UDP-glucose 4-epimerase

Details

Name
UDP-glucose 4-epimerase
Synonyms
  • 5.1.3.2
  • Galactowaldenase
  • UDP-galactose 4-epimerase
  • UDP-GalNAc 4-epimerase
  • UDP-GlcNAc 4-epimerase
  • UDP-N-acetylgalactosamine 4-epimerase
  • UDP-N-acetylglucosamine 4-epimerase
Gene Name
GALE
Organism
Humans
Amino acid sequence
>lcl|BSEQ0003020|UDP-glucose 4-epimerase
MAEKVLVTGGAGYIGSHTVLELLEAGYLPVVIDNFHNAFRGGGSLPESLRRVQELTGRSV
EFEEMDILDQGALQRLFKKYSFMAVIHFAGLKAVGESVQKPLDYYRVNLTGTIQLLEIMK
AHGVKNLVFSSSATVYGNPQYLPLDEAHPTGGCTNPYGKSKFFIEEMIRDLCQADKTWNA
VLLRYFNPTGAHASGCIGEDPQGIPNNLMPYVSQVAIGRREALNVFGNDYDTEDGTGVRD
YIHVVDLAKGHIAALRKLKEQCGCRIYNLGTGTGYSVLQMVQAMEKASGKKIPYKVVARR
EGDVAACYANPSLAQEELGWTAALGLDRMCEDLWRWQKQNPSGFGTQA
Number of residues
348
Molecular Weight
38281.435
Theoretical pI
6.71
GO Classification
Functions
protein homodimerization activity / UDP-glucose 4-epimerase activity / UDP-N-acetylglucosamine 4-epimerase activity
Processes
carbohydrate metabolic process / galactose catabolic process / small molecule metabolic process
Components
cytosol / extracellular exosome
General Function
Udp-n-acetylglucosamine 4-epimerase activity
Specific Function
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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0011076|UDP-glucose 4-epimerase (GALE)
ATGGCAGAGAAGGTGCTGGTAACAGGTGGGGCTGGCTACATTGGCAGCCACACGGTGCTG
GAGCTGCTGGAGGCTGGCTACTTGCCTGTGGTCATCGATAACTTCCATAATGCCTTCCGT
GGAGGGGGCTCCCTGCCTGAGAGCCTGCGGCGGGTCCAGGAGCTGACAGGCCGCTCTGTG
GAGTTTGAGGAGATGGACATTTTGGACCAGGGAGCCCTACAGCGTCTCTTCAAAAAGTAC
AGCTTTATGGCGGTCATCCACTTTGCGGGGCTCAAGGCCGTGGGCGAGTCGGTGCAGAAG
CCTCTGGATTATTACAGAGTTAACCTGACCGGGACCATCCAGCTTCTGGAGATCATGAAG
GCCCACGGGGTGAAGAACCTGGTGTTCAGCAGCTCAGCCACTGTGTACGGGAACCCCCAG
TACCTGCCCCTTGATGAGGCCCACCCCACGGGTGGTTGTACCAACCCTTACGGCAAGTCC
AAGTTCTTCATCGAGGAAATGATCCGGGACCTGTGCCAGGCAGACAAGACTTGGAACGCA
GTGCTGCTGCGCTATTTCAACCCCACAGGTGCCCATGCCTCTGGCTGCATTGGTGAGGAT
CCCCAGGGCATACCCAACAACCTCATGCCTTATGTCTCCCAGGTGGCGATCGGGCGACGG
GAGGCCCTGAATGTCTTTGGCAATGACTATGACACAGAGGATGGCACAGGTGTCCGGGAT
TACATCCATGTCGTGGATCTGGCCAAGGGCCACATTGCAGCCTTAAGGAAGCTGAAAGAA
CAGTGTGGCTGCCGGATCTACAACCTGGGCACGGGCACAGGCTATTCAGTGCTGCAGATG
GTCCAGGCTATGGAGAAGGCCTCTGGGAAGAAGATCCCGTACAAGGTGGTGGCACGGCGG
GAAGGTGATGTGGCAGCCTGTTACGCCAACCCCAGCCTGGCCCAAGAGGAGCTGGGGTGG
ACAGCAGCCTTAGGGCTGGACAGGATGTGTGAGGATCTCTGGCGCTGGCAGAAGCAGAAT
CCTTCAGGCTTTGGCACGCAAGCCTGA
Chromosome Location
1
Locus
1p36-p35
External Identifiers
ResourceLink
UniProtKB IDQ14376
UniProtKB Entry NameGALE_HUMAN
GenBank Protein ID1119217
GenBank Gene IDL41668
GenAtlas IDGALE
HGNC IDHGNC:4116
General References
  1. Daude N, Gallaher TK, Zeschnigk M, Starzinski-Powitz A, Petry KG, Haworth IS, Reichardt JK: Molecular cloning, characterization, and mapping of a full-length cDNA encoding human UDP-galactose 4'-epimerase. Biochem Mol Med. 1995 Oct;56(1):1-7. [PubMed:8593531]
  2. Maceratesi P, Daude N, Dallapiccola B, Novelli G, Allen R, Okano Y, Reichardt J: Human UDP-galactose 4' epimerase (GALE) gene and identification of five missense mutations in patients with epimerase-deficiency galactosemia. Mol Genet Metab. 1998 Jan;63(1):26-30. [PubMed:9538513]
  3. Openo KK, Schulz JM, Vargas CA, Orton CS, Epstein MP, Schnur RE, Scaglia F, Berry GT, Gottesman GS, Ficicioglu C, Slonim AE, Schroer RJ, Yu C, Rangel VE, Keenan J, Lamance K, Fridovich-Keil JL: Epimerase-deficiency galactosemia is not a binary condition. Am J Hum Genet. 2006 Jan;78(1):89-102. Epub 2005 Nov 14. [PubMed:16385452]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  5. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [PubMed:16710414]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  7. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  8. Daenzer JM, Sanders RD, Hang D, Fridovich-Keil JL: UDP-galactose 4'-epimerase activities toward UDP-Gal and UDP-GalNAc play different roles in the development of Drosophila melanogaster. PLoS Genet. 2012;8(5):e1002721. doi: 10.1371/journal.pgen.1002721. Epub 2012 May 24. [PubMed:22654673]
  9. Timson DJ, Lindert S: Comparison of dynamics of wildtype and V94M human UDP-galactose 4-epimerase-A computational perspective on severe epimerase-deficiency galactosemia. Gene. 2013 Sep 10;526(2):318-24. doi: 10.1016/j.gene.2013.05.027. Epub 2013 May 31. [PubMed:23732289]
  10. Schulz JM, Watson AL, Sanders R, Ross KL, Thoden JB, Holden HM, Fridovich-Keil JL: Determinants of function and substrate specificity in human UDP-galactose 4'-epimerase. J Biol Chem. 2004 Jul 30;279(31):32796-803. Epub 2004 Jun 2. [PubMed:15175331]
  11. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  12. Thoden JB, Wohlers TM, Fridovich-Keil JL, Holden HM: Crystallographic evidence for Tyr 157 functioning as the active site base in human UDP-galactose 4-epimerase. Biochemistry. 2000 May 16;39(19):5691-701. [PubMed:10801319]
  13. Thoden JB, Wohlers TM, Fridovich-Keil JL, Holden HM: Human UDP-galactose 4-epimerase. Accommodation of UDP-N-acetylglucosamine within the active site. J Biol Chem. 2001 May 4;276(18):15131-6. Epub 2001 Jan 26. [PubMed:11279032]
  14. Thoden JB, Wohlers TM, Fridovich-Keil JL, Holden HM: Molecular basis for severe epimerase deficiency galactosemia. X-ray structure of the human V94m-substituted UDP-galactose 4-epimerase. J Biol Chem. 2001 Jun 8;276(23):20617-23. Epub 2001 Mar 7. [PubMed:11279193]
  15. Quimby BB, Alano A, Almashanu S, DeSandro AM, Cowan TM, Fridovich-Keil JL: Characterization of two mutations associated with epimerase-deficiency galactosemia, by use of a yeast expression system for human UDP-galactose-4-epimerase. Am J Hum Genet. 1997 Sep;61(3):590-8. [PubMed:9326324]
  16. Wohlers TM, Christacos NC, Harreman MT, Fridovich-Keil JL: Identification and characterization of a mutation, in the human UDP-galactose-4-epimerase gene, associated with generalized epimerase-deficiency galactosemia. Am J Hum Genet. 1999 Feb;64(2):462-70. [PubMed:9973283]
  17. Wohlers TM, Fridovich-Keil JL: Studies of the V94M-substituted human UDPgalactose-4-epimerase enzyme associated with generalized epimerase-deficiency galactosaemia. J Inherit Metab Dis. 2000 Nov;23(7):713-29. [PubMed:11117433]
  18. Henderson JM, Huguenin SM, Cowan TM, Fridovich-Keil JL: A PCR-based method for detecting known mutations in the human UDP galactose-4'-epimerase gene associated with epimerase-deficiency galactosemia. Clin Genet. 2001 Nov;60(5):350-5. [PubMed:11903335]
  19. Timson DJ: Functional analysis of disease-causing mutations in human UDP-galactose 4-epimerase. FEBS J. 2005 Dec;272(23):6170-7. [PubMed:16302980]
  20. Park HD, Park KU, Kim JQ, Shin CH, Yang SW, Lee DH, Song YH, Song J: The molecular basis of UDP-galactose-4-epimerase (GALE) deficiency galactosemia in Korean patients. Genet Med. 2005 Nov-Dec;7(9):646-9. [PubMed:16301867]
  21. Wasilenko J, Lucas ME, Thoden JB, Holden HM, Fridovich-Keil JL: Functional characterization of the K257R and G319E-hGALE alleles found in patients with ostensibly peripheral epimerase deficiency galactosemia. Mol Genet Metab. 2005 Jan;84(1):32-8. [PubMed:15639193]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01861Uridine diphosphate glucoseexperimentalunknownDetails
DB02196Uridine-Diphosphate-N-AcetylgalactosamineexperimentalunknownDetails
DB03095Tetramethylammonium IonexperimentalunknownDetails
DB03397Uridine-Diphosphate-N-AcetylglucosamineexperimentalunknownDetails
DB03501Galactose-uridine-5'-diphosphateexperimentalunknownDetails
DB03041UDP-alpha-D-glucuronic acidexperimentalunknownsubstrateDetails