KCS18_ARATH
ID KCS18_ARATH Reviewed; 506 AA.
AC Q38860;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=3-ketoacyl-CoA synthase 18 {ECO:0000303|PubMed:18465198};
DE Short=KCS-18 {ECO:0000303|PubMed:18465198};
DE EC=2.3.1.199 {ECO:0000269|PubMed:11341960, ECO:0000269|PubMed:12135493, ECO:0000269|PubMed:16765910};
DE AltName: Full=Protein FATTY ACID ELONGATION 1 {ECO:0000303|PubMed:7734965};
DE AltName: Full=Very long-chain fatty acid condensing enzyme 18 {ECO:0000303|PubMed:18465198};
DE Short=VLCFA condensing enzyme 18 {ECO:0000303|PubMed:18465198};
GN Name=FAE1 {ECO:0000303|PubMed:7734965};
GN Synonyms=KCS18 {ECO:0000303|PubMed:18465198};
GN OrderedLocusNames=At4g34520 {ECO:0000312|Araport:AT4G34520};
GN ORFNames=T4L20.100 {ECO:0000312|EMBL:CAA18831.1};
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], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=cv. Wassilewskija;
RX PubMed=7734965; DOI=10.2307/3869853;
RA James D.W. Jr., Lim E., Keller J., Plooy I., Ralston E., Dooner H.K.;
RT "Directed tagging of the Arabidopsis FATTY ACID ELONGATION1 (FAE1) gene
RT with the maize transposon activator.";
RL Plant Cell 7:309-319(1995).
RN [2]
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 [3]
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX AGRICOLA=IND90051597; DOI=10.1007/BF00224392;
RA Lemieux B., Miquel M., Somerville C., Browse J.;
RT "Mutants of Arabidopsis with alterations in seed lipid fatty acid
RT composition.";
RL Theor. Appl. Genet. 80:234-240(1990).
RN [5]
RP FUNCTION.
RX AGRICOLA=IND90051598; DOI=10.1007/BF00224393;
RA James D.W. Jr., Dooner H.K.;
RT "Isolation of EMS-induced mutants in Arabidopsis altered in seed fatty acid
RT composition.";
RL Theor. Appl. Genet. 80:241-245(1990).
RN [6]
RP FUNCTION.
RX PubMed=9263455; DOI=10.1046/j.1365-313x.1997.12010121.x;
RA Millar A.A., Kunst L.;
RT "Very-long-chain fatty acid biosynthesis is controlled through the
RT expression and specificity of the condensing enzyme.";
RL Plant J. 12:121-131(1997).
RN [7]
RP CATALYTIC ACTIVITY, ACTIVE SITES, AND MUTAGENESIS OF CYS-84; CYS-223;
RP CYS-270; HIS-302; CYS-312; HIS-387; CYS-389; HIS-391; HIS-420 AND CYS-460.
RX PubMed=11341960; DOI=10.1016/s1388-1981(00)00168-2;
RA Ghanevati M., Jaworski J.G.;
RT "Active-site residues of a plant membrane-bound fatty acid elongase beta-
RT ketoacyl-CoA synthase, FAE1 KCS.";
RL Biochim. Biophys. Acta 1530:77-85(2001).
RN [8]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11575726; DOI=10.1023/a:1011603923889;
RA Rossak M., Smith M., Kunst L.;
RT "Expression of the FAE1 gene and FAE1 promoter activity in developing seeds
RT of Arabidopsis thaliana.";
RL Plant Mol. Biol. 46:717-725(2001).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, ACTIVE SITES, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-223;
RP HIS-391 AND ASN-424.
RX PubMed=12135493; DOI=10.1046/j.1432-1033.2002.03039.x;
RA Ghanevati M., Jaworski J.G.;
RT "Engineering and mechanistic studies of the Arabidopsis FAE1 beta-ketoacyl-
RT CoA synthase, FAE1 KCS.";
RL Eur. J. Biochem. 269:3531-3539(2002).
RN [10]
RP INDUCTION, AND GENE FAMILY.
RX PubMed=12916765; DOI=10.1002/ps.714;
RA Lechelt-Kunze C., Meissner R.C., Drewes M., Tietjen K.;
RT "Flufenacet herbicide treatment phenocopies the fiddlehead mutant in
RT Arabidopsis thaliana.";
RL Pest Manag. Sci. 59:847-856(2003).
RN [11]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=15277688; DOI=10.1073/pnas.0404600101;
RA Trenkamp S., Martin W., Tietjen K.;
RT "Specific and differential inhibition of very-long-chain fatty acid
RT elongases from Arabidopsis thaliana by different herbicides.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:11903-11908(2004).
RN [12]
RP FUNCTION.
RX PubMed=16765910; DOI=10.1016/j.bbrc.2006.05.162;
RA Blacklock B.J., Jaworski J.G.;
RT "Substrate specificity of Arabidopsis 3-ketoacyl-CoA synthases.";
RL Biochem. Biophys. Res. Commun. 346:583-590(2006).
RN [13]
RP GENE FAMILY, NOMENCLATURE, 3D-STRUCTURE MODELING, AND TISSUE SPECIFICITY.
RX PubMed=18465198; DOI=10.1007/s11103-008-9339-z;
RA Joubes J., Raffaele S., Bourdenx B., Garcia C., Laroche-Traineau J.,
RA Moreau P., Domergue F., Lessire R.;
RT "The VLCFA elongase gene family in Arabidopsis thaliana: phylogenetic
RT analysis, 3D modelling and expression profiling.";
RL Plant Mol. Biol. 67:547-566(2008).
RN [14]
RP ACTIVITY REGULATION.
RX PubMed=22284369; DOI=10.1016/j.phytochem.2011.12.023;
RA Tresch S., Heilmann M., Christiansen N., Looser R., Grossmann K.;
RT "Inhibition of saturated very-long-chain fatty acid biosynthesis by
RT mefluidide and perfluidone, selective inhibitors of 3-ketoacyl-CoA
RT synthases.";
RL Phytochemistry 76:162-171(2012).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23145136; DOI=10.1371/journal.pone.0049261;
RA Jasinski S., Lecureuil A., Miquel M., Loudet O., Raffaele S., Froissard M.,
RA Guerche P.;
RT "Natural variation in seed very long chain fatty acid content is controlled
RT by a new isoform of KCS18 in Arabidopsis thaliana.";
RL PLoS ONE 7:E49261-E49261(2012).
CC -!- FUNCTION: Contributes to fatty acids elongation and stockage in
CC developing seeds. Active on both saturated and mono-unsaturated acyl-
CC CoAs of 16 and 18 carbons. Required for the elongation of C18 to C20
CC and of C20 to C22 fatty acids. Mediates also the synthesis of VLCFAs
CC from 20 to 26 carbons in length (e.g. C20:1, C20, C22:1, C22, C24:1,
CC C24, C26) (PubMed:15277688, PubMed:16765910, PubMed:7734965,
CC PubMed:9263455, Ref.4, Ref.5, PubMed:12135493, PubMed:23145136). Has no
CC activity with polyunsaturated C18:2 and C18:3 or with acyl-CoAs having
CC 22 carbons or longer chain length (PubMed:12135493).
CC {ECO:0000269|PubMed:12135493, ECO:0000269|PubMed:15277688,
CC ECO:0000269|PubMed:16765910, ECO:0000269|PubMed:23145136,
CC ECO:0000269|PubMed:7734965, ECO:0000269|PubMed:9263455,
CC ECO:0000269|Ref.4, ECO:0000269|Ref.5}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a very-long-chain acyl-CoA + H(+) + malonyl-CoA = a very-long-
CC chain 3-oxoacyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:32727,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:90725, ChEBI:CHEBI:90736;
CC EC=2.3.1.199; Evidence={ECO:0000269|PubMed:11341960,
CC ECO:0000269|PubMed:12135493, ECO:0000269|PubMed:16765910};
CC -!- ACTIVITY REGULATION: Inhibited by K3 herbicides such as allidochlor,
CC cafenstrole and flufenacet (PubMed:15277688). Strongly inhibited by
CC metazachlor and only slightly by mefluidide (PubMed:22284369).
CC {ECO:0000269|PubMed:15277688, ECO:0000269|PubMed:22284369}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6.6-7.5. {ECO:0000269|PubMed:12135493};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC -!- SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:12135493};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed specifically in seeds, especially in
CC embryos (PubMed:11575726, PubMed:7734965). Expressed in siliques
CC (PubMed:18465198). {ECO:0000269|PubMed:11575726,
CC ECO:0000269|PubMed:18465198, ECO:0000269|PubMed:7734965}.
CC -!- DEVELOPMENTAL STAGE: Accumulates in upper part of roots, hypocotyls and
CC cotyledons of developing embryo. Levels increase in early stages
CC (torpedo, 4 days after flowering) and decrease during late stages of
CC embryo development. {ECO:0000269|PubMed:11575726}.
CC -!- INDUCTION: Repressed by herbicides such as flufenacet and benfuresate.
CC {ECO:0000269|PubMed:12916765}.
CC -!- DISRUPTION PHENOTYPE: Strong fatty acid chain length ratio (CLR)
CC reduction. {ECO:0000269|PubMed:23145136}.
CC -!- MISCELLANEOUS: CLR.2, the major quantitative trait loci (QTL) involved
CC in seed lipid metabolism is associated with the single point mutation
CC L407V. {ECO:0000269|PubMed:23145136}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Chalcone/stilbene
CC synthases family. {ECO:0000305}.
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DR EMBL; U29142; AAA70154.1; -; Genomic_DNA.
DR EMBL; AL023094; CAA18831.1; -; Genomic_DNA.
DR EMBL; AL161585; CAB80169.1; -; Genomic_DNA.
DR EMBL; CP002687; AEE86388.1; -; Genomic_DNA.
DR PIR; T05272; T05272.
DR RefSeq; NP_195178.1; NM_119617.2.
DR AlphaFoldDB; Q38860; -.
DR SMR; Q38860; -.
DR STRING; 3702.AT4G34520.1; -.
DR ChEMBL; CHEMBL2242735; -.
DR PaxDb; Q38860; -.
DR PRIDE; Q38860; -.
DR ProteomicsDB; 247149; -.
DR EnsemblPlants; AT4G34520.1; AT4G34520.1; AT4G34520.
DR GeneID; 829603; -.
DR Gramene; AT4G34520.1; AT4G34520.1; AT4G34520.
DR KEGG; ath:AT4G34520; -.
DR Araport; AT4G34520; -.
DR TAIR; locus:2139599; AT4G34520.
DR eggNOG; ENOG502QPKZ; Eukaryota.
DR HOGENOM; CLU_013238_2_1_1; -.
DR InParanoid; Q38860; -.
DR OMA; NPREIGI; -.
DR OrthoDB; 801187at2759; -.
DR PhylomeDB; Q38860; -.
DR BioCyc; ARA:AT4G34520-MON; -.
DR BioCyc; MetaCyc:AT4G34520-MON; -.
DR UniPathway; UPA00094; -.
DR PRO; PR:Q38860; -.
DR Proteomes; UP000006548; Chromosome 4.
DR ExpressionAtlas; Q38860; baseline and differential.
DR Genevisible; Q38860; AT.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009922; F:fatty acid elongase activity; IDA:TAIR.
DR GO; GO:0102756; F:very-long-chain 3-ketoacyl-CoA synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR012392; 3-ktacl-CoA_syn.
DR InterPro; IPR013747; ACP_syn_III_C.
DR InterPro; IPR013601; FAE1_typ3_polyketide_synth.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR31561; PTHR31561; 1.
DR Pfam; PF08541; ACP_syn_III_C; 1.
DR Pfam; PF08392; FAE1_CUT1_RppA; 1.
DR PIRSF; PIRSF036417; 3-ktacl-CoA_syn; 1.
DR SUPFAM; SSF53901; SSF53901; 2.
PE 1: Evidence at protein level;
KW Acyltransferase; Endoplasmic reticulum; Membrane; Microsome; NAD; NADP;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..506
FT /note="3-ketoacyl-CoA synthase 18"
FT /id="PRO_0000249110"
FT TRANSMEM 13..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 52..72
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 69..368
FT /note="FAE"
FT ACT_SITE 223
FT /evidence="ECO:0000269|PubMed:11341960,
FT ECO:0000269|PubMed:12135493"
FT ACT_SITE 302
FT /evidence="ECO:0000269|PubMed:11341960"
FT ACT_SITE 387
FT /evidence="ECO:0000269|PubMed:11341960"
FT ACT_SITE 391
FT /evidence="ECO:0000269|PubMed:11341960,
FT ECO:0000269|PubMed:12135493"
FT ACT_SITE 420
FT /evidence="ECO:0000269|PubMed:11341960"
FT ACT_SITE 424
FT /evidence="ECO:0000269|PubMed:12135493"
FT MUTAGEN 84
FT /note="C->A,S: Normal activity."
FT /evidence="ECO:0000269|PubMed:11341960"
FT MUTAGEN 223
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11341960"
FT MUTAGEN 223
FT /note="C->S: Normal activity."
FT /evidence="ECO:0000269|PubMed:11341960"
FT MUTAGEN 270
FT /note="C->A: Normal activity."
FT /evidence="ECO:0000269|PubMed:11341960"
FT MUTAGEN 270
FT /note="C->S: Reduced activity."
FT /evidence="ECO:0000269|PubMed:11341960"
FT MUTAGEN 302
FT /note="H->A,K: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11341960"
FT MUTAGEN 312
FT /note="C->A: Normal activity."
FT /evidence="ECO:0000269|PubMed:11341960"
FT MUTAGEN 312
FT /note="C->S: Reduced activity."
FT /evidence="ECO:0000269|PubMed:11341960"
FT MUTAGEN 387
FT /note="H->A,K: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11341960"
FT MUTAGEN 389
FT /note="C->A,S: Normal activity."
FT /evidence="ECO:0000269|PubMed:11341960"
FT MUTAGEN 391
FT /note="H->A,K: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11341960,
FT ECO:0000269|PubMed:12135493"
FT MUTAGEN 391
FT /note="H->Q: Reduced activity."
FT /evidence="ECO:0000269|PubMed:12135493"
FT MUTAGEN 420
FT /note="H->A,K: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11341960"
FT MUTAGEN 424
FT /note="N->D: Reduced activity."
FT /evidence="ECO:0000269|PubMed:12135493"
FT MUTAGEN 424
FT /note="N->H: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12135493"
FT MUTAGEN 460
FT /note="C->A,S: Normal activity."
FT /evidence="ECO:0000269|PubMed:11341960"
SQ SEQUENCE 506 AA; 56264 MW; 4516D0EF8E453D18 CRC64;
MTSVNVKLLY RYVLTNFFNL CLFPLTAFLA GKASRLTIND LHNFLSYLQH NLITVTLLFA
FTVFGLVLYI VTRPNPVYLV DYSCYLPPPH LKVSVSKVMD IFYQIRKADT SSRNVACDDP
SSLDFLRKIQ ERSGLGDETY SPEGLIHVPP RKTFAASREE TEKVIIGALE NLFENTKVNP
REIGILVVNS SMFNPTPSLS AMVVNTFKLR SNIKSFNLGG MGCSAGVIAI DLAKDLLHVH
KNTYALVVST ENITQGIYAG ENRSMMVSNC LFRVGGAAIL LSNKSGDRRR SKYKLVHTVR
THTGADDKSF RCVQQEDDES GKIGVCLSKD ITNVAGTTLT KNIATLGPLI LPLSEKFLFF
ATFVAKKLLK DKIKHYYVPD FKLAVDHFCI HAGGRAVIDE LEKNLGLSPI DVEASRSTLH
RFGNTSSSSI WYELAYIEAK GRMKKGNKAW QIALGSGFKC NSAVWVALRN VKASANSPWQ
HCIDRYPVKI DSDLSKSKTH VQNGRS
