AK1H_ECOLI
ID AK1H_ECOLI Reviewed; 820 AA.
AC P00561; Q47659; Q6LEL0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 29-AUG-2003, sequence version 2.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Bifunctional aspartokinase/homoserine dehydrogenase 1;
DE AltName: Full=Aspartokinase I/homoserine dehydrogenase I;
DE Short=AKI-HDI;
DE Includes:
DE RecName: Full=Aspartokinase;
DE EC=2.7.2.4;
DE Includes:
DE RecName: Full=Homoserine dehydrogenase;
DE EC=1.1.1.3;
GN Name=thrA; Synonyms=thrA1, thrA2; OrderedLocusNames=b0002, JW0001;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7003595; DOI=10.1073/pnas.77.10.5730;
RA Katinka M., Cossart P., Sibilli L., Saint-Girons I., Chalvignac M.A.,
RA le Bras G., Cohen G.N., Yaniv M.;
RT "Nucleotide sequence of the thrA gene of Escherichia coli.";
RL Proc. Natl. Acad. Sci. U.S.A. 77:5730-5733(1980).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=1630901; DOI=10.1093/nar/20.13.3305;
RA Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K.,
RA Mizobuchi K., Nakata A.;
RT "Systematic sequencing of the Escherichia coli genome: analysis of the 0-
RT 2.4 min region.";
RL Nucleic Acids Res. 20:3305-3308(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=7610040; DOI=10.1093/nar/23.12.2105;
RA Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L., Blattner F.R.;
RT "Analysis of the Escherichia coli genome VI: DNA sequence of the region
RT from 92.8 through 100 minutes.";
RL Nucleic Acids Res. 23:2105-2119(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND SEQUENCE REVISION.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-10.
RX PubMed=6277952; DOI=10.1016/s0021-9258(18)34867-1;
RA Gardner J.F.;
RT "Initiation, pausing, and termination of transcription in the threonine
RT operon regulatory region of Escherichia coli.";
RL J. Biol. Chem. 257:3896-3904(1982).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-10.
RX PubMed=2410621; DOI=10.1016/0022-2836(85)90169-x;
RA Lynn S.P., Bauer C.E., Chapman K.A., Gardner J.F.;
RT "Identification and characterization of mutants affecting transcription
RT termination at the threonine operon attenuator.";
RL J. Mol. Biol. 183:529-541(1985).
RN [8]
RP PROTEIN SEQUENCE OF 51-129.
RX PubMed=387092; DOI=10.1016/s0300-9084(79)80174-1;
RA Sibilli L., le Bras G., Cossart P., Chalvignac M.A., le Bras G.,
RA Briley P.A., Cohen G.N.;
RT "The primary structure of Escherichia coli K 12 aspartokinase I-homoserine
RT dehydrogenase I: sequence of cyanogen bromide peptide CB 3.";
RL Biochimie 61:733-739(1979).
RN [9]
RP SEQUENCE REVISION TO 11.
RX PubMed=6298218; DOI=10.1016/s0021-9258(18)32824-2;
RA Zakin M.M., Duchange N., Ferrara P., Cohen G.N.;
RT "Nucleotide sequence of the metL gene of Escherichia coli. Its product, the
RT bifunctional aspartokinase II-homoserine dehydrogenase II, and the
RT bifunctional product of the thrA gene, aspartokinase I-homoserine
RT dehydrogenase I, derive from a common ancestor.";
RL J. Biol. Chem. 258:3028-3031(1983).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 553-588.
RX PubMed=390305; DOI=10.1007/bf00267853;
RA Cossart P., Katinka M., Yaniv M.;
RT "Construction and expression of a hybrid plasmid containing the Escherichia
RT coli thrA and thrB genes.";
RL Mol. Gen. Genet. 175:39-44(1979).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-homoserine + NADP(+) = H(+) + L-aspartate 4-semialdehyde +
CC NADPH; Xref=Rhea:RHEA:15761, ChEBI:CHEBI:15378, ChEBI:CHEBI:57476,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:537519; EC=1.1.1.3;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-homoserine + NAD(+) = H(+) + L-aspartate 4-semialdehyde +
CC NADH; Xref=Rhea:RHEA:15757, ChEBI:CHEBI:15378, ChEBI:CHEBI:57476,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:537519; EC=1.1.1.3;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-aspartate = 4-phospho-L-aspartate + ADP;
CC Xref=Rhea:RHEA:23776, ChEBI:CHEBI:29991, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:57535, ChEBI:CHEBI:456216; EC=2.7.2.4;
CC -!- ACTIVITY REGULATION: The enzyme activities are regulated allosterically
CC by L-threonine.
CC -!- PATHWAY: Amino-acid biosynthesis; L-lysine biosynthesis via DAP
CC pathway; (S)-tetrahydrodipicolinate from L-aspartate: step 1/4.
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-homoserine from L-aspartate: step 1/3.
CC -!- PATHWAY: Amino-acid biosynthesis; L-methionine biosynthesis via de novo
CC pathway; L-homoserine from L-aspartate: step 3/3.
CC -!- PATHWAY: Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine
CC from L-aspartate: step 1/5.
CC -!- PATHWAY: Amino-acid biosynthesis; L-threonine biosynthesis; L-threonine
CC from L-aspartate: step 3/5.
CC -!- SUBUNIT: Homotetramer.
CC -!- MISCELLANEOUS: Aspartokinase II-homoserine dehydrogenase II and
CC aspartokinase III also catalyze the same reaction(s).
CC -!- SIMILARITY: In the N-terminal section; belongs to the aspartokinase
CC family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the homoserine
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; V00361; CAA23660.1; -; Genomic_DNA.
DR EMBL; J01706; AAA83914.1; -; Genomic_DNA.
DR EMBL; U14003; AAA97301.1; -; Genomic_DNA.
DR EMBL; U00096; AAC73113.1; -; Genomic_DNA.
DR EMBL; AP009048; BAB96579.2; -; Genomic_DNA.
DR EMBL; V00360; CAA23659.1; -; Genomic_DNA.
DR EMBL; X68872; CAA48734.1; -; Genomic_DNA.
DR EMBL; M28570; AAA24673.1; -; Genomic_DNA.
DR EMBL; M10644; AAA24671.1; -; Genomic_DNA.
DR PIR; B64720; DEECK.
DR RefSeq; NP_414543.1; NC_000913.3.
DR RefSeq; WP_001264707.1; NZ_LN832404.1.
DR PDB; 6MX1; X-ray; 1.67 A; A/B=301-460.
DR PDBsum; 6MX1; -.
DR AlphaFoldDB; P00561; -.
DR SMR; P00561; -.
DR BioGRID; 4261933; 242.
DR DIP; DIP-2907N; -.
DR IntAct; P00561; 7.
DR STRING; 511145.b0002; -.
DR BindingDB; P00561; -.
DR jPOST; P00561; -.
DR PaxDb; P00561; -.
DR PRIDE; P00561; -.
DR EnsemblBacteria; AAC73113; AAC73113; b0002.
DR EnsemblBacteria; BAB96579; BAB96579; BAB96579.
DR GeneID; 945803; -.
DR KEGG; ecj:JW0001; -.
DR KEGG; eco:b0002; -.
DR PATRIC; fig|1411691.4.peg.2281; -.
DR EchoBASE; EB0991; -.
DR eggNOG; COG0460; Bacteria.
DR eggNOG; COG0527; Bacteria.
DR HOGENOM; CLU_009116_7_1_6; -.
DR InParanoid; P00561; -.
DR OMA; CNKIACS; -.
DR PhylomeDB; P00561; -.
DR BioCyc; EcoCyc:ASPKINIHOMOSERDEHYDROGI-MON; -.
DR BioCyc; MetaCyc:ASPKINIHOMOSERDEHYDROGI-MON; -.
DR BRENDA; 1.1.1.3; 2026.
DR BRENDA; 2.7.2.4; 2026.
DR SABIO-RK; P00561; -.
DR UniPathway; UPA00034; UER00015.
DR UniPathway; UPA00050; UER00063.
DR UniPathway; UPA00050; UER00461.
DR UniPathway; UPA00051; UER00462.
DR UniPathway; UPA00051; UER00465.
DR PRO; PR:P00561; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0004072; F:aspartate kinase activity; IDA:EcoCyc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004412; F:homoserine dehydrogenase activity; IDA:EcoCyc.
DR GO; GO:0042802; F:identical protein binding; IDA:EcoCyc.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0009090; P:homoserine biosynthetic process; IDA:EcoCyc.
DR GO; GO:0009089; P:lysine biosynthetic process via diaminopimelate; IDA:EcoCyc.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0051289; P:protein homotetramerization; IDA:EcoCyc.
DR GO; GO:0009088; P:threonine biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd04257; AAK_AK-HSDH; 1.
DR Gene3D; 3.40.1160.10; -; 1.
DR InterPro; IPR036393; AceGlu_kinase-like_sf.
DR InterPro; IPR045865; ACT-like_dom_sf.
DR InterPro; IPR002912; ACT_dom.
DR InterPro; IPR041743; AK-HSDH_N.
DR InterPro; IPR001048; Asp/Glu/Uridylate_kinase.
DR InterPro; IPR005106; Asp/hSer_DH_NAD-bd.
DR InterPro; IPR001341; Asp_kinase.
DR InterPro; IPR018042; Aspartate_kinase_CS.
DR InterPro; IPR011147; Bifunc_aspartokin/hSer_DH.
DR InterPro; IPR027795; CASTOR_ACT_dom.
DR InterPro; IPR001342; HDH_cat.
DR InterPro; IPR019811; HDH_CS.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR43070; PTHR43070; 1.
DR Pfam; PF00696; AA_kinase; 1.
DR Pfam; PF01842; ACT; 1.
DR Pfam; PF13840; ACT_7; 1.
DR Pfam; PF00742; Homoserine_dh; 1.
DR Pfam; PF03447; NAD_binding_3; 1.
DR PIRSF; PIRSF000727; ThrA; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53633; SSF53633; 1.
DR SUPFAM; SSF55021; SSF55021; 2.
DR TIGRFAMs; TIGR00657; asp_kinases; 1.
DR PROSITE; PS51671; ACT; 2.
DR PROSITE; PS00324; ASPARTOKINASE; 1.
DR PROSITE; PS01042; HOMOSER_DHGENASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Amino-acid biosynthesis; ATP-binding;
KW Direct protein sequencing; Kinase; Multifunctional enzyme; NADP;
KW Nucleotide-binding; Oxidoreductase; Reference proteome; Repeat;
KW Threonine biosynthesis; Transferase.
FT CHAIN 1..820
FT /note="Bifunctional aspartokinase/homoserine dehydrogenase
FT 1"
FT /id="PRO_0000066681"
FT DOMAIN 320..394
FT /note="ACT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT DOMAIN 401..478
FT /note="ACT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT REGION 1..249
FT /note="Aspartokinase"
FT REGION 250..470
FT /note="Interface"
FT REGION 471..820
FT /note="Homoserine dehydrogenase"
FT BINDING 471..478
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255"
FT CONFLICT 11
FT /note="V -> L (in Ref. 1; CAA23660/AAA83914)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="Q -> E (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="D -> N (in Ref. 1; CAA23660/AAA83914)"
FT /evidence="ECO:0000305"
FT CONFLICT 375
FT /note="Q -> L (in Ref. 1; CAA23660/AAA83914)"
FT /evidence="ECO:0000305"
FT CONFLICT 393
FT /note="T -> A (in Ref. 1; CAA23660/AAA83914)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="M -> L (in Ref. 1; CAA23660/AAA83914)"
FT /evidence="ECO:0000305"
FT CONFLICT 553
FT /note="D -> N (in Ref. 1; CAA23660/AAA83914)"
FT /evidence="ECO:0000305"
FT CONFLICT 587..588
FT /note="DY -> IT (in Ref. 10; AAA24671)"
FT /evidence="ECO:0000305"
FT CONFLICT 607
FT /note="T -> I (in Ref. 1; CAA23660/AAA83914)"
FT /evidence="ECO:0000305"
FT CONFLICT 658
FT /note="T -> R (in Ref. 1; CAA23660/AAA83914)"
FT /evidence="ECO:0000305"
FT STRAND 306..320
FT /evidence="ECO:0007829|PDB:6MX1"
FT TURN 325..327
FT /evidence="ECO:0007829|PDB:6MX1"
FT HELIX 331..341
FT /evidence="ECO:0007829|PDB:6MX1"
FT STRAND 348..353
FT /evidence="ECO:0007829|PDB:6MX1"
FT STRAND 358..363
FT /evidence="ECO:0007829|PDB:6MX1"
FT HELIX 364..366
FT /evidence="ECO:0007829|PDB:6MX1"
FT HELIX 367..377
FT /evidence="ECO:0007829|PDB:6MX1"
FT HELIX 379..383
FT /evidence="ECO:0007829|PDB:6MX1"
FT STRAND 391..406
FT /evidence="ECO:0007829|PDB:6MX1"
FT HELIX 409..422
FT /evidence="ECO:0007829|PDB:6MX1"
FT STRAND 429..432
FT /evidence="ECO:0007829|PDB:6MX1"
FT STRAND 434..444
FT /evidence="ECO:0007829|PDB:6MX1"
FT HELIX 445..447
FT /evidence="ECO:0007829|PDB:6MX1"
FT HELIX 448..459
FT /evidence="ECO:0007829|PDB:6MX1"
SQ SEQUENCE 820 AA; 89120 MW; 0BF28E9EECAB10ED CRC64;
MRVLKFGGTS VANAERFLRV ADILESNARQ GQVATVLSAP AKITNHLVAM IEKTISGQDA
LPNISDAERI FAELLTGLAA AQPGFPLAQL KTFVDQEFAQ IKHVLHGISL LGQCPDSINA
ALICRGEKMS IAIMAGVLEA RGHNVTVIDP VEKLLAVGHY LESTVDIAES TRRIAASRIP
ADHMVLMAGF TAGNEKGELV VLGRNGSDYS AAVLAACLRA DCCEIWTDVD GVYTCDPRQV
PDARLLKSMS YQEAMELSYF GAKVLHPRTI TPIAQFQIPC LIKNTGNPQA PGTLIGASRD
EDELPVKGIS NLNNMAMFSV SGPGMKGMVG MAARVFAAMS RARISVVLIT QSSSEYSISF
CVPQSDCVRA ERAMQEEFYL ELKEGLLEPL AVTERLAIIS VVGDGMRTLR GISAKFFAAL
ARANINIVAI AQGSSERSIS VVVNNDDATT GVRVTHQMLF NTDQVIEVFV IGVGGVGGAL
LEQLKRQQSW LKNKHIDLRV CGVANSKALL TNVHGLNLEN WQEELAQAKE PFNLGRLIRL
VKEYHLLNPV IVDCTSSQAV ADQYADFLRE GFHVVTPNKK ANTSSMDYYH QLRYAAEKSR
RKFLYDTNVG AGLPVIENLQ NLLNAGDELM KFSGILSGSL SYIFGKLDEG MSFSEATTLA
REMGYTEPDP RDDLSGMDVA RKLLILARET GRELELADIE IEPVLPAEFN AEGDVAAFMA
NLSQLDDLFA ARVAKARDEG KVLRYVGNID EDGVCRVKIA EVDGNDPLFK VKNGENALAF
YSHYYQPLPL VLRGYGAGND VTAAGVFADL LRTLSWKLGV
