ID   TCMO_ARATH              Reviewed;         505 AA.
AC   P92994; O04995; O49834; P92993;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   27-MAR-2024, entry version 177.
DE   RecName: Full=Trans-cinnamate 4-monooxygenase;
DE            EC=1.14.14.91 {ECO:0000250|UniProtKB:Q04468};
DE   AltName: Full=Cinnamic acid 4-hydroxylase;
DE            Short=C4H;
DE            Short=CA4H;
DE   AltName: Full=Cytochrome P450 73;
DE   AltName: Full=Cytochrome P450C4H;
DE   AltName: Full=Protein REDUCED EPIDERMAL FLUORESCENCE 3 {ECO:0000303|PubMed:19682296};
GN   Name=CYP73A5 {ECO:0000303|PubMed:9085571};
GN   Synonyms=CYP73 {ECO:0000303|PubMed:9085571}, REF3
GN   {ECO:0000303|PubMed:19682296};
GN   OrderedLocusNames=At2g30490 {ECO:0000312|Araport:AT2G30490};
GN   ORFNames=T6B20.16 {ECO:0000312|EMBL:AAB63088.1};
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 [GENOMIC DNA / MRNA], TISSUE SPECIFICITY, AND INDUCTION
RP   BY WOUNDING.
RC   STRAIN=cv. Columbia, and cv. Landsberg erecta;
RX   PubMed=9085570; DOI=10.1104/pp.113.3.729;
RA   Bell-Lelong D.A., Cusumano J.C., Meyer K., Chapple C.;
RT   "Cinnamate-4-hydroxylase expression in Arabidopsis. Regulation in response
RT   to development and the environment.";
RL   Plant Physiol. 113:729-738(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION BY WOUNDING.
RC   STRAIN=cv. Columbia; TISSUE=Seedling;
RX   PubMed=9085571; DOI=10.1104/pp.113.3.755;
RA   Mizutani M., Ohta D., Sato R.;
RT   "Isolation of a cDNA and a genomic clone encoding cinnamate 4-hydroxylase
RT   from Arabidopsis and its expression manner in planta.";
RL   Plant Physiol. 113:755-763(1997).
RN   [3]
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   [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   FUNCTION, AND MUTAGENESIS OF GLY-99; ARG-249 AND ALA-306.
RX   PubMed=19682296; DOI=10.1111/j.1365-313x.2009.03996.x;
RA   Schilmiller A.L., Stout J., Weng J.K., Humphreys J., Ruegger M.O.,
RA   Chapple C.;
RT   "Mutations in the cinnamate 4-hydroxylase gene impact metabolism, growth
RT   and development in Arabidopsis.";
RL   Plant J. 60:771-782(2009).
RN   [7]
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 first oxidative step of the phenylpropanoid
CC       pathway in higher plants by transforming trans-cinnamate into p-
CC       coumarate (By similarity). The compounds formed by this pathway are
CC       essential components for lignification, pollination, and defense
CC       against ultraviolet light, predators and pathogens (PubMed:19682296).
CC       {ECO:0000250|UniProtKB:Q04468, ECO:0000269|PubMed:19682296}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(E)-cinnamate + O2 + reduced [NADPH--hemoprotein reductase] =
CC         (E)-4-coumarate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC         reductase]; Xref=Rhea:RHEA:10608, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC         COMP:11965, ChEBI:CHEBI:12876, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:15669, ChEBI:CHEBI:57618,
CC         ChEBI:CHEBI:58210; EC=1.14.14.91;
CC         Evidence={ECO:0000250|UniProtKB:Q04468};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:Q94IP1};
CC   -!- PATHWAY: Phenylpropanoid metabolism; trans-4-coumarate biosynthesis;
CC       trans-4-coumarate from trans-cinnamate: step 1/1. {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Expressed in roots, leaves, stems, flowers and
CC       siliques. {ECO:0000269|PubMed:9085570, ECO:0000269|PubMed:9085571}.
CC   -!- INDUCTION: Induced by wounding. {ECO:0000269|PubMed:9085570,
CC       ECO:0000269|PubMed:9085571}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; U71081; AAB58356.1; -; mRNA.
DR   EMBL; U71080; AAB58355.1; -; Genomic_DNA.
DR   EMBL; D78596; BAA24355.1; -; mRNA.
DR   EMBL; U93215; AAB63088.1; -; Genomic_DNA.
DR   EMBL; CP002685; AEC08397.1; -; Genomic_DNA.
DR   EMBL; AY065145; AAL38321.1; -; mRNA.
DR   EMBL; BT008875; AAP68314.1; -; mRNA.
DR   PIR; A84709; A84709.
DR   RefSeq; NP_180607.1; NM_128601.3.
DR   AlphaFoldDB; P92994; -.
DR   SMR; P92994; -.
DR   BioGRID; 2948; 11.
DR   IntAct; P92994; 9.
DR   STRING; 3702.P92994; -.
DR   PaxDb; 3702-AT2G30490-1; -.
DR   ProteomicsDB; 246431; -.
DR   EnsemblPlants; AT2G30490.1; AT2G30490.1; AT2G30490.
DR   GeneID; 817599; -.
DR   Gramene; AT2G30490.1; AT2G30490.1; AT2G30490.
DR   KEGG; ath:AT2G30490; -.
DR   Araport; AT2G30490; -.
DR   TAIR; AT2G30490; C4H.
DR   eggNOG; KOG0156; Eukaryota.
DR   HOGENOM; CLU_001570_4_0_1; -.
DR   InParanoid; P92994; -.
DR   OMA; QKCAYVA; -.
DR   OrthoDB; 2900138at2759; -.
DR   PhylomeDB; P92994; -.
DR   BioCyc; ARA:AT2G30490-MONOMER; -.
DR   BioCyc; MetaCyc:AT2G30490-MONOMER; -.
DR   SABIO-RK; P92994; -.
DR   UniPathway; UPA00825; UER00789.
DR   PRO; PR:P92994; -.
DR   Proteomes; UP000006548; Chromosome 2.
DR   ExpressionAtlas; P92994; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:TAIR.
DR   GO; GO:0005794; C:Golgi apparatus; HDA:TAIR.
DR   GO; GO:0005777; C:peroxisome; HDA:TAIR.
DR   GO; GO:0009505; C:plant-type cell wall; HDA:TAIR.
DR   GO; GO:0000325; C:plant-type vacuole; HDA:TAIR.
DR   GO; GO:0005886; C:plasma membrane; HDA:TAIR.
DR   GO; GO:0009506; C:plasmodesma; 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:0016710; F:trans-cinnamate 4-monooxygenase activity; IDA:TAIR.
DR   GO; GO:0032502; P:developmental process; IMP:TAIR.
DR   GO; GO:0009808; P:lignin metabolic process; IMP:TAIR.
DR   GO; GO:0009698; P:phenylpropanoid metabolic process; IMP:TAIR.
DR   GO; GO:0009555; P:pollen development; IMP:TAIR.
DR   GO; GO:0006744; P:ubiquinone biosynthetic process; IMP:TAIR.
DR   CDD; cd11074; CYP73; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 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   PANTHER; PTHR47948; TRANS-CINNAMATE 4-MONOOXYGENASE; 1.
DR   PANTHER; PTHR47948:SF12; TRANS-CINNAMATE 4-MONOOXYGENASE; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
DR   Genevisible; P92994; AT.
PE   1: Evidence at protein level;
KW   Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..505
FT                   /note="Trans-cinnamate 4-monooxygenase"
FT                   /id="PRO_0000052242"
FT   TRANSMEM        3..23
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   BINDING         213..218
FT                   /ligand="(E)-cinnamate"
FT                   /ligand_id="ChEBI:CHEBI:15669"
FT                   /evidence="ECO:0000250|UniProtKB:Q94IP1"
FT   BINDING         306
FT                   /ligand="(E)-cinnamate"
FT                   /ligand_id="ChEBI:CHEBI:15669"
FT                   /evidence="ECO:0000250|UniProtKB:Q94IP1"
FT   BINDING         447
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:Q94IP1"
FT   VARIANT         92
FT                   /note="L -> H (in strain: cv. Landsberg erecta)"
FT   MUTAGEN         99
FT                   /note="G->E: In ref3-3; reduces lignin deposition and
FT                   alters lignin monomer content; dwarf phenotype, male
FT                   sterility and development of swellings at branch
FT                   junctions."
FT                   /evidence="ECO:0000269|PubMed:19682296"
FT   MUTAGEN         249
FT                   /note="R->K: In ref3-2; reduces lignin deposition and
FT                   alters lignin monomer content; dwarf phenotype, male
FT                   sterility and development of swellings at branch
FT                   junctions."
FT                   /evidence="ECO:0000269|PubMed:19682296"
FT   MUTAGEN         306
FT                   /note="A->T: In ref3-1; reduces lignin deposition and
FT                   alters lignin monomer content; dwarf phenotype, male
FT                   sterility and development of swellings at branch
FT                   junctions."
FT                   /evidence="ECO:0000269|PubMed:19682296"
FT   CONFLICT        184
FT                   /note="N -> T (in Ref. 2; BAA24355)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        333
FT                   /note="R -> G (in Ref. 2; BAA24355)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   505 AA;  57792 MW;  61DEAAA9463362CF CRC64;
     MDLLLLEKSL IAVFVAVILA TVISKLRGKK LKLPPGPIPI PIFGNWLQVG DDLNHRNLVD
     YAKKFGDLFL LRMGQRNLVV VSSPDLTKEV LLTQGVEFGS RTRNVVFDIF TGKGQDMVFT
     VYGEHWRKMR RIMTVPFFTN KVVQQNREGW EFEAASVVED VKKNPDSATK GIVLRKRLQL
     MMYNNMFRIM FDRRFESEDD PLFLRLKALN GERSRLAQSF EYNYGDFIPI LRPFLRGYLK
     ICQDVKDRRI ALFKKYFVDE RKQIASSKPT GSEGLKCAID HILEAEQKGE INEDNVLYIV
     ENINVAAIET TLWSIEWGIA ELVNHPEIQS KLRNELDTVL GPGVQVTEPD LHKLPYLQAV
     VKETLRLRMA IPLLVPHMNL HDAKLAGYDI PAESKILVNA WWLANNPNSW KKPEEFRPER
     FFEEESHVEA NGNDFRYVPF GVGRRSCPGI ILALPILGIT IGRMVQNFEL LPPPGQSKVD
     TSEKGGQFSL HILNHSIIVM KPRNC
//