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Protein

Bifunctional aspartokinase/homoserine dehydrogenase 2

Gene

metL

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.

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 bindingi464 – 4718NADPSequence analysis

GO - Molecular functioni

  • 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
  • methionine biosynthetic process Source: UniProtKB-KW
  • threonine biosynthetic process Source: UniProtKB-UniPathway

Keywords - Molecular functioni

Kinase, Oxidoreductase, Transferase

Keywords - Biological processi

Amino-acid biosynthesis, Methionine biosynthesis

Keywords - Ligandi

ATP-binding, NADP, Nucleotide-binding

Enzyme and pathway databases

BioCyciEcoCyc:ASPKINIIHOMOSERDEHYDROGII-MONOMER.
ECOL316407:JW3911-MONOMER.
MetaCyc:ASPKINIIHOMOSERDEHYDROGII-MONOMER.
UniPathwayiUPA00034; UER00015.
UPA00050; UER00063.
UPA00050; UER00461.
UPA00051; UER00462.
UPA00051; UER00465.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional aspartokinase/homoserine dehydrogenase 2
Alternative name(s):
Aspartokinase II/homoserine dehydrogenase II
Short name:
AKII-HDII
Including the following 2 domains:
Aspartokinase (EC:2.7.2.4)
Homoserine dehydrogenase (EC:1.1.1.3)
Gene namesi
Name:metL
Synonyms:metM
Ordered Locus Names:b3940, JW3911
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10590. metL.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: EcoCyc

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 810809Bifunctional aspartokinase/homoserine dehydrogenase 2PRO_0000066683Add
BLAST

Proteomic databases

PaxDbiP00562.
PRIDEiP00562.

Interactioni

Subunit structurei

Homotetramer.

Protein-protein interaction databases

BioGridi4261101. 411 interactions.
DIPiDIP-10197N.
IntActiP00562. 3 interactions.
STRINGi511145.b3940.

Structurei

3D structure databases

ProteinModelPortaliP00562.
SMRiP00562. Positions 16-455, 457-809.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 252251AspartokinaseAdd
BLAST
Regioni253 – 463211InterfaceAdd
BLAST
Regioni464 – 810347Homoserine 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

Phylogenomic databases

eggNOGiENOG4105CFH. Bacteria.
COG0460. LUCA.
COG0527. LUCA.
HOGENOMiHOG000271594.
InParanoidiP00562.
KOiK12525.
OMAiTLQYPEF.
PhylomeDBiP00562.

Family and domain databases

Gene3Di3.40.1160.10. 2 hits.
3.40.50.720. 1 hit.
InterProiIPR001048. Asp/Glu/Uridylate_kinase.
IPR005106. Asp/hSer_DH_NAD-bd.
IPR001341. Asp_kinase_dom.
IPR018042. Aspartate_kinase_CS.
IPR011147. Bifunc_aspartokin/hSer_DH.
IPR001342. HDH_cat.
IPR019811. HDH_CS.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF00696. AA_kinase. 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.
PROSITEiPS00324. ASPARTOKINASE. 1 hit.
PS01042. HOMOSER_DHGENASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P00562-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSVIAQAGAK GRQLHKFGGS SLADVKCYLR VAGIMAEYSQ PDDMMVVSAA
60 70 80 90 100
GSTTNQLINW LKLSQTDRLS AHQVQQTLRR YQCDLISGLL PAEEADSLIS
110 120 130 140 150
AFVSDLERLA ALLDSGINDA VYAEVVGHGE VWSARLMSAV LNQQGLPAAW
160 170 180 190 200
LDAREFLRAE RAAQPQVDEG LSYPLLQQLL VQHPGKRLVV TGFISRNNAG
210 220 230 240 250
ETVLLGRNGS DYSATQIGAL AGVSRVTIWS DVAGVYSADP RKVKDACLLP
260 270 280 290 300
LLRLDEASEL ARLAAPVLHA RTLQPVSGSE IDLQLRCSYT PDQGSTRIER
310 320 330 340 350
VLASGTGARI VTSHDDVCLI EFQVPASQDF KLAHKEIDQI LKRAQVRPLA
360 370 380 390 400
VGVHNDRQLL QFCYTSEVAD SALKILDEAG LPGELRLRQG LALVAMVGAG
410 420 430 440 450
VTRNPLHCHR FWQQLKGQPV EFTWQSDDGI SLVAVLRTGP TESLIQGLHQ
460 470 480 490 500
SVFRAEKRIG LVLFGKGNIG SRWLELFARE QSTLSARTGF EFVLAGVVDS
510 520 530 540 550
RRSLLSYDGL DASRALAFFN DEAVEQDEES LFLWMRAHPY DDLVVLDVTA
560 570 580 590 600
SQQLADQYLD FASHGFHVIS ANKLAGASDS NKYRQIHDAF EKTGRHWLYN
610 620 630 640 650
ATVGAGLPIN HTVRDLIDSG DTILSISGIF SGTLSWLFLQ FDGSVPFTEL
660 670 680 690 700
VDQAWQQGLT EPDPRDDLSG KDVMRKLVIL AREAGYNIEP DQVRVESLVP
710 720 730 740 750
AHCEGGSIDH FFENGDELNE QMVQRLEAAR EMGLVLRYVA RFDANGKARV
760 770 780 790 800
GVEAVREDHP LASLLPCDNV FAIESRWYRD NPLVIRGPGA GRDVTAGAIQ
810
SDINRLAQLL
Length:810
Mass (Da):88,888
Last modified:January 23, 2007 - v3
Checksum:iBD2515E3554F9B44
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti56 – 561Q → R in CAA23585 (PubMed:6298218).Curated
Sequence conflicti59 – 591N → S in CAA23585 (PubMed:6298218).Curated
Sequence conflicti333 – 3331A → G in CAA23585 (PubMed:6298218).Curated
Sequence conflicti674 – 6741M → S in CAA23585 (PubMed:6298218).Curated
Sequence conflicti762 – 7621A → R in CAA23585 (PubMed:6298218).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00305 Genomic DNA. Translation: CAA23585.1.
L19201 Genomic DNA. Translation: AAB03072.1.
U00096 Genomic DNA. Translation: AAC76922.1.
AP009048 Genomic DNA. Translation: BAE77370.1.
PIRiS40883. DEECK2.
RefSeqiNP_418375.1. NC_000913.3.
WP_000110772.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC76922; AAC76922; b3940.
BAE77370; BAE77370; BAE77370.
GeneIDi948433.
KEGGiecj:JW3911.
eco:b3940.
PATRICi32123399. VBIEscCol129921_4060.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
V00305 Genomic DNA. Translation: CAA23585.1.
L19201 Genomic DNA. Translation: AAB03072.1.
U00096 Genomic DNA. Translation: AAC76922.1.
AP009048 Genomic DNA. Translation: BAE77370.1.
PIRiS40883. DEECK2.
RefSeqiNP_418375.1. NC_000913.3.
WP_000110772.1. NZ_LN832404.1.

3D structure databases

ProteinModelPortaliP00562.
SMRiP00562. Positions 16-455, 457-809.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4261101. 411 interactions.
DIPiDIP-10197N.
IntActiP00562. 3 interactions.
STRINGi511145.b3940.

Proteomic databases

PaxDbiP00562.
PRIDEiP00562.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC76922; AAC76922; b3940.
BAE77370; BAE77370; BAE77370.
GeneIDi948433.
KEGGiecj:JW3911.
eco:b3940.
PATRICi32123399. VBIEscCol129921_4060.

Organism-specific databases

EchoBASEiEB0585.
EcoGeneiEG10590. metL.

Phylogenomic databases

eggNOGiENOG4105CFH. Bacteria.
COG0460. LUCA.
COG0527. LUCA.
HOGENOMiHOG000271594.
InParanoidiP00562.
KOiK12525.
OMAiTLQYPEF.
PhylomeDBiP00562.

Enzyme and pathway databases

UniPathwayiUPA00034; UER00015.
UPA00050; UER00063.
UPA00050; UER00461.
UPA00051; UER00462.
UPA00051; UER00465.
BioCyciEcoCyc:ASPKINIIHOMOSERDEHYDROGII-MONOMER.
ECOL316407:JW3911-MONOMER.
MetaCyc:ASPKINIIHOMOSERDEHYDROGII-MONOMER.

Miscellaneous databases

PROiP00562.

Family and domain databases

Gene3Di3.40.1160.10. 2 hits.
3.40.50.720. 1 hit.
InterProiIPR001048. Asp/Glu/Uridylate_kinase.
IPR005106. Asp/hSer_DH_NAD-bd.
IPR001341. Asp_kinase_dom.
IPR018042. Aspartate_kinase_CS.
IPR011147. Bifunc_aspartokin/hSer_DH.
IPR001342. HDH_cat.
IPR019811. HDH_CS.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF00696. AA_kinase. 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.
PROSITEiPS00324. ASPARTOKINASE. 1 hit.
PS01042. HOMOSER_DHGENASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAK2H_ECOLI
AccessioniPrimary (citable) accession number: P00562
Secondary accession number(s): P77856, Q2M8N6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 152 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

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.