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P60716 (LIPA_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lipoyl synthase

EC=2.8.1.8
Alternative name(s):
Lip-syn
Short name=LS
Lipoate synthase
Lipoic acid synthase
Sulfur insertion protein LipA
Gene names
Name:lipA
Synonyms:lip
Ordered Locus Names:b0628, JW0623
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length321 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.8 Ref.9

Catalytic activity

Protein N(6)-(octanoyl)lysine + 2 sulfur-(sulfur carrier) + 2 S-adenosyl-L-methionine = protein N(6)-(lipoyl)lysine + 2 (sulfur carrier) + 2 L-methionine + 2 5'-deoxyadenosine. Ref.9

Cofactor

Binds 2 4Fe-4S clusters per subunit. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine. Ref.10

Enzyme regulation

Inhibited by the AdoMet analog S-adenosyl homocysteine. HAMAP-Rule MF_00206

Pathway

Protein modification; protein lipoylation via endogenous pathway; protein N(6)-(lipoyl)lysine from octanoyl-[acyl-carrier-protein]: step 2/2. Ref.11

Subunit structure

Monomer or homodimer.

Subcellular location

Cytoplasm HAMAP-Rule MF_00206.

Miscellaneous

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

Sequence similarities

Belongs to the radical SAM superfamily. Lipoyl synthase family.

Sequence caution

The sequence AAA24072.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 321321Lipoyl synthase HAMAP-Rule MF_00206
PRO_0000102313

Sites

Metal binding681Iron-sulfur 1 (4Fe-4S)
Metal binding731Iron-sulfur 1 (4Fe-4S)
Metal binding791Iron-sulfur 1 (4Fe-4S)
Metal binding941Iron-sulfur 2 (4Fe-4S-S-AdoMet)
Metal binding981Iron-sulfur 2 (4Fe-4S-S-AdoMet)
Metal binding1011Iron-sulfur 2 (4Fe-4S-S-AdoMet)

Experimental info

Mutagenesis68 – 7912CEEAS…NLAEC → AEEASAPNLAEA: Loss of 1 4Fe-4S cluster binding. Loss of activity. Ref.10
Mutagenesis94 – 1018CTRRCPFC → ATRRAPFA: Loss of 1 4Fe-4S cluster binding. Loss of activity. Ref.10
Sequence conflict351L → V Ref.1
Sequence conflict351L → V Ref.2

Sequences

Sequence LengthMass (Da)Tools
P60716 [UniParc].

Last modified April 13, 2004. Version 1.
Checksum: BE7BF32A4E3AA358

FASTA32136,072
        10         20         30         40         50         60 
MSKPIVMERG VKYRDADKMA LIPVKNVATE REALLRKPEW MKIKLPADST RIQGIKAAMR 

        70         80         90        100        110        120 
KNGLHSVCEE ASCPNLAECF NHGTATFMIL GAICTRRCPF CDVAHGRPVA PDANEPVKLA 

       130        140        150        160        170        180 
QTIADMALRY VVITSVDRDD LRDGGAQHFA DCITAIREKS PQIKIETLVP DFRGRMDRAL 

       190        200        210        220        230        240 
DILTATPPDV FNHNLENVPR IYRQVRPGAD YNWSLKLLER FKEAHPEIPT KSGLMVGLGE 

       250        260        270        280        290        300 
TNEEIIEVMR DLRRHGVTML TLGQYLQPSR HHLPVQRYVS PDEFDEMKAE ALAMGFTHAA 

       310        320 
CGPFVRSSYH ADLQAKGMEV K 

« Hide

References

« Hide 'large scale' references
[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]"A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map."
Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K., Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S., Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K. expand/collapse author list , Mori H., Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G., Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M., Horiuchi T.
DNA Res. 3:137-155(1996) [PubMed] [Europe PMC] [Abstract]
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]"The complete genome sequence of Escherichia coli K-12."
Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y.
Science 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRB64797.
RefSeqNP_415161.1. NC_000913.3.
YP_488919.1. NC_007779.1.

3D structure databases

ProteinModelPortalP60716.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-48008N.
IntActP60716. 13 interactions.
MINTMINT-1310776.
STRING511145.b0628.

Proteomic databases

PaxDbP60716.
PRIDEP60716.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC73729; AAC73729; b0628.
BAA35271; BAA35271; BAA35271.
GeneID12931644.
945227.
KEGGecj:Y75_p0618.
eco:b0628.
PATRIC32116437. VBIEscCol129921_0658.

Organism-specific databases

EchoBASEEB1283.
EcoGeneEG11306. lipA.

Phylogenomic databases

eggNOGCOG0320.
HOGENOMHOG000235997.
KOK03644.
OMAHPHIPTK.
OrthoDBEOG6038ZS.
PhylomeDBP60716.

Enzyme and pathway databases

BioCycEcoCyc:EG11306-MONOMER.
ECOL316407:JW0623-MONOMER.
MetaCyc:EG11306-MONOMER.
UniPathwayUPA00538; UER00593.

Gene expression databases

GenevestigatorP60716.

Family and domain databases

Gene3D3.20.20.70. 1 hit.
HAMAPMF_00206. Lipoyl_synth.
InterProIPR013785. Aldolase_TIM.
IPR006638. Elp3/MiaB/NifB.
IPR003698. Lipoyl_synth.
IPR007197. rSAM.
[Graphical view]
PANTHERPTHR10949. PTHR10949. 1 hit.
PfamPF04055. Radical_SAM. 1 hit.
[Graphical view]
PIRSFPIRSF005963. Lipoyl_synth. 1 hit.
SMARTSM00729. Elp3. 1 hit.
[Graphical view]
TIGRFAMsTIGR00510. lipA. 1 hit.
ProtoNetSearch...

Other

PROP60716.

Entry information

Entry nameLIPA_ECOLI
AccessionPrimary (citable) accession number: P60716
Secondary accession number(s): P25845, P77595
Entry history
Integrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: April 13, 2004
Last modified: June 11, 2014
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene