C98A3_ARATH
ID C98A3_ARATH Reviewed; 508 AA.
AC O22203; Q0WWH4; Q940C7;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Cytochrome P450 98A3;
DE EC=1.14.-.-;
DE AltName: Full=Protein REDUCED EPIDERMAL FLUORESCENCE 8;
DE AltName: Full=p-coumaroylshikimate/quinate 3'-hydrolxylase;
DE Short=C3'H;
GN Name=CYP98A3; Synonyms=C3'H, REF8; OrderedLocusNames=At2g40890;
GN ORFNames=T20B5.9;
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=10617197; DOI=10.1038/45471;
RA Lin X., Kaul S., Rounsley S.D., Shea T.P., Benito M.-I., Town C.D.,
RA Fujii C.Y., Mason T.M., Bowman C.L., Barnstead M.E., Feldblyum T.V.,
RA Buell C.R., Ketchum K.A., Lee J.J., Ronning C.M., Koo H.L., Moffat K.S.,
RA Cronin L.A., Shen M., Pai G., Van Aken S., Umayam L., Tallon L.J.,
RA Gill J.E., Adams M.D., Carrera A.J., Creasy T.H., Goodman H.M.,
RA Somerville C.R., Copenhaver G.P., Preuss D., Nierman W.C., White O.,
RA Eisen J.A., Salzberg S.L., Fraser C.M., Venter J.C.;
RT "Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana.";
RL Nature 402:761-768(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] OF 79-508.
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RA Totoki Y., Seki M., Ishida J., Nakajima M., Enju A., Kamiya A.,
RA Narusaka M., Shin-i T., Nakagawa M., Sakamoto N., Oishi K., Kohara Y.,
RA Kobayashi M., Toyoda A., Sakaki Y., Sakurai T., Iida K., Akiyama K.,
RA Satou M., Toyoda T., Konagaya A., Carninci P., Kawai J., Hayashizaki Y.,
RA Shinozaki K.;
RT "Large-scale analysis of RIKEN Arabidopsis full-length (RAFL) cDNAs.";
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, TISSUE SPECIFICITY, AND INDUCTION BY WOUNDING.
RC STRAIN=cv. Columbia;
RX PubMed=11429408; DOI=10.1074/jbc.m104047200;
RA Schoch G., Goepfert S., Morant M., Hehn A., Meyer D., Ullmann P.,
RA Werck-Reichhart D.;
RT "CYP98A3 from Arabidopsis thaliana is a 3'-hydroxylase of phenolic esters,
RT a missing link in the phenylpropanoid pathway.";
RL J. Biol. Chem. 276:36566-36574(2001).
RN [6]
RP FUNCTION, MUTAGENESIS OF GLY-444, TISSUE SPECIFICITY, CATALYTIC ACTIVITY,
RP AND SUBSTRATE SPECIFICITY.
RX PubMed=11967091; DOI=10.1046/j.1365-313x.2002.01266.x;
RA Franke R., Humphreys J.M., Hemm M.R., Denault J.W., Ruegger M.O.,
RA Cusumano J.C., Chapple C.;
RT "The Arabidopsis REF8 gene encodes the 3-hydroxylase of phenylpropanoid
RT metabolism.";
RL Plant J. 30:33-45(2002).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=cv. Columbia;
RX PubMed=11967092; DOI=10.1046/j.1365-313x.2002.01267.x;
RA Franke R., Hemm M.R., Denault J.W., Ruegger M.O., Humphreys J.M.,
RA Chapple C.;
RT "Changes in secondary metabolism and deposition of an unusual lignin in the
RT ref8 mutant of Arabidopsis.";
RL Plant J. 30:47-59(2002).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=cv. Columbia;
RX PubMed=16405932; DOI=10.1016/j.phytochem.2005.11.006;
RA Kai K., Shimizu B., Mizutani M., Watanabe K., Sakata K.;
RT "Accumulation of coumarins in Arabidopsis thaliana.";
RL Phytochemistry 67:379-386(2006).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16377748; DOI=10.1104/pp.105.069690;
RA Abdulrazzak N., Pollet B., Ehlting J., Larsen K., Asnaghi C., Ronseau S.,
RA Proux C., Erhardt M., Seltzer V., Renou J.P., Ullmann P., Pauly M.,
RA Lapierre C., Werck-Reichhart D.;
RT "A coumaroyl-ester-3-hydroxylase insertion mutant reveals the existence of
RT nonredundant meta-hydroxylation pathways and essential roles for phenolic
RT precursors in cell expansion and plant growth.";
RL Plant Physiol. 140:30-48(2006).
RN [10]
RP CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND 3D-STRUCTURE MODELING.
RX PubMed=19779199; DOI=10.1126/science.1174095;
RA Matsuno M., Compagnon V., Schoch G.A., Schmitt M., Debayle D.,
RA Bassard J.E., Pollet B., Hehn A., Heintz D., Ullmann P., Lapierre C.,
RA Bernier F., Ehlting J., Werck-Reichhart D.;
RT "Evolution of a novel phenolic pathway for pollen development.";
RL Science 325:1688-1692(2009).
RN [11]
RP CRYSTALLIZATION.
RX PubMed=21549841; DOI=10.1016/j.pep.2011.04.013;
RA Kim Y.H., Kwon T., Yang H.J., Kim W., Youn H., Lee J.Y., Youn B.;
RT "Gene engineering, purification, crystallization and preliminary X-ray
RT diffraction of cytochrome P450 p-coumarate-3-hydroxylase (C3H), the
RT Arabidopsis membrane protein.";
RL Protein Expr. Purif. 79:149-155(2011).
CC -!- FUNCTION: Cytochrome P450 which catalyzes 3'-hydroxylation of p-
CC coumaric esters of shikimic/quinic acids to form lignin monomers. Can
CC use p-coumarate, p-coumaraldehyde, p-coumaroyl methyl ester, 5-O-(4-
CC coumaroyl) D-quinate and 5-O-(4-coumaroyl) shikimate as substrates, but
CC not p-coumaryl alcohol, p-coumaroyl CoA, 1-O-p-coumaroyl-beta-D-
CC glucose, p-hydroxy-cinnamyl alcohol, cinnamate, caffeate or ferulate.
CC Has a weak activity on tri(p-coumaroyl)spermidine, but none on
CC triferuloylspermidine. Hydroxylates preferentially the 5-O-isomer, but
CC can also convert the 4-O- and 3-O-isomers with a lower efficiency.
CC Involved in the biosynthesis of the coumarins scopoletin and scopolin.
CC Essential for the biosynthesis of lignin. {ECO:0000269|PubMed:11429408,
CC ECO:0000269|PubMed:11967091, ECO:0000269|PubMed:11967092,
CC ECO:0000269|PubMed:16377748, ECO:0000269|PubMed:16405932}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7 uM for 5-O-(4-coumaroyl) shikimate
CC {ECO:0000269|PubMed:11429408};
CC KM=18 uM for 5-O-(4-coumaroyl) quinate {ECO:0000269|PubMed:11429408};
CC Note=kcat is 612 min(-1) with 5-O-(4-coumaroyl) shikimate as
CC substrate. kcat is 399 min(-1) with 5-O-(4-coumaroyl) quinate as
CC substrate. {ECO:0000269|PubMed:11429408};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in stems, roots and siliques.
CC Detected in leaves flowers and seedlings. Highest expression detected
CC in differentiating xylem. {ECO:0000269|PubMed:11429408,
CC ECO:0000269|PubMed:11967091, ECO:0000269|PubMed:19779199}.
CC -!- INDUCTION: Up-regulated by wounding. {ECO:0000269|PubMed:11429408}.
CC -!- DISRUPTION PHENOTYPE: Dwarf. 91% and 97% reduction of the levels of
CC scopoletin and scopolin respectively, but increased levels of skimmin,
CC the beta-glucoside of umbelliferone. Altered lignin composition and
CC increased susceptiblity to fungal colonization.
CC {ECO:0000269|PubMed:11967092, ECO:0000269|PubMed:16377748,
CC ECO:0000269|PubMed:16405932}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB86449.2; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; AC002409; AAB86449.2; ALT_INIT; Genomic_DNA.
DR EMBL; CP002685; AEC09893.1; -; Genomic_DNA.
DR EMBL; AY056105; AAL06992.1; -; mRNA.
DR EMBL; AK226377; BAE98524.1; -; mRNA.
DR PIR; T00753; T00753.
DR RefSeq; NP_850337.1; NM_180006.2.
DR AlphaFoldDB; O22203; -.
DR SMR; O22203; -.
DR BioGRID; 4023; 4.
DR IntAct; O22203; 3.
DR STRING; 3702.AT2G40890.1; -.
DR PaxDb; O22203; -.
DR PRIDE; O22203; -.
DR ProteomicsDB; 240390; -.
DR EnsemblPlants; AT2G40890.1; AT2G40890.1; AT2G40890.
DR GeneID; 818686; -.
DR Gramene; AT2G40890.1; AT2G40890.1; AT2G40890.
DR KEGG; ath:AT2G40890; -.
DR Araport; AT2G40890; -.
DR TAIR; locus:2058440; AT2G40890.
DR eggNOG; KOG0156; Eukaryota.
DR HOGENOM; CLU_001570_4_0_1; -.
DR InParanoid; O22203; -.
DR OMA; NYGFRIE; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; O22203; -.
DR BioCyc; ARA:AT2G40890-MON; -.
DR BioCyc; MetaCyc:AT2G40890-MON; -.
DR SABIO-RK; O22203; -.
DR PRO; PR:O22203; -.
DR Proteomes; UP000006548; Chromosome 2.
DR ExpressionAtlas; O22203; baseline and differential.
DR Genevisible; O22203; AT.
DR GO; GO:0005829; C:cytosol; HDA:TAIR.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:TAIR.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:TAIR.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; HDA:TAIR.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IPI:TAIR.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IDA:TAIR.
DR GO; GO:0016709; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen; IBA:GO_Central.
DR GO; GO:0046409; F:p-coumarate 3-hydroxylase activity; IDA:TAIR.
DR GO; GO:0009805; P:coumarin biosynthetic process; IMP:TAIR.
DR GO; GO:0009813; P:flavonoid biosynthetic process; IMP:TAIR.
DR GO; GO:0009809; P:lignin biosynthetic process; IMP:TAIR.
DR GO; GO:0009699; P:phenylpropanoid biosynthetic process; IMP: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..508
FT /note="Cytochrome P450 98A3"
FT /id="PRO_0000052199"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 438
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"
FT MUTAGEN 444
FT /note="G->D: In ref8; loss of activity."
FT /evidence="ECO:0000269|PubMed:11967091"
FT CONFLICT 202
FT /note="G -> E (in Ref. 3; AAL06992)"
FT /evidence="ECO:0000305"
FT CONFLICT 466
FT /note="G -> V (in Ref. 4; BAE98524)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 508 AA; 57927 MW; BD22A574F6B16C35 CRC64;
MSWFLIAVAT IAAVVSYKLI QRLRYKFPPG PSPKPIVGNL YDIKPVRFRC YYEWAQSYGP
IISVWIGSIL NVVVSSAELA KEVLKEHDQK LADRHRNRST EAFSRNGQDL IWADYGPHYV
KVRKVCTLEL FTPKRLESLR PIREDEVTAM VESVFRDCNL PENRAKGLQL RKYLGAVAFN
NITRLAFGKR FMNAEGVVDE QGLEFKAIVS NGLKLGASLS IAEHIPWLRW MFPADEKAFA
EHGARRDRLT RAIMEEHTLA RQKSSGAKQH FVDALLTLKD QYDLSEDTII GLLWDMITAG
MDTTAITAEW AMAEMIKNPR VQQKVQEEFD RVVGLDRILT EADFSRLPYL QCVVKESFRL
HPPTPLMLPH RSNADVKIGG YDIPKGSNVH VNVWAVARDP AVWKNPFEFR PERFLEEDVD
MKGHDFRLLP FGAGRRVCPG AQLGINLVTS MMSHLLHHFV WTPPQGTKPE EIDMSENPGL
VTYMRTPVQA VATPRLPSDL YKRVPYDM
