GMD1_CAEEL
ID GMD1_CAEEL Reviewed; 399 AA.
AC Q18801; Q067Y3; Q067Y4; Q067Y5; Q1H8X5; Q1H8X6; Q8T8N2; Q8T8N3;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 3.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=GDP-mannose 4,6 dehydratase 1;
DE EC=4.2.1.47;
DE AltName: Full=Bacillus thuringiensis toxin-resistant protein 1;
DE Short=Bt toxin-resistant protein 1;
DE AltName: Full=GDP-D-mannose dehydratase;
DE Short=GMD;
GN Name=bre-1; Synonyms=gmd-1; ORFNames=C53B4.7;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DEVELOPMENTAL STAGE, AND
RP ALTERNATIVE SPLICING.
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], AND ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP IDENTIFICATION, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10924467; DOI=10.1093/genetics/155.4.1693;
RA Marroquin L.D., Elyassnia D., Griffitts J.S., Feitelson J.S., Aroian R.V.;
RT "Bacillus thuringiensis (Bt) toxin susceptibility and isolation of
RT resistance mutants in the nematode Caenorhabditis elegans.";
RL Genetics 155:1693-1699(2000).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF GLY-232.
RX PubMed=17135259; DOI=10.1074/jbc.m606621200;
RA Barrows B.D., Haslam S.M., Bischof L.J., Morris H.R., Dell A., Aroian R.V.;
RT "Resistance to Bacillus thuringiensis toxin in Caenorhabditis elegans from
RT loss of fucose.";
RL J. Biol. Chem. 282:3302-3311(2007).
RN [5]
RP FUNCTION.
RX PubMed=17482642; DOI=10.1016/j.jip.2007.04.002;
RA Barrows B.D., Griffitts J.S., Aroian R.V.;
RT "Resistance is non-futile: resistance to Cry5B in the nematode
RT Caenorhabditis elegans.";
RL J. Invertebr. Pathol. 95:198-200(2007).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF GLY-232.
RX PubMed=20062796; DOI=10.1371/journal.ppat.1000717;
RA Butschi A., Titz A., Waelti M.A., Olieric V., Paschinger K., Noebauer K.,
RA Guo X., Seeberger P.H., Wilson I.B., Aebi M., Hengartner M.O., Kuenzler M.;
RT "Caenorhabditis elegans N-glycan core beta-galactoside confers sensitivity
RT towards nematotoxic fungal galectin CGL2.";
RL PLoS Pathog. 6:E1000717-E1000717(2010).
CC -!- FUNCTION: Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-
CC deoxy-D-mannose (PubMed:16650000). Involved in susceptibility to pore-
CC forming crystal toxins in conjunction with bre-2, bre-3, bre-4, and
CC bre-5 (PubMed:10924467, PubMed:17135259, PubMed:17482642). Involved in
CC susceptibility to the nematotoxic C.cinerea galectin Cgl2, likely by
CC contributing to the synthesis of N-glycans to which Cgl2 binds
CC (PubMed:20062796). Has a role in determining brood size
CC (PubMed:10924467). {ECO:0000269|PubMed:10924467,
CC ECO:0000269|PubMed:16650000, ECO:0000269|PubMed:17135259,
CC ECO:0000269|PubMed:17482642, ECO:0000269|PubMed:20062796}.
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:0000269|PubMed:16650000};
CC -!- COFACTOR:
CC Name=NADP(+); Xref=ChEBI:CHEBI:58349; Evidence={ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=b;
CC IsoId=Q18801-1; Sequence=Displayed;
CC Name=a;
CC IsoId=Q18801-2; Sequence=VSP_013810;
CC Name=c;
CC IsoId=Q18801-3; Sequence=VSP_032084;
CC Name=d;
CC IsoId=Q18801-4; Sequence=VSP_032086;
CC Name=e;
CC IsoId=Q18801-5; Sequence=VSP_032085;
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development, showing up-
CC regulation between stages L2 and L4. {ECO:0000269|PubMed:16650000}.
CC -!- DISRUPTION PHENOTYPE: Worms exhibit resistance to the Cry5B toxin
CC produced by Bacillus thuringiensis. This is thought to be due to
CC mutants having reduced population of glycolipids which are targeted by
CC the Cry5B protein. Mutants also have reduced brood sizes at only 12% of
CC wild-type N2. {ECO:0000269|PubMed:10924467}.
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; AM231683; CAJ77752.1; -; mRNA.
DR EMBL; AM231684; CAJ77753.1; -; mRNA.
DR EMBL; Z68215; CAA92455.2; -; Genomic_DNA.
DR EMBL; Z68215; CAC42269.1; -; Genomic_DNA.
DR EMBL; Z68215; CAC42270.1; -; Genomic_DNA.
DR EMBL; Z68215; CAL49435.1; -; Genomic_DNA.
DR EMBL; Z68215; CAL49436.1; -; Genomic_DNA.
DR PIR; T20182; T20182.
DR RefSeq; NP_001076668.1; NM_001083199.2. [Q18801-3]
DR RefSeq; NP_001076669.1; NM_001083200.2. [Q18801-4]
DR RefSeq; NP_001076670.1; NM_001083201.2. [Q18801-5]
DR RefSeq; NP_501563.1; NM_069162.6. [Q18801-2]
DR RefSeq; NP_501564.1; NM_069163.3. [Q18801-1]
DR AlphaFoldDB; Q18801; -.
DR SMR; Q18801; -.
DR BioGRID; 42823; 7.
DR STRING; 6239.C53B4.7b; -.
DR iPTMnet; Q18801; -.
DR EPD; Q18801; -.
DR PaxDb; Q18801; -.
DR PeptideAtlas; Q18801; -.
DR EnsemblMetazoa; C53B4.7a.1; C53B4.7a.1; WBGene00000266. [Q18801-2]
DR EnsemblMetazoa; C53B4.7b.1; C53B4.7b.1; WBGene00000266. [Q18801-1]
DR EnsemblMetazoa; C53B4.7c.1; C53B4.7c.1; WBGene00000266. [Q18801-3]
DR EnsemblMetazoa; C53B4.7d.1; C53B4.7d.1; WBGene00000266. [Q18801-4]
DR EnsemblMetazoa; C53B4.7e.1; C53B4.7e.1; WBGene00000266. [Q18801-5]
DR GeneID; 177717; -.
DR KEGG; cel:CELE_C53B4.7; -.
DR UCSC; C53B4.7a.1; c. elegans. [Q18801-1]
DR CTD; 177717; -.
DR WormBase; C53B4.7a; CE27116; WBGene00000266; bre-1. [Q18801-2]
DR WormBase; C53B4.7b; CE27117; WBGene00000266; bre-1. [Q18801-1]
DR WormBase; C53B4.7c; CE23608; WBGene00000266; bre-1. [Q18801-3]
DR WormBase; C53B4.7d; CE40447; WBGene00000266; bre-1. [Q18801-4]
DR WormBase; C53B4.7e; CE40448; WBGene00000266; bre-1. [Q18801-5]
DR eggNOG; KOG1372; Eukaryota.
DR GeneTree; ENSGT00440000033640; -.
DR InParanoid; Q18801; -.
DR OMA; TDCLYLG; -.
DR OrthoDB; 877551at2759; -.
DR PhylomeDB; Q18801; -.
DR Reactome; R-CEL-6787639; GDP-fucose biosynthesis.
DR UniPathway; UPA00128; UER00190.
DR PRO; PR:Q18801; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00000266; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:WormBase.
DR GO; GO:0030017; C:sarcomere; HDA:WormBase.
DR GO; GO:0055120; C:striated muscle dense body; HDA:WormBase.
DR GO; GO:0008446; F:GDP-mannose 4,6-dehydratase activity; IDA:UniProtKB.
DR GO; GO:0042351; P:'de novo' GDP-L-fucose biosynthetic process; IBA:GO_Central.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; HEP:WormBase.
DR GO; GO:0042350; P:GDP-L-fucose biosynthetic process; IDA:WormBase.
DR GO; GO:0019673; P:GDP-mannose metabolic process; IDA:WormBase.
DR GO; GO:0009636; P:response to toxic substance; IMP:UniProtKB.
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 Alternative splicing; Insecticide resistance; Lyase; NADP;
KW Reference proteome.
FT CHAIN 1..399
FT /note="GDP-mannose 4,6 dehydratase 1"
FT /id="PRO_0000201708"
FT ACT_SITE 183
FT /evidence="ECO:0000250"
FT ACT_SITE 185
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 207
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 57..62
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 114..115
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 136..140
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 151
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 211
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 BINDING 242
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..31
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_032084"
FT VAR_SEQ 1..24
FT /note="MPTGKSESSDISEVVGNMEISKVE -> MDSSAEQ (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_032086"
FT VAR_SEQ 1..24
FT /note="MPTGKSESSDISEVVGNMEISKVE -> MNSHDSKIFCQTCSNGNNQ (in
FT isoform e)"
FT /evidence="ECO:0000305"
FT /id="VSP_032085"
FT VAR_SEQ 1..23
FT /note="MPTGKSESSDISEVVGNMEISKV -> MADQNAKI (in isoform a)"
FT /evidence="ECO:0000303|PubMed:16650000"
FT /id="VSP_013810"
FT MUTAGEN 232
FT /note="G->E: In ye4; resistant to Bacillus thuringiensis
FT crystal5B toxin and reduced brood size. Resistant to
FT C.cinerea galectin Cgl2."
FT /evidence="ECO:0000269|PubMed:17135259,
FT ECO:0000269|PubMed:20062796"
SQ SEQUENCE 399 AA; 44489 MW; 51E3A872ACF0983A CRC64;
MPTGKSESSD ISEVVGNMEI SKVEGLEACI GMSHEVSTTP AAELAAFRAR KVALITGISG
QDGSYLAELL LSKGYKVHGI IRRSSSFNTA RIEHLYSNPI THHGDSSFSL HYGDMTDSSC
LIKLISTIEP TEVYHLAAQS HVKVSFDLPE YTAEVDAVGT LRLLDAIHAC RLTEKVRFYQ
ASTSELYGKV QEIPQSEKTP FYPRSPYAVA KMYGYWIVVN YREAYNMFAC NGILFNHESP
RRGETFVTRK ITRSVAKISL GQQESIELGN LSALRDWGHA REYVEAMWRI LQHDSPDDFV
IATGKQFSVR EFCNLAFAEI GEVLQWEGEG VEEVGKNKDG VIRVKVSPKY YRPTEVETLL
GNAEKAKKTL GWEAKVTVPE LVKEMVASDI ILMKSNPMA
