EXT1
entrez
2131
canonical
uniprot
Q16394
canonical
ensembl
ENSG00000182197
resolver
ensp
ENSP00000367446
resolver
enst
ENST00000378204
resolver
genesymbol
EXT1
resolver
hgnc
HGNC:3512
resolver
uniprot
B2R7V2
resolver
uniprot
Q9BVI9
resolver
uniprot_entry
EXT1_HUMAN
resolver
uniprot_sec
B2R7V2
resolver
uniprot_sec
Q9BVI9
resolver
amino_acid_sequence
MQAKKRYFILLSAGSCLALLFYFGGLQFRASRSHSRREEHSGRNGLHHPSPDHFWPRFPDALRPFVPWDQLENEDSSVHISPRQKRDANSSIYKGKKCRMESCFDFTLCKKNGFKVYVYPQQKGEKIAESYQNILAAIEGSRFYTSDPSQACLFVLSLDTLDRDQLSPQYVHNLRSKVQSLHLWNNGRNHLIFNLYSGTWPDYTEDVGFDIGQAMLAKASISTENFRPNFDVSIPLFSKDHPRTGGERGFLKFNTIPPLRKYMLVFKGKRYLTGIGSDTRNALYHVHNGEDVVLLTTCKHGKDWQKHKDSRCDRDNTEYEKYDYREMLHNATFCLVPRGRRLGSFRFLEALQAACVPVMLSNGWELPFSEVINWNQAAVIGDERLLLQIPSTIRSIHQDKILALRQQTQFLWEAYFSSVEKIVLTTLEIIQDRIFKHISRNSLIWNKHPGGLFVLPQYSSYLGDFPYYYANLGLKPPSKFTAVIHAVTPLVSQSQPVLKLLVAAAKSQYCAQIIVLWNCDKPLPAKHRWPATAVPVVVIEGESKVMSSRFLPYDNIITDAVLSLDEDTVLSTTEVDFAFTVWQSFPERIVGYPARSHFWDNSKERWGYTSKWTNDYSMVLTGAAIYHKYYHYLYSHYLPASLKNMVDQLANCEDILMNFLVSAVTKLPPIKVTQKKQYKETMMGQTSRASRWADPDHFAQRQSCMNTFASWFGYMPLIHSQMRLDPVLFKDQVSILRKKYRDIERL
uniprot
proteins
disease_involvement
DISEASE: Hereditary multiple exostoses 1 (EXT1) [MIM:133700]: EXT 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. {ECO:0000269|PubMed:10441575, ECO:0000269|PubMed:10480354, ECO:0000269|PubMed:10639137, ECO:0000269|PubMed:10679296, ECO:0000269|PubMed:11169766, ECO:0000269|PubMed:11391482, ECO:0000269|PubMed:8981950, ECO:0000269|PubMed:9326317, ECO:0000269|PubMed:9463333, ECO:0000269|PubMed:9521425, ECO:0000269|PubMed:9620772}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Chondrosarcoma (CHDSA) [MIM:215300]: A malignant neoplasm derived from cartilage cells. Chondrosarcomas range from slow-growing non-metastasizing lesions to highly aggressive metastasizing sarcomas. {ECO:0000269|PubMed:8981950}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.4.1.225
uniprot
proteins
function
FUNCTION: Glycosyltransferase forming with EXT2 the heterodimeric heparan sulfate polymerase which catalyzes the elongation of the heparan sulfate glycan backbone (PubMed:10639137, PubMed:22660413, PubMed:36402845, PubMed:36593275, PubMed:9620772). Glycan backbone extension consists in the alternating transfer of (1->4)-beta-D-GlcA and (1->4)-alpha-D-GlcNAc residues from their respective UDP-sugar donors. Both EXT1 and EXT2 are required for the full activity of the polymerase since EXT1 bears the N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity within the complex while EXT2 carries the glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity (PubMed:36402845, PubMed:36593275). Heparan sulfate proteoglycans are ubiquitous components of the extracellular matrix and play an important role in tissue homeostasis and signaling (PubMed:10639137, PubMed:11391482, PubMed:22660413, PubMed:9620772). {ECO:0000269|PubMed:10639137, ECO:0000269|PubMed:11391482, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:36402845, ECO:0000269|PubMed:36593275, ECO:0000269|PubMed:9620772}.
uniprot
proteins
mass_dalton
86255
uniprot
proteins
mutagenesis
MUTAGEN 27; /note="Q->A,P: No effect on heparan sulfate proteoglycan biosynthetic process."; /evidence="ECO:0000269|PubMed:11391482"; MUTAGEN 27; /note="Missing: No effect on heparan sulfate proteoglycan biosynthetic process."; /evidence="ECO:0000269|PubMed:11391482"; MUTAGEN 162; /note="D->N: Loss of N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity; when associated with N-164."; /evidence="ECO:0000269|PubMed:36402845"; MUTAGEN 164; /note="D->E: Loss of heparan sulfate proteoglycan biosynthetic process."; /evidence="ECO:0000269|PubMed:11391482"; MUTAGEN 164; /note="D->N: Loss of N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity; when associated with N-162."; /evidence="ECO:0000269|PubMed:36402845"; MUTAGEN 164; /note="Missing: Loss of heparan sulfate proteoglycan biosynthetic process."; /evidence="ECO:0000269|PubMed:11391482"; MUTAGEN 269; /note="K->A: Loss of N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity. No effect on glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity."; /evidence="ECO:0000269|PubMed:36593275"; MUTAGEN 280; /note="R->A: Loss of N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity."; /evidence="ECO:0000269|PubMed:36402845"; MUTAGEN 316; /note="N->A: No effect on heparan sulfate proteoglycan biosynthetic process."; /evidence="ECO:0000269|PubMed:11391482"; MUTAGEN 316; /note="Missing: No effect on heparan sulfate proteoglycan biosynthetic process."; /evidence="ECO:0000269|PubMed:11391482"; MUTAGEN 340; /note="R->A: Loss of N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity. No effect on glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity."; /evidence="ECO:0000269|PubMed:36593275"; MUTAGEN 341; /note="R->A: Loss of N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity. No effect on glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity."; /evidence="ECO:0000269|PubMed:36593275"; MUTAGEN 346; /note="R->A: Loss of N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity. No effect on glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity."; /evidence="ECO:0000269|PubMed:36402845, ECO:0000269|PubMed:36593275"; MUTAGEN 486; /note="A->H: No effect on heparan sulfate proteoglycan biosynthetic process."; /evidence="ECO:0000269|PubMed:11391482"; MUTAGEN 486; /note="Missing: No effect on heparan sulfate proteoglycan biosynthetic process."; /evidence="ECO:0000269|PubMed:11391482"; MUTAGEN 496; /note="P->H: No effect on heparan sulfate proteoglycan biosynthetic process."; /evidence="ECO:0000269|PubMed:11391482"; MUTAGEN 496; /note="Missing: No effect on heparan sulfate proteoglycan biosynthetic process."; /evidence="ECO:0000269|PubMed:11391482"; MUTAGEN 565; /note="D->A: Decreased N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity. No effect on glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity."; /evidence="ECO:0000269|PubMed:36593275"; MUTAGEN 565; /note="D->N: Decreased glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; when associated with N-567."; /evidence="ECO:0000269|PubMed:36402845"; MUTAGEN 567; /note="D->A: Decreased N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity. No effect on glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity."; /evidence="ECO:0000269|PubMed:36593275"; MUTAGEN 567; /note="D->N: Decreased glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity; when associated with N-565."; /evidence="ECO:0000269|PubMed:36402845"; MUTAGEN 595; /note="R->A: Decreased N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity. No effect on glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity."; /evidence="ECO:0000269|PubMed:36593275"; MUTAGEN 612; /note="W->A: Decreased N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity. No effect on glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity."; /evidence="ECO:0000269|PubMed:36593275"; MUTAGEN 692; /note="W->A: Increased N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity. No effect on glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity."; /evidence="ECO:0000269|PubMed:36593275
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein glycosylation. {ECO:0000269|PubMed:10639137, ECO:0000269|PubMed:11391482, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:9620772}.
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:9620772}.
uniprot
proteins
protein_family
Glycosyltransferase 47 family
uniprot
proteins
pubmed
10441575
uniprot
proteins
pubmed
10480354
uniprot
proteins
pubmed
10639137
uniprot
proteins
pubmed
10679296
uniprot
proteins
pubmed
11169766
uniprot
proteins
pubmed
11391482
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
22660413
uniprot
proteins
pubmed
35137078
uniprot
proteins
pubmed
36402845
uniprot
proteins
pubmed
36593275
uniprot
proteins
pubmed
7550340
uniprot
proteins
pubmed
8981950
uniprot
proteins
pubmed
9119404
uniprot
proteins
pubmed
9326317
uniprot
proteins
pubmed
9463333
uniprot
proteins
pubmed
9521425
uniprot
proteins
pubmed
9620772
uniprot
proteins
sequence_length
746
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000269|PubMed:10639137, ECO:0000269|PubMed:10679296}; Single-pass type II membrane protein {ECO:0000255}. Golgi apparatus, cis-Golgi network membrane {ECO:0000269|PubMed:35137078}; Single-pass type II membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:10679296, ECO:0000269|PubMed:9620772}; Single-pass type II membrane protein {ECO:0000255}. Note=The active heparan sulfate polymerase complex composed of EXT1 and EXT2 is localized to the Golgi apparatus. If both proteins are individually detected in the endoplasmic reticulum, the formation of the complex promotes their transport to the Golgi. {ECO:0000269|PubMed:10639137, ECO:0000269|PubMed:10679296, ECO:0000269|PubMed:9620772}.
uniprot
proteins
transmembrane_region
TRANSMEM 8..28; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins