glceb

UniProt ID: F1QR43
Organism: Danio rerio
Review Status: DRAFT
📝 Provide Detailed Feedback

Gene Description

glceb encodes zebrafish D-glucuronyl C5-epimerase B, a Golgi membrane (type II transmembrane) enzyme that converts D-glucuronic acid residues adjacent to N-sulfated sugars into L-iduronic acid during heparan sulfate and heparin chain biosynthesis (heparosan-N-sulfate-glucuronate 5-epimerase, EC 5.1.3.17). It acts as a homodimer with two catalytic sites per dimer and active-site tyrosines (Tyr468/Tyr528/Tyr546) required for catalysis. glceb is one of two zebrafish paralogs (glce-A/glce-B) of the single human GLCE gene. Its epimerase activity tunes heparan sulfate fine structure (IdoA content) that controls morphogen signaling; in zebrafish embryos overexpression causes BMP-like ventralization and morpholino knockdown causes dorsalization, placing glce in BMP-dependent dorsoventral axis formation.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0015012 heparan sulfate proteoglycan biosynthetic process
IBA
GO_REF:0000033 		ACCEPT
Summary: heparan sulfate proteoglycan biosynthetic process (GO:0015012) is supported as the direct pathway context. Glce performs the C5-epimerization step of the HS modification cascade, acting after N-sulfation to generate IdoA residues that are subsequently O-sulfated. In zebrafish, this activity is developmentally regulated and required for HS fine structure that controls morphogen signaling.
Reason: Glce is a heparan sulfate biosynthetic enzyme.
Supporting Evidence:
file:DANRE/glceb/glceb-uniprot.txt
PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
PMID:25568314
D-glucuronyl C5-epimerase (Glce) is a crucial enzyme in HS synthesis
file:DANRE/glceb/glceb-deep-research-falcon.md
Glce participates in the canonical HS modification sequence in which N-sulfation creates substrate contexts for subsequent modifications; GLCE-mediated epimerization creates IdoA residues that can subsequently be O-sulfated and incorporated into high-affinity binding sites
GO:0047464 heparosan-N-sulfate-glucuronate 5-epimerase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: heparosan-N-sulfate-glucuronate 5-epimerase activity (GO:0047464) is the direct supported molecular function.
Reason: The enzyme converts D-glucuronic acid to L-iduronic acid in heparan sulfate/heparin chains.
Supporting Evidence:
file:DANRE/glceb/glceb-uniprot.txt
Converts D-glucuronic acid residues adjacent to N-sulfate
PMID:25568314
converting D-glucuronic acid to L-iduronic
file:DANRE/glceb/glceb-deep-research-falcon.md
converts **D-glucuronic acid (GlcA)** residues to **L-iduronic acid (IdoA)** within the polymer
GO:0005794 Golgi apparatus
IBA
GO_REF:0000033 		ACCEPT
Summary: Golgi apparatus (GO:0005794) is supported for glceb.
Reason: Golgi localization is coherent with the more specific Golgi membrane annotation.
Supporting Evidence:
file:DANRE/glceb/glceb-uniprot.txt
SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0000139 Golgi membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: Golgi membrane (GO:0000139) is supported for glceb. GLCE is a type II transmembrane Golgi-resident glycan modification enzyme; its HS-modified products subsequently act at the cell surface and extracellular matrix.
Reason: UniProt places Glceb at the Golgi apparatus membrane.
Supporting Evidence:
file:DANRE/glceb/glceb-uniprot.txt
SUBCELLULAR LOCATION: Golgi apparatus membrane
file:DANRE/glceb/glceb-deep-research-falcon.md
GLCE/Glce is generally described as a **type II transmembrane protein** in the HS biosynthetic machinery, which is consistent with function as a Golgi-resident glycan modification enzyme
GO:0015012 heparan sulfate proteoglycan biosynthetic process
IEA
GO_REF:0000120 		ACCEPT
Summary: heparan sulfate proteoglycan biosynthetic process (GO:0015012) is supported as the direct pathway context.
Reason: Glce is a heparan sulfate biosynthetic enzyme.
Supporting Evidence:
file:DANRE/glceb/glceb-uniprot.txt
PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
PMID:25568314
D-glucuronyl C5-epimerase (Glce) is a crucial enzyme in HS synthesis
GO:0047464 heparosan-N-sulfate-glucuronate 5-epimerase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: heparosan-N-sulfate-glucuronate 5-epimerase activity (GO:0047464) is the direct supported molecular function.
Reason: The enzyme converts D-glucuronic acid to L-iduronic acid in heparan sulfate/heparin chains.
Supporting Evidence:
file:DANRE/glceb/glceb-uniprot.txt
Converts D-glucuronic acid residues adjacent to N-sulfate
PMID:25568314
converting D-glucuronic acid to L-iduronic
GO:0030210 heparin proteoglycan biosynthetic process
IEA
GO_REF:0000041 		KEEP AS NON CORE
Summary: heparin proteoglycan biosynthetic process (GO:0030210) is supported by pathway context but is not the main zebrafish core annotation.
Reason: UniProt includes heparin biosynthesis, but the central conserved role in this review is heparan sulfate chain epimerization.
Supporting Evidence:
file:DANRE/glceb/glceb-uniprot.txt
PATHWAY: Glycan metabolism; heparin biosynthesis.
GO:0042802 identical protein binding
IPI
PMID:25568314
Structural and functional study of D-glucuronyl C5-epimerase... 		KEEP AS NON CORE
Summary: identical protein binding (GO:0042802) is supported as homodimerization but is not a core function. The zebrafish Glce crystal structure shows a stable dimer with two catalytic sites per dimer; dimerization is thus the functional quaternary state that builds the active sites, but it remains structural context rather than the GO molecular function of the enzyme.
Reason: Dimerization is structural context for the enzyme rather than its GO molecular function.
Supporting Evidence:
file:DANRE/glceb/glceb-uniprot.txt
SUBUNIT: Homodimer.
PMID:25568314
zebrafish Glce has a dimeric structure
file:DANRE/glceb/glceb-deep-research-falcon.md
Glce forms a **stable dimer** in which each dimer contains **two catalytic sites** located in C-terminal helical domains
GO:0000139 Golgi membrane
ISS
GO_REF:0000024 		ACCEPT
Summary: Golgi membrane (GO:0000139) is supported for glceb.
Reason: UniProt places Glceb at the Golgi apparatus membrane.
Supporting Evidence:
file:DANRE/glceb/glceb-uniprot.txt
SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0047464 heparosan-N-sulfate-glucuronate 5-epimerase activity
IDA
PMID:25568314
Structural and functional study of D-glucuronyl C5-epimerase... 		ACCEPT
Summary: heparosan-N-sulfate-glucuronate 5-epimerase activity (GO:0047464) is the direct supported molecular function, experimentally demonstrated for zebrafish Glce. The enzyme epimerizes C5 of D-glucuronic acid to L-iduronic acid within heparan sulfate/heparin chains, and substrate recognition requires N-sulfated glucosamine adjacent to the epimerization site. Structure-guided mutagenesis identified active-site tyrosines (Tyr468, Tyr528, Tyr546) essential for catalysis, confirming F1QR43 is a functional GLCE-family epimerase.
Reason: The enzyme converts D-glucuronic acid to L-iduronic acid in heparan sulfate/heparin chains.
Supporting Evidence:
file:DANRE/glceb/glceb-uniprot.txt
Converts D-glucuronic acid residues adjacent to N-sulfate
PMID:25568314
converting D-glucuronic acid to L-iduronic
file:DANRE/glceb/glceb-deep-research-falcon.md
GLCE preferentially recognizes HS regions where adjacent glucosamine residues are **N-sulfated** (GlcNS)
file:DANRE/glceb/glceb-deep-research-falcon.md
Tyr468, Tyr528, and Tyr546 were identified as essential for enzymatic activity

Core Functions

glceb enables Golgi membrane heparosan-N-sulfate-glucuronate 5-epimerase activity, converting D-glucuronic acid to L-iduronic acid during heparan sulfate proteoglycan biosynthesis.

Molecular Function:
heparosan-N-sulfate-glucuronate 5-epimerase activity
Directly Involved In:
heparan sulfate proteoglycan biosynthetic process
Cellular Locations:
Golgi membrane
Supporting Evidence:
  • file:DANRE/glceb/glceb-uniprot.txt
    Converts D-glucuronic acid residues adjacent to N-sulfate
  • PMID:25568314
    converting D-glucuronic acid to L-iduronic
  • file:DANRE/glceb/glceb-uniprot.txt
    SUBCELLULAR LOCATION: Golgi apparatus membrane
  • file:DANRE/glceb/glceb-deep-research-falcon.md
    converts **D-glucuronic acid (GlcA)** residues to **L-iduronic acid (IdoA)** within the polymer

References

Loading supporting content…

Download this section (compressed HTML)

Suggested Questions for Experts

Q: Do zebrafish glceb (glce-B) and glcea (glce-A) have distinct or redundant roles in HS fine structure and morphogen signaling, given their overlapping expression and similar overexpression/knockdown phenotypes?

Q: Does the reported physical association of Glce with 2-O- and 6-O-sulfotransferases (the proposed 'GAGosome') operate in zebrafish, and is it required for proper IdoA/O-sulfation patterning in vivo?

Suggested Experiments

Experiment: Generate glceb loss-of-function mutants (CRISPR) and assay HS disaccharide composition (IdoA content) together with dorsoventral patterning markers to define the in vivo requirement for glceb specifically versus glcea.

Deep Research

Falcon

(glceb-deep-research-falcon.md)

Loading supporting content…

Download this section (compressed HTML)

📚 Additional Documentation

Notes

(glceb-notes.md)

Notes for DANRE glceb

2026-05-09 review notes

  • Core function is Golgi membrane D-glucuronyl C5 epimerase activity in heparan sulfate biosynthesis [file:DANRE/glceb/glceb-uniprot.txt "Converts D-glucuronic acid residues adjacent to N-sulfate"].
  • Heparin biosynthesis is kept as non-core because UniProt lists it as a pathway, but the central review emphasis is heparan sulfate chain epimerization [file:DANRE/glceb/glceb-uniprot.txt "PATHWAY: Glycan metabolism; heparin biosynthesis."].
  • Identical protein binding reflects homodimerization, not the core catalytic function PMID:25568314.

📄 View Raw YAML

Loading supporting content…

Download this section (compressed HTML)