FCL_HUMAN
ID FCL_HUMAN Reviewed; 321 AA.
AC Q13630; B2R8Y7; D3DWK5; Q567Q9; Q9UDG7;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=GDP-L-fucose synthase {ECO:0000305};
DE EC=1.1.1.271 {ECO:0000269|PubMed:8910301};
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;
DE AltName: Full=Short-chain dehydrogenase/reductase family 4E member 1;
GN Name=GFUS {ECO:0000312|HGNC:HGNC:12390}; Synonyms=SDR4E1, TSTA3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBUNIT.
RC TISSUE=Placenta;
RX PubMed=8910301; DOI=10.1074/jbc.271.44.27274;
RA Tonetti M., Sturla L., Bisso A., Benatti U., De Flora A.;
RT "Synthesis of GDP-L-fucose by the human FX protein.";
RL J. Biol. Chem. 271:27274-27279(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Erythrocyte;
RX PubMed=7803801;
RA Camardella L., Carratore V., Ciardiello A., Damonte G., Benatti U.,
RA De Flora A.;
RT "Primary structure of human erythrocyte nicotinamide adenine dinucleotide
RT phosphate (NADP[H])-binding protein FX: identification with the mouse tum-
RT transplantation antigen P35B.";
RL Blood 85:264-267(1995).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.37 ANGSTROMS) IN COMPLEX WITH NADP, AND SUBUNIT.
RX PubMed=23774504; DOI=10.1093/abbs/gmt066;
RA Zhou H., Sun L., Li J., Xu C., Yu F., Liu Y., Ji C., He J.;
RT "The crystal structure of human GDP-L-fucose synthase.";
RL Acta Biochim. Biophys. Sin. 45:720-725(2013).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 8-321 IN COMPLEXES WITH GDP AND
RP NADP.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human GDP-L-fucose synthase with bound NADP.";
RL Submitted (APR-2013) to the PDB data bank.
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:0000269|PubMed:8910301}.
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:0000269|PubMed:8910301};
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:0000269|PubMed:8910301}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23774504,
CC ECO:0000269|PubMed:8910301}.
CC -!- INTERACTION:
CC Q13630; Q5SYC1: CLVS2; NbExp=3; IntAct=EBI-3910586, EBI-12357161;
CC Q13630; Q13630: GFUS; NbExp=4; IntAct=EBI-3910586, EBI-3910586;
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. Fucose synthase subfamily. {ECO:0000305}.
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DR EMBL; U58766; AAC50786.1; -; mRNA.
DR EMBL; AK313560; BAG36334.1; -; mRNA.
DR EMBL; CH471162; EAW82218.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82220.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82222.1; -; Genomic_DNA.
DR EMBL; BC001941; AAH01941.1; -; mRNA.
DR EMBL; BC093061; AAH93061.1; -; mRNA.
DR CCDS; CCDS6408.1; -.
DR RefSeq; NP_001304712.1; NM_001317783.1.
DR RefSeq; NP_003304.1; NM_003313.3.
DR RefSeq; XP_005251108.2; XM_005251051.3.
DR RefSeq; XP_011515571.1; XM_011517269.1.
DR PDB; 4B8W; X-ray; 2.75 A; A/B=7-320.
DR PDB; 4B8Z; X-ray; 2.75 A; A/B/C/D=8-320.
DR PDB; 4BKP; X-ray; 2.70 A; A/B/C/D=8-321.
DR PDB; 4BL5; X-ray; 2.60 A; A/B/C/D/E/F/G/H/I/J/K/L=8-321.
DR PDB; 4E5Y; X-ray; 2.37 A; A/B/C/D=1-321.
DR PDBsum; 4B8W; -.
DR PDBsum; 4B8Z; -.
DR PDBsum; 4BKP; -.
DR PDBsum; 4BL5; -.
DR PDBsum; 4E5Y; -.
DR AlphaFoldDB; Q13630; -.
DR SMR; Q13630; -.
DR BioGRID; 113115; 39.
DR IntAct; Q13630; 4.
DR STRING; 9606.ENSP00000398803; -.
DR DrugBank; DB00157; NADH.
DR GlyGen; Q13630; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13630; -.
DR PhosphoSitePlus; Q13630; -.
DR SwissPalm; Q13630; -.
DR BioMuta; TSTA3; -.
DR DMDM; 13124123; -.
DR REPRODUCTION-2DPAGE; IPI00014361; -.
DR EPD; Q13630; -.
DR jPOST; Q13630; -.
DR MassIVE; Q13630; -.
DR MaxQB; Q13630; -.
DR PaxDb; Q13630; -.
DR PeptideAtlas; Q13630; -.
DR PRIDE; Q13630; -.
DR ProteomicsDB; 59624; -.
DR Antibodypedia; 14656; 320 antibodies from 30 providers.
DR DNASU; 7264; -.
DR Ensembl; ENST00000425753.7; ENSP00000398803.2; ENSG00000104522.16.
DR Ensembl; ENST00000529064.5; ENSP00000435386.1; ENSG00000104522.16.
DR Ensembl; ENST00000612580.2; ENSP00000478042.1; ENSG00000278243.2.
DR Ensembl; ENST00000633782.1; ENSP00000487640.1; ENSG00000278243.2.
DR GeneID; 7264; -.
DR KEGG; hsa:7264; -.
DR MANE-Select; ENST00000425753.7; ENSP00000398803.2; NM_003313.4; NP_003304.1.
DR UCSC; uc003yza.3; human.
DR CTD; 7264; -.
DR DisGeNET; 7264; -.
DR GeneCards; GFUS; -.
DR HGNC; HGNC:12390; GFUS.
DR HPA; ENSG00000104522; Low tissue specificity.
DR MIM; 137020; gene.
DR neXtProt; NX_Q13630; -.
DR OpenTargets; ENSG00000104522; -.
DR PharmGKB; PA37056; -.
DR VEuPathDB; HostDB:ENSG00000104522; -.
DR eggNOG; KOG1431; Eukaryota.
DR GeneTree; ENSGT00390000004681; -.
DR InParanoid; Q13630; -.
DR OMA; IHCAGRV; -.
DR OrthoDB; 922791at2759; -.
DR PhylomeDB; Q13630; -.
DR TreeFam; TF314936; -.
DR PathwayCommons; Q13630; -.
DR Reactome; R-HSA-6787639; GDP-fucose biosynthesis.
DR SignaLink; Q13630; -.
DR UniPathway; UPA00128; UER00191.
DR BioGRID-ORCS; 7264; 25 hits in 1082 CRISPR screens.
DR GeneWiki; TSTA3; -.
DR GenomeRNAi; 7264; -.
DR Pharos; Q13630; Tbio.
DR PRO; PR:Q13630; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q13630; protein.
DR Bgee; ENSG00000104522; Expressed in body of stomach and 98 other tissues.
DR ExpressionAtlas; Q13630; baseline and differential.
DR Genevisible; Q13630; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR GO; GO:0042356; F:GDP-4-dehydro-D-rhamnose reductase activity; TAS:UniProtKB.
DR GO; GO:0050577; F:GDP-L-fucose synthase activity; IDA:UniProtKB.
DR GO; GO:0047918; F:GDP-mannose 3,5-epimerase activity; IDA:FlyBase.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042351; P:'de novo' GDP-L-fucose biosynthetic process; IDA:UniProtKB.
DR GO; GO:0019673; P:GDP-mannose metabolic process; IDA:UniProtKB.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; NAS:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:UniProtKB.
DR GO; GO:1904906; P:positive regulation of endothelial cell-matrix adhesion via fibronectin; IMP: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 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Isomerase; Multifunctional enzyme;
KW NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..321
FT /note="GDP-L-fucose synthase"
FT /id="PRO_0000174350"
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:0000269|PubMed:23774504, ECO:0000269|Ref.9"
FT BINDING 147
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:23774504, ECO:0000269|Ref.9"
FT BINDING 170..173
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:23774504, ECO:0000269|Ref.9"
FT BINDING 186
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|Ref.9"
FT BINDING 194
FT /ligand="substrate"
FT /evidence="ECO:0000305|Ref.9"
FT BINDING 208
FT /ligand="substrate"
FT /evidence="ECO:0000305|Ref.9"
FT BINDING 215
FT /ligand="substrate"
FT /evidence="ECO:0000305|Ref.9"
FT BINDING 277
FT /ligand="substrate"
FT /evidence="ECO:0000305|Ref.9"
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"
FT CONFLICT 5
FT /note="Q -> E (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 9..13
FT /evidence="ECO:0007829|PDB:4E5Y"
FT TURN 14..16
FT /evidence="ECO:0007829|PDB:4E5Y"
FT HELIX 18..23
FT /evidence="ECO:0007829|PDB:4E5Y"
FT TURN 27..29
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 37..40
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:4E5Y"
FT HELIX 51..60
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 64..68
FT /evidence="ECO:0007829|PDB:4E5Y"
FT TURN 74..77
FT /evidence="ECO:0007829|PDB:4BKP"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:4E5Y"
FT HELIX 83..103
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 107..112
FT /evidence="ECO:0007829|PDB:4E5Y"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:4E5Y"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 138..140
FT /evidence="ECO:0007829|PDB:4B8W"
FT HELIX 141..161
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 164..170
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:4E5Y"
FT TURN 182..184
FT /evidence="ECO:0007829|PDB:4E5Y"
FT HELIX 187..199
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:4E5Y"
FT HELIX 220..232
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:4E5Y"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:4BL5"
FT HELIX 252..263
FT /evidence="ECO:0007829|PDB:4E5Y"
FT STRAND 269..272
FT /evidence="ECO:0007829|PDB:4BL5"
FT HELIX 287..292
FT /evidence="ECO:0007829|PDB:4E5Y"
FT HELIX 301..314
FT /evidence="ECO:0007829|PDB:4E5Y"
FT TURN 315..318
FT /evidence="ECO:0007829|PDB:4E5Y"
SQ SEQUENCE 321 AA; 35893 MW; 94BB1FF61658007C CRC64;
MGEPQGSMRI LVTGGSGLVG KAIQKVVADG AGLPGEDWVF VSSKDADLTD TAQTRALFEK
VQPTHVIHLA AMVGGLFRNI KYNLDFWRKN VHMNDNVLHS AFEVGARKVV SCLSTCIFPD
KTTYPIDETM IHNGPPHNSN FGYSYAKRMI DVQNRAYFQQ YGCTFTAVIP TNVFGPHDNF
NIEDGHVLPG LIHKVHLAKS SGSALTVWGT GNPRRQFIYS LDLAQLFIWV LREYNEVEPI
ILSVGEEDEV SIKEAAEAVV EAMDFHGEVT FDTTKSDGQF KKTASNSKLR TYLPDFRFTP
FKQAVKETCA WFTDNYEQAR K
