C82C4_ARATH
ID C82C4_ARATH Reviewed; 524 AA.
AC Q9SZ46;
DT 27-JUL-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Xanthotoxin 5-hydroxylase CYP82C4 {ECO:0000305|PubMed:18291319};
DE Short=8-methoxypsoralen 5-hydroxylase CYP82C4 {ECO:0000303|PubMed:18291319};
DE EC=1.14.14.- {ECO:0000269|PubMed:18291319};
DE AltName: Full=Cytochrome P450 82C4 {ECO:0000303|PubMed:21315474};
DE AltName: Full=Fraxetin 5-hydroxylase CYP82C4 {ECO:0000305|PubMed:29581584};
DE EC=1.14.14.164 {ECO:0000269|PubMed:29581584};
GN Name=CYP82C4 {ECO:0000303|PubMed:21315474};
GN OrderedLocusNames=At4g31940 {ECO:0000312|Araport:AT4G31940};
GN ORFNames=F10N7.250 {ECO:0000312|EMBL:CAA16595.1};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=10617198; DOI=10.1038/47134;
RA Mayer K.F.X., Schueller C., Wambutt R., Murphy G., Volckaert G., Pohl T.,
RA Duesterhoeft A., Stiekema W., Entian K.-D., Terryn N., Harris B.,
RA Ansorge W., Brandt P., Grivell L.A., Rieger M., Weichselgartner M.,
RA de Simone V., Obermaier B., Mache R., Mueller M., Kreis M., Delseny M.,
RA Puigdomenech P., Watson M., Schmidtheini T., Reichert B., Portetelle D.,
RA Perez-Alonso M., Boutry M., Bancroft I., Vos P., Hoheisel J.,
RA Zimmermann W., Wedler H., Ridley P., Langham S.-A., McCullagh B.,
RA Bilham L., Robben J., van der Schueren J., Grymonprez B., Chuang Y.-J.,
RA Vandenbussche F., Braeken M., Weltjens I., Voet M., Bastiaens I., Aert R.,
RA Defoor E., Weitzenegger T., Bothe G., Ramsperger U., Hilbert H., Braun M.,
RA Holzer E., Brandt A., Peters S., van Staveren M., Dirkse W., Mooijman P.,
RA Klein Lankhorst R., Rose M., Hauf J., Koetter P., Berneiser S., Hempel S.,
RA Feldpausch M., Lamberth S., Van den Daele H., De Keyser A., Buysshaert C.,
RA Gielen J., Villarroel R., De Clercq R., van Montagu M., Rogers J.,
RA Cronin A., Quail M.A., Bray-Allen S., Clark L., Doggett J., Hall S.,
RA Kay M., Lennard N., McLay K., Mayes R., Pettett A., Rajandream M.A.,
RA Lyne M., Benes V., Rechmann S., Borkova D., Bloecker H., Scharfe M.,
RA Grimm M., Loehnert T.-H., Dose S., de Haan M., Maarse A.C., Schaefer M.,
RA Mueller-Auer S., Gabel C., Fuchs M., Fartmann B., Granderath K., Dauner D.,
RA Herzl A., Neumann S., Argiriou A., Vitale D., Liguori R., Piravandi E.,
RA Massenet O., Quigley F., Clabauld G., Muendlein A., Felber R., Schnabl S.,
RA Hiller R., Schmidt W., Lecharny A., Aubourg S., Chefdor F., Cooke R.,
RA Berger C., Monfort A., Casacuberta E., Gibbons T., Weber N., Vandenbol M.,
RA Bargues M., Terol J., Torres A., Perez-Perez A., Purnelle B., Bent E.,
RA Johnson S., Tacon D., Jesse T., Heijnen L., Schwarz S., Scholler P.,
RA Heber S., Francs P., Bielke C., Frishman D., Haase D., Lemcke K.,
RA Mewes H.-W., Stocker S., Zaccaria P., Bevan M., Wilson R.K.,
RA de la Bastide M., Habermann K., Parnell L., Dedhia N., Gnoj L., Schutz K.,
RA Huang E., Spiegel L., Sekhon M., Murray J., Sheet P., Cordes M.,
RA Abu-Threideh J., Stoneking T., Kalicki J., Graves T., Harmon G.,
RA Edwards J., Latreille P., Courtney L., Cloud J., Abbott A., Scott K.,
RA Johnson D., Minx P., Bentley D., Fulton B., Miller N., Greco T., Kemp K.,
RA Kramer J., Fulton L., Mardis E., Dante M., Pepin K., Hillier L.W.,
RA Nelson J., Spieth J., Ryan E., Andrews S., Geisel C., Layman D., Du H.,
RA Ali J., Berghoff A., Jones K., Drone K., Cotton M., Joshu C., Antonoiu B.,
RA Zidanic M., Strong C., Sun H., Lamar B., Yordan C., Ma P., Zhong J.,
RA Preston R., Vil D., Shekher M., Matero A., Shah R., Swaby I.K.,
RA O'Shaughnessy A., Rodriguez M., Hoffman J., Till S., Granat S., Shohdy N.,
RA Hasegawa A., Hameed A., Lodhi M., Johnson A., Chen E., Marra M.A.,
RA Martienssen R., McCombie W.R.;
RT "Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.";
RL Nature 402:769-777(1999).
RN [2]
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 [3]
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 [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18291319; DOI=10.1016/j.chembiol.2008.01.008;
RA Kruse T., Ho K., Yoo H.D., Johnson T., Hippely M., Park J.H., Flavell R.,
RA Bobzin S.;
RT "In planta biocatalysis screen of P450s identifies 8-methoxypsoralen as a
RT substrate for the CYP82C subfamily, yielding original chemical
RT structures.";
RL Chem. Biol. 15:149-156(2008).
RN [5]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21315474; DOI=10.1016/j.jplph.2010.11.020;
RA Murgia I., Tarantino D., Soave C., Morandini P.;
RT "Arabidopsis CYP82C4 expression is dependent on Fe availability and
RT circadian rhythm, and correlates with genes involved in the early Fe
RT deficiency response.";
RL J. Plant Physiol. 168:894-902(2011).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, INDUCTION BY
RP IRON-DEFICIENCY, PATHWAY, AND TISSUE SPECIFICITY.
RC STRAIN=cv. Columbia;
RX PubMed=29581584; DOI=10.1038/s41589-018-0019-2;
RA Rajniak J., Giehl R.F.H., Chang E., Murgia I., von Wiren N., Sattely E.S.;
RT "Biosynthesis of redox-active metabolites in response to iron deficiency in
RT plants.";
RL Nat. Chem. Biol. 14:442-450(2018).
CC -!- FUNCTION: Can hydroxylate xanthotoxin (8-methoxypsoralen) to form 5-
CC hydroxyxanthotoxin (5-hydroxy-8-methoxypsoralen) in vivo and in vitro
CC (PubMed:18291319). Involved in the early iron deficiency response,
CC possibly through an IDE1-like mediated pathway (PubMed:21315474).
CC Involved in the pathway of sideretin biosynthesis from feruloyl CoA, a
CC redox-active catecholic metabolite exuded by roots in response to iron
CC deficiency in order to facilitate the uptake of iron; this pathway
CC consists in the successive conversion from feruloyl CoA to scopoletin,
CC from scopoletin to fraxetin and from fraxetin to sideretin
CC (PubMed:29581584). Catalyzes the biosynthesis of sideretin via fraxetin
CC hydroxylation (PubMed:29581584). {ECO:0000269|PubMed:18291319,
CC ECO:0000269|PubMed:21315474, ECO:0000269|PubMed:29581584}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=fraxetin + O2 + reduced [NADPH--hemoprotein reductase] = H(+)
CC + H2O + oxidized [NADPH--hemoprotein reductase] + sideretin (reduced
CC form); Xref=Rhea:RHEA:57844, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:5169, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142095; EC=1.14.14.164;
CC Evidence={ECO:0000269|PubMed:29581584};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:57845;
CC Evidence={ECO:0000269|PubMed:29581584};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + xanthotoxin = 5-
CC hydroxyxanthotoxin + 2 H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:58064, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18358, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:78326; Evidence={ECO:0000269|PubMed:18291319};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- PATHWAY: Phenylpropanoid metabolism. {ECO:0000269|PubMed:29581584}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in both primary and lateral roots under
CC iron-deficient conditions, except in apical root zones, and mostly in
CC the root epidermal layer. {ECO:0000269|PubMed:29581584}.
CC -!- INDUCTION: By iron deficiency, mainly in roots.
CC {ECO:0000269|PubMed:21315474, ECO:0000269|PubMed:29581584}.
CC -!- DISRUPTION PHENOTYPE: Increased root length at seedling stage
CC (PubMed:21315474). Accumulation of fraxetin, but loss of sideretin root
CC secretion in response to iron deficiency. Slightly increased iron-
CC uptake ability at elevated pH leading to a better fitness of plants,
CC due to the presence of high fraxetin content (PubMed:29581584).
CC {ECO:0000269|PubMed:21315474, ECO:0000269|PubMed:29581584}.
CC -!- MISCELLANEOUS: Plants overexpressing CYP82C4, can hydroxylate and
CC subsequently glycosylate 8-methoxypsoralen.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AY090995; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL021636; CAA16595.1; -; Genomic_DNA.
DR EMBL; AL161580; CAB79912.1; -; Genomic_DNA.
DR EMBL; CP002687; AEE85981.1; -; Genomic_DNA.
DR EMBL; AY090995; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; T04651; T04651.
DR RefSeq; NP_194922.1; NM_119345.3.
DR AlphaFoldDB; Q9SZ46; -.
DR SMR; Q9SZ46; -.
DR STRING; 3702.AT4G31940.1; -.
DR PaxDb; Q9SZ46; -.
DR PRIDE; Q9SZ46; -.
DR ProteomicsDB; 239210; -.
DR EnsemblPlants; AT4G31940.1; AT4G31940.1; AT4G31940.
DR GeneID; 829324; -.
DR Gramene; AT4G31940.1; AT4G31940.1; AT4G31940.
DR KEGG; ath:AT4G31940; -.
DR Araport; AT4G31940; -.
DR TAIR; locus:2116607; AT4G31940.
DR eggNOG; KOG0156; Eukaryota.
DR HOGENOM; CLU_001570_4_0_1; -.
DR InParanoid; Q9SZ46; -.
DR OMA; FNIRLGS; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; Q9SZ46; -.
DR BioCyc; ARA:AT4G31940-MON; -.
DR BioCyc; MetaCyc:AT4G31940-MON; -.
DR BRENDA; 1.14.14.164; 399.
DR PRO; PR:Q9SZ46; -.
DR Proteomes; UP000006548; Chromosome 4.
DR ExpressionAtlas; Q9SZ46; baseline and differential.
DR Genevisible; Q9SZ46; AT.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0106144; F:fraxetin 5-hydroxylase activity; IDA:TAIR.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IDA:UniProtKB.
DR GO; GO:0071281; P:cellular response to iron ion; IEP:TAIR.
DR GO; GO:0098542; P:defense response to other organism; IBA:GO_Central.
DR GO; GO:0010039; P:response to iron ion; IEP:TAIR.
DR GO; GO:0106146; P:sideretin biosynthesis; IDA:TAIR.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..524
FT /note="Xanthotoxin 5-hydroxylase CYP82C4"
FT /id="PRO_0000411199"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 463
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
SQ SEQUENCE 524 AA; 58919 MW; 82AD061802B83E9D CRC64;
MDTSLFSLFV PILVFVFIAL FKKSKKPKYV KAPAPSGAWP IIGHLHLLGG KEQLLYRTLG
KMADHYGPAM SLQLGSNEAF VVSSFEVAKD CFTVNDKALA SRPMTAAAKH MGYNFAVFGF
APYSAFWREM RKIATIELLS NRRLQMLKHV RVSEITMGVK DLYSLWFKNG GTKPVMVDLK
SWLEDMTLNM IVRMVAGKRY FGGGGSVSSE DTEEAMQCKK AIAKFFHLIG IFTVSDAFPT
LSFFDLQGHE KEMKQTGSEL DVILERWIEN HRQQRKFSGT KENDSDFIDV MMSLAEQGKL
SHLQYDANTS IKSTCLALIL GGSDTSASTL TWAISLLLNN KEMLKKAQDE IDIHVGRDRN
VEDSDIENLV YLQAIIKETL RLYPAGPLLG PREAMEDCTV AGYYVPCGTR LIVNVWKIQR
DPKVYMEPNE FRPERFITGE AKEFDVRGQN FELMPFGSGR RSCPGSSLAM QVLHLGLARF
LHSFDVKTVM DMPVDMSENP GLTIPKATPL EVLISPRIKE ELFV
