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Protein

Lipoyl synthase

Gene

lipA

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

Functioni

Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives. Free octanoate is not a substrate for LipA.3 Publications

Catalytic activityi

Protein N(6)-(octanoyl)lysine + 2 sulfur-(sulfur carrier) + 2 S-adenosyl-L-methionine + 2 reduced [2Fe-2S] ferredoxin = protein N(6)-(lipoyl)lysine + 2 (sulfur carrier) + 2 L-methionine + 2 5'-deoxyadenosine + 2 oxidized [2Fe-2S] ferredoxin.1 Publication

Cofactori

[4Fe-4S] cluster1 PublicationNote: Binds 2 [4Fe-4S] clusters per subunit. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.1 Publication

Enzyme regulationi

Inhibited by the AdoMet analog S-adenosyl homocysteine.

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi68 – 681Iron-sulfur 1 (4Fe-4S)
Metal bindingi73 – 731Iron-sulfur 1 (4Fe-4S)
Metal bindingi79 – 791Iron-sulfur 1 (4Fe-4S)
Metal bindingi94 – 941Iron-sulfur 2 (4Fe-4S-S-AdoMet)
Metal bindingi98 – 981Iron-sulfur 2 (4Fe-4S-S-AdoMet)
Metal bindingi101 – 1011Iron-sulfur 2 (4Fe-4S-S-AdoMet)

GO - Molecular functioni

  1. 4 iron, 4 sulfur cluster binding Source: EcoliWiki
  2. alpha-ketoacid dehydrogenase activity Source: CACAO
  3. lipoate synthase activity Source: EcoliWiki
  4. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. lipoate biosynthetic process Source: EcoliWiki
  2. oxidation-reduction process Source: GOC
  3. protein lipoylation Source: EcoliWiki
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Ligandi

4Fe-4S, Iron, Iron-sulfur, Metal-binding, S-adenosyl-L-methionine

Enzyme and pathway databases

BioCyciEcoCyc:EG11306-MONOMER.
ECOL316407:JW0623-MONOMER.
MetaCyc:EG11306-MONOMER.
UniPathwayiUPA00538; UER00593.

Names & Taxonomyi

Protein namesi
Recommended name:
Lipoyl synthase (EC:2.8.1.81 Publication)
Alternative name(s):
Lip-syn
Short name:
LS
Lipoate synthase
Lipoic acid synthase
Sulfur insertion protein LipA
Gene namesi
Name:lipA
Synonyms:lip
Ordered Locus Names:b0628, JW0623
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
ProteomesiUP000000318: Chromosome, UP000000625: Chromosome

Organism-specific databases

EcoGeneiEG11306. lipA.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: EcoliWiki
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi68 – 7912CEEAS…NLAEC → AEEASAPNLAEA: Loss of 1 4Fe-4S cluster binding. Loss of activity. 1 PublicationAdd
BLAST
Mutagenesisi94 – 1018CTRRCPFC → ATRRAPFA: Loss of 1 4Fe-4S cluster binding. Loss of activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 321321Lipoyl synthasePRO_0000102313Add
BLAST

Proteomic databases

PaxDbiP60716.
PRIDEiP60716.

Expressioni

Gene expression databases

GenevestigatoriP60716.

Interactioni

Subunit structurei

Monomer or homodimer.

Protein-protein interaction databases

DIPiDIP-48008N.
IntActiP60716. 13 interactions.
MINTiMINT-1310776.
STRINGi511145.b0628.

Structurei

3D structure databases

ProteinModelPortaliP60716.
SMRiP60716. Positions 38-311.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0320.
HOGENOMiHOG000235997.
InParanoidiP60716.
KOiK03644.
OMAiEEYVTPE.
OrthoDBiEOG6038ZS.
PhylomeDBiP60716.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_00206. Lipoyl_synth.
InterProiIPR013785. Aldolase_TIM.
IPR006638. Elp3/MiaB/NifB.
IPR003698. Lipoyl_synth.
IPR007197. rSAM.
[Graphical view]
PANTHERiPTHR10949. PTHR10949. 1 hit.
PfamiPF04055. Radical_SAM. 1 hit.
[Graphical view]
PIRSFiPIRSF005963. Lipoyl_synth. 1 hit.
SMARTiSM00729. Elp3. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00510. lipA. 1 hit.

Sequencei

Sequence statusi: Complete.

P60716-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSKPIVMERG VKYRDADKMA LIPVKNVATE REALLRKPEW MKIKLPADST
60 70 80 90 100
RIQGIKAAMR KNGLHSVCEE ASCPNLAECF NHGTATFMIL GAICTRRCPF
110 120 130 140 150
CDVAHGRPVA PDANEPVKLA QTIADMALRY VVITSVDRDD LRDGGAQHFA
160 170 180 190 200
DCITAIREKS PQIKIETLVP DFRGRMDRAL DILTATPPDV FNHNLENVPR
210 220 230 240 250
IYRQVRPGAD YNWSLKLLER FKEAHPEIPT KSGLMVGLGE TNEEIIEVMR
260 270 280 290 300
DLRRHGVTML TLGQYLQPSR HHLPVQRYVS PDEFDEMKAE ALAMGFTHAA
310 320
CGPFVRSSYH ADLQAKGMEV K
Length:321
Mass (Da):36,072
Last modified:April 13, 2004 - v1
Checksum:iBE7BF32A4E3AA358
GO

Sequence cautioni

The sequence AAA24072.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti35 – 351L → V (PubMed:1577793).Curated
Sequence conflicti35 – 351L → V (PubMed:8444795).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M82805 Genomic DNA. Translation: AAA24072.1. Different initiation.
L07636 Genomic DNA. Translation: AAA66345.1.
U82598 Genomic DNA. Translation: AAB40828.1.
U00096 Genomic DNA. Translation: AAC73729.1.
AP009048 Genomic DNA. Translation: BAA35271.1.
PIRiB64797.
RefSeqiNP_415161.1. NC_000913.3.
YP_488919.1. NC_007779.1.

Genome annotation databases

EnsemblBacteriaiAAC73729; AAC73729; b0628.
BAA35271; BAA35271; BAA35271.
GeneIDi12931644.
945227.
KEGGiecj:Y75_p0618.
eco:b0628.
PATRICi32116437. VBIEscCol129921_0658.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M82805 Genomic DNA. Translation: AAA24072.1. Different initiation.
L07636 Genomic DNA. Translation: AAA66345.1.
U82598 Genomic DNA. Translation: AAB40828.1.
U00096 Genomic DNA. Translation: AAC73729.1.
AP009048 Genomic DNA. Translation: BAA35271.1.
PIRiB64797.
RefSeqiNP_415161.1. NC_000913.3.
YP_488919.1. NC_007779.1.

3D structure databases

ProteinModelPortaliP60716.
SMRiP60716. Positions 38-311.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-48008N.
IntActiP60716. 13 interactions.
MINTiMINT-1310776.
STRINGi511145.b0628.

Proteomic databases

PaxDbiP60716.
PRIDEiP60716.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC73729; AAC73729; b0628.
BAA35271; BAA35271; BAA35271.
GeneIDi12931644.
945227.
KEGGiecj:Y75_p0618.
eco:b0628.
PATRICi32116437. VBIEscCol129921_0658.

Organism-specific databases

EchoBASEiEB1283.
EcoGeneiEG11306. lipA.

Phylogenomic databases

eggNOGiCOG0320.
HOGENOMiHOG000235997.
InParanoidiP60716.
KOiK03644.
OMAiEEYVTPE.
OrthoDBiEOG6038ZS.
PhylomeDBiP60716.

Enzyme and pathway databases

UniPathwayiUPA00538; UER00593.
BioCyciEcoCyc:EG11306-MONOMER.
ECOL316407:JW0623-MONOMER.
MetaCyc:EG11306-MONOMER.

Miscellaneous databases

PROiP60716.

Gene expression databases

GenevestigatoriP60716.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
HAMAPiMF_00206. Lipoyl_synth.
InterProiIPR013785. Aldolase_TIM.
IPR006638. Elp3/MiaB/NifB.
IPR003698. Lipoyl_synth.
IPR007197. rSAM.
[Graphical view]
PANTHERiPTHR10949. PTHR10949. 1 hit.
PfamiPF04055. Radical_SAM. 1 hit.
[Graphical view]
PIRSFiPIRSF005963. Lipoyl_synth. 1 hit.
SMARTiSM00729. Elp3. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00510. lipA. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The biosynthesis of lipoic acid. Cloning of lip, a lipoate biosynthetic locus of Escherichia coli."
    Hayden M.A., Huang I., Bussiere D.E., Ashley G.W.
    J. Biol. Chem. 267:9512-9515(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12.
  2. "Lipoic acid metabolism in Escherichia coli: sequencing and functional characterization of the lipA and lipB genes."
    Reed K.E., Cronan J.E. Jr.
    J. Bacteriol. 175:1325-1336(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  4. "Sequence of minutes 4-25 of Escherichia coli."
    Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M., Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D., Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.
    Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  6. "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.
  7. "Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein."
    Miller J.R., Busby R.W., Jordan S.W., Cheek J., Henshaw T.F., Ashley G.W., Broderick J.B., Cronan J.E. Jr., Marletta M.A.
    Biochemistry 39:15166-15178(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, EPR SPECTROSCOPY OF IRON-SULFUR CLUSTERS.
    Strain: BL21-DE3.
  8. "Assembly of the covalent linkage between lipoic acid and its cognate enzymes."
    Zhao X., Miller J.R., Jiang Y., Marletta M.A., Cronan J.E. Jr.
    Chem. Biol. 10:1293-1302(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
    Strain: K12 / JK1.
  9. "Lipoyl synthase requires two equivalents of S-adenosyl-L-methionine to synthesize one equivalent of lipoic acid."
    Cicchillo R.M., Iwig D.F., Jones A.D., Nesbitt N.M., Baleanu-Gogonea C., Souder M.G., Tu L., Booker S.J.
    Biochemistry 43:6378-6386(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY.
  10. "Escherichia coli lipoyl synthase binds two distinct [4Fe-4S] clusters per polypeptide."
    Cicchillo R.M., Lee K.-H., Baleanu-Gogonea C., Nesbitt N.M., Krebs C., Booker S.J.
    Biochemistry 43:11770-11781(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: COFACTOR, CHARACTERIZATION, MOESSBAUER SPECTROSCOPY, EPR SPECTROSCOPY, MUTAGENESIS OF 68-CYS--CYS-79 AND 94-CYS--CYS-101.
  11. "Unraveling the pathway of lipoic acid biosynthesis."
    Booker S.J.
    Chem. Biol. 11:10-12(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PATHWAY.
  12. "Mechanistic investigations of lipoic acid biosynthesis in Escherichia coli: both sulfur atoms in lipoic acid are contributed by the same lipoyl synthase polypeptide."
    Cicchillo R.M., Booker S.J.
    J. Am. Chem. Soc. 127:2860-2861(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: REACTION MECHANISM.

Entry informationi

Entry nameiLIPA_ECOLI
AccessioniPrimary (citable) accession number: P60716
Secondary accession number(s): P25845, P77595
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: April 13, 2004
Last modified: March 4, 2015
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

The source of sulfurs is the LipA protein itself, most likely one 4Fe-4S cluster.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3

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 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.