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Protein

Exostosin-like 3

Gene

EXTL3

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

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

UDP-N-acetyl-alpha-D-glucosamine + [protein]-3-O-(beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine = UDP + [protein]-3-O-(alpha-D-GlcNAc-(1->4)-beta-D-GlcA-(1->3)-beta-D-Gal-(1->3)-beta-D-Gal-(1->4)-beta-D-Xyl)-L-serine.2 Publications

Cofactori

Mn2+By similarity

Pathwayi: heparan sulfate biosynthesis

This protein is involved in the pathway heparan sulfate biosynthesis, which is part of Glycan metabolism.2 Publications
View all proteins of this organism that are known to be involved in the pathway heparan sulfate biosynthesis and in Glycan metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei697SubstrateBy similarity1
Metal bindingi746Manganese; catalyticBy similarity1
Binding sitei774SubstrateBy similarity1
Active sitei833By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGlycosyltransferase, Transferase
LigandManganese, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS00333-MONOMER
ReactomeiR-HSA-381038 XBP1(S) activates chaperone genes
UniPathwayi
UPA00756

Protein family/group databases

CAZyiGT47 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
Name:EXTL31 PublicationImported
Synonyms:EXTL1L, EXTR1, KIAA0519
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000012232.8
HGNCiHGNC:3518 EXTL3
MIMi605744 gene
neXtProtiNX_O43909

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 30CytoplasmicSequence analysisAdd BLAST30
Transmembranei31 – 51Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini52 – 919LumenalSequence analysisAdd BLAST868

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Immunoskeletal dysplasia with neurodevelopmental abnormalities (ISDNA)2 Publications
The disease is caused by mutations 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.
See also OMIM:617425
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079089339R → W in ISDNA; changed glycosaminoglycan synthesis. 1 Publication1
Natural variantiVAR_079091461P → L in ISDNA; changed glycosaminoglycan synthesis. 2 PublicationsCorresponds to variant dbSNP:rs554294508EnsemblClinVar.1
Natural variantiVAR_079092513R → C in ISDNA; changed glycosaminoglycan synthesis; no localization to Golgi apparatus in patient fibroblasts. 1 PublicationCorresponds to variant dbSNP:rs1332006145Ensembl.1
Natural variantiVAR_079093657N → S in ISDNA; changed glycosaminoglycan synthesis. 1 PublicationCorresponds to variant dbSNP:rs770842408EnsemblClinVar.1
Natural variantiVAR_079094670Y → D in ISDNA; changed glycosaminoglycan synthesis. 1 Publication1

Keywords - Diseasei

Disease mutation, Dwarfism, Mental retardation

Organism-specific databases

DisGeNETi2137
MalaCardsiEXTL3
MIMi617425 phenotype
OpenTargetsiENSG00000012232
Orphaneti508533 Skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome
PharmGKBiPA27930

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001496571 – 919Exostosin-like 3Add BLAST919

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi277N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi290N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei362PhosphoserineBy similarity1
Glycosylationi592N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi790N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi831 ↔ 879By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiO43909
MaxQBiO43909
PaxDbiO43909
PeptideAtlasiO43909
PRIDEiO43909
ProteomicsDBi49226

PTM databases

iPTMnetiO43909
PhosphoSitePlusiO43909

Expressioni

Tissue specificityi

Ubiquitous. Expressed in keratinocytes.1 Publication

Gene expression databases

BgeeiENSG00000012232 Expressed in 170 organ(s), highest expression level in heart left ventricle
CleanExiHS_EXTL3
ExpressionAtlasiO43909 baseline and differential
GenevisibleiO43909 HS

Organism-specific databases

HPAiCAB025387

Interactioni

Subunit structurei

Interacts with REG3A.1 Publication

Protein-protein interaction databases

BioGridi108438, 47 interactors
IntActiO43909, 8 interactors
STRINGi9606.ENSP00000220562

Structurei

3D structure databases

ProteinModelPortaliO43909
SMRiO43909
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni723 – 728Substrate bindingBy similarity6
Regioni744 – 746Substrate bindingBy similarity3
Regioni829 – 833Substrate bindingBy similarity5

Sequence similaritiesi

Belongs to the glycosyltransferase 47 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2264 Eukaryota
ENOG410XNPM LUCA
GeneTreeiENSGT00550000074496
HOGENOMiHOG000007975
HOVERGENiHBG051526
InParanoidiO43909
KOiK02370
OMAiRKSDTQN
OrthoDBiEOG091G03XP
PhylomeDBiO43909
TreeFamiTF314231

Family and domain databases

Gene3Di3.90.550.10, 1 hit
InterProiView protein in InterPro
IPR004263 Exostosin
IPR015338 EXT_C
IPR029044 Nucleotide-diphossugar_trans
PANTHERiPTHR11062 PTHR11062, 1 hit
PfamiView protein in Pfam
PF03016 Exostosin, 1 hit
PF09258 Glyco_transf_64, 1 hit
SUPFAMiSSF53448 SSF53448, 1 hit

Sequence (1+)i

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
« Hide
        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
Length:919
Mass (Da):104,749
Last modified:June 1, 1998 - v1
Checksum:i200ADD4DAB4A39FD
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7ET85E7ET85_HUMAN
Exostosin-like 3
EXTL3
535Annotation score:
E5RK02E5RK02_HUMAN
Exostosin-like 3
EXTL3
137Annotation score:
H0YBJ7H0YBJ7_HUMAN
Exostosin-like 3
EXTL3
201Annotation score:
E5RIV6E5RIV6_HUMAN
Exostosin-like 3
EXTL3
118Annotation score:
H0YB01H0YB01_HUMAN
Exostosin-like 3
EXTL3
75Annotation score:

Sequence cautioni

The sequence BAA25445 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_079089339R → W in ISDNA; changed glycosaminoglycan synthesis. 1 Publication1
Natural variantiVAR_079090442V → L1 PublicationCorresponds to variant dbSNP:rs116659770EnsemblClinVar.1
Natural variantiVAR_079091461P → L in ISDNA; changed glycosaminoglycan synthesis. 2 PublicationsCorresponds to variant dbSNP:rs554294508EnsemblClinVar.1
Natural variantiVAR_079092513R → C in ISDNA; changed glycosaminoglycan synthesis; no localization to Golgi apparatus in patient fibroblasts. 1 PublicationCorresponds to variant dbSNP:rs1332006145Ensembl.1
Natural variantiVAR_061194550A → V. Corresponds to variant dbSNP:rs35781576Ensembl.1
Natural variantiVAR_080762646S → C Found in a small consanguineous family with intellectual disability; unknown pathological significance. 1 Publication1
Natural variantiVAR_079093657N → S in ISDNA; changed glycosaminoglycan synthesis. 1 PublicationCorresponds to variant dbSNP:rs770842408EnsemblClinVar.1
Natural variantiVAR_079094670Y → D in ISDNA; changed glycosaminoglycan synthesis. 1 Publication1
Natural variantiVAR_049229706L → 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.
CCDSiCCDS6070.1
PIRiJC5934
RefSeqiNP_001431.1, NM_001440.3
XP_011542742.1, XM_011544440.2
UniGeneiHs.491354
Hs.744019

Genome annotation databases

EnsembliENST00000220562; ENSP00000220562; ENSG00000012232
GeneIDi2137
KEGGihsa:2137
UCSCiuc003xgz.3 human

Keywords - Coding sequence diversityi

Polymorphism

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.
CCDSiCCDS6070.1
PIRiJC5934
RefSeqiNP_001431.1, NM_001440.3
XP_011542742.1, XM_011544440.2
UniGeneiHs.491354
Hs.744019

3D structure databases

ProteinModelPortaliO43909
SMRiO43909
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108438, 47 interactors
IntActiO43909, 8 interactors
STRINGi9606.ENSP00000220562

Protein family/group databases

CAZyiGT47 Glycosyltransferase Family 47
GT64 Glycosyltransferase Family 64

PTM databases

iPTMnetiO43909
PhosphoSitePlusiO43909

Proteomic databases

EPDiO43909
MaxQBiO43909
PaxDbiO43909
PeptideAtlasiO43909
PRIDEiO43909
ProteomicsDBi49226

Protocols and materials databases

DNASUi2137
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000220562; ENSP00000220562; ENSG00000012232
GeneIDi2137
KEGGihsa:2137
UCSCiuc003xgz.3 human

Organism-specific databases

CTDi2137
DisGeNETi2137
EuPathDBiHostDB:ENSG00000012232.8
GeneCardsiEXTL3
HGNCiHGNC:3518 EXTL3
HPAiCAB025387
MalaCardsiEXTL3
MIMi605744 gene
617425 phenotype
neXtProtiNX_O43909
OpenTargetsiENSG00000012232
Orphaneti508533 Skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome
PharmGKBiPA27930
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2264 Eukaryota
ENOG410XNPM LUCA
GeneTreeiENSGT00550000074496
HOGENOMiHOG000007975
HOVERGENiHBG051526
InParanoidiO43909
KOiK02370
OMAiRKSDTQN
OrthoDBiEOG091G03XP
PhylomeDBiO43909
TreeFamiTF314231

Enzyme and pathway databases

UniPathwayi
UPA00756

BioCyciMetaCyc:HS00333-MONOMER
ReactomeiR-HSA-381038 XBP1(S) activates chaperone genes

Miscellaneous databases

ChiTaRSiEXTL3 human
GeneWikiiEXTL3
GenomeRNAii2137
PROiPR:O43909
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000012232 Expressed in 170 organ(s), highest expression level in heart left ventricle
CleanExiHS_EXTL3
ExpressionAtlasiO43909 baseline and differential
GenevisibleiO43909 HS

Family and domain databases

Gene3Di3.90.550.10, 1 hit
InterProiView protein in InterPro
IPR004263 Exostosin
IPR015338 EXT_C
IPR029044 Nucleotide-diphossugar_trans
PANTHERiPTHR11062 PTHR11062, 1 hit
PfamiView protein in Pfam
PF03016 Exostosin, 1 hit
PF09258 Glyco_transf_64, 1 hit
SUPFAMiSSF53448 SSF53448, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiEXTL3_HUMAN
AccessioniPrimary (citable) accession number: O43909
Secondary accession number(s): D3DST8, O00225, Q53XT3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: November 7, 2018
This is version 173 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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