UniProtKB - O43909 (EXTL3_HUMAN)
Protein
Exostosin-like 3
Gene
EXTL3
Organism
Homo sapiens (Human)
Status
Functioni
Glycosyltransferase which regulates the biosynthesis of heparan sulfate (HS). Important for both skeletal development and hematopoiesis, through the formation of HS proteoglycans (HSPGs) (PubMed:28132690, PubMed:28148688). Required for the function of REG3A in regulating keratinocyte proliferation and differentiation (PubMed:22727489).3 Publications
Caution
It is uncertain whether Met-1, Met-6 or Met-20 is the initiator.Curated
Catalytic activityi
- 3-O-(β-D-GlcA-(1→3)-β-D-Gal-(1→3)-β-D-Gal-(1→4)-β-D-Xyl)-L-seryl-[protein] + UDP-N-acetyl-α-D-glucosamine = 3-O-(α-D-GlcNAc-(1→4)-β-D-GlcA-(1→3)-β-D-Gal-(1→3)-β-D-Gal-(1→4)-β-D-Xyl)-L-seryl-[protein] + H+ + UDP2 PublicationsEC:2.4.1.2232 Publications
Cofactori
Mn2+By similarity
: heparan sulfate biosynthesis Pathwayi
This protein is involved in the pathway heparan sulfate biosynthesis, which is part of Glycan metabolism.2 PublicationsView all proteins of this organism that are known to be involved in the pathway heparan sulfate biosynthesis and in Glycan metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 697 | SubstrateBy similarity | 1 | |
Metal bindingi | 746 | Manganese; catalyticBy similarity | 1 | |
Binding sitei | 774 | SubstrateBy similarity | 1 | |
Active sitei | 833 | By similarity | 1 |
GO - Molecular functioni
- glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity Source: UniProtKB-EC
- metal ion binding Source: UniProtKB-KW
- transferase activity, transferring glycosyl groups Source: UniProtKB
GO - Biological processi
- heparan sulfate proteoglycan biosynthetic process Source: UniProtKB
- IRE1-mediated unfolded protein response Source: Reactome
- positive regulation of cell growth Source: Ensembl
- protein glycosylation Source: InterPro
Keywordsi
Molecular function | Glycosyltransferase, Transferase |
Ligand | Manganese, Metal-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:HS00333-MONOMER |
PathwayCommonsi | O43909 |
Reactomei | R-HSA-381038, XBP1(S) activates chaperone genes |
UniPathwayi | UPA00756 |
Protein family/group databases
CAZyi | GT47, Glycosyltransferase Family 47 GT64, Glycosyltransferase Family 64 |
Names & Taxonomyi
Protein namesi | Recommended name: Exostosin-like 31 Publication (EC:2.4.1.2232 Publications)Alternative name(s): EXT-related protein 11 Publication Glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase Hereditary multiple exostoses gene isolog1 Publication Multiple exostosis-like protein 31 Publication Putative tumor suppressor protein EXTL31 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3518, EXTL3 |
MIMi | 605744, gene |
neXtProti | NX_O43909 |
VEuPathDBi | HostDB:ENSG00000012232.8 |
Subcellular locationi
Golgi apparatus
- Golgi apparatus 1 Publication
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Single-pass type II membrane protein 1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: BHF-UCL
- endoplasmic reticulum membrane Source: Reactome
Golgi apparatus
- Golgi apparatus Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 30 | CytoplasmicSequence analysisAdd BLAST | 30 | |
Transmembranei | 31 – 51 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 52 – 919 | LumenalSequence analysisAdd BLAST | 868 |
Keywords - Cellular componenti
Endoplasmic reticulum, Golgi apparatus, MembranePathology & Biotechi
Involvement in diseasei
Immunoskeletal dysplasia with neurodevelopmental abnormalities (ISDNA)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by variable skeletal abnormalities and neurodevelopmental defects. Neurologic manifestations include intellectual disability and motor delay. Some patients manifest hypotonia and seizures. Skeletal features include disproportionate short stature, cervical malformations, epiphyseal and metaphyseal dysplasia, and rarely premature craniosynostosis with progressive microcephaly. Severe combined immunodeficiency with a complete absence of T cells is observed in some patients.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_079089 | 339 | R → W in ISDNA; changed glycosaminoglycan synthesis. 1 PublicationCorresponds to variant dbSNP:rs747676107EnsemblClinVar. | 1 | |
Natural variantiVAR_079091 | 461 | P → L in ISDNA; changed glycosaminoglycan synthesis. 2 PublicationsCorresponds to variant dbSNP:rs554294508EnsemblClinVar. | 1 | |
Natural variantiVAR_079092 | 513 | R → C in ISDNA; changed glycosaminoglycan synthesis; no localization to Golgi apparatus in patient fibroblasts. 1 PublicationCorresponds to variant dbSNP:rs1332006145Ensembl. | 1 | |
Natural variantiVAR_079093 | 657 | N → S in ISDNA; changed glycosaminoglycan synthesis. 1 PublicationCorresponds to variant dbSNP:rs770842408EnsemblClinVar. | 1 | |
Natural variantiVAR_079094 | 670 | Y → D in ISDNA; changed glycosaminoglycan synthesis. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Dwarfism, Mental retardationOrganism-specific databases
DisGeNETi | 2137 |
MalaCardsi | EXTL3 |
MIMi | 617425, phenotype |
OpenTargetsi | ENSG00000012232 |
Orphaneti | 508533, Skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome |
PharmGKBi | PA27930 |
Miscellaneous databases
Pharosi | O43909, Tbio |
Genetic variation databases
BioMutai | EXTL3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000149657 | 1 – 919 | Exostosin-like 3Add BLAST | 919 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 277 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 290 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 362 | PhosphoserineBy similarity | 1 | |
Glycosylationi | 592 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 790 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 831 ↔ 879 | By similarity |
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
EPDi | O43909 |
jPOSTi | O43909 |
MassIVEi | O43909 |
MaxQBi | O43909 |
PaxDbi | O43909 |
PeptideAtlasi | O43909 |
PRIDEi | O43909 |
ProteomicsDBi | 49226 |
PTM databases
GlyGeni | O43909, 5 sites, 1 O-linked glycan (1 site) |
iPTMneti | O43909 |
PhosphoSitePlusi | O43909 |
Expressioni
Tissue specificityi
Ubiquitous. Expressed in keratinocytes.1 Publication
Gene expression databases
Bgeei | ENSG00000012232, Expressed in stromal cell of endometrium and 189 other tissues |
ExpressionAtlasi | O43909, baseline and differential |
Genevisiblei | O43909, HS |
Organism-specific databases
HPAi | ENSG00000012232, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with REG3A.
1 PublicationBinary interactionsi
O43909
With | #Exp. | IntAct |
---|---|---|
ATXN1 [P54253] | 3 | EBI-1754679,EBI-930964 |
Protein-protein interaction databases
BioGRIDi | 108438, 51 interactors |
IntActi | O43909, 25 interactors |
STRINGi | 9606.ENSP00000220562 |
Miscellaneous databases
RNActi | O43909, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 723 – 728 | Substrate bindingBy similarity | 6 | |
Regioni | 744 – 746 | Substrate bindingBy similarity | 3 | |
Regioni | 829 – 833 | Substrate bindingBy similarity | 5 |
Sequence similaritiesi
Belongs to the glycosyltransferase 47 family.Curated
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2264, Eukaryota |
GeneTreei | ENSGT00940000156692 |
HOGENOMi | CLU_013906_3_0_1 |
InParanoidi | O43909 |
OMAi | HAWDVNH |
OrthoDBi | 789556at2759 |
PhylomeDBi | O43909 |
TreeFami | TF314231 |
Family and domain databases
Gene3Di | 3.90.550.10, 1 hit |
InterProi | View protein in InterPro IPR004263, Exostosin IPR040911, Exostosin_GT47 IPR015338, GT64 IPR029044, Nucleotide-diphossugar_trans |
PANTHERi | PTHR11062, PTHR11062, 1 hit |
Pfami | View protein in Pfam PF03016, Exostosin, 1 hit PF09258, Glyco_transf_64, 1 hit |
SUPFAMi | SSF53448, SSF53448, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All
O43909-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MTGYTMLRNG GAGNGGQTCM LRWSNRIRLT WLSFTLFVIL VFFPLIAHYY
60 70 80 90 100
LTTLDEADEA GKRIFGPRVG NELCEVKHVL DLCRIRESVS EELLQLEAKR
110 120 130 140 150
QELNSEIAKL NLKIEACKKS IENAKQDLLQ LKNVISQTEH SYKELMAQNQ
160 170 180 190 200
PKLSLPIRLL PEKDDAGLPP PKATRGCRLH NCFDYSRCPL TSGFPVYVYD
210 220 230 240 250
SDQFVFGSYL DPLVKQAFQA TARANVYVTE NADIACLYVI LVGEMQEPVV
260 270 280 290 300
LRPAELEKQL YSLPHWRTDG HNHVIINLSR KSDTQNLLYN VSTGRAMVAQ
310 320 330 340 350
STFYTVQYRP GFDLVVSPLV HAMSEPNFME IPPQVPVKRK YLFTFQGEKI
360 370 380 390 400
ESLRSSLQEA RSFEEEMEGD PPADYDDRII ATLKAVQDSK LDQVLVEFTC
410 420 430 440 450
KNQPKPSLPT EWALCGERED RLELLKLSTF ALIITPGDPR LVISSGCATR
460 470 480 490 500
LFEALEVGAV PVVLGEQVQL PYQDMLQWNE AALVVPKPRV TEVHFLLRSL
510 520 530 540 550
SDSDLLAMRR QGRFLWETYF STADSIFNTV LAMIRTRIQI PAAPIREEAA
560 570 580 590 600
AEIPHRSGKA AGTDPNMADN GDLDLGPVET EPPYASPRYL RNFTLTVTDF
610 620 630 640 650
YRSWNCAPGP FHLFPHTPFD PVLPSEAKFL GSGTGFRPIG GGAGGSGKEF
660 670 680 690 700
QAALGGNVPR EQFTVVMLTY EREEVLMNSL ERLNGLPYLN KVVVVWNSPK
710 720 730 740 750
LPSEDLLWPD IGVPIMVVRT EKNSLNNRFL PWNEIETEAI LSIDDDAHLR
760 770 780 790 800
HDEIMFGFRV WREARDRIVG FPGRYHAWDI PHQSWLYNSN YSCELSMVLT
810 820 830 840 850
GAAFFHKYYA YLYSYVMPQA IRDMVDEYIN CEDIAMNFLV SHITRKPPIK
860 870 880 890 900
VTSRWTFRCP GCPQALSHDD SHFHERHKCI NFFVKVYGYM PLLYTQFRVD
910
SVLFKTRLPH DKTKCFKFI
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE7ET85 | E7ET85_HUMAN | Exostosin-like 3 | EXTL3 | 535 | Annotation score: | ||
E5RK02 | E5RK02_HUMAN | Exostosin-like 3 | EXTL3 | 137 | Annotation score: | ||
H0YBJ7 | H0YBJ7_HUMAN | Exostosin-like 3 | EXTL3 | 201 | Annotation score: | ||
E5RIV6 | E5RIV6_HUMAN | Exostosin-like 3 | EXTL3 | 118 | Annotation score: | ||
H0YB01 | H0YB01_HUMAN | Exostosin-like 3 | EXTL3 | 75 | Annotation score: |
Sequence cautioni
The sequence BAA25445 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_079089 | 339 | R → W in ISDNA; changed glycosaminoglycan synthesis. 1 PublicationCorresponds to variant dbSNP:rs747676107EnsemblClinVar. | 1 | |
Natural variantiVAR_079090 | 442 | V → L1 PublicationCorresponds to variant dbSNP:rs116659770EnsemblClinVar. | 1 | |
Natural variantiVAR_079091 | 461 | P → L in ISDNA; changed glycosaminoglycan synthesis. 2 PublicationsCorresponds to variant dbSNP:rs554294508EnsemblClinVar. | 1 | |
Natural variantiVAR_079092 | 513 | R → C in ISDNA; changed glycosaminoglycan synthesis; no localization to Golgi apparatus in patient fibroblasts. 1 PublicationCorresponds to variant dbSNP:rs1332006145Ensembl. | 1 | |
Natural variantiVAR_061194 | 550 | A → V. Corresponds to variant dbSNP:rs35781576EnsemblClinVar. | 1 | |
Natural variantiVAR_080762 | 646 | S → C Found in a small consanguineous family with intellectual disability; unknown pathological significance. 1 Publication | 1 | |
Natural variantiVAR_079093 | 657 | N → S in ISDNA; changed glycosaminoglycan synthesis. 1 PublicationCorresponds to variant dbSNP:rs770842408EnsemblClinVar. | 1 | |
Natural variantiVAR_079094 | 670 | Y → D in ISDNA; changed glycosaminoglycan synthesis. 1 Publication | 1 | |
Natural variantiVAR_049229 | 706 | L → P. Corresponds to variant dbSNP:rs2269452Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF001690 mRNA Translation: AAC39598.1 U76188 mRNA Translation: AAB93670.1 AB007042 mRNA Translation: BAA24080.1 AB011091 mRNA Translation: BAA25445.2 Different initiation. AF029231 mRNA Translation: AAD01877.1 AF083551 mRNA Translation: AAD42041.1 BT007353 mRNA Translation: AAP36017.1 CH471080 Genomic DNA Translation: EAW63507.1 CH471080 Genomic DNA Translation: EAW63508.1 CH471080 Genomic DNA Translation: EAW63509.1 BC006363 mRNA Translation: AAH06363.1 U96629 Genomic DNA Translation: AAB67602.1 Sequence problems. |
CCDSi | CCDS6070.1 |
PIRi | JC5934 |
RefSeqi | NP_001431.1, NM_001440.3 XP_011542742.1, XM_011544440.2 |
Genome annotation databases
Ensembli | ENST00000220562; ENSP00000220562; ENSG00000012232 |
GeneIDi | 2137 |
KEGGi | hsa:2137 |
UCSCi | uc003xgz.3, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Functional Glycomics Gateway - GTase Exostosin-like 3 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF001690 mRNA Translation: AAC39598.1 U76188 mRNA Translation: AAB93670.1 AB007042 mRNA Translation: BAA24080.1 AB011091 mRNA Translation: BAA25445.2 Different initiation. AF029231 mRNA Translation: AAD01877.1 AF083551 mRNA Translation: AAD42041.1 BT007353 mRNA Translation: AAP36017.1 CH471080 Genomic DNA Translation: EAW63507.1 CH471080 Genomic DNA Translation: EAW63508.1 CH471080 Genomic DNA Translation: EAW63509.1 BC006363 mRNA Translation: AAH06363.1 U96629 Genomic DNA Translation: AAB67602.1 Sequence problems. |
CCDSi | CCDS6070.1 |
PIRi | JC5934 |
RefSeqi | NP_001431.1, NM_001440.3 XP_011542742.1, XM_011544440.2 |
3D structure databases
SMRi | O43909 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 108438, 51 interactors |
IntActi | O43909, 25 interactors |
STRINGi | 9606.ENSP00000220562 |
Protein family/group databases
CAZyi | GT47, Glycosyltransferase Family 47 GT64, Glycosyltransferase Family 64 |
PTM databases
GlyGeni | O43909, 5 sites, 1 O-linked glycan (1 site) |
iPTMneti | O43909 |
PhosphoSitePlusi | O43909 |
Genetic variation databases
BioMutai | EXTL3 |
Proteomic databases
EPDi | O43909 |
jPOSTi | O43909 |
MassIVEi | O43909 |
MaxQBi | O43909 |
PaxDbi | O43909 |
PeptideAtlasi | O43909 |
PRIDEi | O43909 |
ProteomicsDBi | 49226 |
Protocols and materials databases
Antibodypediai | 23127, 262 antibodies |
DNASUi | 2137 |
Genome annotation databases
Ensembli | ENST00000220562; ENSP00000220562; ENSG00000012232 |
GeneIDi | 2137 |
KEGGi | hsa:2137 |
UCSCi | uc003xgz.3, human |
Organism-specific databases
CTDi | 2137 |
DisGeNETi | 2137 |
GeneCardsi | EXTL3 |
HGNCi | HGNC:3518, EXTL3 |
HPAi | ENSG00000012232, Low tissue specificity |
MalaCardsi | EXTL3 |
MIMi | 605744, gene 617425, phenotype |
neXtProti | NX_O43909 |
OpenTargetsi | ENSG00000012232 |
Orphaneti | 508533, Skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome |
PharmGKBi | PA27930 |
VEuPathDBi | HostDB:ENSG00000012232.8 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2264, Eukaryota |
GeneTreei | ENSGT00940000156692 |
HOGENOMi | CLU_013906_3_0_1 |
InParanoidi | O43909 |
OMAi | HAWDVNH |
OrthoDBi | 789556at2759 |
PhylomeDBi | O43909 |
TreeFami | TF314231 |
Enzyme and pathway databases
UniPathwayi | UPA00756 |
BioCyci | MetaCyc:HS00333-MONOMER |
PathwayCommonsi | O43909 |
Reactomei | R-HSA-381038, XBP1(S) activates chaperone genes |
Miscellaneous databases
BioGRID-ORCSi | 2137, 79 hits in 875 CRISPR screens |
ChiTaRSi | EXTL3, human |
GeneWikii | EXTL3 |
GenomeRNAii | 2137 |
Pharosi | O43909, Tbio |
PROi | PR:O43909 |
RNActi | O43909, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000012232, Expressed in stromal cell of endometrium and 189 other tissues |
ExpressionAtlasi | O43909, baseline and differential |
Genevisiblei | O43909, HS |
Family and domain databases
Gene3Di | 3.90.550.10, 1 hit |
InterProi | View protein in InterPro IPR004263, Exostosin IPR040911, Exostosin_GT47 IPR015338, GT64 IPR029044, Nucleotide-diphossugar_trans |
PANTHERi | PTHR11062, PTHR11062, 1 hit |
Pfami | View protein in Pfam PF03016, Exostosin, 1 hit PF09258, Glyco_transf_64, 1 hit |
SUPFAMi | SSF53448, SSF53448, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | EXTL3_HUMAN | |
Accessioni | O43909Primary (citable) accession number: O43909 Secondary accession number(s): D3DST8, O00225, Q53XT3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1999 |
Last sequence update: | June 1, 1998 | |
Last modified: | February 10, 2021 | |
This is version 188 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families