ID   FCL_PONAB               Reviewed;         321 AA.
AC   Q5RBE5;
DT   22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   03-AUG-2022, entry version 87.
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   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) 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; CR858706; CAH90915.1; -; mRNA.
DR   RefSeq; NP_001125522.1; NM_001132050.1.
DR   AlphaFoldDB; Q5RBE5; -.
DR   SMR; Q5RBE5; -.
DR   STRING; 9601.ENSPPYP00000021246; -.
DR   GeneID; 100172434; -.
DR   KEGG; pon:100172434; -.
DR   CTD; 7264; -.
DR   eggNOG; KOG1431; Eukaryota.
DR   InParanoid; Q5RBE5; -.
DR   OrthoDB; 922791at2759; -.
DR   UniPathway; UPA00128; UER00191.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0050577; F:GDP-L-fucose synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0042351; P:'de novo' GDP-L-fucose biosynthetic process; IEA:UniProtKB-UniPathway.
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   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;
KW   Reference proteome.
FT   CHAIN           1..321
FT                   /note="GDP-L-fucose synthase"
FT                   /id="PRO_0000174352"
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;  35840 MW;  16208EB544AFF589 CRC64;
     MGEPQGSMRI LVTGGSGLVG KAIQKVVADG AGLPGEDWVF VSSKDADLTD AAQTRALLEK
     VRPTHVIHLA AMVGGLFRNI KYNLDFWRKN VHINDNVLHS AFEVGARKVV SCLSTCIFPD
     KTTYPIDETM IHNGPPHSSN FGYSYVKRMI DVQNRAYFQQ YGCTFTAVIP TNVFGPHDNF
     NIEDGHVLPG LIHKVHLAKS SGSALTVWGT GKPRRQFIYS LDLAQLFIWV LREYNEVEPI
     ILSVGEDDEV SIKEAAEAVV EAMDFHGEVT FDTTKSDGQF KKTASNSKLR TYLPDFRFTP
     FKQAVKETCA WFTDNYEQAR K