CLSA_ECOLI
ID CLSA_ECOLI Reviewed; 486 AA.
AC P0A6H8; P31071; P94720; P94730; P94733; P94740;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Cardiolipin synthase A {ECO:0000255|HAMAP-Rule:MF_00190};
DE Short=CL synthase {ECO:0000255|HAMAP-Rule:MF_00190};
DE EC=2.7.8.- {ECO:0000255|HAMAP-Rule:MF_00190, ECO:0000269|PubMed:1663113};
GN Name=clsA {ECO:0000255|HAMAP-Rule:MF_00190, ECO:0000303|PubMed:22988102};
GN Synonyms=cls, nov, yciJ; OrderedLocusNames=b1249, JW1241;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8170937; DOI=10.1073/pnas.91.9.3510;
RA Milkman R.;
RT "An Escherichia coli homologue of eukaryotic potassium channel proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:3510-3514(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=7896699; DOI=10.1128/jb.177.7.1766-1771.1995;
RA Ivanisevic R., Milic M., Ajdic D., Rakonjac J.V., Savic D.J.;
RT "Nucleotide sequence, mutational analysis, transcriptional start site, and
RT product analysis of nov, the gene which affects Escherichia coli K-12
RT resistance to the gyrase inhibitor novobiocin.";
RL J. Bacteriol. 177:1766-1771(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / C600 / CR34 / ATCC 23724 / DSM 3925 / LMG 3041 / NCIB 10222;
RA Shibuya I., Asami Y., Uetake N., Ohta A., Matsuzaki H., Matsumoto K.;
RL Submitted (NOV-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RA Xia W., Dowhan W.;
RL Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12, and Various ECOR strains;
RA Milkman R.;
RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=9097039; DOI=10.1093/dnares/3.6.363;
RA Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K., Itoh T.,
RA Kasai H., Kashimoto K., Kimura S., Kitakawa M., Kitagawa M., Makino K.,
RA Miki T., Mizobuchi K., Mori H., Mori T., Motomura K., Nakade S.,
RA Nakamura Y., Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G.,
RA Seki Y., Sivasundaram S., Tagami H., Takeda J., Takemoto K., Takeuchi Y.,
RA Wada C., Yamamoto Y., Horiuchi T.;
RT "A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 28.0-40.1 min region on the linkage map.";
RL DNA Res. 3:363-377(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [9]
RP IDENTIFICATION OF CLS AS NOV, AND DISRUPTION PHENOTYPE.
RX PubMed=7665497; DOI=10.1128/jb.177.17.5155-5157.1995;
RA Tropp B.E., Ragolia L., Xia W., Dowhan W., Milkman R., Rudd K.E.,
RA Ivanisevic R., Savic D.J.;
RT "Identity of the Escherichia coli cls and nov genes.";
RL J. Bacteriol. 177:5155-5157(1995).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=K12;
RX PubMed=1663113; DOI=10.1093/oxfordjournals.jbchem.a123600;
RA Hiraoka S., Nukui K., Uetake N., Ohta A., Shibuya I.;
RT "Amplification and substantial purification of cardiolipin synthase of
RT Escherichia coli.";
RL J. Biochem. 110:443-449(1991).
RN [11]
RP REVIEW.
RX PubMed=9370333; DOI=10.1016/s0005-2760(97)00100-8;
RA Tropp B.E.;
RT "Cardiolipin synthase from Escherichia coli.";
RL Biochim. Biophys. Acta 1348:192-200(1997).
RN [12]
RP SUBCELLULAR LOCATION.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=15919996; DOI=10.1126/science.1109730;
RA Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.;
RT "Global topology analysis of the Escherichia coli inner membrane
RT proteome.";
RL Science 308:1321-1323(2005).
RN [13]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 2-THR--GLU-60; 7-LYS-VAL-8;
RP 30-LYS--ARG-32 AND GLY-59.
RX PubMed=19341704; DOI=10.1016/j.bbamem.2009.03.016;
RA Quigley B.R., Tropp B.E.;
RT "E. coli cardiolipin synthase: function of N-terminal conserved residues.";
RL Biochim. Biophys. Acta 1788:2107-2113(2009).
RN [14]
RP FUNCTION, DISRUPTION PHENOTYPE, AND GENE NAME.
RX PubMed=22988102; DOI=10.1073/pnas.1212797109;
RA Tan B.K., Bogdanov M., Zhao J., Dowhan W., Raetz C.R., Guan Z.;
RT "Discovery of a cardiolipin synthase utilizing phosphatidylethanolamine and
RT phosphatidylglycerol as substrates.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:16504-16509(2012).
CC -!- FUNCTION: Catalyzes the reversible phosphatidyl group transfer from one
CC phosphatidylglycerol molecule to another to form cardiolipin (CL)
CC (diphosphatidylglycerol) and glycerol. {ECO:0000255|HAMAP-
CC Rule:MF_00190, ECO:0000269|PubMed:1663113,
CC ECO:0000269|PubMed:22988102}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol) = a
CC cardiolipin + glycerol; Xref=Rhea:RHEA:31451, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:62237, ChEBI:CHEBI:64716; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_00190, ECO:0000269|PubMed:1663113};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.0. {ECO:0000269|PubMed:1663113};
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000255|HAMAP-
CC Rule:MF_00190, ECO:0000269|PubMed:15919996, ECO:0000269|PubMed:1663113,
CC ECO:0000269|PubMed:19341704}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_00190, ECO:0000269|PubMed:15919996,
CC ECO:0000269|PubMed:1663113}.
CC -!- PTM: Seems to be post-translationally processed from a 53-55 kDa form
CC to a 45-46 kDa form (PubMed:7665497 and PubMed:19341704).
CC -!- DISRUPTION PHENOTYPE: Mutants have increased sensitivity to novobiocin.
CC Triple deletion of clsA, clsB and clsC results in a complete lack of
CC cardiolipin, regardless of growth phase or growth conditions.
CC {ECO:0000269|PubMed:22988102, ECO:0000269|PubMed:7665497}.
CC -!- MISCELLANEOUS: All three cardiolipin synthases (ClsA, ClsB and ClsC)
CC contribute to CL synthesis in stationary phase. Only ClsA contributes
CC to synthesis during logarithmic growth phase.
CC {ECO:0000305|PubMed:22988102}.
CC -!- SIMILARITY: Belongs to the phospholipase D family. Cardiolipin synthase
CC subfamily. ClsA sub-subfamily. {ECO:0000255|HAMAP-Rule:MF_00190}.
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DR EMBL; L12044; AAA66948.1; -; Genomic_DNA.
DR EMBL; U01911; AAA82872.1; -; Genomic_DNA.
DR EMBL; D38779; BAA07636.1; -; Genomic_DNA.
DR EMBL; U15986; AAA53368.1; -; Genomic_DNA.
DR EMBL; U24206; AAB60160.1; -; Genomic_DNA.
DR EMBL; U24195; AAB60072.1; -; Genomic_DNA.
DR EMBL; U24196; AAB60080.1; -; Genomic_DNA.
DR EMBL; U24197; AAB60088.1; -; Genomic_DNA.
DR EMBL; U24198; AAB60096.1; -; Genomic_DNA.
DR EMBL; U24199; AAB60104.1; -; Genomic_DNA.
DR EMBL; U24200; AAB60112.1; -; Genomic_DNA.
DR EMBL; U24201; AAB60120.1; -; Genomic_DNA.
DR EMBL; U24202; AAB60128.1; -; Genomic_DNA.
DR EMBL; U24203; AAB60136.1; -; Genomic_DNA.
DR EMBL; U24204; AAB60144.1; -; Genomic_DNA.
DR EMBL; U24205; AAB60152.1; -; Genomic_DNA.
DR EMBL; U00096; AAC74331.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA14781.1; -; Genomic_DNA.
DR PIR; A56145; A56145.
DR RefSeq; NP_415765.1; NC_000913.3.
DR RefSeq; WP_000214516.1; NZ_STEB01000005.1.
DR AlphaFoldDB; P0A6H8; -.
DR SMR; P0A6H8; -.
DR BioGRID; 4260112; 332.
DR STRING; 511145.b1249; -.
DR jPOST; P0A6H8; -.
DR PaxDb; P0A6H8; -.
DR PRIDE; P0A6H8; -.
DR EnsemblBacteria; AAC74331; AAC74331; b1249.
DR EnsemblBacteria; BAA14781; BAA14781; BAA14781.
DR GeneID; 66674930; -.
DR GeneID; 945821; -.
DR KEGG; ecj:JW1241; -.
DR KEGG; eco:b1249; -.
DR PATRIC; fig|1411691.4.peg.1034; -.
DR EchoBASE; EB1565; -.
DR eggNOG; COG1502; Bacteria.
DR HOGENOM; CLU_038053_1_0_6; -.
DR InParanoid; P0A6H8; -.
DR OMA; TRFILDW; -.
DR PhylomeDB; P0A6H8; -.
DR BioCyc; EcoCyc:CARDIOLIPSYN-MON; -.
DR BioCyc; MetaCyc:CARDIOLIPSYN-MON; -.
DR BRENDA; 2.7.8.B10; 2026.
DR PRO; PR:P0A6H8; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:EcoCyc.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008808; F:cardiolipin synthase activity; IDA:EcoCyc.
DR GO; GO:0032049; P:cardiolipin biosynthetic process; IMP:EcoCyc.
DR HAMAP; MF_00190; Cardiolipin_synth_ClsA; 1.
DR InterPro; IPR022924; Cardiolipin_synthase.
DR InterPro; IPR030840; CL_synthase_A.
DR InterPro; IPR027379; CLS_N.
DR InterPro; IPR025202; PLD-like_dom.
DR InterPro; IPR001736; PLipase_D/transphosphatidylase.
DR Pfam; PF13091; PLDc_2; 2.
DR Pfam; PF13396; PLDc_N; 1.
DR SMART; SM00155; PLDc; 2.
DR TIGRFAMs; TIGR04265; bac_cardiolipin; 1.
DR PROSITE; PS50035; PLD; 2.
PE 1: Evidence at protein level;
KW Cell inner membrane; Cell membrane; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Phospholipid biosynthesis; Phospholipid metabolism;
KW Reference proteome; Repeat; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..486
FT /note="Cardiolipin synthase A"
FT /id="PRO_0000201253"
FT TRANSMEM 3..23
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00190"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00190"
FT DOMAIN 219..246
FT /note="PLD phosphodiesterase 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00190"
FT DOMAIN 399..426
FT /note="PLD phosphodiesterase 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00190"
FT ACT_SITE 224
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00190"
FT ACT_SITE 226
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00190"
FT ACT_SITE 231
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00190"
FT ACT_SITE 404
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00190"
FT ACT_SITE 406
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00190"
FT ACT_SITE 411
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00190"
FT VARIANT 113
FT /note="I -> S (in strain: ECOR 60)"
FT VARIANT 283
FT /note="E -> G (in strain: ECOR 50)"
FT VARIANT 378
FT /note="G -> S (in strain: ECOR 16)"
FT VARIANT 426
FT /note="S -> R (in strain: ECOR 46)"
FT MUTAGEN 2..60
FT /note="Missing: Remains membrane associated and retains in
FT vitro and in vivo activity."
FT /evidence="ECO:0000269|PubMed:19341704"
FT MUTAGEN 7..8
FT /note="LV->SS: Retains in vitro activity, but loses most of
FT its in vivo activity. Higher apparent molecular mass than
FT wild-type protein."
FT /evidence="ECO:0000269|PubMed:19341704"
FT MUTAGEN 30..32
FT /note="KRR->TTT: Undergoes altered post-translational
FT processing and has much lower in vivo and in vitro
FT activity."
FT /evidence="ECO:0000269|PubMed:19341704"
FT MUTAGEN 59
FT /note="G->A: Does not affect CL synthase processing or
FT activity."
FT /evidence="ECO:0000269|PubMed:19341704"
SQ SEQUENCE 486 AA; 54822 MW; C8BDD69AA5AA37DB CRC64;
MTTVYTLVSW LAILGYWLLI AGVTLRILMK RRAVPSAMAW LLIIYILPLV GIIAYLAVGE
LHLGKRRAER ARAMWPSTAK WLNDLKACKH IFAEENSSVA APLFKLCERR QGIAGVKGNQ
LQLMTESDDV MQALIRDIQL ARHNIEMVFY IWQPGGMADQ VAESLMAAAR RGIHCRLMLD
SAGSVAFFRS PWPELMRNAG IEVVEALKVN LMRVFLRRMD LRQHRKMIMI DNYIAYTGSM
NMVDPRYFKQ DAGVGQWIDL MARMEGPIAT AMGIIYSCDW EIETGKRILP PPPDVNIMPF
EQASGHTIHT IASGPGFPED LIHQALLTAA YSAREYLIMT TPYFVPSDDL LHAICTAAQR
GVDVSIILPR KNDSMLVGWA SRAFFTELLA AGVKIYQFEG GLLHTKSVLV DGELSLVGTV
NLDMRSLWLN FEITLAIDDK GFGADLAAVQ DDYISRSRLL DARLWLKRPL WQRVAERLFY
FFSPLL
