GALE_DROME
ID GALE_DROME Reviewed; 350 AA.
AC Q9W0P5;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=UDP-glucose 4-epimerase {ECO:0000303|PubMed:20519568, ECO:0000303|PubMed:22654673};
DE EC=5.1.3.2 {ECO:0000269|PubMed:20519568, ECO:0000269|PubMed:22654673};
DE AltName: Full=Galactowaldenase;
DE AltName: Full=UDP-N-acetylgalactosamine 4-epimerase {ECO:0000303|PubMed:22654673};
DE Short=UDP-GalNAc 4-epimerase {ECO:0000303|PubMed:22654673};
DE AltName: Full=UDP-N-acetylglucosamine 4-epimerase {ECO:0000303|PubMed:22654673};
DE Short=UDP-GlcNAc 4-epimerase {ECO:0000303|PubMed:22654673};
DE EC=5.1.3.7 {ECO:0000269|PubMed:22654673};
DE AltName: Full=UDP-galactose 4-epimerase {ECO:0000303|PubMed:20519568, ECO:0000303|PubMed:22654673};
GN Name=Gale; ORFNames=CG12030;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20519568; DOI=10.1242/dmm.005058;
RA Sanders R.D., Sefton J.M., Moberg K.H., Fridovich-Keil J.L.;
RT "UDP-galactose 4' epimerase (GALE) is essential for development of
RT Drosophila melanogaster.";
RL Dis. Model. Mech. 3:628-638(2010).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=22654673; DOI=10.1371/journal.pgen.1002721;
RA Daenzer J.M., Sanders R.D., Hang D., Fridovich-Keil J.L.;
RT "UDP-galactose 4'-epimerase activities toward UDP-Gal and UDP-GalNAc play
RT different roles in the development of Drosophila melanogaster.";
RL PLoS Genet. 8:E1002721-E1002721(2012).
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 (PubMed:20519568, PubMed:22654673). The reaction
CC with UDP-Gal plays a critical role in the Leloir pathway of galactose
CC catabolism in which galactose is converted to the glycolytic
CC intermediate glucose 6-phosphate. It contributes to the catabolism of
CC dietary galactose and enables the endogenous biosynthesis of both UDP-
CC Gal and UDP-GalNAc when exogenous sources are limited
CC (PubMed:22654673). Both UDP-sugar interconversions are important in the
CC synthesis of glycoproteins and glycolipids.
CC {ECO:0000269|PubMed:20519568, ECO:0000269|PubMed:22654673}.
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:0000269|PubMed:20519568,
CC ECO:0000269|PubMed:22654673};
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:0000269|PubMed:22654673};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000250|UniProtKB:Q14376};
CC -!- PATHWAY: Carbohydrate metabolism; galactose metabolism.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q14376}.
CC -!- DISRUPTION PHENOTYPE: Required from embryogenesis through pupation,
CC even in the absence of galactose. Loss of Gale during pupation leads to
CC defects in fecundity, both in male and female. Gale activity toward
CC UDP-Gal is both necessary and sufficient for male fecundity, but Gale
CC activities toward both UDP-Gal and UDP-GalNAc are required for female
CC fecundity. Eggs may require a more substantial pool of specific UDP-
CC sugar substrates than sperm. Individual loss of one activity or the
CC other later in development results in differential sensitivity to
CC galactose. Both male and female deficient in Gale activity toward UDP-
CC Gal exhibit a reduced lifespan when exposed to galactose; this effect
CC is not seen in flies uniquely deficient in Gale activity toward UDP-
CC GalNAc. {ECO:0000269|PubMed:22654673}.
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. {ECO:0000305}.
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DR EMBL; AE014296; AAF47398.1; -; Genomic_DNA.
DR EMBL; AY058582; AAL13811.1; -; mRNA.
DR RefSeq; NP_001246537.1; NM_001259608.2.
DR RefSeq; NP_612044.1; NM_138200.4.
DR AlphaFoldDB; Q9W0P5; -.
DR SMR; Q9W0P5; -.
DR BioGRID; 63631; 30.
DR DIP; DIP-20343N; -.
DR IntAct; Q9W0P5; 2.
DR STRING; 7227.FBpp0072455; -.
DR PaxDb; Q9W0P5; -.
DR PRIDE; Q9W0P5; -.
DR DNASU; 38076; -.
DR EnsemblMetazoa; FBtr0072556; FBpp0072455; FBgn0035147.
DR EnsemblMetazoa; FBtr0306917; FBpp0297771; FBgn0035147.
DR GeneID; 38076; -.
DR KEGG; dme:Dmel_CG12030; -.
DR UCSC; CG12030-RA; d. melanogaster.
DR CTD; 2582; -.
DR FlyBase; FBgn0035147; Gale.
DR VEuPathDB; VectorBase:FBgn0035147; -.
DR eggNOG; KOG1371; Eukaryota.
DR HOGENOM; CLU_007383_1_10_1; -.
DR InParanoid; Q9W0P5; -.
DR OMA; GEHLICN; -.
DR OrthoDB; 662484at2759; -.
DR PhylomeDB; Q9W0P5; -.
DR BRENDA; 5.1.3.2; 1994.
DR Reactome; R-DME-70370; Galactose catabolism.
DR UniPathway; UPA00214; -.
DR BioGRID-ORCS; 38076; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 38076; -.
DR PRO; PR:Q9W0P5; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0035147; Expressed in capitellum (Drosophila) and 37 other tissues.
DR ExpressionAtlas; Q9W0P5; baseline and differential.
DR Genevisible; Q9W0P5; DM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0003978; F:UDP-glucose 4-epimerase activity; IMP:FlyBase.
DR GO; GO:0003974; F:UDP-N-acetylglucosamine 4-epimerase activity; IMP:FlyBase.
DR GO; GO:0033499; P:galactose catabolic process via UDP-galactose; IBA:GO_Central.
DR GO; GO:0006012; P:galactose metabolic process; IMP:FlyBase.
DR GO; GO:0035167; P:larval lymph gland hemopoiesis; IMP:FlyBase.
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 Carbohydrate metabolism; Galactose metabolism; Isomerase; NAD;
KW Reference proteome.
FT CHAIN 1..350
FT /note="UDP-glucose 4-epimerase"
FT /id="PRO_0000183192"
FT ACT_SITE 158
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 13..15
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 34..38
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 67..68
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 89
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 93
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q14376"
FT BINDING 133..135
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"
SQ SEQUENCE 350 AA; 38697 MW; 0F14EDCCB089ADF5 CRC64;
MAPPTVLVTG GAGYIGSHTV LEMLNAGYNV ICVDNLCNAY SSGAKLPEAL SRVQEITGKK
VNFYRVDITD REQVRSVFQE HKIDMVAHFA ALKAVGESCR IPLQYYHNNM TGTNVLLEAM
ADNNVFKFVY SSSATVYGEP KFLPVTEEHP TGNCTSPYGK TKYFTEEILK DLCKSDKRWA
VVSLRYFNPV GAHISGRIGE DPNGEPNNLM PYIAQVAVGR RPSLSVYGSD FPTHDGTGVR
DYIHIVDLAE GHVKALDKLR NIAETGFFAY NLGTGVGYSV LDMVKAFEKA SGKKVNYTLV
DRRSGDVATC YADATLADKK LGWKAERGID KMCEDTWRWQ SQNPNGYANK
