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Protein

Bifunctional aspartokinase/homoserine dehydrogenase 1

Gene

thrA

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

Functioni

Catalytic activityi

L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H.
ATP + L-aspartate = ADP + 4-phospho-L-aspartate.

Enzyme regulationi

The enzyme activities are regulated allosterically by L-threonine.

Pathwayi: L-lysine biosynthesis via DAP pathway

This protein is involved in step 1 of the subpathway that synthesizes (S)-tetrahydrodipicolinate from L-aspartate.
Proteins known to be involved in the 4 steps of the subpathway in this organism are:
  1. Lysine-sensitive aspartokinase 3 (lysC), Bifunctional aspartokinase/homoserine dehydrogenase 1 (thrA), Bifunctional aspartokinase/homoserine dehydrogenase 2 (metL)
  2. Aspartate-semialdehyde dehydrogenase (asd)
  3. 4-hydroxy-tetrahydrodipicolinate synthase (dapA)
  4. 4-hydroxy-tetrahydrodipicolinate reductase (dapB)
This subpathway is part of the pathway L-lysine biosynthesis via DAP pathway, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes (S)-tetrahydrodipicolinate from L-aspartate, the pathway L-lysine biosynthesis via DAP pathway and in Amino-acid biosynthesis.

Pathwayi: L-methionine biosynthesis via de novo pathway

This protein is involved in step 1 and 3 of the subpathway that synthesizes L-homoserine from L-aspartate.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. Bifunctional aspartokinase/homoserine dehydrogenase 1 (thrA), Bifunctional aspartokinase/homoserine dehydrogenase 2 (metL)
  2. Aspartate-semialdehyde dehydrogenase (asd)
  3. Bifunctional aspartokinase/homoserine dehydrogenase 1 (thrA), Bifunctional aspartokinase/homoserine dehydrogenase 2 (metL)
This subpathway is part of the pathway L-methionine biosynthesis via de novo pathway, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-homoserine from L-aspartate, the pathway L-methionine biosynthesis via de novo pathway and in Amino-acid biosynthesis.

Pathwayi: L-threonine biosynthesis

This protein is involved in step 1 and 3 of the subpathway that synthesizes L-threonine from L-aspartate.
Proteins known to be involved in the 5 steps of the subpathway in this organism are:
  1. Bifunctional aspartokinase/homoserine dehydrogenase 1 (thrA), Bifunctional aspartokinase/homoserine dehydrogenase 2 (metL)
  2. Aspartate-semialdehyde dehydrogenase (asd)
  3. Bifunctional aspartokinase/homoserine dehydrogenase 1 (thrA), Bifunctional aspartokinase/homoserine dehydrogenase 2 (metL)
  4. Homoserine kinase (thrB)
  5. Threonine synthase (thrC)
This subpathway is part of the pathway L-threonine biosynthesis, which is itself part of Amino-acid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-threonine from L-aspartate, the pathway L-threonine biosynthesis and in Amino-acid biosynthesis.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi471 – 4788NADPSequence analysis

GO - Molecular functioni

  • amino acid binding Source: InterPro
  • aspartate kinase activity Source: EcoCyc
  • ATP binding Source: UniProtKB-KW
  • homoserine dehydrogenase activity Source: EcoCyc
  • NADP binding Source: InterPro

GO - Biological processi

  • homoserine biosynthetic process Source: EcoCyc
  • lysine biosynthetic process via diaminopimelate Source: EcoCyc
  • threonine biosynthetic process Source: UniProtKB-UniPathway

Keywords - Molecular functioni

Kinase, Oxidoreductase, Transferase

Keywords - Biological processi

Amino-acid biosynthesis, Threonine biosynthesis

Keywords - Ligandi

ATP-binding, NADP, Nucleotide-binding

Enzyme and pathway databases

BioCyciEcoCyc:ASPKINIHOMOSERDEHYDROGI-MONOMER.
ECOL316407:JW0001-MONOMER.
MetaCyc:ASPKINIHOMOSERDEHYDROGI-MONOMER.
SABIO-RKP00561.
UniPathwayiUPA00034; UER00015.
UPA00050; UER00063.
UPA00050; UER00461.
UPA00051; UER00462.
UPA00051; UER00465.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional aspartokinase/homoserine dehydrogenase 1
Alternative name(s):
Aspartokinase I/homoserine dehydrogenase I
Short name:
AKI-HDI
Including the following 2 domains:
Aspartokinase (EC:2.7.2.4)
Homoserine dehydrogenase (EC:1.1.1.3)
Gene namesi
Name:thrA
Synonyms:thrA1, thrA2
Ordered Locus Names:b0002, JW0001
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10998. thrA.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 820820Bifunctional aspartokinase/homoserine dehydrogenase 1PRO_0000066681Add
BLAST

Proteomic databases

EPDiP00561.
PaxDbiP00561.
PRIDEiP00561.

Interactioni

Subunit structurei

Homotetramer.

Protein-protein interaction databases

BioGridi4261933. 229 interactions.
DIPiDIP-2907N.
IntActiP00561. 7 interactions.
MINTiMINT-1288804.
STRINGi511145.b0002.

Chemistry

BindingDBiP00561.

Structurei

3D structure databases

ProteinModelPortaliP00561.
SMRiP00561. Positions 3-457, 462-793.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini320 – 39475ACT 1PROSITE-ProRule annotationAdd
BLAST
Domaini401 – 47878ACT 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 249249AspartokinaseAdd
BLAST
Regioni250 – 470221InterfaceAdd
BLAST
Regioni471 – 820350Homoserine dehydrogenaseAdd
BLAST

Sequence similaritiesi

In the N-terminal section; belongs to the aspartokinase family.Curated
In the C-terminal section; belongs to the homoserine dehydrogenase family.Curated
Contains 2 ACT domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG4105CFH. Bacteria.
COG0460. LUCA.
COG0527. LUCA.
HOGENOMiHOG000271593.
InParanoidiP00561.
KOiK12524.
OMAiQAYDESS.
OrthoDBiEOG6M0T34.
PhylomeDBiP00561.

Family and domain databases

Gene3Di3.40.1160.10. 2 hits.
3.40.50.720. 1 hit.
InterProiIPR002912. ACT_dom.
IPR001048. Asp/Glu/Uridylate_kinase.
IPR005106. Asp/hSer_DH_NAD-bd.
IPR001341. Asp_kinase_dom.
IPR018042. Aspartate_kinase_CS.
IPR011147. Bifunc_aspartokin/hSer_DH.
IPR027795. GATS-like_ACT_dom.
IPR001342. HDH_cat.
IPR019811. HDH_CS.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF00696. AA_kinase. 1 hit.
PF01842. ACT. 1 hit.
PF13840. ACT_7. 1 hit.
PF00742. Homoserine_dh. 1 hit.
PF03447. NAD_binding_3. 1 hit.
[Graphical view]
PIRSFiPIRSF000727. ThrA. 1 hit.
SUPFAMiSSF51735. SSF51735. 1 hit.
SSF53633. SSF53633. 1 hit.
TIGRFAMsiTIGR00657. asp_kinases. 1 hit.
PROSITEiPS51671. ACT. 2 hits.
PS00324. ASPARTOKINASE. 1 hit.
PS01042. HOMOSER_DHGENASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P00561-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRVLKFGGTS VANAERFLRV ADILESNARQ GQVATVLSAP AKITNHLVAM
60 70 80 90 100
IEKTISGQDA LPNISDAERI FAELLTGLAA AQPGFPLAQL KTFVDQEFAQ
110 120 130 140 150
IKHVLHGISL LGQCPDSINA ALICRGEKMS IAIMAGVLEA RGHNVTVIDP
160 170 180 190 200
VEKLLAVGHY LESTVDIAES TRRIAASRIP ADHMVLMAGF TAGNEKGELV
210 220 230 240 250
VLGRNGSDYS AAVLAACLRA DCCEIWTDVD GVYTCDPRQV PDARLLKSMS
260 270 280 290 300
YQEAMELSYF GAKVLHPRTI TPIAQFQIPC LIKNTGNPQA PGTLIGASRD
310 320 330 340 350
EDELPVKGIS NLNNMAMFSV SGPGMKGMVG MAARVFAAMS RARISVVLIT
360 370 380 390 400
QSSSEYSISF CVPQSDCVRA ERAMQEEFYL ELKEGLLEPL AVTERLAIIS
410 420 430 440 450
VVGDGMRTLR GISAKFFAAL ARANINIVAI AQGSSERSIS VVVNNDDATT
460 470 480 490 500
GVRVTHQMLF NTDQVIEVFV IGVGGVGGAL LEQLKRQQSW LKNKHIDLRV
510 520 530 540 550
CGVANSKALL TNVHGLNLEN WQEELAQAKE PFNLGRLIRL VKEYHLLNPV
560 570 580 590 600
IVDCTSSQAV ADQYADFLRE GFHVVTPNKK ANTSSMDYYH QLRYAAEKSR
610 620 630 640 650
RKFLYDTNVG AGLPVIENLQ NLLNAGDELM KFSGILSGSL SYIFGKLDEG
660 670 680 690 700
MSFSEATTLA REMGYTEPDP RDDLSGMDVA RKLLILARET GRELELADIE
710 720 730 740 750
IEPVLPAEFN AEGDVAAFMA NLSQLDDLFA ARVAKARDEG KVLRYVGNID
760 770 780 790 800
EDGVCRVKIA EVDGNDPLFK VKNGENALAF YSHYYQPLPL VLRGYGAGND
810 820
VTAAGVFADL LRTLSWKLGV
Length:820
Mass (Da):89,120
Last modified:August 29, 2003 - v2
Checksum:i0BF28E9EECAB10ED
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti11 – 111V → L in CAA23660 (PubMed:7003595).Curated
Sequence conflicti11 – 111V → L in AAA83914 (PubMed:7003595).Curated
Sequence conflicti113 – 1131Q → E AA sequence (PubMed:387092).Curated
Sequence conflicti230 – 2301D → N in CAA23660 (PubMed:7003595).Curated
Sequence conflicti230 – 2301D → N in AAA83914 (PubMed:7003595).Curated
Sequence conflicti375 – 3751Q → L in CAA23660 (PubMed:7003595).Curated
Sequence conflicti375 – 3751Q → L in AAA83914 (PubMed:7003595).Curated
Sequence conflicti393 – 3931T → A in CAA23660 (PubMed:7003595).Curated
Sequence conflicti393 – 3931T → A in AAA83914 (PubMed:7003595).Curated
Sequence conflicti406 – 4061M → L in CAA23660 (PubMed:7003595).Curated
Sequence conflicti406 – 4061M → L in AAA83914 (PubMed:7003595).Curated
Sequence conflicti553 – 5531D → N in CAA23660 (PubMed:7003595).Curated
Sequence conflicti553 – 5531D → N in AAA83914 (PubMed:7003595).Curated
Sequence conflicti587 – 5882DY → IT in AAA24671 (PubMed:390305).Curated
Sequence conflicti607 – 6071T → I in CAA23660 (PubMed:7003595).Curated
Sequence conflicti607 – 6071T → I in AAA83914 (PubMed:7003595).Curated
Sequence conflicti658 – 6581T → R in CAA23660 (PubMed:7003595).Curated
Sequence conflicti658 – 6581T → R in AAA83914 (PubMed:7003595).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00361 Genomic DNA. Translation: CAA23660.1.
J01706 Genomic DNA. Translation: AAA83914.1.
U14003 Genomic DNA. Translation: AAA97301.1.
U00096 Genomic DNA. Translation: AAC73113.1.
AP009048 Genomic DNA. Translation: BAB96579.2.
V00360 Genomic DNA. Translation: CAA23659.1.
X68872 Genomic DNA. Translation: CAA48734.1.
M28570 Genomic DNA. Translation: AAA24673.1.
M10644 Genomic DNA. Translation: AAA24671.1.
PIRiB64720. DEECK.
RefSeqiNP_414543.1. NC_000913.3.
WP_001264707.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC73113; AAC73113; b0002.
BAB96579; BAB96579; BAB96579.
GeneIDi945803.
KEGGiecj:JW0001.
eco:b0002.
PATRICi32115099. VBIEscCol129921_0001.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00361 Genomic DNA. Translation: CAA23660.1.
J01706 Genomic DNA. Translation: AAA83914.1.
U14003 Genomic DNA. Translation: AAA97301.1.
U00096 Genomic DNA. Translation: AAC73113.1.
AP009048 Genomic DNA. Translation: BAB96579.2.
V00360 Genomic DNA. Translation: CAA23659.1.
X68872 Genomic DNA. Translation: CAA48734.1.
M28570 Genomic DNA. Translation: AAA24673.1.
M10644 Genomic DNA. Translation: AAA24671.1.
PIRiB64720. DEECK.
RefSeqiNP_414543.1. NC_000913.3.
WP_001264707.1. NZ_LN832404.1.

3D structure databases

ProteinModelPortaliP00561.
SMRiP00561. Positions 3-457, 462-793.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4261933. 229 interactions.
DIPiDIP-2907N.
IntActiP00561. 7 interactions.
MINTiMINT-1288804.
STRINGi511145.b0002.

Chemistry

BindingDBiP00561.

Proteomic databases

EPDiP00561.
PaxDbiP00561.
PRIDEiP00561.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC73113; AAC73113; b0002.
BAB96579; BAB96579; BAB96579.
GeneIDi945803.
KEGGiecj:JW0001.
eco:b0002.
PATRICi32115099. VBIEscCol129921_0001.

Organism-specific databases

EchoBASEiEB0991.
EcoGeneiEG10998. thrA.

Phylogenomic databases

eggNOGiENOG4105CFH. Bacteria.
COG0460. LUCA.
COG0527. LUCA.
HOGENOMiHOG000271593.
InParanoidiP00561.
KOiK12524.
OMAiQAYDESS.
OrthoDBiEOG6M0T34.
PhylomeDBiP00561.

Enzyme and pathway databases

UniPathwayiUPA00034; UER00015.
UPA00050; UER00063.
UPA00050; UER00461.
UPA00051; UER00462.
UPA00051; UER00465.
BioCyciEcoCyc:ASPKINIHOMOSERDEHYDROGI-MONOMER.
ECOL316407:JW0001-MONOMER.
MetaCyc:ASPKINIHOMOSERDEHYDROGI-MONOMER.
SABIO-RKP00561.

Miscellaneous databases

PROiP00561.

Family and domain databases

Gene3Di3.40.1160.10. 2 hits.
3.40.50.720. 1 hit.
InterProiIPR002912. ACT_dom.
IPR001048. Asp/Glu/Uridylate_kinase.
IPR005106. Asp/hSer_DH_NAD-bd.
IPR001341. Asp_kinase_dom.
IPR018042. Aspartate_kinase_CS.
IPR011147. Bifunc_aspartokin/hSer_DH.
IPR027795. GATS-like_ACT_dom.
IPR001342. HDH_cat.
IPR019811. HDH_CS.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF00696. AA_kinase. 1 hit.
PF01842. ACT. 1 hit.
PF13840. ACT_7. 1 hit.
PF00742. Homoserine_dh. 1 hit.
PF03447. NAD_binding_3. 1 hit.
[Graphical view]
PIRSFiPIRSF000727. ThrA. 1 hit.
SUPFAMiSSF51735. SSF51735. 1 hit.
SSF53633. SSF53633. 1 hit.
TIGRFAMsiTIGR00657. asp_kinases. 1 hit.
PROSITEiPS51671. ACT. 2 hits.
PS00324. ASPARTOKINASE. 1 hit.
PS01042. HOMOSER_DHGENASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region."
    Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K., Mizobuchi K., Nakata A.
    Nucleic Acids Res. 20:3305-3308(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12.
  3. "Analysis of the Escherichia coli genome VI: DNA sequence of the region from 92.8 through 100 minutes."
    Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L., Blattner F.R.
    Nucleic Acids Res. 23:2105-2119(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  5. "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], SEQUENCE REVISION.
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  6. "Initiation, pausing, and termination of transcription in the threonine operon regulatory region of Escherichia coli."
    Gardner J.F.
    J. Biol. Chem. 257:3896-3904(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-10.
  7. "Identification and characterization of mutants affecting transcription termination at the threonine operon attenuator."
    Lynn S.P., Bauer C.E., Chapman K.A., Gardner J.F.
    J. Mol. Biol. 183:529-541(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-10.
  8. "The primary structure of Escherichia coli K 12 aspartokinase I-homoserine dehydrogenase I: sequence of cyanogen bromide peptide CB 3."
    Sibilli L., le Bras G., Cossart P., Chalvignac M.A., le Bras G., Briley P.A., Cohen G.N.
    Biochimie 61:733-739(1979) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 51-129.
  9. "Nucleotide sequence of the metL gene of Escherichia coli. Its product, the bifunctional aspartokinase II-homoserine dehydrogenase II, and the bifunctional product of the thrA gene, aspartokinase I-homoserine dehydrogenase I, derive from a common ancestor."
    Zakin M.M., Duchange N., Ferrara P., Cohen G.N.
    J. Biol. Chem. 258:3028-3031(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: SEQUENCE REVISION TO 11.
  10. "Construction and expression of a hybrid plasmid containing the Escherichia coli thrA and thrB genes."
    Cossart P., Katinka M., Yaniv M.
    Mol. Gen. Genet. 175:39-44(1979) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 553-588.

Entry informationi

Entry nameiAK1H_ECOLI
AccessioniPrimary (citable) accession number: P00561
Secondary accession number(s): Q47659, Q6LEL0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 29, 2003
Last modified: March 16, 2016
This is version 166 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Aspartokinase II-homoserine dehydrogenase II and aspartokinase III also catalyze the same reaction(s).

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Direct protein sequencing, Multifunctional enzyme, 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

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.