss of activity. 1 Publication1
Natural variantiVAR_002377627Missing in EXT1; loss of activity. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S79639 mRNA. Translation: AAB62283.1.
AK313129 mRNA. Translation: BAG35949.1.
CH471060 Genomic DNA. Translation: EAW91972.1.
BC001174 mRNA. Translation: AAH01174.1.
U70539 Genomic DNA. Translation: AAC51154.1.
CCDSiCCDS6324.1.
RefSeqiNP_000118.2. NM_000127.2.
UniGeneiHs.492618.

Genome annotation databases

EnsembliENST00000378204; ENSP00000367446; ENSG00000182197.
GeneIDi2131.
KEGGihsa:2131.
UCSCiuc003yok.3. human.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S79639 mRNA. Translation: AAB62283.1.
AK313129 mRNA. Translation: BAG35949.1.
CH471060 Genomic DNA. Translation: EAW91972.1.
BC001174 mRNA. Translation: AAH01174.1.
U70539 Genomic DNA. Translation: AAC51154.1.
CCDSiCCDS6324.1.
RefSeqiNP_000118.2. NM_000127.2.
UniGeneiHs.492618.

3D structure databases

ProteinModelPortaliQ16394.
SMRiQ16394.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108432. 23 interactors.
IntActiQ16394. 2 interactors.
MINTiMINT-120274.
STRINGi9606.ENSP00000367446.

Protein family/group databases

CAZyiGT47. Glycosyltransferase Family 47.
GT64. Glycosyltransferase Family 64.

PTM databases

iPTMnetiQ16394.
PhosphoSitePlusiQ16394.

Polymorphism and mutation databases

BioMutaiEXT1.
DMDMi20141422.

Proteomic databases

EPDiQ16394.
MaxQBiQ16394.
PaxDbiQ16394.
PeptideAtlasiQ16394.
PRIDEiQ16394.

Protocols and materials databases

DNASUi2131.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000378204; ENSP00000367446; ENSG00000182197.
GeneIDi2131.
KEGGihsa:2131.
UCSCiuc003yok.3. human.

Organism-specific databases

CTDi2131.
DisGeNETi2131.
GeneCardsiEXT1.
GeneReviewsiEXT1.
HGNCiHGNC:3512. EXT1.
HPAiHPA044394.
MalaCardsiEXT1.
MIMi133700. phenotype.
150230. phenotype.
215300. phenotype.
608177. gene.
neXtProtiNX_Q16394.
OpenTargetsiENSG00000182197.
Orphaneti55880. Chondrosarcoma.
502. Langer-Giedion syndrome.
321. Multiple osteochondromas.
PharmGKBiPA27924.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1021. Eukaryota.
ENOG410XTFH. LUCA.
GeneTreeiENSGT00550000074496.
HOGENOMiHOG000266990.
HOVERGENiHBG003459.
InParanoidiQ16394.
KOiK02366.
OMAiVTTCKHG.
OrthoDBiEOG091G0BDR.
PhylomeDBiQ16394.
TreeFamiTF314231.

Enzyme and pathway databases

UniPathwayiUPA00378.
BioCyciMetaCyc:HS00012-MONOMER.
ZFISH:HS00012-MONOMER.
BRENDAi2.4.1.224. 2681.
2.4.1.225. 2681.
ReactomeiR-HSA-2022928. HS-GAG biosynthesis.
SIGNORiQ16394.

Miscellaneous databases

ChiTaRSiEXT1. human.
GeneWikiiEXT1.
GenomeRNAii2131.
PROiQ16394.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182197.
CleanExiHS_EXT1.
ExpressionAtlasiQ16394. baseline and differential.
GenevisibleiQ16394. HS.

Family and domain databases

Gene3Di3.90.550.10. 1 hit.
InterProiIPR004263. Exostosin.
IPR027670. Exostosin-1.
IPR015338. EXT_C.
IPR029044. Nucleotide-diphossugar_trans.
[Graphical view]
PANTHERiPTHR11062:SF97. PTHR11062:SF97. 2 hits.
PfamiPF03016. Exostosin. 1 hit.
PF09258. Glyco_transf_64. 1 hit.
[Graphical view]
SUPFAMiSSF53448. SSF53448. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiEXT1_HUMAN
AccessioniPrimary (citable) accession number: Q16394
Secondary accession number(s): B2R7V2, Q9BVI9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: March 27, 2002
Last modified: November 30, 2016
This is version 173 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.