ID GALE_HUMAN Reviewed; 348 AA. AC Q14376; A0A024RAH5; B3KQ39; Q38G75; Q86W41; Q9BVE3; Q9UJB4; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 10-MAY-2005, sequence version 2. DT 22-APR-2020, entry version 204. DE RecName: Full=UDP-glucose 4-epimerase {ECO:0000303|PubMed:22654673}; DE EC=5.1.3.2 {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:22654673}; GN Name=GALE {ECO:0000312|HGNC:HGNC:4116}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-180. RX PubMed=8593531; DOI=10.1006/bmme.1995.1048; RA Daude N., Gallaher T.K., Zeschnigk M., Starzinski-Powitz A., Petry K.G., RA Haworth I.S., Reichardt J.K.V.; RT "Molecular cloning, characterization, and mapping of a full-length cDNA RT encoding human UDP-galactose 4'-epimerase."; RL Biochem. Mol. Med. 56:1-7(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS EDG GLU-90; GLY-103; RP ARG-257; MET-313 AND GLU-319. RX PubMed=9538513; DOI=10.1006/mgme.1997.2645; RA Maceratesi P., Daude N., Dallapiccola B., Novelli G., Allen R., Okano Y., RA Reichardt J.K.V.; RT "Human UDP-galactose 4'epimerase (GALE) gene and identification of five RT missense mutations in patients with epimerase deficiency galactosemia."; RL Mol. Genet. Metab. 63:26-30(1998). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RX PubMed=16385452; DOI=10.1086/498985; RA Openo K.K., Schulz J.M., Vargas C.A., Orton C.S., Epstein M.P., RA Schnur R.E., Scaglia F., Berry G.T., Gottesman G.S., Ficicioglu C., RA Slonim A.E., Schroer R.J., Yu C., Rangel V.E., Keenan J., Lamance K., RA Fridovich-Keil J.L.; RT "Epimerase-deficiency galactosemia is not a binary condition."; RL Am. J. Hum. Genet. 78:89-102(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Colon, and Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Cervix, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR. 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). RN [10] RP FUNCTION. RX PubMed=23732289; DOI=10.1016/j.gene.2013.05.027; RA Timson D.J., Lindert S.; RT "Comparison of dynamics of wildtype and V94M human UDP-galactose 4- RT epimerase-A computational perspective on severe epimerase-deficiency RT galactosemia."; RL Gene 526:318-324(2013). RN [11] RP MUTAGENESIS OF SER-132; TYR-157 AND CYS-307. RX PubMed=15175331; DOI=10.1074/jbc.m405005200; RA Schulz J.M., Watson A.L., Sanders R., Ross K.L., Thoden J.B., Holden H.M., RA Fridovich-Keil J.L.; RT "Determinants of function and substrate specificity in human UDP-galactose RT 4'-epimerase."; RL J. Biol. Chem. 279:32796-32803(2004). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [13] RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) IN COMPLEX WITH NAD AND THE RP SUBSTRATE UDP-D-GLUCOSE, AND SUBUNIT. RX PubMed=10801319; DOI=10.1021/bi000215l; RA Thoden J.B., Wohlers T.M., Fridovich-Keil J.L., Holden H.M.; RT "Crystallographic evidence for Tyr 157 functioning as the active site RT Proton acceptor in human UDP-galactose 4-epimerase."; RL Biochemistry 39:5691-5701(2000). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) IN COMPLEX WITH NAD AND THE RP SUBSTRATE UDP-N-ACETYL-ALPHA-D-GLUCOSAMINE. RX PubMed=11279032; DOI=10.1074/jbc.m100220200; RA Thoden J.B., Wohlers T.M., Fridovich-Keil J.L., Holden H.M.; RT "Human UDP-galactose 4-epimerase. Accommodation of UDP-N-acetylglucosamine RT within the active site."; RL J. Biol. Chem. 276:15131-15136(2001). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF VARIANT EDG MET-94 IN COMPLEXES RP WITH NAD AND THE SUBSTRATE ANALOGS UDP-D-GALACTOSE; RP UDP-N-ACETYL-ALPHA-D-GLUCOSAMINE; UDP-D-GLUCOSE. RX PubMed=11279193; DOI=10.1074/jbc.m101304200; RA Thoden J.B., Wohlers T.M., Fridovich-Keil J.L., Holden H.M.; RT "Molecular basis for severe epimerase deficiency galactosemia. X-ray RT structure of the human V94m-substituted UDP-galactose 4-epimerase."; RL J. Biol. Chem. 276:20617-20623(2001). RN [16] RP VARIANTS EDG SER-34 AND PRO-183, AND VARIANT VAL-180. RX PubMed=9326324; DOI=10.1086/515517; RA Quimby B.B., Alano A., Almashanu S., Desandro A.M., Cowan T.M., RA Fridovich-Keil J.L.; RT "Characterization of two mutations associated with epimerase-deficiency RT galactosemia, by use of a yeast expression system for human UDP-galactose- RT 4-epimerase."; RL Am. J. Hum. Genet. 61:590-598(1997). RN [17] RP VARIANT EDG MET-94, AND CHARACTERIZATION OF VARIANTS EDG GLU-90; MET-94; RP GLY-103 AND MET-313. RX PubMed=9973283; DOI=10.1086/302263; RA Wohlers T.M., Christacos N.C., Harreman M.T., Fridovich-Keil J.L.; RT "Identification and characterization of a mutation, in the human UDP- RT galactose-4-epimerase gene, associated with generalized epimerase- RT deficiency galactosemia."; RL Am. J. Hum. Genet. 64:462-470(1999). RN [18] RP BIOPHYSICOCHEMICAL PROPERTIES, AND CHARACTERIZATION OF VARIANT MET-94. RX PubMed=11117433; DOI=10.1023/a:1005682913784; RA Wohlers T.M., Fridovich-Keil J.L.; RT "Studies of the V94M-substituted human UDPgalactose-4-epimerase enzyme RT associated with generalized epimerase-deficiency galactosaemia."; RL J. Inherit. Metab. Dis. 23:713-729(2000). RN [19] RP VARIANTS EDG SER-34; GLU-90; MET-94; GLY-103; PRO-183; ARG-257; MET-313; RP GLU-319 AND HIS-335. RX PubMed=11903335; DOI=10.1034/j.1399-0004.2001.600505.x; RA Henderson J.M., Huguenin S.M., Cowan T.M., Fridovich-Keil J.L.; RT "A PCR-based method for detecting known mutations in the human UDP RT galactose-4'-epimerase gene associated with epimerase-deficiency RT galactosemia."; RL Clin. Genet. 60:350-355(2001). RN [20] RP BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION OF VARIANTS EDG SER-34; RP GLU-90; MET-94; GLY-103; PRO-183; ARG-257; MET-313; GLU-319 AND HIS-335, RP AND SUBUNIT. RX PubMed=16302980; DOI=10.1111/j.1742-4658.2005.05017.x; RA Timson D.J.; RT "Functional analysis of disease-causing mutations in human UDP-galactose 4- RT epimerase."; RL FEBS J. 272:6170-6177(2005). RN [21] RP VARIANTS EDG VAL-25; CYS-40; GLU-69; LYS-165; TRP-169; TRP-239; ASP-302 AND RP HIS-335. RX PubMed=16301867; DOI=10.109701.gim.0000194023.27802.2d; RA Park H.-D., Park K.U., Kim J.Q., Shin C.H., Yang S.W., Lee D.H., RA Song Y.-H., Song J.; RT "The molecular basis of UDP-galactose-4-epimerase (GALE) deficiency RT galactosemia in Korean patients."; RL Genet. Med. 7:646-649(2005). RN [22] RP CHARACTERIZATION OF VARIANTS EDG ARG-257 AND GLU-319. RX PubMed=15639193; DOI=10.1016/j.ymgme.2004.09.003; RA Wasilenko J., Lucas M.E., Thoden J.B., Holden H.M., Fridovich-Keil J.L.; RT "Functional characterization of the K257R and G319E-hGALE alleles found in RT patients with ostensibly peripheral epimerase deficiency galactosemia."; RL Mol. Genet. Metab. 84:32-38(2005). 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 in CC the synthesis of glycoproteins and glycolipids. CC {ECO:0000269|PubMed:22654673, ECO:0000303|PubMed:23732289}. 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: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:0000269|PubMed:10801319, ECO:0000269|PubMed:22654673, CC ECO:0000303|PubMed:11279032, ECO:0000303|PubMed:11279193}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=69 uM for UDP-galactose (at 37 degrees Celsius and pH 8.8) CC {ECO:0000269|PubMed:11117433, ECO:0000269|PubMed:16302980}; CC Vmax=1.22 mmol/min/mg enzyme with UDP-galactose as substrate CC {ECO:0000269|PubMed:11117433, ECO:0000269|PubMed:16302980}; CC -!- PATHWAY: Carbohydrate metabolism; galactose metabolism. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10801319, CC ECO:0000269|PubMed:16302980}. CC -!- INTERACTION: CC Q14376; Q14376; NbExp=7; IntAct=EBI-750057, EBI-750057; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q14376-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14376-2; Sequence=VSP_056822; CC -!- DISEASE: Epimerase-deficiency galactosemia (EDG) [MIM:230350]: Clinical CC features include early-onset cataracts, liver damage, deafness and CC mental retardation. There are two clinically distinct forms of EDG. (1) CC A benign, or 'peripheral' form with no detectable GALE activity in red CC blood cells and characterized by mild symptoms. Some patients may CC suffer no symptoms beyond raised levels of galactose-1-phosphate in the CC blood. (2) A much rarer 'generalized' form with undetectable levels of CC GALE activity in all tissues and resulting in severe features such as CC restricted growth and mental development. {ECO:0000269|PubMed:11279193, CC ECO:0000269|PubMed:11903335, ECO:0000269|PubMed:15639193, CC ECO:0000269|PubMed:16301867, ECO:0000269|PubMed:16302980, CC ECO:0000269|PubMed:9326324, ECO:0000269|PubMed:9538513, CC ECO:0000269|PubMed:9973283}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Contrary to the human enzyme, the E.coli ortholog (AC CC P09147) does not catalyze the epimerization of UDP-N-acetylglucosamine CC to UDP-N-acetylgalactosamine. Compared to the E.coli enzyme, the sugar- CC binding pocket of the active site is 15% larger for the human enzyme, CC making it possible to accommodate the acetyl group. CC {ECO:0000269|PubMed:11279032}. CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase CC family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=EAW95083.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=EAW95084.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=EAW95086.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=EAW95090.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=EAW95091.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=EAW95092.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=EAW95093.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Galactosemia Proteins Database; CC URL="http://www.protein-variants.eu/galactosemia/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L41668; AAB86498.1; -; mRNA. DR EMBL; AF022382; AAC39645.1; -; Genomic_DNA. DR EMBL; DQ233667; ABB04109.1; -; Genomic_DNA. DR EMBL; DQ233668; ABB04110.1; -; mRNA. DR EMBL; AK057302; BAG51901.1; -; mRNA. DR EMBL; AK314397; BAG37021.1; -; mRNA. DR EMBL; AL031295; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471134; EAW95083.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471134; EAW95084.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471134; EAW95086.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471134; EAW95090.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471134; EAW95091.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471134; EAW95092.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471134; EAW95093.1; ALT_SEQ; Genomic_DNA. DR EMBL; BC001273; AAH01273.1; -; mRNA. DR EMBL; BC050685; AAH50685.2; -; mRNA. DR CCDS; CCDS242.1; -. [Q14376-1] DR RefSeq; NP_000394.2; NM_000403.3. [Q14376-1] DR RefSeq; NP_001008217.1; NM_001008216.1. [Q14376-1] DR RefSeq; NP_001121093.1; NM_001127621.1. [Q14376-1] DR PDB; 1EK5; X-ray; 1.80 A; A=1-348. DR PDB; 1EK6; X-ray; 1.50 A; A/B=1-348. DR PDB; 1HZJ; X-ray; 1.50 A; A/B=1-348. DR PDB; 1I3K; X-ray; 1.50 A; A/B=1-348. DR PDB; 1I3L; X-ray; 1.50 A; A/B=1-348. DR PDB; 1I3M; X-ray; 1.50 A; A/B=1-348. DR PDB; 1I3N; X-ray; 1.50 A; A/B=1-348. DR PDBsum; 1EK5; -. DR PDBsum; 1EK6; -. DR PDBsum; 1HZJ; -. DR PDBsum; 1I3K; -. DR PDBsum; 1I3L; -. DR PDBsum; 1I3M; -. DR PDBsum; 1I3N; -. DR SMR; Q14376; -. DR BioGrid; 108855; 28. DR IntAct; Q14376; 2. DR STRING; 9606.ENSP00000483375; -. DR BindingDB; Q14376; -. DR ChEMBL; CHEMBL5843; -. DR DrugBank; DB03501; Galactose-uridine-5'-diphosphate. DR DrugBank; DB03095; Tetramethylammonium Ion. DR DrugBank; DB03041; UDP-alpha-D-glucuronic acid. DR DrugBank; DB01861; Uridine diphosphate glucose. DR DrugBank; DB02196; Uridine-Diphosphate-N-Acetylgalactosamine. DR DrugBank; DB03397; Uridine-Diphosphate-N-Acetylglucosamine. DR DrugCentral; Q14376; -. DR iPTMnet; Q14376; -. DR MetOSite; Q14376; -. DR PhosphoSitePlus; Q14376; -. DR SwissPalm; Q14376; -. DR BioMuta; GALE; -. DR DMDM; 68056598; -. DR EPD; Q14376; -. DR jPOST; Q14376; -. DR MassIVE; Q14376; -. DR PaxDb; Q14376; -. DR PeptideAtlas; Q14376; -. DR PRIDE; Q14376; -. DR ProteomicsDB; 59972; -. [Q14376-1] DR TopDownProteomics; Q14376-1; -. [Q14376-1] DR Antibodypedia; 1527; 292 antibodies. DR DNASU; 2582; -. DR Ensembl; ENST00000374497; ENSP00000363621; ENSG00000117308. [Q14376-1] DR Ensembl; ENST00000617979; ENSP00000483375; ENSG00000117308. [Q14376-1] DR GeneID; 2582; -. DR KEGG; hsa:2582; -. DR UCSC; uc001bhv.2; human. [Q14376-1] DR CTD; 2582; -. DR DisGeNET; 2582; -. DR GeneCards; GALE; -. DR GeneReviews; GALE; -. DR HGNC; HGNC:4116; GALE. DR HPA; ENSG00000117308; Low tissue specificity. DR MalaCards; GALE; -. DR MIM; 230350; phenotype. DR MIM; 606953; gene. DR neXtProt; NX_Q14376; -. DR OpenTargets; ENSG00000117308; -. DR Orphanet; 308473; Erythrocyte galactose epimerase deficiency. DR Orphanet; 308487; Generalized galactose epimerase deficiency. DR PharmGKB; PA28531; -. DR eggNOG; KOG1371; Eukaryota. DR eggNOG; COG1087; LUCA. DR GeneTree; ENSGT00940000158000; -. DR InParanoid; Q14376; -. DR KO; K01784; -. DR OMA; GEHLICN; -. DR OrthoDB; 662484at2759; -. DR PhylomeDB; Q14376; -. DR TreeFam; TF105800; -. DR BioCyc; MetaCyc:HS04117-MONOMER; -. DR BRENDA; 5.1.3.2; 2681. DR Reactome; R-HSA-5609977; Defective GALE can cause Epimerase-deficiency galactosemia (EDG). DR Reactome; R-HSA-70370; Galactose catabolism. DR SABIO-RK; Q14376; -. DR UniPathway; UPA00214; -. DR EvolutionaryTrace; Q14376; -. DR GenomeRNAi; 2582; -. DR Pharos; Q14376; Tchem. DR PRO; PR:Q14376; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q14376; protein. DR Bgee; ENSG00000117308; Expressed in lower esophagus mucosa and 195 other tissues. DR ExpressionAtlas; Q14376; baseline and differential. DR Genevisible; Q14376; HS. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0003978; F:UDP-glucose 4-epimerase activity; IDA:UniProtKB. DR GO; GO:0003974; F:UDP-N-acetylglucosamine 4-epimerase activity; IEA:UniProtKB-EC. DR GO; GO:0019388; P:galactose catabolic process; IDA:UniProtKB. DR GO; GO:0033499; P:galactose catabolic process via UDP-galactose; IBA:GO_Central. 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 3D-structure; Alternative splicing; Carbohydrate metabolism; KW Disease mutation; Galactose metabolism; Isomerase; NAD; Polymorphism; KW Reference proteome. FT CHAIN 1..348 FT /note="UDP-glucose 4-epimerase" FT /id="PRO_0000183189" FT NP_BIND 12..14 FT /note="NAD" FT /evidence="ECO:0000269|PubMed:10801319, FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193" FT NP_BIND 33..37 FT /note="NAD" FT /evidence="ECO:0000269|PubMed:10801319, FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193" FT NP_BIND 66..67 FT /note="NAD" FT /evidence="ECO:0000269|PubMed:10801319, FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193" FT REGION 132..134 FT /note="Substrate binding" FT /evidence="ECO:0000269|PubMed:10801319, FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193, FT ECO:0000303|PubMed:15175331" FT REGION 185..187 FT /note="Substrate binding" FT /evidence="ECO:0000269|PubMed:11279032, FT ECO:0000269|PubMed:11279193" FT REGION 206..208 FT /note="Substrate binding" FT /evidence="ECO:0000269|PubMed:10801319, FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193" FT REGION 224..226 FT /note="Substrate binding" FT /evidence="ECO:0000269|PubMed:10801319, FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193" FT REGION 300..303 FT /note="Substrate binding" FT /evidence="ECO:0000269|PubMed:11279032, FT ECO:0000269|PubMed:11279193" FT ACT_SITE 157 FT /note="Proton acceptor" FT /evidence="ECO:0000269|PubMed:10801319, FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193, FT ECO:0000303|PubMed:15175331" FT BINDING 88 FT /note="NAD; via carbonyl oxygen" FT /evidence="ECO:0000269|PubMed:10801319, FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193" FT BINDING 92 FT /note="NAD" FT /evidence="ECO:0000269|PubMed:10801319, FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193" FT BINDING 161 FT /note="NAD" FT /evidence="ECO:0000269|PubMed:10801319, FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193" FT BINDING 185 FT /note="NAD" FT /evidence="ECO:0000269|PubMed:10801319" FT BINDING 239 FT /note="Substrate" FT /evidence="ECO:0000269|PubMed:10801319, FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193" FT VAR_SEQ 1..79 FT /note="MAEKVLVTGGAGYIGSHTVLELLEAGYLPVVIDNFHNAFRGGGSLPESLRRV FT QELTGRSVEFEEMDILDQGALQRLFKK -> MSPLQ (in isoform 2)" FT /id="VSP_056822" FT VARIANT 25 FT /note="A -> V (in EDG; dbSNP:rs1431772923)" FT /evidence="ECO:0000269|PubMed:16301867" FT /id="VAR_037733" FT VARIANT 34 FT /note="N -> S (in EDG; peripheral; nearly normal activity FT towards UDP-galactose; dbSNP:rs121908046)" FT /evidence="ECO:0000269|PubMed:11903335, FT ECO:0000269|PubMed:16302980, ECO:0000269|PubMed:9326324" FT /id="VAR_002539" FT VARIANT 40 FT /note="R -> C (in EDG; dbSNP:rs144492228)" FT /evidence="ECO:0000269|PubMed:16301867" FT /id="VAR_037734" FT VARIANT 69 FT /note="D -> E (in EDG; dbSNP:rs1261697960)" FT /evidence="ECO:0000269|PubMed:16301867" FT /id="VAR_037735" FT VARIANT 90 FT /note="G -> E (in EDG; 800-fold decrease in UDP-galactose FT epimerization activity; dbSNP:rs28940882)" FT /evidence="ECO:0000269|PubMed:11903335, FT ECO:0000269|PubMed:16302980, ECO:0000269|PubMed:9538513, FT ECO:0000269|PubMed:9973283" FT /id="VAR_002540" FT VARIANT 94 FT /note="V -> M (in EDG; generalized; 30-fold decrease in FT UDP-galactose epimerization activity; 2-fold decrease in FT affinity for UDP-galactose; 24% of normal activity with FT respect to UDP-N-acetylgalactosamine; dbSNP:rs121908047)" FT /evidence="ECO:0000269|PubMed:11117433, FT ECO:0000269|PubMed:11903335, ECO:0000269|PubMed:16302980, FT ECO:0000269|PubMed:9973283" FT /id="VAR_010058" FT VARIANT 103 FT /note="D -> G (in EDG; 7-fold decrease in UDP-galactose FT epimerization activity; very mild decrease in activity FT towards UDP-N-acetylgalactosamine; dbSNP:rs28940883)" FT /evidence="ECO:0000269|PubMed:11903335, FT ECO:0000269|PubMed:16302980, ECO:0000269|PubMed:9538513, FT ECO:0000269|PubMed:9973283" FT /id="VAR_002541" FT VARIANT 165 FT /note="E -> K (in EDG; dbSNP:rs528467258)" FT /evidence="ECO:0000269|PubMed:16301867" FT /id="VAR_037736" FT VARIANT 169 FT /note="R -> W (in EDG; dbSNP:rs137853859)" FT /evidence="ECO:0000269|PubMed:16301867" FT /id="VAR_037737" FT VARIANT 180 FT /note="A -> V (in dbSNP:rs3204468)" FT /evidence="ECO:0000269|PubMed:8593531, FT ECO:0000269|PubMed:9326324" FT /id="VAR_002542" FT VARIANT 183 FT /note="L -> P (in EDG; peripheral; 3-fold decrease in UDP- FT galactose epimerization activity; dbSNP:rs121908045)" FT /evidence="ECO:0000269|PubMed:11903335, FT ECO:0000269|PubMed:16302980, ECO:0000269|PubMed:9326324" FT /id="VAR_002543" FT VARIANT 239 FT /note="R -> W (in EDG; dbSNP:rs137853860)" FT /evidence="ECO:0000269|PubMed:16301867" FT /id="VAR_037738" FT VARIANT 257 FT /note="K -> R (in EDG; 7-fold decrease in UDP-galactose FT epimerization activity; does not affect affinity for UDP- FT galactose; dbSNP:rs28940884)" FT /evidence="ECO:0000269|PubMed:11903335, FT ECO:0000269|PubMed:15639193, ECO:0000269|PubMed:16302980, FT ECO:0000269|PubMed:9538513" FT /id="VAR_002544" FT VARIANT 302 FT /note="G -> D (in EDG; dbSNP:rs137853861)" FT /evidence="ECO:0000269|PubMed:16301867" FT /id="VAR_037739" FT VARIANT 313 FT /note="L -> M (in EDG; 6-fold decrease in UDP-galactose FT epimerization activity; very mild decrease in activity FT towards UDP-N-acetylgalactosamine; dbSNP:rs3180383)" FT /evidence="ECO:0000269|PubMed:11903335, FT ECO:0000269|PubMed:16302980, ECO:0000269|PubMed:9538513, FT ECO:0000269|PubMed:9973283" FT /id="VAR_002545" FT VARIANT 319 FT /note="G -> E (in EDG; nearly normal activity towards UDP- FT galactose; mild impairment under conditions of substrate FT limitation; dbSNP:rs28940885)" FT /evidence="ECO:0000269|PubMed:11903335, FT ECO:0000269|PubMed:15639193, ECO:0000269|PubMed:16302980, FT ECO:0000269|PubMed:9538513" FT /id="VAR_002546" FT VARIANT 335 FT /note="R -> H (in EDG; 2-fold decrease in UDP-galactose FT epimerization activity; dbSNP:rs368637540)" FT /evidence="ECO:0000269|PubMed:11903335, FT ECO:0000269|PubMed:16301867, ECO:0000269|PubMed:16302980" FT /id="VAR_037740" FT MUTAGEN 132 FT /note="S->A: Loss of activity." FT /evidence="ECO:0000269|PubMed:15175331" FT MUTAGEN 157 FT /note="Y->F: Loss of activity." FT /evidence="ECO:0000269|PubMed:15175331" FT MUTAGEN 307 FT /note="C->Y: No effect on activity towards UDP-galactose. FT Loss of activity towards UDP-N-acetylgalactosamine." FT /evidence="ECO:0000269|PubMed:15175331" FT CONFLICT 293 FT /note="P -> S (in Ref. 4; BAG51901)" FT STRAND 3..8 FT /evidence="ECO:0000244|PDB:1EK6" FT TURN 9..11 FT /evidence="ECO:0000244|PDB:1EK6" FT HELIX 13..24 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 29..33 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 35..38 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 42..46 FT /evidence="ECO:0000244|PDB:1EK6" FT HELIX 47..56 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 61..64 FT /evidence="ECO:0000244|PDB:1EK6" FT HELIX 70..79 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 82..87 FT /evidence="ECO:0000244|PDB:1EK6" FT HELIX 94..99 FT /evidence="ECO:0000244|PDB:1EK6" FT HELIX 101..121 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 126..132 FT /evidence="ECO:0000244|PDB:1EK6" FT HELIX 133..136 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 140..144 FT /evidence="ECO:0000244|PDB:1EK6" FT HELIX 156..174 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 179..185 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 187..189 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 195..197 FT /evidence="ECO:0000244|PDB:1EK5" FT STRAND 202..204 FT /evidence="ECO:0000244|PDB:1EK6" FT HELIX 208..216 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 219..221 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 223..226 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 230..236 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 241..243 FT /evidence="ECO:0000244|PDB:1EK6" FT HELIX 244..258 FT /evidence="ECO:0000244|PDB:1EK6" FT TURN 259..261 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 264..269 FT /evidence="ECO:0000244|PDB:1EK6" FT HELIX 277..288 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 294..297 FT /evidence="ECO:0000244|PDB:1EK6" FT STRAND 305..307 FT /evidence="ECO:0000244|PDB:1EK6" FT HELIX 312..316 FT /evidence="ECO:0000244|PDB:1EK6" FT HELIX 326..339 FT /evidence="ECO:0000244|PDB:1EK6" SQ SEQUENCE 348 AA; 38282 MW; 06FDBF9B1943DF49 CRC64; MAEKVLVTGG AGYIGSHTVL ELLEAGYLPV VIDNFHNAFR GGGSLPESLR RVQELTGRSV EFEEMDILDQ GALQRLFKKY SFMAVIHFAG LKAVGESVQK PLDYYRVNLT GTIQLLEIMK AHGVKNLVFS SSATVYGNPQ YLPLDEAHPT GGCTNPYGKS KFFIEEMIRD LCQADKTWNA VLLRYFNPTG AHASGCIGED PQGIPNNLMP YVSQVAIGRR EALNVFGNDY DTEDGTGVRD YIHVVDLAKG HIAALRKLKE QCGCRIYNLG TGTGYSVLQM VQAMEKASGK KIPYKVVARR EGDVAACYAN PSLAQEELGW TAALGLDRMC EDLWRWQKQN PSGFGTQA //