Full text data of TSTA3
TSTA3
(SDR4E1)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
GDP-L-fucose synthase; 1.1.1.271 (GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase; Protein FX; Red cell NADP(H)-binding protein; Short-chain dehydrogenase/reductase family 4E member 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
GDP-L-fucose synthase; 1.1.1.271 (GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase; Protein FX; Red cell NADP(H)-binding protein; Short-chain dehydrogenase/reductase family 4E member 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00014361
IPI00014361 GDP-L-fucose synthetase Red cell NADP(H)-binding protein, Two step NADP-dependent conversion of GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a reductase reaction soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00014361 GDP-L-fucose synthetase Red cell NADP(H)-binding protein, Two step NADP-dependent conversion of GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a reductase reaction soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
Q13630
ID FCL_HUMAN Reviewed; 321 AA.
AC Q13630; B2R8Y7; D3DWK5; Q567Q9; Q9UDG7;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=GDP-L-fucose synthase;
DE EC=1.1.1.271;
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=TSTA3; Synonyms=SDR4E1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT dinucleotide phosphate (NADP[H])-binding protein FX: identification
RT with the mouse tum-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.,
RA Buerckstuemmer T., 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 X-RAY CRYSTALLOGRAPHY (2.37 ANGSTROMS) IN COMPLEX WITH NADP, AND
RP 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 [8]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 8-321 IN COMPLEXES WITH GDP
RP AND 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-
CC 4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase
CC and a reductase reaction.
CC -!- CATALYTIC ACTIVITY: GDP-beta-L-fucose + NADP(+) = GDP-4-dehydro-6-
CC deoxy-alpha-D-mannose + NADPH.
CC -!- PATHWAY: Nucleotide-sugar biosynthesis; GDP-L-fucose biosynthesis
CC via de novo pathway; GDP-L-fucose from GDP-alpha-D-mannose: step
CC 2/2.
CC -!- SUBUNIT: Homodimer.
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. Fucose synthase subfamily.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 RefSeq; NP_003304.1; NM_003313.3.
DR UniGene; Hs.404119; -.
DR PDB; 4B8W; X-ray; 2.75 A; A/B=7-320.
DR PDB; 4B8Z; X-ray; 2.75 A; A/B/C/D=7-320.
DR PDB; 4BKP; X-ray; 2.70 A; A/B/C/D=7-321.
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; 4E5Y; -.
DR ProteinModelPortal; Q13630; -.
DR SMR; Q13630; 4-321.
DR IntAct; Q13630; 2.
DR STRING; 9606.ENSP00000353243; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; Q13630; -.
DR DMDM; 13124123; -.
DR REPRODUCTION-2DPAGE; IPI00014361; -.
DR PaxDb; Q13630; -.
DR PeptideAtlas; Q13630; -.
DR PRIDE; Q13630; -.
DR DNASU; 7264; -.
DR Ensembl; ENST00000425753; ENSP00000398803; ENSG00000104522.
DR Ensembl; ENST00000529064; ENSP00000435386; ENSG00000104522.
DR GeneID; 7264; -.
DR KEGG; hsa:7264; -.
DR UCSC; uc003yza.2; human.
DR CTD; 7264; -.
DR GeneCards; GC08M144694; -.
DR HGNC; HGNC:12390; TSTA3.
DR HPA; HPA023361; -.
DR MIM; 137020; gene.
DR neXtProt; NX_Q13630; -.
DR PharmGKB; PA37056; -.
DR eggNOG; COG0451; -.
DR HOGENOM; HOG000168011; -.
DR HOVERGEN; HBG000059; -.
DR InParanoid; Q13630; -.
DR KO; K02377; -.
DR OMA; IHCAGRV; -.
DR PhylomeDB; Q13630; -.
DR UniPathway; UPA00128; UER00191.
DR GeneWiki; TSTA3; -.
DR GenomeRNAi; 7264; -.
DR NextBio; 28399; -.
DR PRO; PR:Q13630; -.
DR ArrayExpress; Q13630; -.
DR Bgee; Q13630; -.
DR CleanEx; HS_TSTA3; -.
DR Genevestigator; Q13630; -.
DR GO; GO:0005737; C:cytoplasm; IC:UniProtKB.
DR GO; GO:0050662; F:coenzyme binding; IEA:InterPro.
DR GO; GO:0009055; F:electron carrier 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:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0042351; P:'de novo' GDP-L-fucose biosynthetic process; IDA:UniProtKB.
DR GO; GO:0019835; P:cytolysis; IEA:Ensembl.
DR GO; GO:0019673; P:GDP-mannose metabolic process; IDA:UniProtKB.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; NAS:UniProtKB.
DR Gene3D; 3.40.50.720; -; 1.
DR HAMAP; MF_00956; GDP_fucose_synth; 1; -.
DR InterPro; IPR001509; Epimerase_deHydtase.
DR InterPro; IPR028614; GDP_fucose_synth.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR Pfam; PF01370; Epimerase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Direct protein sequencing; Isomerase;
KW Multifunctional enzyme; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1 321 GDP-L-fucose synthase.
FT /FTId=PRO_0000174350.
FT NP_BIND 14 20 NADP.
FT NP_BIND 170 173 NADP.
FT ACT_SITE 143 143 Proton donor/acceptor (By similarity).
FT BINDING 147 147 NADP.
FT BINDING 186 186 NADP.
FT BINDING 194 194 Substrate.
FT BINDING 208 208 Substrate.
FT BINDING 215 215 Substrate.
FT BINDING 277 277 Substrate.
FT SITE 114 114 Important for catalytic activity (By
FT similarity).
FT SITE 116 116 Important for catalytic activity (By
FT similarity).
FT SITE 147 147 Lowers pKa of active site Tyr (By
FT similarity).
FT CONFLICT 5 5 Q -> E (in Ref. 5; AA sequence).
FT STRAND 9 13
FT TURN 14 16
FT HELIX 18 23
FT TURN 27 29
FT STRAND 37 40
FT STRAND 43 46
FT HELIX 51 60
FT STRAND 64 68
FT TURN 74 77
FT STRAND 78 80
FT HELIX 83 103
FT STRAND 107 112
FT HELIX 115 117
FT STRAND 118 121
FT STRAND 124 126
FT HELIX 128 130
FT STRAND 138 140
FT HELIX 141 161
FT STRAND 164 170
FT STRAND 172 175
FT TURN 182 184
FT HELIX 187 199
FT STRAND 201 203
FT STRAND 207 209
FT STRAND 217 219
FT HELIX 220 232
FT STRAND 240 242
FT HELIX 246 248
FT HELIX 252 263
FT STRAND 269 272
FT HELIX 287 292
FT HELIX 301 314
FT TURN 315 318
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
//
ID FCL_HUMAN Reviewed; 321 AA.
AC Q13630; B2R8Y7; D3DWK5; Q567Q9; Q9UDG7;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=GDP-L-fucose synthase;
DE EC=1.1.1.271;
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=TSTA3; Synonyms=SDR4E1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT dinucleotide phosphate (NADP[H])-binding protein FX: identification
RT with the mouse tum-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.,
RA Buerckstuemmer T., 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 X-RAY CRYSTALLOGRAPHY (2.37 ANGSTROMS) IN COMPLEX WITH NADP, AND
RP 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 [8]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 8-321 IN COMPLEXES WITH GDP
RP AND 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-
CC 4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase
CC and a reductase reaction.
CC -!- CATALYTIC ACTIVITY: GDP-beta-L-fucose + NADP(+) = GDP-4-dehydro-6-
CC deoxy-alpha-D-mannose + NADPH.
CC -!- PATHWAY: Nucleotide-sugar biosynthesis; GDP-L-fucose biosynthesis
CC via de novo pathway; GDP-L-fucose from GDP-alpha-D-mannose: step
CC 2/2.
CC -!- SUBUNIT: Homodimer.
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. Fucose synthase subfamily.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 RefSeq; NP_003304.1; NM_003313.3.
DR UniGene; Hs.404119; -.
DR PDB; 4B8W; X-ray; 2.75 A; A/B=7-320.
DR PDB; 4B8Z; X-ray; 2.75 A; A/B/C/D=7-320.
DR PDB; 4BKP; X-ray; 2.70 A; A/B/C/D=7-321.
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; 4E5Y; -.
DR ProteinModelPortal; Q13630; -.
DR SMR; Q13630; 4-321.
DR IntAct; Q13630; 2.
DR STRING; 9606.ENSP00000353243; -.
DR DrugBank; DB00157; NADH.
DR PhosphoSite; Q13630; -.
DR DMDM; 13124123; -.
DR REPRODUCTION-2DPAGE; IPI00014361; -.
DR PaxDb; Q13630; -.
DR PeptideAtlas; Q13630; -.
DR PRIDE; Q13630; -.
DR DNASU; 7264; -.
DR Ensembl; ENST00000425753; ENSP00000398803; ENSG00000104522.
DR Ensembl; ENST00000529064; ENSP00000435386; ENSG00000104522.
DR GeneID; 7264; -.
DR KEGG; hsa:7264; -.
DR UCSC; uc003yza.2; human.
DR CTD; 7264; -.
DR GeneCards; GC08M144694; -.
DR HGNC; HGNC:12390; TSTA3.
DR HPA; HPA023361; -.
DR MIM; 137020; gene.
DR neXtProt; NX_Q13630; -.
DR PharmGKB; PA37056; -.
DR eggNOG; COG0451; -.
DR HOGENOM; HOG000168011; -.
DR HOVERGEN; HBG000059; -.
DR InParanoid; Q13630; -.
DR KO; K02377; -.
DR OMA; IHCAGRV; -.
DR PhylomeDB; Q13630; -.
DR UniPathway; UPA00128; UER00191.
DR GeneWiki; TSTA3; -.
DR GenomeRNAi; 7264; -.
DR NextBio; 28399; -.
DR PRO; PR:Q13630; -.
DR ArrayExpress; Q13630; -.
DR Bgee; Q13630; -.
DR CleanEx; HS_TSTA3; -.
DR Genevestigator; Q13630; -.
DR GO; GO:0005737; C:cytoplasm; IC:UniProtKB.
DR GO; GO:0050662; F:coenzyme binding; IEA:InterPro.
DR GO; GO:0009055; F:electron carrier 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:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0042351; P:'de novo' GDP-L-fucose biosynthetic process; IDA:UniProtKB.
DR GO; GO:0019835; P:cytolysis; IEA:Ensembl.
DR GO; GO:0019673; P:GDP-mannose metabolic process; IDA:UniProtKB.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; NAS:UniProtKB.
DR Gene3D; 3.40.50.720; -; 1.
DR HAMAP; MF_00956; GDP_fucose_synth; 1; -.
DR InterPro; IPR001509; Epimerase_deHydtase.
DR InterPro; IPR028614; GDP_fucose_synth.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR Pfam; PF01370; Epimerase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Direct protein sequencing; Isomerase;
KW Multifunctional enzyme; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1 321 GDP-L-fucose synthase.
FT /FTId=PRO_0000174350.
FT NP_BIND 14 20 NADP.
FT NP_BIND 170 173 NADP.
FT ACT_SITE 143 143 Proton donor/acceptor (By similarity).
FT BINDING 147 147 NADP.
FT BINDING 186 186 NADP.
FT BINDING 194 194 Substrate.
FT BINDING 208 208 Substrate.
FT BINDING 215 215 Substrate.
FT BINDING 277 277 Substrate.
FT SITE 114 114 Important for catalytic activity (By
FT similarity).
FT SITE 116 116 Important for catalytic activity (By
FT similarity).
FT SITE 147 147 Lowers pKa of active site Tyr (By
FT similarity).
FT CONFLICT 5 5 Q -> E (in Ref. 5; AA sequence).
FT STRAND 9 13
FT TURN 14 16
FT HELIX 18 23
FT TURN 27 29
FT STRAND 37 40
FT STRAND 43 46
FT HELIX 51 60
FT STRAND 64 68
FT TURN 74 77
FT STRAND 78 80
FT HELIX 83 103
FT STRAND 107 112
FT HELIX 115 117
FT STRAND 118 121
FT STRAND 124 126
FT HELIX 128 130
FT STRAND 138 140
FT HELIX 141 161
FT STRAND 164 170
FT STRAND 172 175
FT TURN 182 184
FT HELIX 187 199
FT STRAND 201 203
FT STRAND 207 209
FT STRAND 217 219
FT HELIX 220 232
FT STRAND 240 242
FT HELIX 246 248
FT HELIX 252 263
FT STRAND 269 272
FT HELIX 287 292
FT HELIX 301 314
FT TURN 315 318
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
//
MIM
137020
*RECORD*
*FIELD* NO
137020
*FIELD* TI
*137020 TISSUE-SPECIFIC TRANSPLANTATION ANTIGEN 3; TSTA3
;;GDP-KETO-6-DEOXYMANNOSE 3,5-EPIMERASE, 4-REDUCTASE;;
read moreRED CELL NADP(H)-BINDING PROTEIN;;
FX
*FIELD* TX
Red cells contain a specific NADP(H)-binding protein, designated as FX
(Morelli and De Flora, 1977). Lenzerini et al. (1981) concluded that
there is a common genetic polymorphism at the locus or loci that control
the level of the FX protein. The conclusion was based on the finding of
large variation in FX levels in unrelated persons and a very strong
'family effect.' That a major X-linked locus is not involved was
indicated by the positive correlation between fathers and sons, and the
lack of significant correlation in the values of FX between maternal
grandfathers and their grandsons.
CLONING
Tonetti et al. (1996) used PCR to obtain the complete sequence of the
human FX cDNA. They found that the FX gene encodes a 320-amino acid
polypeptide with a predicted molecular mass of 35.7 kD. This finding is
in agreement with previous data showing that the FX protein forms a
homodimer of 68 kD. Database analysis demonstrated that human FX protein
is 92.6% identical to the mouse tumor rejection antigen P35B and has a
lower level of homology to 3 bacterial proteins, 1 of which may be
involved in sugar metabolism.
GENE FUNCTION
Tonetti et al. (1996) examined the role of FX in GDP-D-mannose
metabolism. GDP-fucose is synthesized from GDP-mannose in a 3-step
pathway. The first step is catalyzed by GDP-mannose 4,6-dehydratase, or
GMD (602884). The second and third steps are an epimerization and a
reduction reaction, respectively. The authors found that FX can catalyze
both the epimerase and the reductase reactions, converting
GDP-4-keto-6-D-deoxymannose to GDP-L-fucose. GDP-L-fucose is the
substrate of several fucosyltransferases involved in the expression of
many glycoconjugates, including blood group ABH antigens and
developmental adhesion antigens. Using purified GMD and FX, Sullivan et
al. (1998) showed that the 2 proteins alone are sufficient to convert
GDP-mannose to GDP-fucose in vitro. They suggested that mutations in one
of these 2 enzymes may cause leukocyte adhesion deficiency, type II
(LAD2; 266265), since cells from 2 LAD2 patients appeared to have a
specific defect in this pathway.
MAPPING
By fluorescence in situ hybridization, Sullivan et al. (1998) mapped the
FX gene to 8q24.3.
ANIMAL MODEL
Smith et al. (2002) induced a null mutation in the Fx locus in mice.
Mice with this mutation exhibited complete deficiency of cellular
fucosylation and variable intrauterine fatality. Liveborn Fx-null mice
exhibited postnatal failure to thrive that was suppressed with a
fucose-supplemented diet. Homozygous adults suffered from an extreme
neutrophilia, myeloproliferation, and absence of leukocyte selectin
ligand (600738) expression reminiscent of LAD2. Restoration of leukocyte
and endothelial selectin ligand expression, general cellular
fucosylation, and normal postnatal physiology was achieved by modulating
dietary fucose to supply a salvage pathway for GDP-fucose synthesis.
*FIELD* RF
1. Lenzerini, L.; Benatti, U.; Morelli, A.; Pontremoli, S.; De Flora,
A.; Piazza, A.; Rinaldi, A.; Filippi, G.; Siniscalco, M.: Genetic
variation in the quantitative levels of an NADP(H)-binding protein
(FX) in human erythrocytes. Blood 57: 209-217, 1981.
2. Morelli, A.; De Flora, A.: Isolation and partial characterization
of an NADP- and NADPH-binding protein from human erythrocytes. Arch.
Biochem. Biophys. 179: 698-705, 1977.
3. Smith, P. L.; Myers, J. T.; Rogers, C. E.; Zhou, L.; Petryniak,
B.; Becker, D. J.; Homeister, J. W.; Lowe, J. B.: Conditional control
of selectin ligand expression and global fucosylation events in mice
with a targeted mutation at the FX locus. J. Cell. Biol. 158: 801-815,
2002.
4. Sullivan, F. X.; Kumar, R.; Kriz, R.; Stahl, M.; Xu, G.-Y.; Rouse,
J.; Chang, X.; Boodhoo, A.; Potvin, B.; Cumming, D. A.: Molecular
cloning of human GDP-mannose 4,6-dehydratase and reconstitution of
GDP-fucose biosynthesis in vitro. J. Biol. Chem. 273: 8193-8202,
1998.
5. Tonetti, M.; Sturla, L.; Bisso, A.; Benatti, U.; De Flora, A.:
Synthesis of GDP-L-fucose by the human FX protein. J. Biol. Chem. 271:
27274-27279, 1996.
*FIELD* CN
Patricia A. Hartz - updated: 4/21/2003
Rebekah S. Rasooly - updated: 7/22/1998
Jennifer P. Macke - updated: 4/24/1997
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
cwells: 04/24/2003
terry: 4/21/2003
alopez: 7/23/1998
alopez: 7/22/1998
alopez: 6/4/1997
alopez: 5/16/1997
alopez: 4/24/1997
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
marie: 3/25/1988
reenie: 10/17/1986
reenie: 6/4/1986
*RECORD*
*FIELD* NO
137020
*FIELD* TI
*137020 TISSUE-SPECIFIC TRANSPLANTATION ANTIGEN 3; TSTA3
;;GDP-KETO-6-DEOXYMANNOSE 3,5-EPIMERASE, 4-REDUCTASE;;
read moreRED CELL NADP(H)-BINDING PROTEIN;;
FX
*FIELD* TX
Red cells contain a specific NADP(H)-binding protein, designated as FX
(Morelli and De Flora, 1977). Lenzerini et al. (1981) concluded that
there is a common genetic polymorphism at the locus or loci that control
the level of the FX protein. The conclusion was based on the finding of
large variation in FX levels in unrelated persons and a very strong
'family effect.' That a major X-linked locus is not involved was
indicated by the positive correlation between fathers and sons, and the
lack of significant correlation in the values of FX between maternal
grandfathers and their grandsons.
CLONING
Tonetti et al. (1996) used PCR to obtain the complete sequence of the
human FX cDNA. They found that the FX gene encodes a 320-amino acid
polypeptide with a predicted molecular mass of 35.7 kD. This finding is
in agreement with previous data showing that the FX protein forms a
homodimer of 68 kD. Database analysis demonstrated that human FX protein
is 92.6% identical to the mouse tumor rejection antigen P35B and has a
lower level of homology to 3 bacterial proteins, 1 of which may be
involved in sugar metabolism.
GENE FUNCTION
Tonetti et al. (1996) examined the role of FX in GDP-D-mannose
metabolism. GDP-fucose is synthesized from GDP-mannose in a 3-step
pathway. The first step is catalyzed by GDP-mannose 4,6-dehydratase, or
GMD (602884). The second and third steps are an epimerization and a
reduction reaction, respectively. The authors found that FX can catalyze
both the epimerase and the reductase reactions, converting
GDP-4-keto-6-D-deoxymannose to GDP-L-fucose. GDP-L-fucose is the
substrate of several fucosyltransferases involved in the expression of
many glycoconjugates, including blood group ABH antigens and
developmental adhesion antigens. Using purified GMD and FX, Sullivan et
al. (1998) showed that the 2 proteins alone are sufficient to convert
GDP-mannose to GDP-fucose in vitro. They suggested that mutations in one
of these 2 enzymes may cause leukocyte adhesion deficiency, type II
(LAD2; 266265), since cells from 2 LAD2 patients appeared to have a
specific defect in this pathway.
MAPPING
By fluorescence in situ hybridization, Sullivan et al. (1998) mapped the
FX gene to 8q24.3.
ANIMAL MODEL
Smith et al. (2002) induced a null mutation in the Fx locus in mice.
Mice with this mutation exhibited complete deficiency of cellular
fucosylation and variable intrauterine fatality. Liveborn Fx-null mice
exhibited postnatal failure to thrive that was suppressed with a
fucose-supplemented diet. Homozygous adults suffered from an extreme
neutrophilia, myeloproliferation, and absence of leukocyte selectin
ligand (600738) expression reminiscent of LAD2. Restoration of leukocyte
and endothelial selectin ligand expression, general cellular
fucosylation, and normal postnatal physiology was achieved by modulating
dietary fucose to supply a salvage pathway for GDP-fucose synthesis.
*FIELD* RF
1. Lenzerini, L.; Benatti, U.; Morelli, A.; Pontremoli, S.; De Flora,
A.; Piazza, A.; Rinaldi, A.; Filippi, G.; Siniscalco, M.: Genetic
variation in the quantitative levels of an NADP(H)-binding protein
(FX) in human erythrocytes. Blood 57: 209-217, 1981.
2. Morelli, A.; De Flora, A.: Isolation and partial characterization
of an NADP- and NADPH-binding protein from human erythrocytes. Arch.
Biochem. Biophys. 179: 698-705, 1977.
3. Smith, P. L.; Myers, J. T.; Rogers, C. E.; Zhou, L.; Petryniak,
B.; Becker, D. J.; Homeister, J. W.; Lowe, J. B.: Conditional control
of selectin ligand expression and global fucosylation events in mice
with a targeted mutation at the FX locus. J. Cell. Biol. 158: 801-815,
2002.
4. Sullivan, F. X.; Kumar, R.; Kriz, R.; Stahl, M.; Xu, G.-Y.; Rouse,
J.; Chang, X.; Boodhoo, A.; Potvin, B.; Cumming, D. A.: Molecular
cloning of human GDP-mannose 4,6-dehydratase and reconstitution of
GDP-fucose biosynthesis in vitro. J. Biol. Chem. 273: 8193-8202,
1998.
5. Tonetti, M.; Sturla, L.; Bisso, A.; Benatti, U.; De Flora, A.:
Synthesis of GDP-L-fucose by the human FX protein. J. Biol. Chem. 271:
27274-27279, 1996.
*FIELD* CN
Patricia A. Hartz - updated: 4/21/2003
Rebekah S. Rasooly - updated: 7/22/1998
Jennifer P. Macke - updated: 4/24/1997
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
cwells: 04/24/2003
terry: 4/21/2003
alopez: 7/23/1998
alopez: 7/22/1998
alopez: 6/4/1997
alopez: 5/16/1997
alopez: 4/24/1997
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
marie: 3/25/1988
reenie: 10/17/1986
reenie: 6/4/1986