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Protein

Cardiolipin synthase A

Gene

clsA

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the reversible phosphatidyl group transfer from one phosphatidylglycerol molecule to another to form cardiolipin (CL) (diphosphatidylglycerol) and glycerol.UniRule annotation2 Publications

Catalytic activityi

2 Phosphatidylglycerol = diphosphatidylglycerol + glycerol.UniRule annotation2 Publications

pH dependencei

Optimum pH is 7.0.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei224 – 2241UniRule annotation
Active sitei226 – 2261UniRule annotation
Active sitei231 – 2311UniRule annotation
Active sitei404 – 4041UniRule annotation
Active sitei406 – 4061UniRule annotation
Active sitei411 – 4111UniRule annotation

GO - Molecular functioni

  • cardiolipin synthase activity Source: EcoCyc

GO - Biological processi

  • cardiolipin biosynthetic process Source: EcoCyc
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Lipid biosynthesis, Lipid metabolism, Phospholipid biosynthesis, Phospholipid metabolism

Enzyme and pathway databases

BioCyciEcoCyc:CARDIOLIPSYN-MONOMER.
ECOL316407:JW1241-MONOMER.
MetaCyc:CARDIOLIPSYN-MONOMER.
BRENDAi2.7.8.B10. 2026.

Names & Taxonomyi

Protein namesi
Recommended name:
Cardiolipin synthase AUniRule annotation (EC:2.7.8.-UniRule annotation)
Short name:
CL synthaseUniRule annotation
Gene namesi
Name:clsAUniRule annotation
Synonyms:cls, nov, yciJ
Ordered Locus Names:b1249, JW1241
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG11608. clsA.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei3 – 2321HelicalUniRule annotationAdd
BLAST
Transmembranei38 – 5821HelicalUniRule annotationAdd
BLAST

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: EcoCyc
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell inner membrane, Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mutants have increased sensitivity to novobiocin. Triple deletion of clsA, clsB and clsC results in a complete lack of cardiolipin, regardless of growth phase or growth conditions.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2 – 6059Missing : Remains membrane associated and retains in vitro and in vivo activity. 1 PublicationAdd
BLAST
Mutagenesisi7 – 82LV → SS: Retains in vitro activity, but loses most of its in vivo activity. Higher apparent molecular mass than wild-type protein. 1 Publication
Mutagenesisi30 – 323KRR → TTT: Undergoes altered post-translational processing and has much lower in vivo and in vitro activity. 1 Publication
Mutagenesisi59 – 591G → A: Does not affect CL synthase processing or activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 486486Cardiolipin synthase APRO_0000201253Add
BLAST

Post-translational modificationi

Seems to be post-translationally processed from a 53-55 kDa form to a 45-46 kDa form (PubMed:7665497 and PubMed:19341704).

Proteomic databases

PaxDbiP0A6H8.
PRIDEiP0A6H8.

Interactioni

Protein-protein interaction databases

BioGridi4260112. 279 interactions.
STRINGi511145.b1249.

Structurei

3D structure databases

ProteinModelPortaliP0A6H8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini219 – 24628PLD phosphodiesterase 1UniRule annotationAdd
BLAST
Domaini399 – 42628PLD phosphodiesterase 2UniRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the phospholipase D family. Cardiolipin synthase subfamily. ClsA sub-subfamily.UniRule annotation
Contains 2 PLD phosphodiesterase domains.UniRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG4105CQX. Bacteria.
COG1502. LUCA.
HOGENOMiHOG000077403.
InParanoidiP0A6H8.
KOiK06131.
OMAiFFKQDSG.
OrthoDBiEOG6Q2ST0.
PhylomeDBiP0A6H8.

Family and domain databases

HAMAPiMF_00190. Cardiolipin_synth_ClsA.
InterProiIPR022924. Cardiolipin_synthase.
IPR030840. CL_synthase_A.
IPR027379. CLS_N.
IPR025202. PLD-like_dom.
IPR001736. PLipase_D/transphosphatidylase.
[Graphical view]
PfamiPF13091. PLDc_2. 2 hits.
PF13396. PLDc_N. 1 hit.
[Graphical view]
SMARTiSM00155. PLDc. 2 hits.
[Graphical view]
TIGRFAMsiTIGR04265. bac_cardiolipin. 1 hit.
PROSITEiPS50035. PLD. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0A6H8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTTVYTLVSW LAILGYWLLI AGVTLRILMK RRAVPSAMAW LLIIYILPLV
60 70 80 90 100
GIIAYLAVGE LHLGKRRAER ARAMWPSTAK WLNDLKACKH IFAEENSSVA
110 120 130 140 150
APLFKLCERR QGIAGVKGNQ LQLMTESDDV MQALIRDIQL ARHNIEMVFY
160 170 180 190 200
IWQPGGMADQ VAESLMAAAR RGIHCRLMLD SAGSVAFFRS PWPELMRNAG
210 220 230 240 250
IEVVEALKVN LMRVFLRRMD LRQHRKMIMI DNYIAYTGSM NMVDPRYFKQ
260 270 280 290 300
DAGVGQWIDL MARMEGPIAT AMGIIYSCDW EIETGKRILP PPPDVNIMPF
310 320 330 340 350
EQASGHTIHT IASGPGFPED LIHQALLTAA YSAREYLIMT TPYFVPSDDL
360 370 380 390 400
LHAICTAAQR GVDVSIILPR KNDSMLVGWA SRAFFTELLA AGVKIYQFEG
410 420 430 440 450
GLLHTKSVLV DGELSLVGTV NLDMRSLWLN FEITLAIDDK GFGADLAAVQ
460 470 480
DDYISRSRLL DARLWLKRPL WQRVAERLFY FFSPLL
Length:486
Mass (Da):54,822
Last modified:March 29, 2005 - v1
Checksum:iC8BDD69AA5AA37DB
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti113 – 1131I → S in strain: ECOR 60.
Natural varianti283 – 2831E → G in strain: ECOR 50.
Natural varianti378 – 3781G → S in strain: ECOR 16.
Natural varianti426 – 4261S → R in strain: ECOR 46.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L12044 Genomic DNA. Translation: AAA66948.1.
U01911 Genomic DNA. Translation: AAA82872.1.
D38779 Genomic DNA. Translation: BAA07636.1.
U15986 Genomic DNA. Translation: AAA53368.1.
U24206 Genomic DNA. Translation: AAB60160.1.
U24195 Genomic DNA. Translation: AAB60072.1.
U24196 Genomic DNA. Translation: AAB60080.1.
U24197 Genomic DNA. Translation: AAB60088.1.
U24198 Genomic DNA. Translation: AAB60096.1.
U24199 Genomic DNA. Translation: AAB60104.1.
U24200 Genomic DNA. Translation: AAB60112.1.
U24201 Genomic DNA. Translation: AAB60120.1.
U24202 Genomic DNA. Translation: AAB60128.1.
U24203 Genomic DNA. Translation: AAB60136.1.
U24204 Genomic DNA. Translation: AAB60144.1.
U24205 Genomic DNA. Translation: AAB60152.1.
U00096 Genomic DNA. Translation: AAC74331.1.
AP009048 Genomic DNA. Translation: BAA14781.1.
PIRiA56145.
RefSeqiNP_415765.1. NC_000913.3.
WP_000214516.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC74331; AAC74331; b1249.
BAA14781; BAA14781; BAA14781.
GeneIDi945821.
KEGGiecj:JW1241.
eco:b1249.
PATRICi32117758. VBIEscCol129921_1299.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L12044 Genomic DNA. Translation: AAA66948.1.
U01911 Genomic DNA. Translation: AAA82872.1.
D38779 Genomic DNA. Translation: BAA07636.1.
U15986 Genomic DNA. Translation: AAA53368.1.
U24206 Genomic DNA. Translation: AAB60160.1.
U24195 Genomic DNA. Translation: AAB60072.1.
U24196 Genomic DNA. Translation: AAB60080.1.
U24197 Genomic DNA. Translation: AAB60088.1.
U24198 Genomic DNA. Translation: AAB60096.1.
U24199 Genomic DNA. Translation: AAB60104.1.
U24200 Genomic DNA. Translation: AAB60112.1.
U24201 Genomic DNA. Translation: AAB60120.1.
U24202 Genomic DNA. Translation: AAB60128.1.
U24203 Genomic DNA. Translation: AAB60136.1.
U24204 Genomic DNA. Translation: AAB60144.1.
U24205 Genomic DNA. Translation: AAB60152.1.
U00096 Genomic DNA. Translation: AAC74331.1.
AP009048 Genomic DNA. Translation: BAA14781.1.
PIRiA56145.
RefSeqiNP_415765.1. NC_000913.3.
WP_000214516.1. NZ_LN832404.1.

3D structure databases

ProteinModelPortaliP0A6H8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4260112. 279 interactions.
STRINGi511145.b1249.

Proteomic databases

PaxDbiP0A6H8.
PRIDEiP0A6H8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC74331; AAC74331; b1249.
BAA14781; BAA14781; BAA14781.
GeneIDi945821.
KEGGiecj:JW1241.
eco:b1249.
PATRICi32117758. VBIEscCol129921_1299.

Organism-specific databases

EchoBASEiEB1565.
EcoGeneiEG11608. clsA.

Phylogenomic databases

eggNOGiENOG4105CQX. Bacteria.
COG1502. LUCA.
HOGENOMiHOG000077403.
InParanoidiP0A6H8.
KOiK06131.
OMAiFFKQDSG.
OrthoDBiEOG6Q2ST0.
PhylomeDBiP0A6H8.

Enzyme and pathway databases

BioCyciEcoCyc:CARDIOLIPSYN-MONOMER.
ECOL316407:JW1241-MONOMER.
MetaCyc:CARDIOLIPSYN-MONOMER.
BRENDAi2.7.8.B10. 2026.

Miscellaneous databases

PROiP0A6H8.

Family and domain databases

HAMAPiMF_00190. Cardiolipin_synth_ClsA.
InterProiIPR022924. Cardiolipin_synthase.
IPR030840. CL_synthase_A.
IPR027379. CLS_N.
IPR025202. PLD-like_dom.
IPR001736. PLipase_D/transphosphatidylase.
[Graphical view]
PfamiPF13091. PLDc_2. 2 hits.
PF13396. PLDc_N. 1 hit.
[Graphical view]
SMARTiSM00155. PLDc. 2 hits.
[Graphical view]
TIGRFAMsiTIGR04265. bac_cardiolipin. 1 hit.
PROSITEiPS50035. PLD. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "An Escherichia coli homologue of eukaryotic potassium channel proteins."
    Milkman R.
    Proc. Natl. Acad. Sci. U.S.A. 91:3510-3514(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  2. "Nucleotide sequence, mutational analysis, transcriptional start site, and product analysis of nov, the gene which affects Escherichia coli K-12 resistance to the gyrase inhibitor novobiocin."
    Ivanisevic R., Milic M., Ajdic D., Rakonjac J.V., Savic D.J.
    J. Bacteriol. 177:1766-1771(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  3. Shibuya I., Asami Y., Uetake N., Ohta A., Matsuzaki H., Matsumoto K.
    Submitted (NOV-1994) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12 / C600 / ATCC 23724 / DSM 3925 / LMG 3041 / NCIB 10222.
  4. Xia W., Dowhan W.
    Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12.
  5. Milkman R.
    Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12 and Various ECOR strains.
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  8. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
    Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
    Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  9. "Identity of the Escherichia coli cls and nov genes."
    Tropp B.E., Ragolia L., Xia W., Dowhan W., Milkman R., Rudd K.E., Ivanisevic R., Savic D.J.
    J. Bacteriol. 177:5155-5157(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION OF CLS AS NOV, DISRUPTION PHENOTYPE.
  10. "Amplification and substantial purification of cardiolipin synthase of Escherichia coli."
    Hiraoka S., Nukui K., Uetake N., Ohta A., Shibuya I.
    J. Biochem. 110:443-449(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
    Strain: K12.
  11. "Cardiolipin synthase from Escherichia coli."
    Tropp B.E.
    Biochim. Biophys. Acta 1348:192-200(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  12. "Global topology analysis of the Escherichia coli inner membrane proteome."
    Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.
    Science 308:1321-1323(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
    Strain: K12 / MG1655 / ATCC 47076.
  13. "E. coli cardiolipin synthase: function of N-terminal conserved residues."
    Quigley B.R., Tropp B.E.
    Biochim. Biophys. Acta 1788:2107-2113(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, GENE NAME.
  14. "Discovery of a cardiolipin synthase utilizing phosphatidylethanolamine and phosphatidylglycerol as substrates."
    Tan B.K., Bogdanov M., Zhao J., Dowhan W., Raetz C.R., Guan Z.
    Proc. Natl. Acad. Sci. U.S.A. 109:16504-16509(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 2-THR--GLU-60; 7-LYS-VAL-8; 30-LYS--ARG-32 AND GLY-59.

Entry informationi

Entry nameiCLSA_ECOLI
AccessioniPrimary (citable) accession number: P0A6H8
Secondary accession number(s): P31071
, P94720, P94730, P94733, P94740
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: March 29, 2005
Last modified: January 20, 2016
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

All three cardiolipin synthases (ClsA, ClsB and ClsC) contribute to CL synthesis in stationary phase. Only ClsA contributes to synthesis during logarithmic growth phase (PubMed:22988102).1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.