EXTL3 exostosin like glycosyltransferase 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: EXTL3provided by HGNC
Official Full Name: exostosin like glycosyltransferase 3provided by HGNC
Primary source: HGNC:HGNC:3518
See related: Ensembl:ENSG00000012232 MIM:605744; AllianceGenome:HGNC:3518
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: RPR; BOTV; REGR; EXTR1; ISDNA; EXTL1L
Summary: This gene encodes a single-pass membrane protein which functions as a glycosyltransferase. The encoded protein catalyzes the transfer of N-acetylglucosamine to glycosaminoglycan chains. This reaction is important in heparin and heparan sulfate synthesis. Alternative splicing results in the multiple transcript variants. [provided by RefSeq, Nov 2012]
Expression: Ubiquitous expression in heart (RPKM 14.3), brain (RPKM 13.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8p21.1

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (28607736..28755599)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (28885904..29033822)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (28559018..28613116)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Glycosyltransferases EXTL2 and EXTL3 cellular balance dictates heparan sulfate biosynthesis and shapes gastric cancer cell motility and invasion.
Title: Glycosyltransferases EXTL2 and EXTL3 cellular balance dictates heparan sulfate biosynthesis and shapes gastric cancer cell motility and invasion.
Spondyloepimetaphyseal dysplasia EXTL3-deficient type: Long-term follow-up and review of the literature.
Title: Spondyloepimetaphyseal dysplasia EXTL3-deficient type: Long-term follow-up and review of the literature.
REG3A/REG3B promotes acinar to ductal metaplasia through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway.
Title: REG3A/REG3B promotes acinar to ductal metaplasia through binding to EXTL3 and activating the RAS-RAF-MEK-ERK signaling pathway.
EXTL3-interacting endometriosis-specific serum factors induce colony formation of endometrial stromal cells.
Title: EXTL3-interacting endometriosis-specific serum factors induce colony formation of endometrial stromal cells.
EXTL3 mutations are associated with spondylo-epi-metaphyseal dysplasia with immunodeficiency.
Title: Expanding the spectrum of skeletal dysplasia with immunodeficiency: a commentary on identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia.
Human lumenal N-glycosylated EXTL3 (EXTL3DeltaN) was cloned, expressed in human embryonic kidney cells, and purified. Various biophysical and biochemical approaches were then employed to elucidate the N-glycosylation sites and the function of their attached N-glycans.
Title: Structural and Biophysical Characterization of Human EXTL3: Domain Organization, Glycosylation, and Solution Structure.
EXTL3 missense mutation is associated with spondylo-epi-metaphyseal dysplasia.
Title: Identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia.
EXTL3 mutations as a novel cause of severe immune deficiency with skeletal dysplasia and developmental delay and underline a crucial role of HS in thymopoiesis and skeletal and brain development.
Title: EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay.
We show that biallelic mutations in EXTL3 disturb glycosaminoglycan synthesis and thus lead to a recognizable syndrome characterized by variable expression of skeletal, neurological, and immunological abnormalities.
Title: Mutations in EXTL3 Cause Neuro-immuno-skeletal Dysplasia Syndrome.
Recombinant EXTL2 showed weak ability to transfer N-acetylgalactosamine to heparan sulfate precursor molecules but also, that EXTL2 exhibited much stronger in vitro N-acetylglucosamine-transferase activity related to elongation of heparan sulfate chains.
Title: Reduced Expression of EXTL2, a Member of the Exostosin (EXT) Family of Glycosyltransferases, in Human Embryonic Kidney 293 Cells Results in Longer Heparan Sulfate Chains.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Immunoskeletal dysplasia with neurodevelopmental abnormalities MedGen: C4479452 OMIM: 617425 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 interacts with EXTL3; predicted interaction to be within the endoplasmic reticulum	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2279 (e-PCR)
- UniSTS:473907

D8S1402E (e-PCR)
- UniSTS:6282

D8S1403E (e-PCR)
- UniSTS:151197

STS-M79217 (e-PCR)
- UniSTS:7074

RH121646 (e-PCR)
- UniSTS:134328

SHGC-110015 (e-PCR)
- UniSTS:170188

Extl3 (e-PCR), detects polymorphism
- UniSTS:546765

A002S41 (e-PCR)
- UniSTS:45263

RH15942 (e-PCR)
- UniSTS:66540

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables glycosyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glycosyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-hormone receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein-hormone receptor activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed

Process	Evidence Code	Pubs
involved_in heparan sulfate proteoglycan biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in heparan sulfate proteoglycan biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cytokine production involved in inflammatory response	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of inflammatory response	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of inflammatory response to wounding	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of keratinocyte differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell growth	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of detection of glucose	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in protein glycosylation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in Golgi apparatus	IBA Inferred from Biological aspect of Ancestor more info
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: exostosin-like 3

Names: EXT-related 1; epididymis secretory sperm binding protein; exostoses (multiple)-like 3; exostosin tumor-like 3; glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase; hereditary multiple exostoses gene isolog; putative tumor suppressor protein EXTL3; reg receptor

NP_001431.1

EC 2.4.1.223

XP_011542742.1

EC 2.4.1.223

XP_024302862.1

EC 2.4.1.223

XP_024302864.1

EC 2.4.1.223

XP_047277470.1

EC 2.4.1.223

XP_047277471.1

EC 2.4.1.223

XP_047277472.1

EC 2.4.1.223

XP_047277473.1

EC 2.4.1.223

XP_047277474.1

EC 2.4.1.223

XP_054216003.1

EC 2.4.1.223

XP_054216004.1

EC 2.4.1.223

XP_054216005.1

EC 2.4.1.223

XP_054216006.1

EC 2.4.1.223

XP_054216007.1

EC 2.4.1.223

XP_054216008.1

EC 2.4.1.223

XP_054216009.1

EC 2.4.1.223

XP_054216010.1

EC 2.4.1.223

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001440.4 → NP_001431.1 exostosin-like 3

See identical proteins and their annotated locations for NP_001431.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the functional protein.

Source sequence(s)

AB011091, AC131969, AW105691, DA757362

Consensus CDS

CCDS6070.1

UniProtKB/Swiss-Prot

D3DST8, O00225, O43909, Q53XT3

UniProtKB/TrEMBL

A0A384NPY9, A0A8Q3SIF4

Related

ENSP00000220562.4, ENST00000220562.9

Conserved Domains (3) summary

pfam03016
Location:190 → 500

Exostosin; Exostosin family

pfam07926
Location:71 → 150

TPR_MLP1_2; TPR/MLP1/MLP2-like protein

pfam09258
Location:663 → 900

Glyco_transf_64; Glycosyl transferase family 64 domain

RNA

NR_073468.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks two internal exons, compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon, found in variant 1.

Source sequence(s)

AB011091, AC131969, AW105691, DA222815, DA757362

Related

ENST00000696182.1
NR_073469.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) has multiple differences compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region found in variant 1.

Source sequence(s)

AF029231, AW105691, BI911162, DA757362

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

28607736..28755599

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024447096.2 → XP_024302864.1 exostosin-like 3 isoform X1

UniProtKB/Swiss-Prot

D3DST8, O00225, O43909, Q53XT3

UniProtKB/TrEMBL

A0A384NPY9, A0A8Q3SIF4

Conserved Domains (3) summary

pfam03016
Location:190 → 500

Exostosin; Exostosin family

pfam07926
Location:71 → 150

TPR_MLP1_2; TPR/MLP1/MLP2-like protein

pfam09258
Location:663 → 900

Glyco_transf_64; Glycosyl transferase family 64 domain
XM_047421516.1 → XP_047277472.1 exostosin-like 3 isoform X1

UniProtKB/Swiss-Prot

D3DST8, O00225, O43909, Q53XT3

UniProtKB/TrEMBL

A0A384NPY9
XM_047421518.1 → XP_047277474.1 exostosin-like 3 isoform X1

UniProtKB/Swiss-Prot

D3DST8, O00225, O43909, Q53XT3

UniProtKB/TrEMBL

A0A384NPY9
XM_047421514.1 → XP_047277470.1 exostosin-like 3 isoform X1

UniProtKB/Swiss-Prot

D3DST8, O00225, O43909, Q53XT3

UniProtKB/TrEMBL

A0A384NPY9
XM_024447094.2 → XP_024302862.1 exostosin-like 3 isoform X1

UniProtKB/Swiss-Prot

D3DST8, O00225, O43909, Q53XT3

UniProtKB/TrEMBL

A0A384NPY9, A0A8Q3SIF4

Related

ENSP00000512468.1, ENST00000696178.1

Conserved Domains (3) summary

pfam03016
Location:190 → 500

Exostosin; Exostosin family

pfam07926
Location:71 → 150

TPR_MLP1_2; TPR/MLP1/MLP2-like protein

pfam09258
Location:663 → 900

Glyco_transf_64; Glycosyl transferase family 64 domain
XM_047421515.1 → XP_047277471.1 exostosin-like 3 isoform X1

UniProtKB/Swiss-Prot

D3DST8, O00225, O43909, Q53XT3

UniProtKB/TrEMBL

A0A384NPY9
XM_047421517.1 → XP_047277473.1 exostosin-like 3 isoform X1

UniProtKB/Swiss-Prot

D3DST8, O00225, O43909, Q53XT3

UniProtKB/TrEMBL

A0A384NPY9
XM_011544440.4 → XP_011542742.1 exostosin-like 3 isoform X1

See identical proteins and their annotated locations for XP_011542742.1

UniProtKB/Swiss-Prot

D3DST8, O00225, O43909, Q53XT3

UniProtKB/TrEMBL

A0A384NPY9, A0A8Q3SIF4

Related

ENSP00000512474.1, ENST00000696186.1

Conserved Domains (3) summary

pfam03016
Location:190 → 500

Exostosin; Exostosin family

pfam07926
Location:71 → 150

TPR_MLP1_2; TPR/MLP1/MLP2-like protein

pfam09258
Location:663 → 900

Glyco_transf_64; Glycosyl transferase family 64 domain