GME_ARATH
ID GME_ARATH Reviewed; 377 AA.
AC Q93VR3;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=GDP-mannose 3,5-epimerase;
DE Short=GDP-Man 3,5-epimerase;
DE EC=5.1.3.18 {ECO:0000269|PubMed:11752432, ECO:0000269|PubMed:12954627};
GN OrderedLocusNames=At5g28840; ORFNames=F7P1.20;
OS Arabidopsis thaliana (Mouse-ear cress).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX NCBI_TaxID=3702;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=11130714; DOI=10.1038/35048507;
RA Tabata S., Kaneko T., Nakamura Y., Kotani H., Kato T., Asamizu E.,
RA Miyajima N., Sasamoto S., Kimura T., Hosouchi T., Kawashima K., Kohara M.,
RA Matsumoto M., Matsuno A., Muraki A., Nakayama S., Nakazaki N., Naruo K.,
RA Okumura S., Shinpo S., Takeuchi C., Wada T., Watanabe A., Yamada M.,
RA Yasuda M., Sato S., de la Bastide M., Huang E., Spiegel L., Gnoj L.,
RA O'Shaughnessy A., Preston R., Habermann K., Murray J., Johnson D.,
RA Rohlfing T., Nelson J., Stoneking T., Pepin K., Spieth J., Sekhon M.,
RA Armstrong J., Becker M., Belter E., Cordum H., Cordes M., Courtney L.,
RA Courtney W., Dante M., Du H., Edwards J., Fryman J., Haakensen B.,
RA Lamar E., Latreille P., Leonard S., Meyer R., Mulvaney E., Ozersky P.,
RA Riley A., Strowmatt C., Wagner-McPherson C., Wollam A., Yoakum M., Bell M.,
RA Dedhia N., Parnell L., Shah R., Rodriguez M., Hoon See L., Vil D.,
RA Baker J., Kirchoff K., Toth K., King L., Bahret A., Miller B., Marra M.A.,
RA Martienssen R., McCombie W.R., Wilson R.K., Murphy G., Bancroft I.,
RA Volckaert G., Wambutt R., Duesterhoeft A., Stiekema W., Pohl T.,
RA Entian K.-D., Terryn N., Hartley N., Bent E., Johnson S., Langham S.-A.,
RA McCullagh B., Robben J., Grymonprez B., Zimmermann W., Ramsperger U.,
RA Wedler H., Balke K., Wedler E., Peters S., van Staveren M., Dirkse W.,
RA Mooijman P., Klein Lankhorst R., Weitzenegger T., Bothe G., Rose M.,
RA Hauf J., Berneiser S., Hempel S., Feldpausch M., Lamberth S.,
RA Villarroel R., Gielen J., Ardiles W., Bents O., Lemcke K., Kolesov G.,
RA Mayer K.F.X., Rudd S., Schoof H., Schueller C., Zaccaria P., Mewes H.-W.,
RA Bevan M., Fransz P.F.;
RT "Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.";
RL Nature 408:823-826(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=cv. Columbia;
RX PubMed=27862469; DOI=10.1111/tpj.13415;
RA Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA Town C.D.;
RT "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT genome.";
RL Plant J. 89:789-804(2017).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=14593172; DOI=10.1126/science.1088305;
RA Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA Ecker J.R.;
RT "Empirical analysis of transcriptional activity in the Arabidopsis
RT genome.";
RL Science 302:842-846(2003).
RN [4]
RP PATHWAY.
RX PubMed=9620799; DOI=10.1038/30728;
RA Wheeler G.L., Jones M.A., Smirnoff N.;
RT "The biosynthetic pathway of vitamin C in higher plants.";
RL Nature 393:365-369(1998).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, ENZYME ACTIVITY, COFACTOR, SUBUNIT,
RP AND INTERACTION WITH HSC70-3.
RX PubMed=11752432; DOI=10.1073/pnas.011578198;
RA Wolucka B.A., Persiau G., Van Doorsselaere J., Davey M.W., Demol H.,
RA Vandekerckhove J., Van Montagu M., Zabeau M., Boerjan W.;
RT "Partial purification and identification of GDP-mannose 3',5'-epimerase of
RT Arabidopsis thaliana, a key enzyme of the plant vitamin C pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:14843-14848(2001).
RN [6]
RP FUNCTION, ENZYME ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=12954627; DOI=10.1074/jbc.m309135200;
RA Wolucka B.A., Van Montagu M.;
RT "GDP-mannose 3',5'-epimerase forms GDP-L-gulose, a putative intermediate
RT for the de novo biosynthesis of vitamin C in plants.";
RL J. Biol. Chem. 278:47483-47490(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-369, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19376835; DOI=10.1104/pp.109.138677;
RA Reiland S., Messerli G., Baerenfaller K., Gerrits B., Endler A.,
RA Grossmann J., Gruissem W., Baginsky S.;
RT "Large-scale Arabidopsis phosphoproteome profiling reveals novel
RT chloroplast kinase substrates and phosphorylation networks.";
RL Plant Physiol. 150:889-903(2009).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLY-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1-377 IN COMPLEX WITH NAD AND
RP SUBSTRATES, SUBUNIT, AND MUTAGENESIS OF CYS-145; TYR-174; LYS-178; LYS-217
RP AND ARG-306.
RX PubMed=16366586; DOI=10.1021/ja056490i;
RA Major L.L., Wolucka B.A., Naismith J.H.;
RT "Structure and function of GDP-mannose-3',5'-epimerase: an enzyme which
RT performs three chemical reactions at the same active site.";
RL J. Am. Chem. Soc. 127:18309-18320(2005).
CC -!- FUNCTION: Catalyzes a reversible epimerization of GDP-D-mannose that
CC precedes the committed step in the biosynthesis of vitamin C (L-
CC ascorbate), resulting in the hydrolysis of the highly energetic
CC glycosyl-pyrophosphoryl linkage. Able to catalyze 2 distinct
CC epimerization reactions and can release both GDP-L-galactose and GDP-L-
CC gulose from GDP-mannose. {ECO:0000269|PubMed:12954627}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GDP-alpha-D-mannose = GDP-beta-L-gulose; Xref=Rhea:RHEA:63800,
CC ChEBI:CHEBI:57527, ChEBI:CHEBI:149550; EC=5.1.3.18;
CC Evidence={ECO:0000269|PubMed:11752432, ECO:0000269|PubMed:12954627};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GDP-beta-L-gulose = GDP-beta-L-galactose;
CC Xref=Rhea:RHEA:63804, ChEBI:CHEBI:61454, ChEBI:CHEBI:149550;
CC EC=5.1.3.18; Evidence={ECO:0000269|PubMed:11752432,
CC ECO:0000269|PubMed:12954627};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000269|PubMed:11752432};
CC -!- ACTIVITY REGULATION: Inhibited by GDP and GDP-D-glucose.
CC {ECO:0000269|PubMed:12954627}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.5 uM for GDP-mannose {ECO:0000269|PubMed:12954627};
CC Vmax=1.76 umol/h/mg enzyme with GDP-mannose as substrate
CC {ECO:0000269|PubMed:12954627};
CC -!- PATHWAY: Cofactor biosynthesis; L-ascorbate biosynthesis via GDP-alpha-
CC D-mannose pathway; L-ascorbate from GDP-alpha-D-mannose: step 1/5.
CC {ECO:0000269|PubMed:9620799}.
CC -!- SUBUNIT: Homodimer. Interacts with chaperone Hsc70-3 protein, which may
CC regulate epimerase activity. {ECO:0000269|PubMed:11752432,
CC ECO:0000269|PubMed:16366586}.
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. {ECO:0000305}.
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DR EMBL; AF272706; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CP002688; AED93843.1; -; Genomic_DNA.
DR EMBL; CP002688; AED93844.1; -; Genomic_DNA.
DR EMBL; AY057660; AAL15291.1; -; mRNA.
DR EMBL; AY057694; AAL15324.1; -; mRNA.
DR EMBL; AY116953; AAM51587.1; -; mRNA.
DR RefSeq; NP_001190417.1; NM_001203488.1.
DR RefSeq; NP_198236.1; NM_122767.4.
DR PDB; 2C54; X-ray; 1.50 A; A/B=1-377.
DR PDB; 2C59; X-ray; 2.00 A; A/B=1-377.
DR PDB; 2C5A; X-ray; 1.40 A; A/B=1-377.
DR PDB; 2C5E; X-ray; 1.70 A; A/B=1-377.
DR PDBsum; 2C54; -.
DR PDBsum; 2C59; -.
DR PDBsum; 2C5A; -.
DR PDBsum; 2C5E; -.
DR AlphaFoldDB; Q93VR3; -.
DR SMR; Q93VR3; -.
DR BioGRID; 18274; 15.
DR STRING; 3702.AT5G28840.2; -.
DR iPTMnet; Q93VR3; -.
DR PaxDb; Q93VR3; -.
DR PRIDE; Q93VR3; -.
DR ProteomicsDB; 248535; -.
DR EnsemblPlants; AT5G28840.1; AT5G28840.1; AT5G28840.
DR EnsemblPlants; AT5G28840.2; AT5G28840.2; AT5G28840.
DR GeneID; 833002; -.
DR Gramene; AT5G28840.1; AT5G28840.1; AT5G28840.
DR Gramene; AT5G28840.2; AT5G28840.2; AT5G28840.
DR KEGG; ath:AT5G28840; -.
DR Araport; AT5G28840; -.
DR TAIR; locus:2150441; AT5G28840.
DR eggNOG; KOG1429; Eukaryota.
DR HOGENOM; CLU_007383_4_2_1; -.
DR InParanoid; Q93VR3; -.
DR OMA; MTEELCK; -.
DR OrthoDB; 662484at2759; -.
DR PhylomeDB; Q93VR3; -.
DR BioCyc; ARA:AT5G28840-MON; -.
DR BioCyc; MetaCyc:AT5G28840-MON; -.
DR BRENDA; 5.1.3.18; 399.
DR SABIO-RK; Q93VR3; -.
DR UniPathway; UPA00990; UER00931.
DR EvolutionaryTrace; Q93VR3; -.
DR PRO; PR:Q93VR3; -.
DR Proteomes; UP000006548; Chromosome 5.
DR ExpressionAtlas; Q93VR3; baseline and differential.
DR Genevisible; Q93VR3; AT.
DR GO; GO:0005829; C:cytosol; HDA:TAIR.
DR GO; GO:0009536; C:plastid; HDA:TAIR.
DR GO; GO:0047918; F:GDP-mannose 3,5-epimerase activity; IDA:TAIR.
DR GO; GO:0051287; F:NAD binding; TAS:TAIR.
DR GO; GO:0019853; P:L-ascorbic acid biosynthetic process; TAS:TAIR.
DR CDD; cd05273; GME-like_SDR_e; 1.
DR InterPro; IPR001509; Epimerase_deHydtase.
DR InterPro; IPR033890; GDP-Man_epi.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01370; Epimerase; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Ascorbate biosynthesis; Isomerase; NAD;
KW Nucleotide-binding; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895"
FT CHAIN 2..377
FT /note="GDP-mannose 3,5-epimerase"
FT /id="PRO_0000183267"
FT ACT_SITE 174
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 34..60
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:16366586"
FT BINDING 58
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:16366586"
FT BINDING 78
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:16366586"
FT BINDING 103
FT /ligand="substrate"
FT BINDING 143..145
FT /ligand="substrate"
FT BINDING 174
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:16366586"
FT BINDING 178
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:16366586"
FT BINDING 203
FT /ligand="substrate"
FT BINDING 216..218
FT /ligand="substrate"
FT BINDING 225
FT /ligand="substrate"
FT BINDING 241..243
FT /ligand="substrate"
FT BINDING 306
FT /ligand="substrate"
FT BINDING 356
FT /ligand="substrate"
FT MOD_RES 2
FT /note="N-acetylglycine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 369
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19376835"
FT MUTAGEN 145
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16366586"
FT MUTAGEN 145
FT /note="C->S: Strong reduction of activity."
FT /evidence="ECO:0000269|PubMed:16366586"
FT MUTAGEN 174
FT /note="Y->F: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16366586"
FT MUTAGEN 178
FT /note="K->R: Strong reduction of activity."
FT /evidence="ECO:0000269|PubMed:16366586"
FT MUTAGEN 217
FT /note="K->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16366586"
FT MUTAGEN 306
FT /note="R->A: Strong reduction of activity."
FT /evidence="ECO:0000269|PubMed:16366586"
FT STRAND 29..33
FT /evidence="ECO:0007829|PDB:2C5A"
FT TURN 34..36
FT /evidence="ECO:0007829|PDB:2C5A"
FT HELIX 38..49
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 53..60
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:2C5A"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:2C5A"
FT HELIX 82..89
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:2C5A"
FT HELIX 105..108
FT /evidence="ECO:0007829|PDB:2C5A"
FT HELIX 112..132
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 136..143
FT /evidence="ECO:0007829|PDB:2C5A"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:2C5A"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 152..157
FT /evidence="ECO:0007829|PDB:2C5A"
FT HELIX 162..165
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:2C54"
FT HELIX 173..192
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 195..201
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:2C5A"
FT HELIX 218..228
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 233..237
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:2C59"
FT HELIX 248..260
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:2C59"
FT HELIX 277..286
FT /evidence="ECO:0007829|PDB:2C5A"
FT TURN 287..289
FT /evidence="ECO:0007829|PDB:2C5A"
FT STRAND 294..297
FT /evidence="ECO:0007829|PDB:2C5A"
FT HELIX 311..317
FT /evidence="ECO:0007829|PDB:2C5A"
FT HELIX 325..346
FT /evidence="ECO:0007829|PDB:2C5A"
FT HELIX 350..354
FT /evidence="ECO:0007829|PDB:2C5A"
SQ SEQUENCE 377 AA; 42758 MW; 91C6C4A4C34CCE57 CRC64;
MGTTNGTDYG AYTYKELERE QYWPSENLKI SITGAGGFIA SHIARRLKHE GHYVIASDWK
KNEHMTEDMF CDEFHLVDLR VMENCLKVTE GVDHVFNLAA DMGGMGFIQS NHSVIMYNNT
MISFNMIEAA RINGIKRFFY ASSACIYPEF KQLETTNVSL KESDAWPAEP QDAYGLEKLA
TEELCKHYNK DFGIECRIGR FHNIYGPFGT WKGGREKAPA AFCRKAQTST DRFEMWGDGL
QTRSFTFIDE CVEGVLRLTK SDFREPVNIG SDEMVSMNEM AEMVLSFEEK KLPIHHIPGP
EGVRGRNSDN NLIKEKLGWA PNMRLKEGLR ITYFWIKEQI EKEKAKGSDV SLYGSSKVVG
TQAPVQLGSL RAADGKE
