GALE_CAEEL
ID GALE_CAEEL Reviewed; 349 AA.
AC Q564Q1; O62107;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=UDP-glucose 4-epimerase {ECO:0000250|UniProtKB:Q14376};
DE EC=5.1.3.2 {ECO:0000305|PubMed:25298520};
DE AltName: Full=Galactowaldenase {ECO:0000305};
DE AltName: Full=UDP-N-acetylgalactosamine 4-epimerase {ECO:0000250|UniProtKB:Q14376};
DE Short=UDP-GalNAc 4-epimerase {ECO:0000250|UniProtKB:Q14376};
DE AltName: Full=UDP-N-acetylglucosamine 4-epimerase {ECO:0000250|UniProtKB:Q14376};
DE Short=UDP-GlcNAc 4-epimerase {ECO:0000250|UniProtKB:Q14376};
DE EC=5.1.3.7 {ECO:0000305|PubMed:25298520};
DE AltName: Full=UDP-galactose 4-epimerase {ECO:0000303|PubMed:25298520};
GN Name=gale-1 {ECO:0000312|WormBase:C47B2.6b};
GN ORFNames=C47B2.6 {ECO:0000312|WormBase:C47B2.6b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND MUTAGENESIS OF PRO-314.
RX PubMed=25298520; DOI=10.1534/genetics.114.170084;
RA Brokate-Llanos A.M., Monje J.M., Murdoch P., Munoz M.J.;
RT "Developmental defects in a Caenorhabditis elegans model for type III
RT galactosemia.";
RL Genetics 198:1559-1569(2014).
CC -!- FUNCTION: Catalyzes two distinct but analogous reactions: the
CC reversible epimerization of UDP-glucose to UDP-galactose and the
CC reversible epimerization of UDP-N-acetylglucosamine to UDP-N-
CC acetylgalactosamine. The reaction with UDP-Gal plays a critical role in
CC the Leloir pathway of galactose catabolism in which galactose is
CC converted to the glycolytic intermediate glucose 6-phosphate. It
CC contributes to the catabolism of dietary galactose and enables the
CC endogenous biosynthesis of both UDP-Gal and UDP-GalNAc when exogenous
CC sources are limited. Both UDP-sugar interconversions are important for
CC the synthesis of glycoproteins and glycolipids.
CC {ECO:0000269|PubMed:25298520}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=UDP-alpha-D-glucose = UDP-alpha-D-galactose;
CC Xref=Rhea:RHEA:22168, ChEBI:CHEBI:58885, ChEBI:CHEBI:66914;
CC EC=5.1.3.2; Evidence={ECO:0000305|PubMed:25298520};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=UDP-N-acetyl-alpha-D-glucosamine = UDP-N-acetyl-alpha-D-
CC galactosamine; Xref=Rhea:RHEA:20517, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:67138; EC=5.1.3.7;
CC Evidence={ECO:0000305|PubMed:25298520};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000255|RuleBase:RU003508};
CC -!- PATHWAY: Carbohydrate metabolism; galactose metabolism.
CC {ECO:0000269|PubMed:25298520}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:C47B2.6b};
CC IsoId=Q564Q1-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:C47B2.6a};
CC IsoId=Q564Q1-2; Sequence=VSP_059051;
CC -!- TISSUE SPECIFICITY: Expressed in gonads, vulva, intestine, hypdermis
CC and nervous system. {ECO:0000269|PubMed:25298520}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos, larvae and adults.
CC {ECO:0000269|PubMed:25298520}.
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. {ECO:0000255|RuleBase:RU003508}.
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DR EMBL; BX284601; CAB16861.1; -; Genomic_DNA.
DR EMBL; BX284601; CAI79146.1; -; Genomic_DNA.
DR PIR; T19989; T19989.
DR RefSeq; NP_001021051.1; NM_001025880.2. [Q564Q1-2]
DR RefSeq; NP_001021052.1; NM_001025881.3. [Q564Q1-1]
DR AlphaFoldDB; Q564Q1; -.
DR SMR; Q564Q1; -.
DR DIP; DIP-26300N; -.
DR IntAct; Q564Q1; 1.
DR STRING; 6239.C47B2.6b; -.
DR World-2DPAGE; 0020:O62107; -.
DR EPD; Q564Q1; -.
DR PaxDb; Q564Q1; -.
DR PeptideAtlas; Q564Q1; -.
DR EnsemblMetazoa; C47B2.6a.1; C47B2.6a.1; WBGene00008132. [Q564Q1-2]
DR EnsemblMetazoa; C47B2.6a.2; C47B2.6a.2; WBGene00008132. [Q564Q1-2]
DR EnsemblMetazoa; C47B2.6b.1; C47B2.6b.1; WBGene00008132. [Q564Q1-1]
DR EnsemblMetazoa; C47B2.6b.2; C47B2.6b.2; WBGene00008132. [Q564Q1-1]
DR GeneID; 173171; -.
DR KEGG; cel:CELE_C47B2.6; -.
DR UCSC; C47B2.6b; c. elegans.
DR CTD; 173171; -.
DR WormBase; C47B2.6a; CE17566; WBGene00008132; gale-1. [Q564Q1-2]
DR WormBase; C47B2.6b; CE38295; WBGene00008132; gale-1. [Q564Q1-1]
DR eggNOG; KOG1371; Eukaryota.
DR GeneTree; ENSGT00940000158000; -.
DR InParanoid; Q564Q1; -.
DR OMA; GEHLICN; -.
DR OrthoDB; 662484at2759; -.
DR PhylomeDB; Q564Q1; -.
DR Reactome; R-CEL-70370; Galactose catabolism.
DR UniPathway; UPA00214; -.
DR PRO; PR:Q564Q1; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00008132; Expressed in adult organism and 4 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0003978; F:UDP-glucose 4-epimerase activity; IMP:UniProtKB.
DR GO; GO:0003974; F:UDP-N-acetylglucosamine 4-epimerase activity; IMP:UniProtKB.
DR GO; GO:0042335; P:cuticle development; IMP:WormBase.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:UniProtKB.
DR GO; GO:0033499; P:galactose catabolic process via UDP-galactose; IBA:GO_Central.
DR GO; GO:0006012; P:galactose metabolic process; IMP:UniProtKB.
DR GO; GO:0035262; P:gonad morphogenesis; IMP:UniProtKB.
DR GO; GO:1900102; P:negative regulation of endoplasmic reticulum unfolded protein response; IMP:UniProtKB.
DR GO; GO:0002119; P:nematode larval development; IMP:UniProtKB.
DR GO; GO:0040026; P:positive regulation of vulval development; IMP:UniProtKB.
DR GO; GO:1903354; P:regulation of distal tip cell migration; IMP:UniProtKB.
DR CDD; cd05247; UDP_G4E_1_SDR_e; 1.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR005886; UDP_G4E.
DR Pfam; PF16363; GDP_Man_Dehyd; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01179; galE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Carbohydrate metabolism; Galactose metabolism;
KW Isomerase; NAD; Reference proteome.
FT CHAIN 1..349
FT /note="UDP-glucose 4-epimerase"
FT /id="PRO_0000441236"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 10..12
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 31..35
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 66..67
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 92
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 132..134
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 162
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 186..188
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 186
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 207..209
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 225..227
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 240
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 303..306
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT VAR_SEQ 39..40
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_059051"
FT MUTAGEN 314
FT /note="P->L: In pv18; at the restrictive temperature of 25
FT degrees Celsius, embryos have cell-cell adhesion defects
FT and die before hatching. The few surviving animals are
FT arrested at the L1 larval stage. At the permissive
FT temperature of 16-20 degrees Celsius, causes a
FT developmental delay. Distal tip cell migration is impaired
FT due to a reduced localization of metalloprotease mig-17 to
FT the gonad basement membrane. Vulva lumen is smaller at the
FT L4 larval stage. Accumulation of UDP-galactose (Gal) and
FT reduction in UDP-N-acetylgalactosamine (GalNAc) levels.
FT Hypersensitivity to a galactose-rich diet characterized by
FT a slow development often resulting in an arrest at the L1
FT larval stage. Up-regulation of ER stress response protein
FT hsp-4; expression is suppressed in an xbp-1 RNAi-mediated
FT knockdown animals. Reduced survival upon E.faecalis or
FT S.aureus-mediated infection."
FT /evidence="ECO:0000269|PubMed:25298520"
SQ SEQUENCE 349 AA; 37883 MW; 0B0FC906186E2105 CRC64;
MHILVTGAAG FIGSHTVLEL LNSGYTVLCI DNFANAISVT DEHGNAISLK RVAQLTGKDV
PFQNVDVCDE AALEKVFSEN KFDGIIHLAA LKAVGESVAK PLQYYSNNLV ASLNLIQMCL
KYNVKNFVFS SSATVYGPPS ELPITEKSQT GQGITNPYGQ TKYMMEQILI DVGKANPEWN
VVLLRYFNPV GAHKSGLIGE DPKGVPNNLM PYVSQVAIGK LPVLTIYGDQ FDTVDGTGVR
DYIHVVDLAK GHVKAFDRIK TVGNIGTEIY NLGTGVGYSV RQMVDALKKV SGRDIPVKIG
VPRPGDVASV YCDPSLAQEK LGWRAETGLE EMCADLWNWQ TKNPQGFSA
