FLS1_ARATH
ID FLS1_ARATH Reviewed; 336 AA.
AC Q96330; O04730; O04731; O04732; O04830; O04831; O04832;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Flavonol synthase/flavanone 3-hydroxylase;
DE EC=1.14.11.9 {ECO:0000250|UniProtKB:Q7XZQ6};
DE EC=1.14.20.6 {ECO:0000250|UniProtKB:Q7XZQ6};
DE AltName: Full=FLS 1;
GN Name=FLS1; Synonyms=FLS; OrderedLocusNames=At5g08640; ORFNames=MAH20.20;
OS Arabidopsis thaliana (Mouse-ear cress).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX NCBI_TaxID=3702;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION BY LIGHT.
RC STRAIN=cv. Landsberg erecta;
RX PubMed=9112784; DOI=10.1104/pp.113.4.1437;
RA Pelletier M.K., Murrell J.R., Shirley B.W.;
RT "Characterization of flavonol synthase and leucoanthocyanidin dioxygenase
RT genes in Arabidopsis. Further evidence for differential regulation of
RT 'early' and 'late' genes.";
RL Plant Physiol. 113:1437-1445(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, INDUCTION BY LIGHT, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=cv. Columbia, and cv. Landsberg erecta;
RX PubMed=9770503; DOI=10.1073/pnas.95.21.12432;
RA Wisman E., Hartmann U., Sagasser M., Baumann E., Palme K., Hahlbrock K.,
RA Saedler H., Weisshaar B.;
RT "Knock-out mutants from an En-1 mutagenized Arabidopsis thaliana population
RT generate phenylpropanoid biosynthesis phenotypes.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:12432-12437(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=9405937; DOI=10.1093/dnares/4.4.291;
RA Kotani H., Nakamura Y., Sato S., Kaneko T., Asamizu E., Miyajima N.,
RA Tabata S.;
RT "Structural analysis of Arabidopsis thaliana chromosome 5. II. Sequence
RT features of the regions of 1,044,062 bp covered by thirteen physically
RT assigned P1 clones.";
RL DNA Res. 4:291-300(1997).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=cv. Columbia;
RX PubMed=27862469; DOI=10.1111/tpj.13415;
RA Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA Town C.D.;
RT "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT genome.";
RL Plant J. 89:789-804(2017).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=14593172; DOI=10.1126/science.1088305;
RA Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA Ecker J.R.;
RT "Empirical analysis of transcriptional activity in the Arabidopsis
RT genome.";
RL Science 302:842-846(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Brover V.V., Troukhan M.E., Alexandrov N.A., Lu Y.-P., Flavell R.B.,
RA Feldmann K.A.;
RT "Full-length cDNA from Arabidopsis thaliana.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=10394944; DOI=10.1023/a:1026414301100;
RA Pelletier M.K., Burbulis I.E., Winkel-Shirley B.;
RT "Disruption of specific flavonoid genes enhances the accumulation of
RT flavonoid enzymes and end-products in Arabidopsis seedlings.";
RL Plant Mol. Biol. 40:45-54(1999).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12126705; DOI=10.1016/s0031-9422(02)00155-3;
RA Prescott A.G., Stamford N.P., Wheeler G., Firmin J.L.;
RT "In vitro properties of a recombinant flavonol synthase from Arabidopsis
RT thaliana.";
RL Phytochemistry 60:589-593(2002).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16153644; DOI=10.1016/j.febslet.2005.08.033;
RA Welford R.W., Kirkpatrick J.M., McNeill L.A., Puri M., Oldham N.J.,
RA Schofield C.J.;
RT "Incorporation of oxygen into the succinate co-product of iron(II) and 2-
RT oxoglutarate dependent oxygenases from bacteria, plants and humans.";
RL FEBS Lett. 579:5170-5174(2005).
RN [10]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15821875; DOI=10.1007/s11103-004-6910-0;
RA Hartmann U., Sagasser M., Mehrtens F., Stracke R., Weisshaar B.;
RT "Differential combinatorial interactions of cis-acting elements recognized
RT by R2R3-MYB, BZIP, and BHLH factors control light-responsive and tissue-
RT specific activation of phenylpropanoid biosynthesis genes.";
RL Plant Mol. Biol. 57:155-171(2005).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF HIS-132 AND LYS-329.
RX PubMed=16106293; DOI=10.1039/b507153d;
RA Welford R.W., Clifton I.J., Turnbull J.J., Wilson S.C., Schofield C.J.;
RT "Structural and mechanistic studies on anthocyanidin synthase catalysed
RT oxidation of flavanone substrates: the effect of C-2 stereochemistry on
RT product selectivity and mechanism.";
RL Org. Biomol. Chem. 3:3117-3126(2005).
RN [12]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF HIS-132;
RP PHE-134; LYS-202; HIS-221; ASP-223; HIS-277; ARG-287; SER-289; PHE-293 AND
RP GLU-295.
RX PubMed=17719613; DOI=10.1016/j.phytochem.2007.07.006;
RA Chua C.S., Biermann D., Goo K.S., Sim T.S.;
RT "Elucidation of active site residues of Arabidopsis thaliana flavonol
RT synthase provides a molecular platform for engineering flavonols.";
RL Phytochemistry 69:66-75(2008).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, GENE FAMILY, NOMENCLATURE, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=cv. Wassilewskija;
RX PubMed=18467451; DOI=10.1104/pp.108.117457;
RA Owens D.K., Alerding A.B., Crosby K.C., Bandara A.B., Westwood J.H.,
RA Winkel B.S.;
RT "Functional analysis of a predicted flavonol synthase gene family in
RT Arabidopsis.";
RL Plant Physiol. 147:1046-1061(2008).
RN [14]
RP FUNCTION.
RX PubMed=19433090; DOI=10.1016/j.febslet.2009.05.006;
RA Preuss A., Stracke R., Weisshaar B., Hillebrecht A., Matern U., Martens S.;
RT "Arabidopsis thaliana expresses a second functional flavonol synthase.";
RL FEBS Lett. 583:1981-1986(2009).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=cv. No-0;
RX PubMed=18998159; DOI=10.1007/s00425-008-0841-y;
RA Stracke R., De Vos R.C., Bartelniewoehner L., Ishihara H., Sagasser M.,
RA Martens S., Weisshaar B.;
RT "Metabolomic and genetic analyses of flavonol synthesis in Arabidopsis
RT thaliana support the in vivo involvement of leucoanthocyanidin
RT dioxygenase.";
RL Planta 229:427-445(2009).
RN [16]
RP INDUCTION.
RX PubMed=21427279; DOI=10.1104/pp.111.172502;
RA Lewis D.R., Ramirez M.V., Miller N.D., Vallabhaneni P., Ray W.K.,
RA Helm R.F., Winkel B.S., Muday G.K.;
RT "Auxin and ethylene induce flavonol accumulation through distinct
RT transcriptional networks.";
RL Plant Physiol. 156:144-164(2011).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21502189; DOI=10.1104/pp.111.175976;
RA Kuhn B.M., Geisler M., Bigler L., Ringli C.;
RT "Flavonols accumulate asymmetrically and affect auxin transport in
RT Arabidopsis.";
RL Plant Physiol. 156:585-595(2011).
RN [18]
RP REVIEW, AND NOMENCLATURE.
RX PubMed=23473981; DOI=10.1016/j.plaphy.2013.02.001;
RA Saito K., Yonekura-Sakakibara K., Nakabayashi R., Higashi Y., Yamazaki M.,
RA Tohge T., Fernie A.R.;
RT "The flavonoid biosynthetic pathway in Arabidopsis: Structural and genetic
RT diversity.";
RL Plant Physiol. Biochem. 72:21-34(2013).
CC -!- FUNCTION: Catalyzes the formation of flavonols from dihydroflavonols.
CC It can act on dihydrokaempferol to produce kaempferol, on
CC dihydroquercetin to produce quercitin and on dihydromyricetin to
CC produce myricetin. In vitro catalyzes the oxidation of both enantiomers
CC of naringenin to give both cis- and trans-dihydrokaempferol.
CC {ECO:0000269|PubMed:12126705, ECO:0000269|PubMed:16106293,
CC ECO:0000269|PubMed:16153644, ECO:0000269|PubMed:17719613,
CC ECO:0000269|PubMed:18467451, ECO:0000269|PubMed:18998159,
CC ECO:0000269|PubMed:19433090, ECO:0000269|PubMed:21502189,
CC ECO:0000269|PubMed:9770503}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a (2R,3R)-dihydroflavonol + O2 = a flavonol +
CC CO2 + H2O + succinate; Xref=Rhea:RHEA:21088, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:28802, ChEBI:CHEBI:30031, ChEBI:CHEBI:138188;
CC EC=1.14.20.6; Evidence={ECO:0000250|UniProtKB:Q7XZQ6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a (2S)-flavan-4-one + O2 = a (2R,3R)-
CC dihydroflavonol + CO2 + succinate; Xref=Rhea:RHEA:18621,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:138188, ChEBI:CHEBI:140377;
CC EC=1.14.11.9; Evidence={ECO:0000250|UniProtKB:Q7XZQ6};
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; Evidence={ECO:0000250};
CC Note=Binds 1 ascorbate molecule per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000305};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000305};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=59 uM for dihydroquercetin {ECO:0000269|PubMed:17719613};
CC -!- PATHWAY: Secondary metabolite biosynthesis; flavonoid biosynthesis.
CC -!- INTERACTION:
CC Q96330; P13114: CHS; NbExp=3; IntAct=EBI-1774454, EBI-1546775;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21502189}. Nucleus
CC {ECO:0000269|PubMed:21502189}.
CC -!- TISSUE SPECIFICITY: Expressed in young seedlings (at protein level).
CC Expressed in roots, emerging leaves, shoot-root transition zone,
CC trichomes, flowers and siliques. In cotyledons, expressed mostly on the
CC adaxial side and only in guard cells on the abaxial side.
CC {ECO:0000269|PubMed:10394944, ECO:0000269|PubMed:15821875,
CC ECO:0000269|PubMed:18467451, ECO:0000269|PubMed:21502189}.
CC -!- INDUCTION: By light, auxin and 1-aminocyclopropane-1-carboxylic acid
CC (ACC). {ECO:0000269|PubMed:15821875, ECO:0000269|PubMed:21427279,
CC ECO:0000269|PubMed:9112784, ECO:0000269|PubMed:9770503}.
CC -!- DISRUPTION PHENOTYPE: Accumulation of anthocyanins and glycosylated
CC forms of dihydroflavonols, and drastic reduction of kaempferol,
CC quercitin and favonol glycosides. {ECO:0000269|PubMed:18467451,
CC ECO:0000269|PubMed:18998159, ECO:0000269|PubMed:9770503}.
CC -!- SIMILARITY: Belongs to the iron/ascorbate-dependent oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; U72631; AAB17393.1; -; Genomic_DNA.
DR EMBL; U84258; AAC69362.1; -; Genomic_DNA.
DR EMBL; U84259; AAC69363.1; -; mRNA.
DR EMBL; U84260; AAB41504.1; -; mRNA.
DR EMBL; AB006697; BAB10013.1; -; Genomic_DNA.
DR EMBL; CP002688; AED91332.1; -; Genomic_DNA.
DR EMBL; CP002688; AED91333.1; -; Genomic_DNA.
DR EMBL; AY058068; AAL24176.1; -; mRNA.
DR EMBL; BT000494; AAN18063.1; -; mRNA.
DR EMBL; AY086328; AAM64397.1; -; mRNA.
DR RefSeq; NP_001190266.1; NM_001203337.1.
DR RefSeq; NP_196481.1; NM_120951.3.
DR AlphaFoldDB; Q96330; -.
DR SMR; Q96330; -.
DR BioGRID; 16043; 4.
DR IntAct; Q96330; 3.
DR MINT; Q96330; -.
DR STRING; 3702.AT5G08640.1; -.
DR PaxDb; Q96330; -.
DR PRIDE; Q96330; -.
DR ProteomicsDB; 230035; -.
DR EnsemblPlants; AT5G08640.1; AT5G08640.1; AT5G08640.
DR EnsemblPlants; AT5G08640.2; AT5G08640.2; AT5G08640.
DR GeneID; 830765; -.
DR Gramene; AT5G08640.1; AT5G08640.1; AT5G08640.
DR Gramene; AT5G08640.2; AT5G08640.2; AT5G08640.
DR KEGG; ath:AT5G08640; -.
DR Araport; AT5G08640; -.
DR TAIR; locus:2159542; AT5G08640.
DR eggNOG; KOG0143; Eukaryota.
DR HOGENOM; CLU_010119_16_2_1; -.
DR InParanoid; Q96330; -.
DR OMA; GEMAEYM; -.
DR OrthoDB; 755371at2759; -.
DR PhylomeDB; Q96330; -.
DR BRENDA; 1.14.20.6; 399.
DR SABIO-RK; Q96330; -.
DR UniPathway; UPA00154; -.
DR PRO; PR:Q96330; -.
DR Proteomes; UP000006548; Chromosome 5.
DR ExpressionAtlas; Q96330; baseline and differential.
DR Genevisible; Q96330; AT.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0051213; F:dioxygenase activity; IBA:GO_Central.
DR GO; GO:0045431; F:flavonol synthase activity; IDA:TAIR.
DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0045486; F:naringenin 3-dioxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0009813; P:flavonoid biosynthetic process; IDA:TAIR.
DR GO; GO:0009733; P:response to auxin; IEP:TAIR.
DR GO; GO:0009416; P:response to light stimulus; IBA:GO_Central.
DR Gene3D; 2.60.120.330; -; 1.
DR InterPro; IPR026992; DIOX_N.
DR InterPro; IPR044861; IPNS-like_FE2OG_OXY.
DR InterPro; IPR027443; IPNS-like_sf.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR Pfam; PF03171; 2OG-FeII_Oxy; 1.
DR Pfam; PF14226; DIOX_N; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Dioxygenase; Flavonoid biosynthesis; Iron; Metal-binding;
KW Nucleus; Oxidoreductase; Reference proteome; Vitamin C.
FT CHAIN 1..336
FT /note="Flavonol synthase/flavanone 3-hydroxylase"
FT /id="PRO_0000067291"
FT DOMAIN 196..296
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT REGION 99..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 204..206
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 221
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 223
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 277
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 287..289
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000305"
FT MUTAGEN 132
FT /note="H->F: Slightly increases activity."
FT /evidence="ECO:0000269|PubMed:16106293,
FT ECO:0000269|PubMed:17719613"
FT MUTAGEN 132
FT /note="H->Y: Slightly decreases activity."
FT /evidence="ECO:0000269|PubMed:16106293,
FT ECO:0000269|PubMed:17719613"
FT MUTAGEN 134
FT /note="F->A: Reduces activity 7-fold."
FT /evidence="ECO:0000269|PubMed:17719613"
FT MUTAGEN 134
FT /note="F->L: Reduces activity 2-fold."
FT /evidence="ECO:0000269|PubMed:17719613"
FT MUTAGEN 202
FT /note="K->M: Reduces activity 25-fold."
FT /evidence="ECO:0000269|PubMed:17719613"
FT MUTAGEN 202
FT /note="K->R: Reduces activity 8-fold."
FT /evidence="ECO:0000269|PubMed:17719613"
FT MUTAGEN 221
FT /note="H->W: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17719613"
FT MUTAGEN 223
FT /note="D->E: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17719613"
FT MUTAGEN 277
FT /note="H->F: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17719613"
FT MUTAGEN 287
FT /note="R->K: Loss of activity."
FT /evidence="ECO:0000269|PubMed:17719613"
FT MUTAGEN 289
FT /note="S->T: Reduces activity 2-fold."
FT /evidence="ECO:0000269|PubMed:17719613"
FT MUTAGEN 293
FT /note="F->A,L: Reduces activity 12-fold."
FT /evidence="ECO:0000269|PubMed:17719613"
FT MUTAGEN 295
FT /note="E->L: Reduces activity 15-fold."
FT /evidence="ECO:0000269|PubMed:17719613"
FT MUTAGEN 295
FT /note="E->Q: Reduces activity 2-fold."
FT /evidence="ECO:0000269|PubMed:17719613"
FT MUTAGEN 329
FT /note="K->N: Reduces activity 4-fold."
FT /evidence="ECO:0000269|PubMed:16106293"
SQ SEQUENCE 336 AA; 38282 MW; 3283E3AFE603D2A9 CRC64;
MEVERVQDIS SSSLLTEAIP LEFIRSEKEQ PAITTFRGPT PAIPVVDLSD PDEESVRRAV
VKASEEWGLF QVVNHGIPTE LIRRLQDVGR KFFELPSSEK ESVAKPEDSK DIEGYGTKLQ
KDPEGKKAWV DHLFHRIWPP SCVNYRFWPK NPPEYREVNE EYAVHVKKLS ETLLGILSDG
LGLKRDALKE GLGGEMAEYM MKINYYPPCP RPDLALGVPA HTDLSGITLL VPNEVPGLQV
FKDDHWFDAE YIPSAVIVHI GDQILRLSNG RYKNVLHRTT VDKEKTRMSW PVFLEPPREK
IVGPLPELTG DDNPPKFKPF AFKDYSYRKL NKLPLD
