ID   FCL_CRIGR               Reviewed;         321 AA.
AC   Q8K3X2;
DT   25-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   03-AUG-2022, entry version 88.
DE   RecName: Full=GDP-L-fucose synthase {ECO:0000305};
DE            EC=1.1.1.271 {ECO:0000250|UniProtKB:Q13630};
DE   AltName: Full=GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase;
DE   AltName: Full=Protein FX;
DE   AltName: Full=Red cell NADP(H)-binding protein;
GN   Name=GFUS; Synonyms=TSTA3;
OS   Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC   Cricetidae; Cricetinae; Cricetulus.
OX   NCBI_TaxID=10029;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Becker D.J., Smith P.L., Petryniak B., Kelly R.J., Myers J.T., Wu B.,
RA   Wang P.G., Lowe J.B.;
RT   "Glycan-dependent regulation of GDP-mannose 4,6-dehydratase activity.";
RL   Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
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:0000250|UniProtKB:Q13630}.
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:0000250|UniProtKB:Q13630};
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       {ECO:0000250|UniProtKB:Q13630}.
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; AF525365; AAM91926.1; -; mRNA.
DR   RefSeq; NP_001233708.1; NM_001246779.1.
DR   RefSeq; XP_007653311.1; XM_007655121.2.
DR   RefSeq; XP_016819321.1; XM_016963832.1.
DR   AlphaFoldDB; Q8K3X2; -.
DR   SMR; Q8K3X2; -.
DR   STRING; 10029.NP_001233708.1; -.
DR   GeneID; 100689348; -.
DR   KEGG; cge:100689348; -.
DR   CTD; 7264; -.
DR   eggNOG; KOG1431; Eukaryota.
DR   OMA; IHCAGRV; -.
DR   OrthoDB; 922791at2759; -.
DR   UniPathway; UPA00128; UER00191.
DR   GO; GO:0050577; F:GDP-L-fucose synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0047918; F:GDP-mannose 3,5-epimerase activity; IEA:Ensembl.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0042351; P:'de novo' GDP-L-fucose biosynthetic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0019673; P:GDP-mannose metabolic process; IEA:Ensembl.
DR   GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB.
DR   GO; GO:1904906; P:positive regulation of endothelial cell-matrix adhesion via fibronectin; ISS:UniProtKB.
DR   GO; GO:0001913; P:T cell mediated cytotoxicity; IEA:Ensembl.
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   2: Evidence at transcript level;
KW   Isomerase; Multifunctional enzyme; NADP; Oxidoreductase.
FT   CHAIN           1..321
FT                   /note="GDP-L-fucose synthase"
FT                   /id="PRO_0000174349"
FT   ACT_SITE        143
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         14..20
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q13630"
FT   BINDING         147
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q13630"
FT   BINDING         170..173
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q13630"
FT   BINDING         186
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q13630"
FT   BINDING         194
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q13630"
FT   BINDING         208
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q13630"
FT   BINDING         215
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q13630"
FT   BINDING         277
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q13630"
FT   SITE            114
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250"
FT   SITE            116
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250"
FT   SITE            147
FT                   /note="Lowers pKa of active site Tyr"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   321 AA;  35837 MW;  134893316F341072 CRC64;
     MGEPQGSRRI LVTGGSGLVG RAIQKVVADG AGLPGEEWVF VSSKDADLTD AAQTQALFQK
     VQPTHVIHLA AMVGGLFRNI KYNLDFWRKN VHINDNVLHS AFEVGTRKVV SCLSTCIFPD
     KTTYPIDETM IHNGPPHSSN FGYSYAKRMI DVQNRAYFQQ HGCTFTAVIP TNVFGPHDNF
     NIEDGHVLPG LIHKVHLAKS NGSALTVWGT GKPRRQFIYS LDLARLFIWV LREYNEVEPI
     ILSVGEEDEV SIKEAAEAVV EAMDFCGEVT FDSTKSDGQY KKTASNGKLR AYLPDFRFTP
     FKQAVKETCA WFTDNYEQAR K