GA2_GIBF5
ID GA2_GIBF5 Reviewed; 500 AA.
AC S0E3D0;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 1.
DT 03-AUG-2022, entry version 32.
DE RecName: Full=Ent-kaurene oxidase P450-4 {ECO:0000303|PubMed:11472927};
DE EC=1.14.14.86 {ECO:0000269|PubMed:11472927};
DE AltName: Full=Cytochrome P450 monooygenase 4 {ECO:0000303|PubMed:11472927};
DE Short=P450-4 {ECO:0000303|PubMed:11472927};
DE AltName: Full=Gibberellin cluster kaurene oxidase {ECO:0000305};
GN Name=P450-4 {ECO:0000303|PubMed:11472927}; ORFNames=FFUJ_14332;
OS Gibberella fujikuroi (strain CBS 195.34 / IMI 58289 / NRRL A-6831) (Bakanae
OS and foot rot disease fungus) (Fusarium fujikuroi).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC Fusarium fujikuroi species complex.
OX NCBI_TaxID=1279085;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND FUNCTION.
RC STRAIN=CBS 195.34 / IMI 58289 / NRRL A-6831;
RX PubMed=23825955; DOI=10.1371/journal.ppat.1003475;
RA Wiemann P., Sieber C.M.K., von Bargen K.W., Studt L., Niehaus E.-M.,
RA Espino J.J., Huss K., Michielse C.B., Albermann S., Wagner D.,
RA Bergner S.V., Connolly L.R., Fischer A., Reuter G., Kleigrewe K., Bald T.,
RA Wingfield B.D., Ophir R., Freeman S., Hippler M., Smith K.M., Brown D.W.,
RA Proctor R.H., Muensterkoetter M., Freitag M., Humpf H.-U., Gueldener U.,
RA Tudzynski B.;
RT "Deciphering the cryptic genome: genome-wide analyses of the rice pathogen
RT Fusarium fujikuroi reveal complex regulation of secondary metabolism and
RT novel metabolites.";
RL PLoS Pathog. 9:E1003475-E1003475(2013).
RN [2]
RP FUNCTION.
RX PubMed=9745028; DOI=10.1007/s002940050392;
RA Tudzynski B., Kawaide H., Kamiya Y.;
RT "Gibberellin biosynthesis in Gibberella fujikuroi: cloning and
RT characterization of the copalyl diphosphate synthase gene.";
RL Curr. Genet. 34:234-240(1998).
RN [3]
RP FUNCTION.
RX PubMed=9917370; DOI=10.1006/fgbi.1998.1095;
RA Tudzynski B., Hoelter K.;
RT "Gibberellin biosynthetic pathway in Gibberella fujikuroi: evidence for a
RT gene cluster.";
RL Fungal Genet. Biol. 25:157-170(1998).
RN [4]
RP FUNCTION.
RX PubMed=10347043; DOI=10.1128/aem.65.6.2558-2564.1999;
RA Linnemannstoens P., Voss T., Hedden P., Gaskin P., Tudzynski B.;
RT "Deletions in the gibberellin biosynthesis gene cluster of Gibberella
RT fujikuroi by restriction enzyme-mediated integration and conventional
RT transformation-mediated mutagenesis.";
RL Appl. Environ. Microbiol. 65:2558-2564(1999).
RN [5]
RP FUNCTION.
RX PubMed=10803977; DOI=10.1271/bbb.64.660;
RA Toyomasu T., Kawaide H., Ishizaki A., Shinoda S., Otsuka M., Mitsuhashi W.,
RA Sassa T.;
RT "Cloning of a full-length cDNA encoding ent-kaurene synthase from
RT Gibberella fujikuroi: functional analysis of a bifunctional diterpene
RT cyclase.";
RL Biosci. Biotechnol. Biochem. 64:660-664(2000).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, INDUCTION, AND PATHWAY.
RX PubMed=11472927; DOI=10.1128/aem.67.8.3514-3522.2001;
RA Tudzynski B., Hedden P., Carrera E., Gaskin P.;
RT "The P450-4 gene of Gibberella fujikuroi encodes ent-kaurene oxidase in the
RT gibberellin biosynthesis pathway.";
RL Appl. Environ. Microbiol. 67:3514-3522(2001).
RN [7]
RP FUNCTION.
RX PubMed=11320210; DOI=10.1073/pnas.091096298;
RA Rojas M.C., Hedden P., Gaskin P., Tudzynski B.;
RT "The P450-1 gene of Gibberella fujikuroi encodes a multifunctional enzyme
RT in gibberellin biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:5838-5843(2001).
RN [8]
RP FUNCTION.
RX PubMed=11943776; DOI=10.1074/jbc.m201651200;
RA Tudzynski B., Rojas M.C., Gaskin P., Hedden P.;
RT "The gibberellin 20-oxidase of Gibberella fujikuroi is a multifunctional
RT monooxygenase.";
RL J. Biol. Chem. 277:21246-21253(2002).
RN [9]
RP FUNCTION.
RX PubMed=12750377; DOI=10.1074/jbc.m301927200;
RA Tudzynski B., Mihlan M., Rojas M.C., Linnemannstons P., Gaskin P.,
RA Hedden P.;
RT "Characterization of the final two genes of the gibberellin biosynthesis
RT gene cluster of Gibberella fujikuroi: des and P450-3 encode GA4 desaturase
RT and the 13-hydroxylase, respectively.";
RL J. Biol. Chem. 278:28635-28643(2003).
RN [10]
RP FUNCTION.
RX PubMed=15925394; DOI=10.1016/j.phytochem.2005.04.012;
RA Malonek S., Boemke C., Bornberg-Bauer E., Rojas M.C., Hedden P.,
RA Hopkins P., Tudzynski B.;
RT "Distribution of gibberellin biosynthetic genes and gibberellin production
RT in the Gibberella fujikuroi species complex.";
RL Phytochemistry 66:1296-1311(2005).
CC -!- FUNCTION: Ent-kaurene oxidase; part of the gene cluster that mediates
CC the biosynthesis of gibberellins (GAs), diterpenoids that may provide a
CC selective advantage during infection of the preferred host plant, rice
CC (PubMed:23825955, PubMed:9917370, PubMed:10347043, PubMed:12750377,
CC PubMed:15925394). Gibberellins (GAs) are diterpenoids and are
CC synthesized via the mevalonate pathway (PubMed:12750377). Biosynthesis
CC of the major metabolite GA3 (gibberellic acid) from geranylgeranyl
CC diphosphate (GGPP) requires 13 steps (PubMed:12750377). The GGPP
CC produced by the geranylgeranyl diphosphate synthase GGS2 is converted
CC to ent-kaurene via ent-copalyldiphosphate in a two-step cyclization
CC reaction performed by the bifunctional ent-copalyl diphosphate
CC synthase/ent-kaurene synthase enzyme (CPS/KS) (PubMed:9745028,
CC PubMed:10803977, PubMed:12750377). Ent-Kaurene is metabolized to GAs by
CC a series of oxidation reactions catalyzed by cytochrome P450
CC monooxygenases (PubMed:9917370, PubMed:12750377). Cytochrome P450
CC monooxygenase P450-4 is an ent-kaurene oxidase that catalyzes the three
CC oxidation steps between ent-kaurene and ent-kaurenoic acid
CC (PubMed:11472927). The highly multifunctional cytochrome P450
CC monooxygenase P450-1 then catalyzes four steps involving oxidation at
CC two carbon atoms, in the main pathway from ent-kaurenoic acid to GA14
CC via GA12-aldehyde as well as producing kaurenolides and fujenoic acids
CC as by-products (PubMed:11320210). The cytochrome P450 monooxygenase
CC P450-2 then converts GA14 to GA4 by removal of C-20 (PubMed:11943776).
CC GA4 is further converted to GA7 by the GA4 desaturase DES via 1,2-
CC desaturation before cytochrome P450 monooxygenase P450-3, a 13-
CC hydroxylase, hydroxylates GA7 to GA3, the final product of the GA-
CC biosynthetic pathway (PubMed:12750377). {ECO:0000269|PubMed:10347043,
CC ECO:0000269|PubMed:10803977, ECO:0000269|PubMed:11320210,
CC ECO:0000269|PubMed:11472927, ECO:0000269|PubMed:11943776,
CC ECO:0000269|PubMed:12750377, ECO:0000269|PubMed:15925394,
CC ECO:0000269|PubMed:23825955, ECO:0000269|PubMed:9745028,
CC ECO:0000269|PubMed:9917370}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ent-kaur-16-ene + 3 O2 + 3 reduced [NADPH--hemoprotein
CC reductase] = ent-kaur-16-en-19-oate + 4 H(+) + 4 H2O + 3 oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:32323, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15415,
CC ChEBI:CHEBI:57297, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC EC=1.14.14.86; Evidence={ECO:0000269|PubMed:11472927};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Plant hormone biosynthesis; gibberellin biosynthesis.
CC {ECO:0000269|PubMed:11472927}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Highly expressed under conditions of Gibberellins (GAs)
CC production, whereas the transcript level is very low in the growth
CC phase (PubMed:11472927). {ECO:0000269|PubMed:11472927}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of gibberellins (GAs) and
CC contains ent-kaurene as the only intermediate in the GA biosynthesis
CC pathway (PubMed:11472927). {ECO:0000269|PubMed:11472927}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; HF679027; CCT69175.1; -; Genomic_DNA.
DR AlphaFoldDB; S0E3D0; -.
DR SMR; S0E3D0; -.
DR STRING; 5127.CCT69175; -.
DR EnsemblFungi; CCT69175; CCT69175; FFUJ_14332.
DR VEuPathDB; FungiDB:FFUJ_14332; -.
DR HOGENOM; CLU_022195_0_1_1; -.
DR UniPathway; UPA00390; -.
DR Proteomes; UP000016800; Chromosome 5.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0052617; F:ent-kaur-16-en-19-al oxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0052616; F:ent-kaur-16-en-19-ol oxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0052615; F:ent-kaurene oxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0009686; P:gibberellin biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
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.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase; NADP;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..500
FT /note="Ent-kaurene oxidase P450-4"
FT /id="PRO_0000442041"
FT TRANSMEM 6..26
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 441
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"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 475
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 500 AA; 57145 MW; 7C77D0AD38CC9014 CRC64;
MPLMDVHWLI YVAFGAWLCS YVIHVLSSSS TVKVPVVGYR SVFEPTWLLR LRFVWEGGSI
IGQGYNKFKD SIFQVRKLGT DIVIIPPNYI DEVRKLSQDK TRSVEPFIND FAGQYTRGMV
FLQSDLQNRV IQQRLTPKLV SLTKVMKEEL DYALTKEMPD MKNDEWVEVD ISSIMVRLIS
RISARVFLGP EHCRNQEWLT TTAEYSESLF ITGFILRVVP HILRPFIAPL LPSYRTLLRN
VSSGRRVIGD IIRSQQGDGN EDILSWMRDA ATGEEKQIDN IAQRMLILSL ASIHTTAMTM
THAMYDLCAC PEYIEPLRDE VKSVVGASGW DKTALNRFHK LDSFLKESQR FNPVFLLTFN
RIYHQSMTLS DGTNIPSGTR IAVPSHAMLQ DSAHVPGPTP PTEFDGFRYS KIRSDSNYAQ
KYLFSMTDSS NMAFGYGKYA CPGRFYASNE MKLTLAILLL QFEFKLPDGK GRPRNITIDS
DMIPDPRARL CVRKRSLRDE
