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Protein

UDP-glucose 4-epimerase

Gene

GALE

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

Functioni

Catalyzes two distinct but analogous reactions: the reversible epimerization of UDP-glucose to UDP-galactose and the reversible epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. The reaction with UDP-Gal plays a critical role in the Leloir pathway of galactose catabolism in which galactose is converted to the glycolytic intermediate glucose 6-phosphate. It contributes to the catabolism of dietary galactose and enables the endogenous biosynthesis of both UDP-Gal and UDP-GalNAc when exogenous sources are limited. Both UDP-sugar interconversions are important in the synthesis of glycoproteins and glycolipids.1 Publication1 Publication

Miscellaneous

Contrary to the human enzyme, the E.coli ortholog (AC P09147) does not catalyze the epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. Compared to the E.coli enzyme, the sugar-binding pocket of the active site is 15% larger for the human enzyme, making it possible to accommodate the acetyl group.1 Publication

Catalytic activityi

UDP-alpha-D-glucose = UDP-alpha-D-galactose.1 Publication
UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-galactosamine.1 Publication

Cofactori

NAD+2 Publications2 Publications

Kineticsi

  1. KM=69 µM for UDP-galactose (at 37 degrees Celsius and pH 8.8)2 Publications
  1. Vmax=1.22 mmol/min/mg enzyme with UDP-galactose as substrate2 Publications

Pathwayi: galactose metabolism

This protein is involved in the pathway galactose metabolism, which is part of Carbohydrate metabolism.
View all proteins of this organism that are known to be involved in the pathway galactose metabolism and in Carbohydrate metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei88NAD; via carbonyl oxygen3 Publications1
Binding sitei92NAD3 Publications1
Active sitei157Proton acceptor1 Publication3 Publications1
Binding sitei161NAD3 Publications1
Binding sitei185NAD1 Publication1
Binding sitei239Substrate3 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi12 – 14NAD3 Publications3
Nucleotide bindingi33 – 37NAD3 Publications5
Nucleotide bindingi66 – 67NAD3 Publications2

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: UniProtKB
  • UDP-glucose 4-epimerase activity Source: UniProtKB
  • UDP-N-acetylglucosamine 4-epimerase activity Source: UniProtKB-EC

GO - Biological processi

  • galactose catabolic process Source: UniProtKB

Keywordsi

Molecular functionIsomerase
Biological processCarbohydrate metabolism, Galactose metabolism
LigandNAD

Enzyme and pathway databases

BioCyciMetaCyc:HS04117-MONOMER
BRENDAi5.1.3.2 2681
ReactomeiR-HSA-5609977 Defective GALE can cause Epimerase-deficiency galactosemia (EDG)
R-HSA-70370 Galactose catabolism
SABIO-RKiQ14376
UniPathwayiUPA00214

Names & Taxonomyi

Protein namesi
Recommended name:
UDP-glucose 4-epimerase1 Publication (EC:5.1.3.21 Publication)
Alternative name(s):
Galactowaldenase
UDP-N-acetylgalactosamine 4-epimerase1 Publication
Short name:
UDP-GalNAc 4-epimerase1 Publication
UDP-N-acetylglucosamine 4-epimerase1 Publication (EC:5.1.3.71 Publication)
Short name:
UDP-GlcNAc 4-epimerase1 Publication
UDP-galactose 4-epimerase1 Publication
Gene namesi
Name:GALEImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000117308.14
HGNCiHGNC:4116 GALE
MIMi606953 gene
neXtProtiNX_Q14376

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

Pathology & Biotechi

Involvement in diseasei

Epimerase-deficiency galactosemia (EDG)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionClinical features include early-onset cataracts, liver damage, deafness and mental retardation. There are two clinically distinct forms of EDG. (1) A benign, or 'peripheral' form with no detectable GALE activity in red blood cells and characterized by mild symptoms. Some patients may suffer no symptoms beyond raised levels of galactose-1-phosphate in the blood. (2) A much rarer 'generalized' form with undetectable levels of GALE activity in all tissues and resulting in severe features such as restricted growth and mental development.
See also OMIM:230350
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03773325A → V in EDG. 1 Publication1
Natural variantiVAR_00253934N → S in EDG; peripheral; nearly normal activity towards UDP-galactose. 3 PublicationsCorresponds to variant dbSNP:rs121908046EnsemblClinVar.1
Natural variantiVAR_03773440R → C in EDG. 1 PublicationCorresponds to variant dbSNP:rs144492228Ensembl.1
Natural variantiVAR_03773569D → E in EDG. 1 Publication1
Natural variantiVAR_00254090G → E in EDG; 800-fold decrease in UDP-galactose epimerization activity. 4 PublicationsCorresponds to variant dbSNP:rs28940882EnsemblClinVar.1
Natural variantiVAR_01005894V → M in EDG; generalized; 30-fold decrease in UDP-galactose epimerization activity; 2-fold decrease in affinity for UDP-galactose; 24% of normal activity with respect to UDP-N-acetylgalactosamine. 4 PublicationsCorresponds to variant dbSNP:rs121908047EnsemblClinVar.1
Natural variantiVAR_002541103D → G in EDG; 7-fold decrease in UDP-galactose epimerization activity; very mild decrease in activity towards UDP-N-acetylgalactosamine. 4 PublicationsCorresponds to variant dbSNP:rs28940883EnsemblClinVar.1
Natural variantiVAR_037736165E → K in EDG. 1 PublicationCorresponds to variant dbSNP:rs528467258Ensembl.1
Natural variantiVAR_037737169R → W in EDG. 1 PublicationCorresponds to variant dbSNP:rs137853859EnsemblClinVar.1
Natural variantiVAR_002543183L → P in EDG; peripheral; 3-fold decrease in UDP-galactose epimerization activity. 3 PublicationsCorresponds to variant dbSNP:rs121908045EnsemblClinVar.1
Natural variantiVAR_037738239R → W in EDG. 1 PublicationCorresponds to variant dbSNP:rs137853860EnsemblClinVar.1
Natural variantiVAR_002544257K → R in EDG; 7-fold decrease in UDP-galactose epimerization activity; does not affect affinity for UDP-galactose. 4 PublicationsCorresponds to variant dbSNP:rs28940884EnsemblClinVar.1
Natural variantiVAR_037739302G → D in EDG. 1 PublicationCorresponds to variant dbSNP:rs137853861EnsemblClinVar.1
Natural variantiVAR_002545313L → M in EDG; 6-fold decrease in UDP-galactose epimerization activity; very mild decrease in activity towards UDP-N-acetylgalactosamine. 4 PublicationsCorresponds to variant dbSNP:rs3180383EnsemblClinVar.1
Natural variantiVAR_002546319G → E in EDG; nearly normal activity towards UDP-galactose; mild impairment under conditions of substrate limitation. 4 PublicationsCorresponds to variant dbSNP:rs28940885EnsemblClinVar.1
Natural variantiVAR_037740335R → H in EDG; 2-fold decrease in UDP-galactose epimerization activity. 3 PublicationsCorresponds to variant dbSNP:rs368637540Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi132S → A: Loss of activity. 1 Publication1
Mutagenesisi157Y → F: Loss of activity. 1 Publication1
Mutagenesisi307C → Y: No effect on activity towards UDP-galactose. Loss of activity towards UDP-N-acetylgalactosamine. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2582
GeneReviewsiGALE
MalaCardsiGALE
MIMi230350 phenotype
OpenTargetsiENSG00000117308
Orphaneti308473 Erythrocyte galactose epimerase deficiency
308487 Generalized galactose epimerase deficiency
PharmGKBiPA28531

Chemistry databases

ChEMBLiCHEMBL5843
DrugBankiDB03501 Galactose-uridine-5'-diphosphate
DB03095 Tetramethylammonium Ion
DB01861 Uridine diphosphate glucose
DB02196 Uridine-Diphosphate-N-Acetylgalactosamine
DB03397 Uridine-Diphosphate-N-Acetylglucosamine

Polymorphism and mutation databases

BioMutaiGALE
DMDMi68056598

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001831891 – 348UDP-glucose 4-epimeraseAdd BLAST348

Proteomic databases

EPDiQ14376
PaxDbiQ14376
PeptideAtlasiQ14376
PRIDEiQ14376
ProteomicsDBi59972
TopDownProteomicsiQ14376-1 [Q14376-1]

PTM databases

iPTMnetiQ14376
PhosphoSitePlusiQ14376
SwissPalmiQ14376

Expressioni

Gene expression databases

BgeeiENSG00000117308
CleanExiHS_GALE
ExpressionAtlasiQ14376 baseline and differential
GenevisibleiQ14376 HS

Organism-specific databases

HPAiHPA007340

Interactioni

Subunit structurei

Homodimer.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-750057,EBI-750057

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi108855, 23 interactors
IntActiQ14376, 2 interactors
STRINGi9606.ENSP00000363621

Chemistry databases

BindingDBiQ14376

Structurei

Secondary structure

1348
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 8Combined sources6
Turni9 – 11Combined sources3
Helixi13 – 24Combined sources12
Beta strandi29 – 33Combined sources5
Beta strandi35 – 38Combined sources4
Beta strandi42 – 46Combined sources5
Helixi47 – 56Combined sources10
Beta strandi61 – 64Combined sources4
Helixi70 – 79Combined sources10
Beta strandi82 – 87Combined sources6
Helixi94 – 99Combined sources6
Helixi101 – 121Combined sources21
Beta strandi126 – 132Combined sources7
Helixi133 – 136Combined sources4
Beta strandi140 – 144Combined sources5
Helixi156 – 174Combined sources19
Beta strandi179 – 185Combined sources7
Beta strandi187 – 189Combined sources3
Beta strandi195 – 197Combined sources3
Beta strandi202 – 204Combined sources3
Helixi208 – 216Combined sources9
Beta strandi219 – 221Combined sources3
Beta strandi223 – 226Combined sources4
Beta strandi230 – 236Combined sources7
Beta strandi241 – 243Combined sources3
Helixi244 – 258Combined sources15
Turni259 – 261Combined sources3
Beta strandi264 – 269Combined sources6
Helixi277 – 288Combined sources12
Beta strandi294 – 297Combined sources4
Beta strandi305 – 307Combined sources3
Helixi312 – 316Combined sources5
Helixi326 – 339Combined sources14

3D structure databases

ProteinModelPortaliQ14376
SMRiQ14376
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14376

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni132 – 134Substrate binding1 Publication3 Publications3
Regioni185 – 187Substrate binding2 Publications3
Regioni206 – 208Substrate binding3 Publications3
Regioni224 – 226Substrate binding3 Publications3
Regioni300 – 303Substrate binding2 Publications4

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1371 Eukaryota
COG1087 LUCA
GeneTreeiENSGT00530000063128
HOGENOMiHOG000168001
HOVERGENiHBG001396
InParanoidiQ14376
KOiK01784
OMAiSCTVYGQ
OrthoDBiEOG091G0ACI
PhylomeDBiQ14376
TreeFamiTF105800

Family and domain databases

CDDicd05247 UDP_G4E_1_SDR_e, 1 hit
InterProiView protein in InterPro
IPR016040 NAD(P)-bd_dom
IPR036291 NAD(P)-bd_dom_sf
IPR008089 Nuc_sugar_epim
IPR005886 UDP_G4E
PfamiView protein in Pfam
PF16363 GDP_Man_Dehyd, 1 hit
PRINTSiPR01713 NUCEPIMERASE
SUPFAMiSSF51735 SSF51735, 1 hit
TIGRFAMsiTIGR01179 galE, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q14376-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAEKVLVTGG AGYIGSHTVL ELLEAGYLPV VIDNFHNAFR GGGSLPESLR
60 70 80 90 100
RVQELTGRSV EFEEMDILDQ GALQRLFKKY SFMAVIHFAG LKAVGESVQK
110 120 130 140 150
PLDYYRVNLT GTIQLLEIMK AHGVKNLVFS SSATVYGNPQ YLPLDEAHPT
160 170 180 190 200
GGCTNPYGKS KFFIEEMIRD LCQADKTWNA VLLRYFNPTG AHASGCIGED
210 220 230 240 250
PQGIPNNLMP YVSQVAIGRR EALNVFGNDY DTEDGTGVRD YIHVVDLAKG
260 270 280 290 300
HIAALRKLKE QCGCRIYNLG TGTGYSVLQM VQAMEKASGK KIPYKVVARR
310 320 330 340
EGDVAACYAN PSLAQEELGW TAALGLDRMC EDLWRWQKQN PSGFGTQA
Length:348
Mass (Da):38,282
Last modified:May 10, 2005 - v2
Checksum:i06FDBF9B1943DF49
GO
Isoform 2 (identifier: Q14376-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: MAEKVLVTGG...QGALQRLFKK → MSPLQ

Note: No experimental confirmation available.Curated
Show »
Length:274
Mass (Da):30,180
Checksum:i1410C9CCFBC96D9E
GO

Sequence cautioni

The sequence EAW95083 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW95084 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW95086 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW95090 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW95091 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW95092 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW95093 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti293P → S in BAG51901 (PubMed:14702039).1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03773325A → V in EDG. 1 Publication1
Natural variantiVAR_00253934N → S in EDG; peripheral; nearly normal activity towards UDP-galactose. 3 PublicationsCorresponds to variant dbSNP:rs121908046EnsemblClinVar.1
Natural variantiVAR_03773440R → C in EDG. 1 PublicationCorresponds to variant dbSNP:rs144492228Ensembl.1
Natural variantiVAR_03773569D → E in EDG. 1 Publication1
Natural variantiVAR_00254090G → E in EDG; 800-fold decrease in UDP-galactose epimerization activity. 4 PublicationsCorresponds to variant dbSNP:rs28940882EnsemblClinVar.1
Natural variantiVAR_01005894V → M in EDG; generalized; 30-fold decrease in UDP-galactose epimerization activity; 2-fold decrease in affinity for UDP-galactose; 24% of normal activity with respect to UDP-N-acetylgalactosamine. 4 PublicationsCorresponds to variant dbSNP:rs121908047EnsemblClinVar.1
Natural variantiVAR_002541103D → G in EDG; 7-fold decrease in UDP-galactose epimerization activity; very mild decrease in activity towards UDP-N-acetylgalactosamine. 4 PublicationsCorresponds to variant dbSNP:rs28940883EnsemblClinVar.1
Natural variantiVAR_037736165E → K in EDG. 1 PublicationCorresponds to variant dbSNP:rs528467258Ensembl.1
Natural variantiVAR_037737169R → W in EDG. 1 PublicationCorresponds to variant dbSNP:rs137853859EnsemblClinVar.1
Natural variantiVAR_002542180A → V2 PublicationsCorresponds to variant dbSNP:rs3204468Ensembl.1
Natural variantiVAR_002543183L → P in EDG; peripheral; 3-fold decrease in UDP-galactose epimerization activity. 3 PublicationsCorresponds to variant dbSNP:rs121908045EnsemblClinVar.1
Natural variantiVAR_037738239R → W in EDG. 1 PublicationCorresponds to variant dbSNP:rs137853860EnsemblClinVar.1
Natural variantiVAR_002544257K → R in EDG; 7-fold decrease in UDP-galactose epimerization activity; does not affect affinity for UDP-galactose. 4 PublicationsCorresponds to variant dbSNP:rs28940884EnsemblClinVar.1
Natural variantiVAR_037739302G → D in EDG. 1 PublicationCorresponds to variant dbSNP:rs137853861EnsemblClinVar.1
Natural variantiVAR_002545313L → M in EDG; 6-fold decrease in UDP-galactose epimerization activity; very mild decrease in activity towards UDP-N-acetylgalactosamine. 4 PublicationsCorresponds to variant dbSNP:rs3180383EnsemblClinVar.1
Natural variantiVAR_002546319G → E in EDG; nearly normal activity towards UDP-galactose; mild impairment under conditions of substrate limitation. 4 PublicationsCorresponds to variant dbSNP:rs28940885EnsemblClinVar.1
Natural variantiVAR_037740335R → H in EDG; 2-fold decrease in UDP-galactose epimerization activity. 3 PublicationsCorresponds to variant dbSNP:rs368637540Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0568221 – 79MAEKV…RLFKK → MSPLQ in isoform 2. Add BLAST79

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L41668 mRNA Translation: AAB86498.1
AF022382 Genomic DNA Translation: AAC39645.1
DQ233667 Genomic DNA Translation: ABB04109.1
DQ233668 mRNA Translation: ABB04110.1
AK057302 mRNA Translation: BAG51901.1
AK314397 mRNA Translation: BAG37021.1
AL031295 Genomic DNA No translation available.
CH471134 Genomic DNA Translation: EAW95083.1 Sequence problems.
CH471134 Genomic DNA Translation: EAW95084.1 Sequence problems.
CH471134 Genomic DNA Translation: EAW95086.1 Sequence problems.
CH471134 Genomic DNA Translation: EAW95090.1 Sequence problems.
CH471134 Genomic DNA Translation: EAW95091.1 Sequence problems.
CH471134 Genomic DNA Translation: EAW95092.1 Sequence problems.
CH471134 Genomic DNA Translation: EAW95093.1 Sequence problems.
BC001273 mRNA Translation: AAH01273.1
BC050685 mRNA Translation: AAH50685.2
CCDSiCCDS242.1 [Q14376-1]
RefSeqiNP_000394.2, NM_000403.3 [Q14376-1]
NP_001008217.1, NM_001008216.1 [Q14376-1]
NP_001121093.1, NM_001127621.1 [Q14376-1]
UniGeneiHs.632380

Genome annotation databases

EnsembliENST00000374497; ENSP00000363621; ENSG00000117308 [Q14376-1]
ENST00000617979; ENSP00000483375; ENSG00000117308 [Q14376-1]
GeneIDi2582
KEGGihsa:2582
UCSCiuc001bhv.2 human [Q14376-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGALE_HUMAN
AccessioniPrimary (citable) accession number: Q14376
Secondary accession number(s): A0A024RAH5
, B3KQ39, Q38G75, Q86W41, Q9BVE3, Q9UJB4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 10, 2005
Last modified: June 20, 2018
This is version 190 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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