CLS_ARATH
ID CLS_ARATH Reviewed; 341 AA.
AC Q93YW7; Q8LBT8; Q9M0Z2; Q9ZS87;
DT 14-MAY-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Cardiolipin synthase (CMP-forming), mitochondrial;
DE Short=CLS;
DE EC=2.7.8.41 {ECO:0000269|PubMed:15527784, ECO:0000269|PubMed:15811335};
DE AltName: Full=Phosphatidylglycerophosphate synthase 3;
DE Short=PGP synthase 3;
DE Flags: Precursor;
GN Name=CLS; Synonyms=PGP3; OrderedLocusNames=At4g04870; ORFNames=T4B21.19;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Brover V.V., Troukhan M.E., Alexandrov N.A., Lu Y.-P., Flavell R.B.,
RA Feldmann K.A.;
RT "Full-length cDNA from Arabidopsis thaliana.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=15527784; DOI=10.1016/j.febslet.2004.10.009;
RA Katayama K., Sakurai I., Wada H.;
RT "Identification of an Arabidopsis thaliana gene for cardiolipin synthase
RT located in mitochondria.";
RL FEBS Lett. 577:193-198(2004).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF GLY-199.
RX PubMed=15811335; DOI=10.1016/j.febslet.2005.03.007;
RA Nowicki M., Muller F., Frentzen M.;
RT "Cardiolipin synthase of Arabidopsis thaliana.";
RL FEBS Lett. 579:2161-2165(2005).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=24151294; DOI=10.1105/tpc.113.118018;
RA Pineau B., Bourge M., Marion J., Mauve C., Gilard F., Maneta-Peyret L.,
RA Moreau P., Satiat-Jeunemaitre B., Brown S.C., De Paepe R., Danon A.;
RT "The importance of cardiolipin synthase for mitochondrial ultrastructure,
RT respiratory function, plant development, and stress responses in
RT Arabidopsis.";
RL Plant Cell 25:4195-4208(2013).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=24443516; DOI=10.1105/tpc.113.121095;
RA Pan R., Jones A.D., Hu J.;
RT "Cardiolipin-mediated mitochondrial dynamics and stress response in
RT Arabidopsis.";
RL Plant Cell 26:391-409(2014).
CC -!- FUNCTION: Catalyzes the synthesis of cardiolipin (CL)
CC (diphosphatidylglycerol) by specifically transferring a phosphatidyl
CC group from CDP-diacylglycerol to phosphatidylglycerol (PG). Cannot
CC catalyze the phosphatidyl group transfer from one PG molecule to
CC another to form CL. Possesses high activity with PG species carrying
CC dioleoyl groups and low activity with species carrying one or two
CC palmitoyl groups. CL is a key phospholipid in mitochondrial membranes
CC and plays important roles in maintaining the functional integrity and
CC dynamics of mitochondria under both optimal and stress conditions. In
CC mitochondrial fission, CL stabilizes the protein complex of the major
CC mitochondrial fission factors, DRP3A and DRP3B.
CC {ECO:0000269|PubMed:15527784, ECO:0000269|PubMed:15811335,
CC ECO:0000269|PubMed:24151294, ECO:0000269|PubMed:24443516}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol) + a CDP-1,2-
CC diacyl-sn-glycerol = a cardiolipin + CMP + H(+);
CC Xref=Rhea:RHEA:32931, ChEBI:CHEBI:15378, ChEBI:CHEBI:58332,
CC ChEBI:CHEBI:60377, ChEBI:CHEBI:62237, ChEBI:CHEBI:64716; EC=2.7.8.41;
CC Evidence={ECO:0000269|PubMed:15527784, ECO:0000269|PubMed:15811335};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15811335};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=150 uM for phosphatidylglycerol (dioleoyl species)
CC {ECO:0000269|PubMed:15811335};
CC KM=4 uM for CDP-dioleoylglycerol {ECO:0000269|PubMed:15811335};
CC pH dependence:
CC Optimum pH is about 9.0. {ECO:0000269|PubMed:15811335};
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Strong dwarf phenotype, small siliques with only
CC a few small-sized and sterile seeds, when grown in long day conditions
CC under low light. Dysfunction of mitochondria: abnormal ultrastructure,
CC reduced content of respiratory complex I/complex III supercomplexes and
CC marked accumulation of tricarboxylic acid cycle derivatives and amino
CC acids. {ECO:0000269|PubMed:24151294, ECO:0000269|PubMed:24443516}.
CC -!- SIMILARITY: Belongs to the CDP-alcohol phosphatidyltransferase class-I
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD03458.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAB80852.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF118223; AAD03458.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL161501; CAB80852.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CP002687; AEE82435.1; -; Genomic_DNA.
DR EMBL; AY059735; AAL24147.1; -; mRNA.
DR EMBL; AY091269; AAM14208.1; -; mRNA.
DR EMBL; AY087000; AAM64561.1; -; mRNA.
DR PIR; C85061; C85061.
DR RefSeq; NP_567273.1; NM_116725.5.
DR AlphaFoldDB; Q93YW7; -.
DR SMR; Q93YW7; -.
DR STRING; 3702.AT4G04870.1; -.
DR PaxDb; Q93YW7; -.
DR PRIDE; Q93YW7; -.
DR ProteomicsDB; 240894; -.
DR EnsemblPlants; AT4G04870.1; AT4G04870.1; AT4G04870.
DR GeneID; 825825; -.
DR Gramene; AT4G04870.1; AT4G04870.1; AT4G04870.
DR KEGG; ath:AT4G04870; -.
DR Araport; AT4G04870; -.
DR TAIR; locus:2138962; AT4G04870.
DR eggNOG; KOG1617; Eukaryota.
DR HOGENOM; CLU_051314_1_0_1; -.
DR InParanoid; Q93YW7; -.
DR OMA; HDMYLPA; -.
DR OrthoDB; 1169813at2759; -.
DR PhylomeDB; Q93YW7; -.
DR BioCyc; ARA:AT4G04870-MON; -.
DR BioCyc; MetaCyc:AT4G04870-MON; -.
DR BRENDA; 2.7.8.41; 399.
DR PRO; PR:Q93YW7; -.
DR Proteomes; UP000006548; Chromosome 4.
DR ExpressionAtlas; Q93YW7; baseline and differential.
DR Genevisible; Q93YW7; AT.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:TAIR.
DR GO; GO:0008808; F:cardiolipin synthase activity; IDA:TAIR.
DR GO; GO:0043337; F:CDP-diacylglycerol-phosphatidylglycerol phosphatidyltransferase activity; IEA:RHEA.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0032049; P:cardiolipin biosynthetic process; IBA:GO_Central.
DR GO; GO:0046474; P:glycerophospholipid biosynthetic process; IBA:GO_Central.
DR Gene3D; 1.20.120.1760; -; 1.
DR InterPro; IPR000462; CDP-OH_P_trans.
DR InterPro; IPR043130; CDP-OH_PTrfase_TM_dom.
DR Pfam; PF01066; CDP-OH_P_transf; 1.
DR PROSITE; PS00379; CDP_ALCOHOL_P_TRANSF; 1.
PE 1: Evidence at protein level;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Phospholipid biosynthesis;
KW Phospholipid metabolism; Reference proteome; Transferase; Transit peptide;
KW Transmembrane; Transmembrane helix.
FT TRANSIT 1..28
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 29..341
FT /note="Cardiolipin synthase (CMP-forming), mitochondrial"
FT /id="PRO_0000429138"
FT TRANSMEM 157..177
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 197..217
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 226..246
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 307..327
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MUTAGEN 199
FT /note="G->D: Decreases activity 10-fold."
FT /evidence="ECO:0000269|PubMed:15811335"
SQ SEQUENCE 341 AA; 38042 MW; B990C1522DD248F8 CRC64;
MAIYRSLRKL VEINHRKTRP FFTAATASGG TVSLTPPQFS PLFPHFSHRL SPLSKWFVPL
NGPLFLSSPP WKLLQSATPL HWRGNGSVLK KVEALNLRLD RIRSRTRFPR QLGLQSVVPN
ILTVDRNDSK EEDGGKLVKS FVNVPNMISM ARLVSGPVLW WMISNEMYSS AFLGLAVSGA
SDWLDGYVAR RMKINSVVGS YLDPLADKVL IGCVAVAMVQ KDLLHPGLVG IVLLRDVALV
GGAVYLRALN LDWKWKTWSD FFNLDGSSPQ KVEPLFISKV NTVFQLTLVA GAILQPEFGN
PDTQTWITYL SWLVASTTMA STAAYGVQYW KKRPISMIKR S
