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Protein

Exostosin-like 3

Gene

EXTL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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.
UniPathwayiUPA00756.

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:EXTL3Imported
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.

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:rs554294508Ensembl.1
Natural variantiVAR_079092513R → C in ISDNA; changed glycosaminoglycan synthesis; no localization to Golgi apparatus in patient fibroblasts. 1 Publication1
Natural variantiVAR_079093657N → S in ISDNA; changed glycosaminoglycan synthesis. 1 Publication1
Natural variantiVAR_079094670Y → D in ISDNA; changed glycosaminoglycan synthesis. 1 Publication1

Keywords - Diseasei

Disease mutation, Dwarfism, Mental retardation

Organism-specific databases

DisGeNETi2137.
MIMi617425. phenotype.
OpenTargetsiENSG00000012232.
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.

PTM databases

iPTMnetiO43909.
PhosphoSitePlusiO43909.

Expressioni

Tissue specificityi

Ubiquitous. Expressed in keratinocytes.1 Publication

Gene expression databases

BgeeiENSG00000012232.
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.
PfamiView protein in Pfam
PF03016. Exostosin. 1 hit.
PF09258. Glyco_transf_64. 1 hit.
SUPFAMiSSF53448. SSF53448. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Sequence cautioni

O43909: 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:rs116659770Ensembl.1
Natural variantiVAR_079091461P → L in ISDNA; changed glycosaminoglycan synthesis. 2 PublicationsCorresponds to variant dbSNP:rs554294508Ensembl.1
Natural variantiVAR_079092513R → C in ISDNA; changed glycosaminoglycan synthesis; no localization to Golgi apparatus in patient fibroblasts. 1 Publication1
Natural variantiVAR_061194550A → V. Corresponds to variant dbSNP:rs35781576Ensembl.1
Natural variantiVAR_079093657N → S in ISDNA; changed glycosaminoglycan synthesis. 1 Publication1
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

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: October 25, 2017
This is version 165 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

Caution

It is uncertain whether Met-1, Met-6 or Met-20 is the initiator.Curated

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