GMDS_DROME
ID GMDS_DROME Reviewed; 395 AA.
AC Q9VMW9; Q1H8X2; Q8T3U5;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=GDP-mannose 4,6 dehydratase;
DE EC=4.2.1.47 {ECO:0000305|PubMed:16650000};
DE AltName: Full=GDP-D-mannose dehydratase;
DE Short=Dm-gmd;
DE AltName: Full=GDP-mannose dehydratase {ECO:0000303|PubMed:16650000};
GN Name=Gmd; ORFNames=CG8890;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP PATHWAY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Ovary;
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]
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 conversion of GDP-D-mannose to GDP-4-dehydro-6-
CC deoxy-D-mannose (also known as GDP-4-keto-6-deoxy-D-mannose or GDP-4-
CC dehydro-alpha-D-rhamnose), an essential step in the synthesis of GDP-
CC fucose from GDP-mannose. {ECO:0000269|PubMed:16650000}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GDP-alpha-D-mannose = GDP-4-dehydro-alpha-D-rhamnose + H2O;
CC Xref=Rhea:RHEA:23820, ChEBI:CHEBI:15377, ChEBI:CHEBI:57527,
CC ChEBI:CHEBI:57964; EC=4.2.1.47;
CC Evidence={ECO:0000305|PubMed:16650000};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23821;
CC Evidence={ECO:0000305|PubMed:16650000};
CC -!- COFACTOR:
CC Name=NADP(+); Xref=ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:16650000};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5-8. {ECO:0000269|PubMed:16650000};
CC Temperature dependence:
CC Optimum temperature is 30 degrees Celsius.
CC {ECO:0000269|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 1/2.
CC {ECO:0000269|PubMed:16650000}.
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. GDP-mannose 4,6-dehydratase subfamily. {ECO:0000305}.
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DR EMBL; AM231687; CAJ77750.1; -; mRNA.
DR EMBL; AE014134; AAF52189.2; -; Genomic_DNA.
DR EMBL; AY089519; AAL90257.1; -; mRNA.
DR RefSeq; NP_608888.2; NM_135044.4.
DR AlphaFoldDB; Q9VMW9; -.
DR SMR; Q9VMW9; -.
DR BioGRID; 59900; 3.
DR STRING; 7227.FBpp0078685; -.
DR PaxDb; Q9VMW9; -.
DR PRIDE; Q9VMW9; -.
DR DNASU; 33716; -.
DR EnsemblMetazoa; FBtr0079049; FBpp0078685; FBgn0031661.
DR GeneID; 33716; -.
DR KEGG; dme:Dmel_CG8890; -.
DR CTD; 33716; -.
DR FlyBase; FBgn0031661; Gmd.
DR VEuPathDB; VectorBase:FBgn0031661; -.
DR eggNOG; KOG1372; Eukaryota.
DR GeneTree; ENSGT00440000033640; -.
DR HOGENOM; CLU_007383_14_0_1; -.
DR InParanoid; Q9VMW9; -.
DR OMA; TDCLYLG; -.
DR OrthoDB; 877551at2759; -.
DR PhylomeDB; Q9VMW9; -.
DR Reactome; R-DME-6787639; GDP-fucose biosynthesis.
DR UniPathway; UPA00128; UER00190.
DR BioGRID-ORCS; 33716; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 33716; -.
DR PRO; PR:Q9VMW9; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0031661; Expressed in embryonic/larval hemocyte (Drosophila) and 38 other tissues.
DR ExpressionAtlas; Q9VMW9; baseline and differential.
DR Genevisible; Q9VMW9; DM.
DR GO; GO:0008446; F:GDP-mannose 4,6-dehydratase activity; IDA:FlyBase.
DR GO; GO:0042351; P:'de novo' GDP-L-fucose biosynthetic process; IMP:FlyBase.
DR GO; GO:0045165; P:cell fate commitment; IMP:FlyBase.
DR GO; GO:0042350; P:GDP-L-fucose biosynthetic process; IDA:FlyBase.
DR GO; GO:0019673; P:GDP-mannose metabolic process; IBA:GO_Central.
DR GO; GO:0048477; P:oogenesis; IMP:FlyBase.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IMP:FlyBase.
DR HAMAP; MF_00955; GDP_Man_dehydratase; 1.
DR InterPro; IPR006368; GDP_Man_deHydtase.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR43715; PTHR43715; 1.
DR Pfam; PF16363; GDP_Man_Dehyd; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR TIGRFAMs; TIGR01472; gmd; 1.
PE 1: Evidence at protein level;
KW Lyase; NADP; Reference proteome.
FT CHAIN 1..395
FT /note="GDP-mannose 4,6 dehydratase"
FT /id="PRO_0000201707"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 178
FT /evidence="ECO:0000250"
FT ACT_SITE 180
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 202
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 53..58
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 109..110
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 131..135
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 146
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 206
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 232
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 237
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT CONFLICT 333
FT /note="N -> S (in Ref. 1; CAJ77750 and 4; AAL90257)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 395 AA; 44784 MW; 533E1B41E69ED36D CRC64;
MLNTRLIAMS TSDGAPETKK QRPESSSNGS KDQNGTEAGA EGDSRDKVAL ITGITGQDGS
YLAEFLLKKD YEVHGIIRRA STFNTTRIEH LYADPKAHKG GRMKLHYGDM TDSSSLVKII
NMVKPTEIYN LAAQSHVKVS FDLSEYTAEV DAVGTLRILD AIRTCGMEKN VRFYQASTSE
LYGKVVETPQ NEQTPFYPRS PYACAKMYGF WIVINYREAY NMYACNGILF NHESPRRGEN
FVTRKITRSV AKIYHKQMEY FELGNLDSKR DWGHASDYVE AMWMMLQRES PSDYVIATGE
THSVREFVEA AFKHIDREIT WKGKGVDEVG VENGTGIVRV RINPKYFRPT EVDLLQGDAS
KANRELNWTP KVTFVELVSD MMKADIELMR KNPIA
