GALE_HUMAN
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 03-AUG-2022, entry version 215.
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 GALAC3 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 GALAC3 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 GALAC3 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 GALAC3 MET-94, AND CHARACTERIZATION OF VARIANTS GALAC3 GLU-90;
RP MET-94; 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 GALAC3 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 GALAC3 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 GALAC3 VAL-25; CYS-40; GLU-69; LYS-165; TRP-169; TRP-239; ASP-302
RP AND HIS-335.
RX PubMed=16301867; DOI=10.1097/01.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 GALAC3 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: GALE; 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: Galactosemia 3 (GALAC3) [MIM:230350]: A form of galactosemia,
CC an inborn error of galactose metabolism typically manifesting in the
CC neonatal period, after ingestion of galactose, with jaundice,
CC hepatosplenomegaly, hepatocellular insufficiency, food intolerance,
CC hypoglycemia, renal tubular dysfunction, muscle hypotonia, sepsis and
CC cataract. GALAC3 is an autosomal recessive form caused by galactose
CC epimerase deficiency. It can manifest as benign, peripheral form with
CC mild symptoms and enzymatic deficiency in circulating blood cells only.
CC A second form, known as generalized epimerase deficiency, is
CC characterized by undetectable levels of enzyme activity in all tissues
CC and severe clinical features, including restricted growth and
CC intellectual disability. {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 variants
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/";
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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 AlphaFoldDB; Q14376; -.
DR SMR; Q14376; -.
DR BioGRID; 108855; 86.
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.
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; 309 antibodies from 30 providers.
DR DNASU; 2582; -.
DR Ensembl; ENST00000374497.7; ENSP00000363621.3; ENSG00000117308.15. [Q14376-1]
DR Ensembl; ENST00000617979.5; ENSP00000483375.1; ENSG00000117308.15. [Q14376-1]
DR GeneID; 2582; -.
DR KEGG; hsa:2582; -.
DR MANE-Select; ENST00000617979.5; ENSP00000483375.1; NM_001008216.2; NP_001008217.1.
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; Tissue enhanced (stomach).
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 VEuPathDB; HostDB:ENSG00000117308; -.
DR eggNOG; KOG1371; Eukaryota.
DR GeneTree; ENSGT00940000158000; -.
DR InParanoid; Q14376; -.
DR OMA; GEHLICN; -.
DR OrthoDB; 662484at2759; -.
DR PhylomeDB; Q14376; -.
DR TreeFam; TF105800; -.
DR BioCyc; MetaCyc:HS04117-MON; -.
DR BRENDA; 5.1.3.2; 2681.
DR BRENDA; 5.1.3.7; 2681.
DR PathwayCommons; Q14376; -.
DR Reactome; R-HSA-5609977; Defective GALE causes EDG.
DR Reactome; R-HSA-70370; Galactose catabolism.
DR SABIO-RK; Q14376; -.
DR SignaLink; Q14376; -.
DR UniPathway; UPA00214; -.
DR BioGRID-ORCS; 2582; 47 hits in 1083 CRISPR screens.
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 161 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 variant; Galactose metabolism; Isomerase; NAD; Reference proteome.
FT CHAIN 1..348
FT /note="UDP-glucose 4-epimerase"
FT /id="PRO_0000183189"
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 12..14
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10801319,
FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193"
FT BINDING 33..37
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10801319,
FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193"
FT BINDING 66..67
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10801319,
FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193"
FT BINDING 88
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10801319,
FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193"
FT BINDING 92
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10801319,
FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193"
FT BINDING 132..134
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10801319,
FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193,
FT ECO:0000303|PubMed:15175331"
FT BINDING 161
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10801319,
FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193"
FT BINDING 185..187
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11279032,
FT ECO:0000269|PubMed:11279193"
FT BINDING 185
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10801319"
FT BINDING 206..208
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10801319,
FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193"
FT BINDING 224..226
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10801319,
FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193"
FT BINDING 239
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:10801319,
FT ECO:0000269|PubMed:11279032, ECO:0000269|PubMed:11279193"
FT BINDING 300..303
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11279032,
FT 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 GALAC3; dbSNP:rs1431772923)"
FT /evidence="ECO:0000269|PubMed:16301867"
FT /id="VAR_037733"
FT VARIANT 34
FT /note="N -> S (in GALAC3; peripheral; nearly normal
FT activity 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 GALAC3; dbSNP:rs144492228)"
FT /evidence="ECO:0000269|PubMed:16301867"
FT /id="VAR_037734"
FT VARIANT 69
FT /note="D -> E (in GALAC3; dbSNP:rs1261697960)"
FT /evidence="ECO:0000269|PubMed:16301867"
FT /id="VAR_037735"
FT VARIANT 90
FT /note="G -> E (in GALAC3; 800-fold decrease in UDP-
FT galactose 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 GALAC3; 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 GALAC3; 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 GALAC3; dbSNP:rs528467258)"
FT /evidence="ECO:0000269|PubMed:16301867"
FT /id="VAR_037736"
FT VARIANT 169
FT /note="R -> W (in GALAC3; 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 GALAC3; peripheral; 3-fold decrease in
FT UDP-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 GALAC3; dbSNP:rs137853860)"
FT /evidence="ECO:0000269|PubMed:16301867"
FT /id="VAR_037738"
FT VARIANT 257
FT /note="K -> R (in GALAC3; 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 GALAC3; dbSNP:rs137853861)"
FT /evidence="ECO:0000269|PubMed:16301867"
FT /id="VAR_037739"
FT VARIANT 313
FT /note="L -> M (in GALAC3; 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 GALAC3; nearly normal activity towards
FT UDP-galactose; mild impairment under conditions of
FT substrate 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 GALAC3; 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:0007829|PDB:1EK6"
FT TURN 9..11
FT /evidence="ECO:0007829|PDB:1EK6"
FT HELIX 13..24
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 42..46
FT /evidence="ECO:0007829|PDB:1EK6"
FT HELIX 47..56
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:1EK6"
FT HELIX 70..79
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:1EK6"
FT HELIX 94..99
FT /evidence="ECO:0007829|PDB:1EK6"
FT HELIX 101..121
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 126..132
FT /evidence="ECO:0007829|PDB:1EK6"
FT HELIX 133..136
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 140..144
FT /evidence="ECO:0007829|PDB:1EK6"
FT HELIX 156..174
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 179..185
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:1EK5"
FT STRAND 202..204
FT /evidence="ECO:0007829|PDB:1EK6"
FT HELIX 208..216
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 219..221
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 223..226
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 230..236
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 241..243
FT /evidence="ECO:0007829|PDB:1EK6"
FT HELIX 244..258
FT /evidence="ECO:0007829|PDB:1EK6"
FT TURN 259..261
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 264..269
FT /evidence="ECO:0007829|PDB:1EK6"
FT HELIX 277..288
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 294..297
FT /evidence="ECO:0007829|PDB:1EK6"
FT STRAND 305..307
FT /evidence="ECO:0007829|PDB:1EK6"
FT HELIX 312..316
FT /evidence="ECO:0007829|PDB:1EK6"
FT HELIX 326..339
FT /evidence="ECO:0007829|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
