Reviewed, UniProtKB/Swiss-Prot P00562 (AK2H_ECOLI)

Names and origin

Protein names

Recommended name:
    Bifunctional aspartokinase/homoserine dehydrogenase 2
Alternative name(s):
    Aspartokinase II/homoserine dehydrogenase II
      Short name=AKII-HDII
Including the following 2 domains:
    1- Recommended name:
            Aspartokinase
              EC=2.7.2.4
    2- Recommended name:
            Homoserine dehydrogenase
              EC=1.1.1.3

Gene names

Name:	metL
Synonyms:	metM
Ordered Locus Names:	b3940, JW3911

Organism

Escherichia coli (strain K12) [Complete proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia

Protein attributes

Sequence length	810 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	L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H. ATP + L-aspartate = ADP + 4-phospho-L-aspartate.
Pathway	Amino-acid biosynthesis; L-lysine biosynthesis via DAP pathway; tetrahydrodipicolinate from L-aspartate: step 1/4. Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-homoserine from L-aspartate: step 1/3. Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-homoserine from L-aspartate: step 3/3. Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine from L-aspartate: step 1/5. Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine from L-aspartate: step 3/5.
Subunit structure	Homotetramer.
Miscellaneous	Aspartokinase I-homoserine dehydrogenase I and aspartokinase III also catalyze the same reaction(s).
Sequence similarities	In the N-terminal section; belongs to the aspartokinase family. In the C-terminal section; belongs to the homoserine dehydrogenase family.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Methionine biosynthesis
Ligand	ATP-binding NADP Nucleotide-binding
Molecular function	Kinase Oxidoreductase Transferase
Technical term	Complete proteome Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological process	methionine biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW NADP or NADPH binding Inferred from electronic annotation. Source: InterPro aspartate kinase activity Inferred from electronic annotation. Source: EC homoserine dehydrogenase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.1
	Chain	2 – 810	809	Bifunctional aspartokinase/homoserine dehydrogenase 2		PRO_0000066683
Regions
	Nucleotide binding	464 – 471	8	NADP Potential
	Region	2 – 252	251	Aspartokinase
	Region	253 – 463	211	Interface
	Region	464 – 810	347	Homoserine dehydrogenase
Experimental info
	Sequence conflict	56	1	Q → R in CAA23585. Ref.1
	Sequence conflict	59	1	N → S in CAA23585. Ref.1
	Sequence conflict	333	1	A → G in CAA23585. Ref.1
	Sequence conflict	674	1	M → S in CAA23585. Ref.1
	Sequence conflict	762	1	A → R in CAA23585. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P00562-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: BD2515E3554F9B44	FASTA	810	88,888
	10 20 30 40 50 60 MSVIAQAGAK GRQLHKFGGS SLADVKCYLR VAGIMAEYSQ PDDMMVVSAA GSTTNQLINW 70 80 90 100 110 120 LKLSQTDRLS AHQVQQTLRR YQCDLISGLL PAEEADSLIS AFVSDLERLA ALLDSGINDA 130 140 150 160 170 180 VYAEVVGHGE VWSARLMSAV LNQQGLPAAW LDAREFLRAE RAAQPQVDEG LSYPLLQQLL 190 200 210 220 230 240 VQHPGKRLVV TGFISRNNAG ETVLLGRNGS DYSATQIGAL AGVSRVTIWS DVAGVYSADP 250 260 270 280 290 300 RKVKDACLLP LLRLDEASEL ARLAAPVLHA RTLQPVSGSE IDLQLRCSYT PDQGSTRIER 310 320 330 340 350 360 VLASGTGARI VTSHDDVCLI EFQVPASQDF KLAHKEIDQI LKRAQVRPLA VGVHNDRQLL 370 380 390 400 410 420 QFCYTSEVAD SALKILDEAG LPGELRLRQG LALVAMVGAG VTRNPLHCHR FWQQLKGQPV 430 440 450 460 470 480 EFTWQSDDGI SLVAVLRTGP TESLIQGLHQ SVFRAEKRIG LVLFGKGNIG SRWLELFARE 490 500 510 520 530 540 QSTLSARTGF EFVLAGVVDS RRSLLSYDGL DASRALAFFN DEAVEQDEES LFLWMRAHPY 550 560 570 580 590 600 DDLVVLDVTA SQQLADQYLD FASHGFHVIS ANKLAGASDS NKYRQIHDAF EKTGRHWLYN 610 620 630 640 650 660 ATVGAGLPIN HTVRDLIDSG DTILSISGIF SGTLSWLFLQ FDGSVPFTEL VDQAWQQGLT 670 680 690 700 710 720 EPDPRDDLSG KDVMRKLVIL AREAGYNIEP DQVRVESLVP AHCEGGSIDH FFENGDELNE 730 740 750 760 770 780 QMVQRLEAAR EMGLVLRYVA RFDANGKARV GVEAVREDHP LASLLPCDNV FAIESRWYRD 790 800 810 NPLVIRGPGA GRDVTAGAIQ SDINRLAQLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 6298218] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-10.
[2]	"Analysis of the Escherichia coli genome. III. DNA sequence of the region from 87.2 to 89.2 minutes." Plunkett G. III, Burland V., Daniels D.L., Blattner F.R. Nucleic Acids Res. 21:3391-3398(1993) [PubMed: 8346018] [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.

Cross-references

Sequence databases
EMBLGenBankDDBJ	V00305 Genomic DNA. Translation: CAA23585.1. L19201 Genomic DNA. Translation: AAB03072.1. U00096 Genomic DNA. Translation: AAC76922.1. AP009048 Genomic DNA. Translation: BAE77370.1.
PIR	DEECK2. S40883.
RefSeq	AP_003869.1. NP_418375.1.
3D structure databases
HSSP	HSSP built from PDB template 1EBF based on UniProtKB P31116.
ModBase	Search...
Genome annotation databases
GeneID	948433.
GenomeReviews	Gene locus JW3911 in contig AP009048_GR. Gene locus b3940 in contig U00096_GR.
KEGG	ecj:JW3911. eco:b3940.
Organism-specific databases
EchoBASE	EB0585.
EcoGene	EG10590. metL.
CMR	Search...
Phylogenomic databases
HOGENOM	P00562.
OMA	P00562. GRDMQRK.
Enzyme and pathway databases
BioCyc	EcoCyc:ASPKINIIHOMOSERDEHYDROGII-MON. MetaCyc:ASPKINIIHOMOSERDEHYDROGII-MON.
Family and domain databases
InterPro	IPR001048. Asp/Glu/Uridylate_kinase. IPR005106. Asp/hSer_DH_NAD-bd. IPR001341. Asp_kin_reg. IPR018042. Aspartate_kinase_CS. IPR011147. bifunc_aspartokin/hSer_DH. IPR001342. Homoserine_dehydrogenase_cat. IPR019811. Homoserine_dehydrogenase_CS. IPR016040. NAD(P)-bd_dom. [Graphical view]
Gene3D	G3DSA:3.40.1160.10. Aa_kinase. 1 hit. G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
Pfam	PF00696. AA_kinase. 1 hit. PF00742. Homoserine_dh. 1 hit. PF03447. NAD_binding_3. 1 hit. [Graphical view]
PIRSF	PIRSF000727. ThrA. 1 hit.
TIGRFAMs	TIGR00657. asp_kinases. 1 hit.
PROSITE	PS00324. ASPARTOKINASE. 1 hit. PS01042. HOMOSER_DHGENASE. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

AK2H_ECOLI

Accession

Primary (citable) accession number: P00562
Secondary accession number(s): P77856, Q2M8N6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 96 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)