Lysine-sensitive aspartokinase 3 - Escherichia coli (strain K12)

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P08660 (AK3_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 109. History...

Clusters with 100%, 90%, 50% identity |

Documents (4) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Lysine-sensitive aspartokinase 3
EC=2.7.2.4

Alternative name(s):
Aspartate kinase III
Short name=AKIII
Lysine-sensitive aspartokinase III

Gene names

Name:	lysC
Synonyms:	apk
Ordered Locus Names:	b4024, JW3984

Organism

Escherichia coli (strain K12)

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein attributes

Sequence length	449 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	ATP + L-aspartate = ADP + 4-phospho-L-aspartate.
Enzyme regulation	Synthesis and activity are sensitive to the allosteric inhibitor lysine, one of the end metabolites of the aspartic acid family branched pathway. Ref.7
Pathway	Amino-acid biosynthesis; L-lysine biosynthesis via DAP pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 1/4.
Subunit structure	Homodimer. In the inactive form a homotetramer is formed. Ref.6 Ref.7
Miscellaneous	Aspartokinases I and II also catalyze the same reaction(s).
Sequence similarities	Belongs to the aspartokinase family. Contains 1 ACT domain.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Lysine biosynthesis
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Allosteric enzyme Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	homoserine biosynthetic process Inferred from direct assay. Source: EcoCyc lysine biosynthetic process via diaminopimelate Inferred from direct assay. Source: EcoCyc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW amino acid binding Inferred from electronic annotation. Source: InterPro aspartate kinase activity Inferred from direct assay. Source: EcoCyc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed

Chain

2 – 449

448

Lysine-sensitive aspartokinase 3

PRO_0000066676

Regions

Domain

309 – 386

ACT

Nucleotide binding

8 – 11

ATP

Nucleotide binding

221 – 222

ATP

Nucleotide binding

257 – 258

ATP

Region

2 – 245

244

Aspartokinase

Region

198 – 201

Substrate binding

Region

246 – 449

204

Interface

Region

299 – 449

151

Required for homodimerization

Region

318 – 321

Allosteric inhibitor binding 1

Region

324 – 325

Allosteric inhibitor binding 1

Region

338 – 340

Allosteric inhibitor binding 2

Region

345 – 346

Allosteric inhibitor binding 1

Sites

Binding site

Substrate

Binding site

119

Substrate

Binding site

227

ATP; via amide nitrogen and carbonyl oxygen

Binding site

232

ATP

Experimental info

Mutagenesis

K → R: Reduces activity about 98%. Increases KM for aspartate about 40-fold, enzyme is less sensitive to lysine inhibition. Ref.6

Mutagenesis

119

E → D: Increases KM for aspartate about 3000-fold. Ref.6

Mutagenesis

198

R → K: Increases KM for aspartate about 200-fold. Ref.6

Mutagenesis

202

D → E: Reduces activity about 98%. Increases KM for aspartate about 40-fold, enzyme is less sensitive to lysine inhibition. Ref.6

Sequence conflict

14 – 15

VA → AS in CAA24910. Ref.5

Sequence conflict

M → E in CAA24910. Ref.5

Sequence conflict

G → C in AAA24095. Ref.1

Sequence conflict

401

G → A in AAA24095. Ref.1

Secondary structure

449

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P08660 [UniParc].

Last modified October 1, 1993. Version 2.
Checksum: 5B41CE3A6E4D984B
Show »

FASTA

449

48,532

        10         20         30         40         50         60 
MSEIVVSKFG GTSVADFDAM NRSADIVLSD ANVRLVVLSA SAGITNLLVA LAEGLEPGER 

        70         80         90        100        110        120 
FEKLDAIRNI QFAILERLRY PNVIREEIER LLENITVLAE AAALATSPAL TDELVSHGEL 

       130        140        150        160        170        180 
MSTLLFVEIL RERDVQAQWF DVRKVMRTND RFGRAEPDIA ALAELAALQL LPRLNEGLVI 

       190        200        210        220        230        240 
TQGFIGSENK GRTTTLGRGG SDYTAALLAE ALHASRVDIW TDVPGIYTTD PRVVSAAKRI 

       250        260        270        280        290        300 
DEIAFAEAAE MATFGAKVLH PATLLPAVRS DIPVFVGSSK DPRAGGTLVC NKTENPPLFR 

       310        320        330        340        350        360 
ALALRRNQTL LTLHSLNMLH SRGFLAEVFG ILARHNISVD LITTSEVSVA LTLDTTGSTS 

       370        380        390        400        410        420 
TGDTLLTQSL LMELSALCRV EVEEGLALVA LIGNDLSKAC GVGKEVFGVL EPFNIRMICY 

       430        440 
GASSHNLCFL VPGEDAEQVV QKLHSNLFE

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequence of lysC gene encoding the lysine-sensitive aspartokinase III of Escherichia coli K12. Evolutionary pathway leading to three isofunctional enzymes." Cassan M., Parsot C., Cohen G.N., Patte J.-C. J. Biol. Chem. 261:1052-1057(1986) [PubMed: 3003049] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-27. Strain: K12.
[2]	"Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes." Blattner F.R., Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L. Nucleic Acids Res. 21:5408-5417(1993) [PubMed: 8265357] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[3]	"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 277:1453-1474(1997) [PubMed: 9278503] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[4]	"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: 16738553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[5]	"Nucleotide sequence of the promoter region of the E. coli lysC gene." Cassan M., Ronceray J., Patte J.-C. Nucleic Acids Res. 11:6157-6166(1983) [PubMed: 6312411] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20.
[6]	"Site-directed mutagenesis of Escherichia coli acetylglutamate kinase and aspartokinase III probes the catalytic and substrate-binding mechanisms of these amino acid kinase family enzymes and allows three-dimensional modelling of aspartokinase." Marco-Marin C., Ramon-Maiques S., Tavarez S., Rubio V. J. Mol. Biol. 334:459-476(2003) [PubMed: 14623187] [Abstract] Cited for: SUBUNIT, INVOLVEMENT OF C-TERMINUS IN DIMERIZATION, MUTAGENESIS OF LYS-8; GLU-119; ARG-198 AND ASP-202.
[7]	"Structures of R- and T-state Escherichia coli aspartokinase III. Mechanisms of the allosteric transition and inhibition by lysine." Kotaka M., Ren J., Lockyer M., Hawkins A.R., Stammers D.K. J. Biol. Chem. 281:31544-31552(2006) [PubMed: 16905770] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN SUBSTRATE-BOUND ACTIVE AND LYS-BOUND INACTIVE STATES, SUBUNIT, ENZYME REGULATION.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M11812 Genomic DNA. Translation: AAA24095.1.
U00006 Genomic DNA. Translation: AAC43118.1.
U00096 Genomic DNA. Translation: AAC76994.1.
AP009048 Genomic DNA. Translation: BAE78026.1.
X00008 Genomic DNA. Translation: CAA24910.1.

PIR

KIECD3. G65209.

RefSeq

NP_418448.1. NC_000913.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2J0W	X-ray	2.50	A	1-449	[»]
2J0X	X-ray	2.80	A/B	1-449	[»]

ProteinModelPortal

P08660.

SMR

P08660. Positions 3-449.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBESCT00000001085; EBESCP00000001085; EBESCG00000000899.
EBESCT00000001086; EBESCP00000001086; EBESCG00000000899.
EBESCT00000016771; EBESCP00000016062; EBESCG00000015830.

GeneID

948531.

GenomeReviews

Gene locus JW3984 in contig AP009048_GR.
Gene locus b4024 in contig U00096_GR.

KEGG

ecj:JW3984.
eco:b4024.

PATRIC

32123577. VBIEscCol129921_4137.

Organism-specific databases

EchoBASE

EB0545.

EcoGene

EG10550. lysC.

Phylogenomic databases

eggNOG

COG0527.

GeneTree

EBGT00050000009086.

HOGENOM

HBG724395.

OMA

FDVRKIM.

PhylomeDB

P08660.

ProtClustDB

PRK09084.

Enzyme and pathway databases

BioCyc

EcoCyc:ASPKINIII-MONOMER.
MetaCyc:ASPKINIII-MONOMER.

Gene expression databases

Genevestigator

P08660.

Family and domain databases

InterPro

IPR002912. ACT-bd.
IPR001048. Asp/Glu/Uridylate_kinase.
IPR005260. Asp_kin_monofn.
IPR001341. Asp_kinase_dom.
IPR018042. Aspartate_kinase_CS.
[Graphical view]

Gene3D

G3DSA:3.40.1160.10. Aa_kinase. 2 hits.

K00928.

Pfam

PF00696. AA_kinase. 1 hit.
PF01842. ACT. 1 hit.
[Graphical view]

PIRSF

PIRSF000726. Asp_kin. 1 hit.

SUPFAM

SSF53633. Aa_kinase. 1 hit.

TIGRFAMs

TIGR00656. Asp_kin_monofn. 1 hit.
TIGR00657. Asp_kinases. 1 hit.

PROSITE

PS00324. ASPARTOKINASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

AK3_ECOLI

Accession

Primary (citable) accession number: P08660
Secondary accession number(s): Q2M6T0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	October 1, 1993
Last modified:	January 25, 2012
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program

Relevant documents

Escherichia coli

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Entry information

Relevant documents