FCL_DROME
ID FCL_DROME Reviewed; 321 AA.
AC Q9W1X8; Q1H8X1; Q8MS16;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Probable GDP-L-fucose synthase;
DE EC=1.1.1.271 {ECO:0000305|PubMed:16650000};
DE AltName: Full=GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase {ECO:0000303|PubMed:16650000};
DE Short=GER {ECO:0000303|PubMed:16650000};
DE AltName: Full=Protein FX;
GN Name=Gmer; ORFNames=CG3495;
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 {ECO:0000312|EMBL:AAL28421.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16650000; DOI=10.1111/j.1742-4658.2006.05239.x;
RA Rhomberg S., Fuchsluger C., Rendic D., Paschinger K., Jantsch V., Kosma P.,
RA Wilson I.B.H.;
RT "Reconstitution in vitro of the GDP-fucose biosynthetic pathways of
RT Caenorhabditis elegans and Drosophila melanogaster.";
RL FEBS J. 273:2244-2256(2006).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
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 [3]
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 [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569};
RC TISSUE=Embryo {ECO:0000269|PubMed:12537569}, and
RC Ovary {ECO:0000269|PubMed:12537569};
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 [5] {ECO:0000305}
RP HOMOLOGY.
RX PubMed=11698403; DOI=10.1074/jbc.m107927200;
RA Roos C., Kolmer M., Mattila P., Renkonen R.;
RT "Composition of Drosophila melanogaster proteome involved in fucosylated
RT glycan metabolism.";
RL J. Biol. Chem. 277:3168-3175(2002).
CC -!- FUNCTION: Catalyzes the two-step NADP-dependent conversion of GDP-4-
CC dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a
CC reductase reaction. {ECO:0000305|PubMed:16650000}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GDP-beta-L-fucose + NADP(+) = GDP-4-dehydro-alpha-D-rhamnose +
CC H(+) + NADPH; Xref=Rhea:RHEA:18885, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57273, ChEBI:CHEBI:57783, ChEBI:CHEBI:57964,
CC ChEBI:CHEBI:58349; EC=1.1.1.271;
CC Evidence={ECO:0000305|PubMed:16650000};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18887;
CC Evidence={ECO:0000305|PubMed:16650000};
CC -!- PATHWAY: Nucleotide-sugar biosynthesis; GDP-L-fucose biosynthesis via
CC de novo pathway; GDP-L-fucose from GDP-alpha-D-mannose: step 2/2.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q13630}.
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. Fucose synthase subfamily. {ECO:0000305}.
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DR EMBL; AM231688; CAJ77751.1; -; mRNA.
DR EMBL; AE013599; AAF46924.1; -; Genomic_DNA.
DR EMBL; AY060873; AAL28421.1; -; mRNA.
DR EMBL; AY119148; AAM51008.1; -; mRNA.
DR RefSeq; NP_611734.1; NM_137890.3.
DR AlphaFoldDB; Q9W1X8; -.
DR SMR; Q9W1X8; -.
DR STRING; 7227.FBpp0071816; -.
DR PaxDb; Q9W1X8; -.
DR PRIDE; Q9W1X8; -.
DR DNASU; 37638; -.
DR EnsemblMetazoa; FBtr0071905; FBpp0071816; FBgn0267823.
DR GeneID; 37638; -.
DR KEGG; dme:Dmel_CG3495; -.
DR CTD; 37638; -.
DR FlyBase; FBgn0267823; Gmer.
DR VEuPathDB; VectorBase:FBgn0267823; -.
DR eggNOG; KOG1431; Eukaryota.
DR GeneTree; ENSGT00390000004681; -.
DR HOGENOM; CLU_007383_18_2_1; -.
DR InParanoid; Q9W1X8; -.
DR OMA; IHCAGRV; -.
DR OrthoDB; 922791at2759; -.
DR PhylomeDB; Q9W1X8; -.
DR BRENDA; 1.1.1.271; 1994.
DR Reactome; R-DME-6787639; GDP-fucose biosynthesis.
DR UniPathway; UPA00128; UER00191.
DR BioGRID-ORCS; 37638; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 37638; -.
DR PRO; PR:Q9W1X8; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0267823; Expressed in oviduct (Drosophila) and 23 other tissues.
DR ExpressionAtlas; Q9W1X8; baseline and differential.
DR Genevisible; Q9W1X8; DM.
DR GO; GO:0050577; F:GDP-L-fucose synthase activity; IDA:FlyBase.
DR GO; GO:0047918; F:GDP-mannose 3,5-epimerase activity; ISS:FlyBase.
DR GO; GO:0042351; P:'de novo' GDP-L-fucose biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0033227; P:dsRNA transport; IMP:FlyBase.
DR GO; GO:0042350; P:GDP-L-fucose biosynthetic process; IDA:FlyBase.
DR CDD; cd05239; GDP_FS_SDR_e; 1.
DR HAMAP; MF_00956; GDP_fucose_synth; 1.
DR InterPro; IPR001509; Epimerase_deHydtase.
DR InterPro; IPR028614; GDP_fucose/colitose_synth.
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 Isomerase; Multifunctional enzyme; NADP; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..321
FT /note="Probable GDP-L-fucose synthase"
FT /id="PRO_0000174353"
FT ACT_SITE 136
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 8..14
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 140
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 163..166
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 179
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 187
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 215
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 277
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 107
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT SITE 109
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT SITE 140
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250"
FT CONFLICT 112
FT /note="P -> R (in Ref. 4; AAM51008)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 321 AA; 36123 MW; E4167CE378D2D8E5 CRC64;
MKKVLVTGGT GLVGKALEAV IKEQSPEDEQ WFFAGSKDAD LTNLAATQAL FAREKPTHVI
HLAAMVGGLF HNMNNNLDFL RNNLLINDNV LQTAHEQGCV KVVSCLSTCI FPDKTSYPID
ETMVHNGPPH PSNYGYSYAK RLIDVQNHAY HDKYGRVYTS VIPCNIFGPH DNYNPEVSHV
IPGMIYRMHQ LVTEKTDVPE NDKVFTVFGS GMPLRQFVYS RDLAELMIWV LRNYESVEPI
ILSADEVQEV TIFEVAQAVA KAFNFNGRLV CDTSKSDGQY KKTASNAKLR SFLPDYAFTD
LETAINASVK WYIENYDQAR K
