L-threonine biosynthesis from L-aspartate

L-threonine synthesis from L-aspartate through five successive transformations, represented by bacterial, fungal and plant enzymes and by two experimentally characterized archaeal steps. Aspartate kinase forms 4-phospho-L-aspartate; NADPH-dependent aspartate-semialdehyde dehydrogenase produces L-aspartate 4-semialdehyde; homoserine dehydrogenase produces L-homoserine; homoserine phosphorylation supplies O-phospho-L-homoserine; and PLP-dependent threonine synthase forms L-threonine. Homoserine phosphorylation can use ATP through a GHMP kinase or phosphoserine through the distinct Pseudomonas ThrH phosphotransferase, which releases serine. In the represented yeasts and E. coli, homoserine is shared with methionine synthesis; in plants the shared intermediate is O-phosphohomoserine, so homoserine kinase does not commit flux exclusively to threonine. Aspartate kinase and homoserine dehydrogenase may be separate proteins or domains of an AK-HSDH fusion. Cofactor preference, feedback sensitivity and oligomeric state are enzyme-specific. Arabidopsis TS1 is activated by S-adenosylmethionine, an allosteric effector rather than a consumed substrate. The aspartate-semialdehyde branch can supply diaminopimelate-pathway lysine synthesis in plants and many prokaryotes; the represented fungi instead use the alpha-aminoadipate lysine pathway. This is a reusable reaction module, not a claim that every member of any named taxon has a complete pathway.

MODULE:aspartate_family_threonine_biosynthesisDRAFTMetabolic Pathwaymodules/aspartate_family_threonine_biosynthesis.yaml
L-threonine biosynthetic processGO:0009088
YeastPathways:HOMOSERSYN-PWY
L-homoserine biosynthesis (S. cerevisiae, SGD YeastPathways)
Source pathway for the trunk: ASPARTATEKIN-RXN (HOM3), ASPARTATE-SEMIALDEHYDE-DEHYDROGENASE-RXN (HOM2) and HOMOSERDEHYDROG-RXN (HOM6). All three gene assignments were retained.
YeastPathways:HOMOSER-THRESYN-PWY
L-threonine biosynthesis (S. cerevisiae, SGD YeastPathways)
Source pathway for the threonine branch: HOMOSERKIN-RXN (THR1) and THRESYN-RXN (THR4). Both assignments were retained.
YeastPathways:THRESYN-PWY
superpathway of L-threonine biosynthesis (S. cerevisiae, SGD YeastPathways)
Superpathway of the five module reactions plus aspartate aminotransferase (AAT1, AAT2), which supplies aspartate and is kept outside this module.
YeastPathways:PWY3O-7
superpathway of threonine biosynthesis (S. cerevisiae, SGD YeastPathways)
Superpathway from oxaloacetate: adds pyruvate carboxylase (PYC1, PYC2) and aspartate aminotransferase (AAT1, AAT2) upstream of the five module reactions. Those supply reactions are kept outside this module.
YeastPathways:P4-PWY-1
superpathway of threonine and methionine biosynthesis (S. cerevisiae, SGD YeastPathways)
Combined threonine and methionine superpathway. Its trunk and threonine reactions are modelled here; the MET2, MET17, MET6 and MET7 reactions belong to methionine_biosynthesis, and AAT1/AAT2 to aspartate supply.
GO:0009088
L-threonine biosynthetic process
Module-level biological process.
GO:0009090
L-homoserine biosynthetic process
Biological process of the aspartate-to-homoserine trunk submodule.
PMID:11352712
The central enzymes of the aspartate family of amino acid biosynthesis.
Review of aspartate kinase, aspartate-semialdehyde dehydrogenase and homoserine dehydrogenase across plants and microorganisms, including their structures and bifunctional fusions.
The aspartate pathway is responsible for the biosynthesis of lysine, threonine, isoleucine, and methionine in most plants and microorganisms.
PMID:2892836
Structure of the yeast HOM3 gene which encodes aspartokinase.
HOM3 is the single-copy structural gene for S. cerevisiae aspartate kinase; hom3 mutants require threonine and methionine and lack aspartokinase activity.
Mutations in HOM3 result in a requirement for threonine and methionine (or homoserine) for growth and a lack of detectable aspartokinase activity.
PMID:6821505
Genetic and biochemical study of threonine-overproducing mutants of Saccharomyces cerevisiae.
Yeast aspartokinase is feedback-inhibited by threonine; loss of this inhibition causes threonine overproduction.
The gene HOM3 codes for aspartokinase (aspartate kinase; EC 2.7.2.4), the first enzyme of the threonine-methionine biosynthetic route, which is subjected to feedback inhibition by threonine.
PMID:1847111
Inhibition by different amino acids of the aspartate kinase and the homoserine kinase of the yeast Saccharomyces cerevisiae.
Of the amino acids tested, only threonine effectively inhibits both yeast aspartate kinase and homoserine kinase.
PMID:2570346
Structure of the HOM2 gene of Saccharomyces cerevisiae and regulation of its expression.
HOM2 encodes S. cerevisiae aspartate-semialdehyde dehydrogenase.
In Saccharomyces cerevisiae the HOM2 gene encodes aspartic semi-aldehyde dehydrogenase (ASA DH).
PMID:11341914
Characterization of yeast homoserine dehydrogenase, an antifungal target: the invariant histidine 309 is important for enzyme integrity.
Purified recombinant S. cerevisiae homoserine dehydrogenase (Hom6) reduces aspartate semialdehyde to homoserine with NADH or NADPH.
HSD efficiently reduces aspartate semialdehyde to homoserine (Hse) using either NADH or NADPH
PMID:2176637
Saccharomyces cerevisiae homoserine kinase is homologous to prokaryotic homoserine kinases.
THR1 encodes yeast homoserine kinase; disruption causes threonine auxotrophy and the protein is homologous to bacterial ThrB.
Disruption of the THR1 gene results in threonine auxotrophy in yeast.
PMID:8082795
Biochemical evidence that the Saccharomyces cerevisiae THR4 gene encodes threonine synthetase.
Threonine synthase activity, measured as threonine formed from O-phosphohomoserine, depends on a functional THR4 gene.
PMID:8204822
Molecular analysis of the aspartate kinase-homoserine dehydrogenase gene from Arabidopsis thaliana.
The Arabidopsis bifunctional AK-HSDH is homologous to the E. coli thrA and metL bifunctional enzymes and carries a chloroplast-targeting sequence.
The A. thaliana ak-hsdh gene is proposed to be the plant thrA homologue coding for the AK isozyme feedback inhibited by threonine.
PMID:12602885
Transcriptional and biochemical regulation of a novel Arabidopsis thaliana bifunctional aspartate kinase-homoserine dehydrogenase gene isolated by functional complementation of a yeast hom6 mutant.
Arabidopsis AKHSDH2 (akthr2, At4g19710), not AKHSDH1, complements yeast hom6 and hom3 mutants and supplies both activities.
PMID:9748328
Allosteric activation of Arabidopsis threonine synthase by S-adenosylmethionine.
Plant threonine synthase, unlike its bacterial counterpart, is strongly activated by S-adenosylmethionine.
Plant threonine synthase, in contrast to its bacterial counterpart, is strongly stimulated by S-adenosylmethionine via a noncovalent interaction
PMID:9636232
The specific features of methionine biosynthesis and metabolism in plants.
In plant chloroplasts O-phosphohomoserine is the branch point between threonine synthase and cystathionine gamma-synthase.
OPH is therefore a branch point intermediate for methionine and threonine syntheses in plants
PMID:10220164
ThrH, a homoserine kinase isozyme with in vivo phosphoserine phosphatase activity in Pseudomonas aeruginosa.
Native P. aeruginosa thrB/thrH double disruption produces threonine auxotrophy. This establishes substitution in vivo; the later biochemical study PMID:14699121 identifies the phosphate donor and distinguishes ThrH from an ATP kinase.
In P. aeruginosa, threonine auxotrophy is observed only when both thrB and thrH are simultaneously inactivated.
PMID:1789001
Four major transcriptional responses in the methionine/threonine biosynthetic pathway of Saccharomyces cerevisiae.
HOM3, HOM2 and THR1 are under general amino acid control; cited by YeastPathways for HOMOSERSYN-PWY.
PMID:17012784
The initial step in the archaeal aspartate biosynthetic pathway catalyzed by a monofunctional aspartokinase.
Direct MJ0571 biochemistry establishes archaeal ATP-dependent aspartate phosphorylation and threonine-sensitive regulation, not a complete archaeal pathway.
mj AK catalyzes phosphoryl transfer to l -aspartate at 310 K with a turnover of 12 s −1 .
PMID:11812229
Overproduction, purification, and characterization of recombinant aspartate semialdehyde dehydrogenase from Arabidopsis thaliana.
Recombinant Arabidopsis ASAD consumes NADPH and aspartyl phosphate. The locus At1g14810 is linked to this primary study by PMID:22303247; the primary abstract itself does not give the locus.
The plant enzyme exhibited a specific activity of 26 micromol NADPH oxidized min(-1) mg(-1) of protein with a K(M) value for NADPH of 92 microM.
PMID:16216875
Identification of six novel allosteric effectors of Arabidopsis thaliana aspartate kinase-homoserine dehydrogenase isoforms. Physiological context sets the specificity.
Both Arabidopsis AKHSDH isoforms were assayed directly. Their kinase and dehydrogenase activities implement the first and third reactions; their regulation differs.
These two activities catalyze the first and the third steps toward the synthesis of the essential amino acids threonine, isoleucine, and methionine.
PMID:10562426
Identification of the gene encoding homoserine kinase from Arabidopsis thaliana and characterization of the recombinant enzyme derived from the gene.
Arabidopsis HSK uses MgATP and supplies the shared plant methionine/threonine intermediate. The primary identifies a chromosome II locus, consistent with At2g17265 rather than the erroneous chromosome IV locus in PMID:22303247.
Homoserine kinase (EC 2.7.1.39) catalyzes the formation of O-phospho-l-homoserine, a branch point intermediate in the pathways for Met and Thr in plants.
PMID:14699121
The thrH gene product of Pseudomonas aeruginosa is a dual activity enzyme with a novel phosphoserine:homoserine phosphotransferase activity.
Direct HPLC assay distinguishes phosphoserine-to-homoserine phosphoryl transfer from ATP-dependent kinase activity.
ThrH is able to further transfer the phosphoryl group to homoserine using phosphoserine as the phosphoryl group donor, indicating that ThrH has a novel phosphoserine:homoserine phosphotransferase activity.
PMID:10429206
Characterization of recombinant Arabidopsis thaliana threonine synthase.
Arabidopsis TS1 catalyzes the PLP-dependent terminal reaction; the same study compares its regulation and assembly with E. coli and yeast enzymes.
Threonine synthase (TS) catalyses the last step in the biosynthesis of threonine, the pyridoxal 5'-phosphate dependent conversion of L-homoserine phosphate (HSerP) into L-threonine and inorganic phosphate.
PMID:11535056
Structural basis for the catalysis and substrate specificity of homoserine kinase.
Direct substrate/ATP-analogue structures of archaeal ThrB support the GHMP kinase implementation.
The high-resolution structures of Methanococcus jannaschii HSK ternary complexes with its amino acid substrate and ATP analogues have been determined by X-ray crystallography.
PMID:29959064
Dihydrodipicolinate synthase is absent in fungi.
Functional testing of fungal DHDPS candidates and sequence comparison support the alpha-aminoadipate boundary; these experiments are in Coccidioides and Fonsecaea, not direct tests of the two yeast exemplars.
The candidate with the highest number of identities (6 of 7), KIW77228 from Fonsecaea pedrosoi, was shown to have trace DHDPS activity in vitro, partially restored by substitution of the seventh critical residue, and to be incapable of complementing DHDPS-deficient E. coli cells.
PMID:19946135
Cohesion group approach for evolutionary analysis of aspartokinase, an enzyme that feeds a branched network of many biochemical pathways.
Comparative review supports variable network branches and architecture/regulatory diversity across domains; its evolutionary scenarios are not treated as PAINT ancestral-node assertions.
ThrA is inhibited by threonine, LysC is inhibited by lysine, and the synthesis of MetL is repressed by methionine
PMID:22303247
Aspartate-Derived Amino Acid Biosynthesis in Arabidopsis thaliana.
Plant review maps the ASAD primary to At1g14810 and supports the phosphohomoserine branchpoint. Its HSK locus At4g35295 is incorrect for the verified target At2g17265; its AK-HSDH paragraph also says threonine dehydrogenase where the primary concerns homoserine dehydrogenase.
In vitro overproduction and analysis of the A. thaliana At1g14810 confirmed the predicted aspartate semialdehyde dehydrogenase activity
PMID:20019093
Recent progress in deciphering the biosynthesis of aspartate-derived amino acids in plants.
Review of plant regulation and metabolic context; only the abstract is available here and no detailed new mechanistic claim is assigned to it.
PMID:19622802
Downy mildew resistance in Arabidopsis by mutation of HOMOSERINE KINASE.
Direct map-based cloning and target sequencing establish Arabidopsis DMR1/HSK as At2g17265, correcting the HSK locus error in the comparative review PMID:22303247.
Single point mutations in the At2g17265 gene were identified by nucleotide sequencing of the dmr1-1 , dmr1-2 , dmr1-3 , and dmr1-4 mutants.
16Nodes
7Parts
4Variant Sets
8Variants
9Annotons
4Connections

Derived QC

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Module deep research

✗ none found

No MODULE:aspartate_family_threonine_biosynthesis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • homoserine_trunk → threonine_branch [NOT_CHECKED]
    Product-to-substrate continuity from the stated reactions. PRECEDES describes biosynthetic direction, not irreversible catalysis, a physical complex, or demonstrated substrate channeling.

Function consistency and core coverage

28 gene-function check(s) reflected in core functions · 0 conflict(s) · 2 evidence or coverage gap(s) (43 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
monofunctional_aspartate_kinase_activity HOM3 (Saccharomyces cerevisiae)
UniProtKB:P10869
Family Representative 		aspartate kinase activity
GO:0004072 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
monofunctional_aspartate_kinase_activity hom3 (Schizosaccharomyces pombe)
UniProtKB:O60163
Family Representative 		aspartate kinase activity
GO:0004072 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
monofunctional_aspartate_kinase_activity lysC (Escherichia coli K-12)
UniProtKB:P08660
Family Representative 		aspartate kinase activity
GO:0004072 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
monofunctional_aspartate_kinase_activity MJ0571 (Methanocaldococcus jannaschii)
UniProtKB:Q57991
Family Representative 		aspartate kinase activity
GO:0004072 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ak_hsdh_aspartate_kinase_activity thrA (Escherichia coli K-12)
UniProtKB:P00561
Family Representative 		aspartate kinase activity
GO:0004072 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ak_hsdh_aspartate_kinase_activity metL (Escherichia coli K-12)
UniProtKB:P00562
Family Representative 		aspartate kinase activity
GO:0004072 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ak_hsdh_aspartate_kinase_activity AKHSDH1 (Arabidopsis thaliana)
UniProtKB:Q9SA18
Family Representative 		aspartate kinase activity
GO:0004072 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ak_hsdh_aspartate_kinase_activity AKHSDH2 (Arabidopsis thaliana)
UniProtKB:O81852
Family Representative 		aspartate kinase activity
GO:0004072 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aspartate_semialdehyde_dehydrogenase_activity HOM2 (Saccharomyces cerevisiae)
UniProtKB:P13663
Family Representative 		aspartate-semialdehyde dehydrogenase (NADP+) activity
GO:0004073 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aspartate_semialdehyde_dehydrogenase_activity hom2 (Schizosaccharomyces pombe)
UniProtKB:P78780
Family Representative 		aspartate-semialdehyde dehydrogenase (NADP+) activity
GO:0004073 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aspartate_semialdehyde_dehydrogenase_activity asd (Escherichia coli K-12)
UniProtKB:P0A9Q9
Family Representative 		aspartate-semialdehyde dehydrogenase (NADP+) activity
GO:0004073 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
aspartate_semialdehyde_dehydrogenase_activity At1g14810 (Arabidopsis thaliana)
UniProtKB:Q8VYI4
Family Representative 		aspartate-semialdehyde dehydrogenase (NADP+) activity
GO:0004073 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
monofunctional_homoserine_dehydrogenase_activity HOM6 (Saccharomyces cerevisiae)
UniProtKB:P31116
Family Representative 		homoserine dehydrogenase activity
GO:0004412 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
monofunctional_homoserine_dehydrogenase_activity hom6 (Schizosaccharomyces pombe)
UniProtKB:O94671
Family Representative 		homoserine dehydrogenase activity
GO:0004412 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ak_hsdh_homoserine_dehydrogenase_activity thrA (Escherichia coli K-12)
UniProtKB:P00561
Family Representative 		homoserine dehydrogenase activity
GO:0004412 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ak_hsdh_homoserine_dehydrogenase_activity metL (Escherichia coli K-12)
UniProtKB:P00562
Family Representative 		homoserine dehydrogenase activity
GO:0004412 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ak_hsdh_homoserine_dehydrogenase_activity AKHSDH1 (Arabidopsis thaliana)
UniProtKB:Q9SA18
Family Representative 		homoserine dehydrogenase activity
GO:0004412 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ak_hsdh_homoserine_dehydrogenase_activity AKHSDH2 (Arabidopsis thaliana)
UniProtKB:O81852
Family Representative 		homoserine dehydrogenase activity
GO:0004412 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
homoserine_kinase_activity THR1 (Saccharomyces cerevisiae)
UniProtKB:P17423
Family Representative 		homoserine kinase activity
GO:0004413 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
homoserine_kinase_activity thr1 (Schizosaccharomyces pombe)
UniProtKB:O43056
Family Representative 		homoserine kinase activity
GO:0004413 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
homoserine_kinase_activity thrB (Escherichia coli K-12)
UniProtKB:P00547
Family Representative 		homoserine kinase activity
GO:0004413 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
homoserine_kinase_activity HSK/DMR1 (Arabidopsis thaliana)
UniProtKB:Q8L7R2
Family Representative 		homoserine kinase activity
GO:0004413 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
homoserine_kinase_activity thrB (Methanocaldococcus jannaschii)
UniProtKB:Q58504
Family Representative 		homoserine kinase activity
GO:0004413 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
phosphoserine_homoserine_phosphotransferase_activity thrH (Pseudomonas aeruginosa PAO1)
UniProtKB:Q9I2Y2
Family Representative 		phosphoserine:homoserine phosphotransferase activity
GO:0043899 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
thrc_type_threonine_synthase_activity THR4 (Saccharomyces cerevisiae)
UniProtKB:P16120
Family Representative 		threonine synthase activity
GO:0004795 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
thrc_type_threonine_synthase_activity SPAC9E9.06c (Schizosaccharomyces pombe)
UniProtKB:Q42598
Family Representative 		threonine synthase activity
GO:0004795 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
thrc_type_threonine_synthase_activity thrC (Escherichia coli K-12)
UniProtKB:P00934
Family Representative 		threonine synthase activity
GO:0004795 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
sam_activated_threonine_synthase_activity TS1/MTO2 (Arabidopsis thaliana)
UniProtKB:Q9S7B5
Family Representative 		threonine synthase activity
GO:0004795 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
monofunctional_aspartate_kinase_activity monofunctional aspartate kinases
PANTHER:PTHR21499:SF59
Family 		aspartate kinase activity
GO:0004072 		Family Supported
Family review supports GO:0004072 FAMILY_WIDE. The module's core activity for this family (monofunctional_aspartate_kinase_activity). PAINT IBD at PTN000487132 from yeast HOM3, E. coli LysC and MetL, B. subtilis YclM and M. tuberculosis Ask; reviewed recipients span every subfamily in the inventory. Yeast HOM3 mutants lack detectable aspartokinase activity and the purified enzyme has been characterised kinetically. The HOM3 gene review accepts the IBA; S. pombe hom3 is a stub. The one member annotated as inactive (H. influenzae HI_1632) is excepted.
ak_hsdh_aspartate_kinase_activity bifunctional aspartate kinase-homoserine dehydrogenases
PANTHER:PTHR43070:SF3
Family 		aspartate kinase activity
GO:0004072 		Family Supported
Family review supports GO:0004072 for PANTHER:PTHR43070:SF3. Architecture-determined. The bifunctional bacterial (SF3 ThrA) and plant (SF6-SF9, and AKHSDH2 in SF5) members carry the N-terminal aspartokinase domain (Pfam AA_kinase, InterPro Asp_kinase) and catalyse the reaction; the fungal monofunctional HDHs that share SF5 lack the domain and are listed as exceptions. PAINT asserts the activity within this family only at the gamma-proteobacterial ThrA node PTN001852279, which is correct; no fungal member receives it.
ak_hsdh_aspartate_kinase_activity bifunctional aspartate kinase-homoserine dehydrogenases
PANTHER:PTHR43070:SF5
Family 		aspartate kinase activity
GO:0004072 		Family Supported
Family review supports GO:0004072 for PANTHER:PTHR43070:SF5. Architecture-determined. The bifunctional bacterial (SF3 ThrA) and plant (SF6-SF9, and AKHSDH2 in SF5) members carry the N-terminal aspartokinase domain (Pfam AA_kinase, InterPro Asp_kinase) and catalyse the reaction; the fungal monofunctional HDHs that share SF5 lack the domain and are listed as exceptions. PAINT asserts the activity within this family only at the gamma-proteobacterial ThrA node PTN001852279, which is correct; no fungal member receives it.
ak_hsdh_aspartate_kinase_activity bifunctional aspartate kinase-homoserine dehydrogenases
PANTHER:PTHR43070:SF6
Family 		aspartate kinase activity
GO:0004072 		Family Supported
Family review supports GO:0004072 for PANTHER:PTHR43070:SF6. Architecture-determined. The bifunctional bacterial (SF3 ThrA) and plant (SF6-SF9, and AKHSDH2 in SF5) members carry the N-terminal aspartokinase domain (Pfam AA_kinase, InterPro Asp_kinase) and catalyse the reaction; the fungal monofunctional HDHs that share SF5 lack the domain and are listed as exceptions. PAINT asserts the activity within this family only at the gamma-proteobacterial ThrA node PTN001852279, which is correct; no fungal member receives it.
aspartate_semialdehyde_dehydrogenase_activity aspartate-semialdehyde dehydrogenases
PANTHER:PTHR46718:SF1
Family 		aspartate-semialdehyde dehydrogenase (NADP+) activity
GO:0004073 		Family Supported
Family review supports GO:0004073 FAMILY_WIDE. The module's activity for this family and a PAINT IBD at PTN002928538 (seeds S. cerevisiae HOM2, Candida, Aspergillus and Cryptococcus). The HOM2 gene review accepts the IBA; S. pombe hom2 is a stub. The malonyl-CoA reductases are excepted.
aspartate_semialdehyde_dehydrogenase_activity aspartate-semialdehyde dehydrogenases
PANTHER:PTHR46278:SF4
Family 		aspartate-semialdehyde dehydrogenase (NADP+) activity
GO:0004073 		Family Supported
Family review supports GO:0004073 FAMILY_WIDE. The module's activity (it uses SF4 for the enterobacterial enzyme) and a PAINT IBD at PTN000019341 with experimental seeds in both subfamilies, so the activity is ancestral to the family. The USG-1 paralogues are the one unverified group: they inherit the term but their activity has not been checked here; they are flagged in the node assessment rather than excepted, because no evidence of loss was found.
aspartate_semialdehyde_dehydrogenase_activity aspartate-semialdehyde dehydrogenases
PANTHER:PTHR46278:SF2
Family 		aspartate-semialdehyde dehydrogenase (NADP+) activity
GO:0004073 		Family Supported
Family review supports GO:0004073 FAMILY_WIDE. The module's activity (it uses SF4 for the enterobacterial enzyme) and a PAINT IBD at PTN000019341 with experimental seeds in both subfamilies, so the activity is ancestral to the family. The USG-1 paralogues are the one unverified group: they inherit the term but their activity has not been checked here; they are flagged in the node assessment rather than excepted, because no evidence of loss was found.
monofunctional_homoserine_dehydrogenase_activity monofunctional homoserine dehydrogenases
PANTHER:PTHR43070:SF5
Family 		homoserine dehydrogenase activity
GO:0004412 		Family Supported
Family review supports GO:0004412 FAMILY_WIDE. Defining activity of every architecture in the family. Asserted independently at the eukaryotic node PTN000487079 (seeds Arabidopsis AKHSDH1 and AKHSDH2 and yeast HOM6) and the gamma-proteobacterial ThrA node PTN001852279 (seed E. coli ThrA). Gene reviews accept it for ThrA, HOM6, S. pombe hom6 and both Arabidopsis enzymes.
ak_hsdh_homoserine_dehydrogenase_activity bifunctional aspartate kinase-homoserine dehydrogenases
PANTHER:PTHR43070:SF3
Family 		homoserine dehydrogenase activity
GO:0004412 		Family Supported
Family review supports GO:0004412 FAMILY_WIDE. Defining activity of every architecture in the family. Asserted independently at the eukaryotic node PTN000487079 (seeds Arabidopsis AKHSDH1 and AKHSDH2 and yeast HOM6) and the gamma-proteobacterial ThrA node PTN001852279 (seed E. coli ThrA). Gene reviews accept it for ThrA, HOM6, S. pombe hom6 and both Arabidopsis enzymes.
ak_hsdh_homoserine_dehydrogenase_activity bifunctional aspartate kinase-homoserine dehydrogenases
PANTHER:PTHR43070:SF5
Family 		homoserine dehydrogenase activity
GO:0004412 		Family Supported
Family review supports GO:0004412 FAMILY_WIDE. Defining activity of every architecture in the family. Asserted independently at the eukaryotic node PTN000487079 (seeds Arabidopsis AKHSDH1 and AKHSDH2 and yeast HOM6) and the gamma-proteobacterial ThrA node PTN001852279 (seed E. coli ThrA). Gene reviews accept it for ThrA, HOM6, S. pombe hom6 and both Arabidopsis enzymes.
ak_hsdh_homoserine_dehydrogenase_activity bifunctional aspartate kinase-homoserine dehydrogenases
PANTHER:PTHR43070:SF6
Family 		homoserine dehydrogenase activity
GO:0004412 		Family Supported
Family review supports GO:0004412 FAMILY_WIDE. Defining activity of every architecture in the family. Asserted independently at the eukaryotic node PTN000487079 (seeds Arabidopsis AKHSDH1 and AKHSDH2 and yeast HOM6) and the gamma-proteobacterial ThrA node PTN001852279 (seed E. coli ThrA). Gene reviews accept it for ThrA, HOM6, S. pombe hom6 and both Arabidopsis enzymes.
homoserine_kinase_activity GHMP-family homoserine kinases
PANTHER:PTHR20861:SF1
Family 		homoserine kinase activity
GO:0004413 		Family Supported
Family review supports GO:0004413 for PANTHER:PTHR20861:SF1. The module's activity for this family (homoserine_kinase_activity, SF1). Yeast THR1 was cloned by complementation, its disruption causes threonine auxotrophy, the purified enzyme was followed by homoserine kinase activity, and it is homologous to the bacterial ThrB enzymes in the same subfamily. Not safe for SF3 or SF6. The obo also lists subfamilies SF8 and SF9 named HOMOSERINE KINASE that have no reviewed members in the inventory; they were not examined. Within SF1 the Aeropyrum shikimate kinase is excepted.
phosphoserine_homoserine_phosphotransferase_activity ThrH phosphoserine:homoserine phosphotransferases
PANTHER:PTHR43344:SF2
Family 		phosphoserine:homoserine phosphotransferase activity
GO:0043899 		Family Function Unreviewed
Family review leaves GO:0043899 UNRESOLVED. Demonstrated only for P. aeruginosa ThrH (Q9I2Y2), which transfers the phosphoryl group of phosphoserine to homoserine and thereby complements thrB mutants. ThrH has no subfamily of its own: PANTHER places it in SF2 together with the canonical phosphoserine phosphatases (human PSPH, yeast SER2, E. coli SerB, S. pombe SPBC3H7.07c), for which the activity has not been reported and is not inferred; its discoverers called it novel. No PAINT node asserts it. The term therefore cannot be scoped to SF2 or to any other subfamily and is left as a member-level property of ThrH, as with amino acid kinase activity in PTHR21064.
thrc_type_threonine_synthase_activity ThrC-type threonine synthases
PANTHER:PTHR42690:SF1
Family 		threonine synthase activity
GO:0004795 		Family Supported
Family review supports GO:0004795 FAMILY_WIDE. Safe for the bacterial ThrC and fungal THR4 members, which make up most of the family and all of the members the aspartate-family threonine module uses (THR4, S. pombe thrc, E. coli thrC). Because PANTHER has one subfamily (SF1) for the whole family, scope cannot be set by subfamily. The vertebrate THNSL2 proteins are the exception: they belong to the same SF1 but do not make threonine, and PAINT already records the loss at PTN000816888.
sam_activated_threonine_synthase_activity plant-type threonine synthases
PANTHER:PTHR10314:SF5
Family 		threonine synthase activity
GO:0004795 		Family Function Unreviewed
The family review has no applicable adjudication supporting or excluding GO:0004795.

Gene-review completeness (24/24 grounded genes reviewed)

20 complete review(s) · 5 with deep research · 0 missing review · 19 reviewed but lacking deep research

Gene Review Complete Deep research
AKHSDH1 Q9SA18 ✓ 24/25 ✗
AKHSDH2 O81852 ✓ ✓ ✗
asd P0A9Q9 ✓ ✓ ✗
HOM2 P13663 ✓ 37/38 ✓
hom2 P78780 ✓ ✓ ✗
hom3 O60163 ✓ ✓ ✗
HOM3 P10869 ✓ ✓ ✓
hom6 O94671 ✓ ✓ ✗
HOM6 P31116 ✓ ✓ ✓
HSK Q8L7R2 ✓ ✓ ✗
lysC P08660 ✓ ✓ ✗
metL P00562 ✓ ✓ ✗
MJ0571 Q57991 ✓ ✓ ✗
Q8VYI4 Q8VYI4 ✓ 12/13 ✗
SPAC9E9.06c Q42598 ✓ ✓ ✗
thr1 O43056 ✓ ✓ ✗
THR1 P17423 ✓ ✓ ✓
THR4 P16120 ✓ ✓ ✓
thrA P00561 ✓ ✓ ✗
thrB P00547 ✓ ✓ ✗
thrB Q58504 ✓ ✓ ✗
thrC P00934 ✓ ✓ ✗
thrH Q9I2Y2 ✓ ✓ ✗
TS1 Q9S7B5 ✓ 14/15 ✗

Details

Context
BacteriaNCBITaxon:2 ArchaeaNCBITaxon:2157 FungiNCBITaxon:4751 ViridiplantaeNCBITaxon:33090

Taxonomic envelope of known pathway implementations and characterized steps, not universal presence. The Methanocaldococcus jannaschii panel establishes aspartate kinase and homoserine kinase individually; it is deliberately insufficient for a complete archaeal-route satisfiability claim. Compartments are implementation-specific: the represented yeast biosynthetic activities are cytosolic and the plant activities are plastid stromal.

L-threonine biosynthesis from L-aspartateMetabolic Pathwayaspartate_family_threonine_biosynthesis
L-threonine biosynthetic processGO:0009088
Context
BacteriaNCBITaxon:2 ArchaeaNCBITaxon:2157 FungiNCBITaxon:4751 ViridiplantaeNCBITaxon:33090

Taxonomic envelope of known pathway implementations and characterized steps, not universal presence. The Methanocaldococcus jannaschii panel establishes aspartate kinase and homoserine kinase individually; it is deliberately insufficient for a complete archaeal-route satisfiability claim. Compartments are implementation-specific: the represented yeast biosynthetic activities are cytosolic and the plant activities are plastid stromal.

Boundary: aspartate supply, phosphoserine supply for ThrH, NADPH/ATP/PLP production, methionine and lysine branches, isoleucine formation, and threonine catabolism are outside the five transformations modeled here. This boundary is not a reason to reject broader GO involvement by an upstream enzyme. All five transformations are required; architecture, donor and synthase variants are alternatives. One fusion protein can satisfy steps 1 and 3, but never bypasses step 2. Representatives orient known implementations and do not prove complete routes in every represented species. No common compartment or universal feedback inhibitor is asserted. The represented yeasts use the alpha-aminoadipate lysine route; modern fungal DHDPS characterization supports this boundary without extrapolating a historical lower-fungi DAP claim. PANTHER membership is checked independently of readable labels: PTHR43070:SF5 mixes mono- and bifunctional architectures, and PTHR10314 has the surprising official name CYSTATHIONINE BETA-SYNTHASE. Independent activity and architecture restrictions therefore accompany these selectors. Six GO-CAM sources were normally refreshed; current source assessments above supersede the old absent-edge/reversed-edge claims. The retained activity links are verified against current enabled-by/MF records. Broad source process labels and AAT1 localization are assessed on biological evidence rather than this module boundary. Inferred product-to-substrate order does not assert substrate channeling. Nuclear silencing/repair-associated findings for yeast pathway proteins are distinct contexts reviewed at gene level and are not steps of this biosynthetic reaction module. Additional architectures discussed in the comparative review, including a phosphoglycerate-mutase-like homoserine-phosphorylation alternative, are not equated with HAD-like ThrH and are not assigned guessed accessions. The present panel documents the two donor implementations supported by its reviewed representatives.

Connections

L-homoserine produced by the trunk is consumed by either ATP-dependent homoserine kinase or phosphoserine-dependent ThrH.
PMID:11341914
Characterization of yeast homoserine dehydrogenase, an antifungal target: the invariant histidine 309 is important for enzyme integrity.
Purified S. cerevisiae Hom6 reduces aspartate semialdehyde to homoserine with NADPH or NADH; this measured donor range is not assigned to all homologues.
HSD efficiently reduces aspartate semialdehyde to homoserine (Hse) using either NADH or NADPH
PMID:8973190
Substrate specificity and identification of functional groups of homoserine kinase from Escherichia coli.
Direct E. coli ThrB homoserine phosphorylation.
Homoserine kinase, an enzyme in the aspartate pathway of amino acid biosynthesis in Escherichia coli, catalyzes the conversion of L-homoserine to L-homoserine phosphate.
PMID:14699121
The thrH gene product of Pseudomonas aeruginosa is a dual activity enzyme with a novel phosphoserine:homoserine phosphotransferase activity.
Direct HPLC assay distinguishes phosphoserine-to-homoserine phosphoryl transfer from ATP-dependent kinase activity.
ThrH is able to further transfer the phosphoryl group to homoserine using phosphoserine as the phosphoryl group donor, indicating that ThrH has a novel phosphoserine:homoserine phosphotransferase activity.
Part 1: aspartate to homoserine (aspartate-family trunk)
L-aspartate to L-homoserineMetabolic Pathwayhomoserine_trunk

Three reactions producing homoserine. Aspartate semialdehyde can also branch toward diaminopimelate-pathway lysine in plants and many prokaryotes. Homoserine supplies methionine and threonine branches in the represented yeasts and E. coli; plant methionine branches after homoserine phosphorylation.

L-homoserine biosynthetic processGO:0009090

Connections

4-phospho-L-aspartate is produced by aspartate kinase and consumed by ASAD.
PMID:17012784
The initial step in the archaeal aspartate biosynthetic pathway catalyzed by a monofunctional aspartokinase.
Direct MJ0571 biochemistry establishes archaeal ATP-dependent aspartate phosphorylation and threonine-sensitive regulation, not a complete archaeal pathway.
mj AK catalyzes phosphoryl transfer to l -aspartate at 310 K with a turnover of 12 s −1 .
PMID:11812229
Overproduction, purification, and characterization of recombinant aspartate semialdehyde dehydrogenase from Arabidopsis thaliana.
Recombinant Arabidopsis ASAD consumes NADPH and aspartyl phosphate. The locus At1g14810 is linked to this primary study by PMID:22303247; the primary abstract itself does not give the locus.
The plant enzyme exhibited a specific activity of 26 micromol NADPH oxidized min(-1) mg(-1) of protein with a K(M) value for NADPH of 92 microM.
L-aspartate 4-semialdehyde is the ASAD product and homoserine-dehydrogenase substrate.
PMID:11812229
Overproduction, purification, and characterization of recombinant aspartate semialdehyde dehydrogenase from Arabidopsis thaliana.
Recombinant Arabidopsis ASAD consumes NADPH and aspartyl phosphate. The locus At1g14810 is linked to this primary study by PMID:22303247; the primary abstract itself does not give the locus.
The plant enzyme exhibited a specific activity of 26 micromol NADPH oxidized min(-1) mg(-1) of protein with a K(M) value for NADPH of 92 microM.
PMID:11341914
Characterization of yeast homoserine dehydrogenase, an antifungal target: the invariant histidine 309 is important for enzyme integrity.
Purified S. cerevisiae Hom6 reduces aspartate semialdehyde to homoserine with NADPH or NADH; this measured donor range is not assigned to all homologues.
HSD efficiently reduces aspartate semialdehyde to homoserine (Hse) using either NADH or NADPH
Part 1: aspartate phosphorylation
L-aspartate to 4-phospho-L-aspartateReactionaspartate_kinase_step
Variant set: Aspartate kinase architecture by enzyme architecture (One Or More)

Monofunctional and bifunctional enzymes can coexist, as in E. coli. The two represented yeasts use separate Hom3 and Hom6 proteins. Architecture does not predict a universal feedback effector: E. coli LysC is lysine-inhibited, ThrA is threonine-inhibited, and MetL expression is methionine-repressible; archaeal MJ0571 is threonine-sensitive despite an older lysC-like annotation.

Monofunctional aspartate kinaseReactionmonofunctional_aspartate_kinase

Annotons

Monofunctional aspartate kinase
monofunctional_aspartate_kinase_activity
Participant: Family: HOM3 / lysC (monofunctional aspartate kinase)
Gene:
HOM3 / lysC (monofunctional aspartate kinase)
Family:
monofunctional aspartate kinases Verified membership of the represented fungal, enterobacterial and archaeal monofunctional aspartate kinases. Family membership does not specify their feedback effector or oligomerization.
Representative Members: HOM3 (Saccharomyces cerevisiae)UniProtKB:P10869 hom3 (Schizosaccharomyces pombe)UniProtKB:O60163 lysC (Escherichia coli K-12)UniProtKB:P08660 MJ0571 (Methanocaldococcus jannaschii)UniProtKB:Q57991

Function

aspartate kinase activityGO:0004072
Substrates: L-aspartate ATP
Products: 4-phospho-L-aspartate ADP

ATP-dependent entry to the aspartate-derived network. Threonine feedback is demonstrated for yeast Hom3 and archaeal MJ0571; E. coli LysC instead responds to lysine. These regulatory differences do not change the required reaction.

PMID:17012784
The initial step in the archaeal aspartate biosynthetic pathway catalyzed by a monofunctional aspartokinase.
Direct MJ0571 biochemistry establishes archaeal ATP-dependent aspartate phosphorylation and threonine-sensitive regulation, not a complete archaeal pathway.
mj AK catalyzes phosphoryl transfer to l -aspartate at 310 K with a turnover of 12 s −1 .
Aspartate kinase domain of a bifunctional AK-HSDHReactionbifunctional_ak_hsdh_kinase

Annotons

AK-HSDH aspartate kinase domain
ak_hsdh_aspartate_kinase_activity
Participant: Family: thrA / metL / AK-HSDH (bifunctional aspartate kinase-homoserine dehydrogenase)
Gene:
thrA / metL / AK-HSDH (bifunctional aspartate kinase-homoserine dehydrogenase)
Family:
bifunctional aspartate kinase-homoserine dehydrogenases These verified subfamilies contain the exemplars, but PTHR43070:SF5 also contains monofunctional fungal homoserine dehydrogenases. The selector is restricted to proteins with the demonstrated AK-HSDH fusion architecture; membership alone does not confer aspartate kinase activity. Official family names are retained verbatim. For E. coli MetL, release-pinned PANTHER assigns PTHR21499:SF29 whereas UniProt assigns PTHR43070:SF3; the index preserves both. The selected SF3 placement is the verified UniProt alternative, not an invented correction, and the fusion architecture is independently established.
Representative Members: thrA (Escherichia coli K-12)UniProtKB:P00561 metL (Escherichia coli K-12)UniProtKB:P00562 AKHSDH1 (Arabidopsis thaliana)UniProtKB:Q9SA18 AKHSDH2 (Arabidopsis thaliana)UniProtKB:O81852

Function

aspartate kinase activityGO:0004072
Substrates: L-aspartate ATP
Products: 4-phospho-L-aspartate ADP

One of two catalytic domains of a verified AK-HSDH fusion. The same protein implements separated steps 1 and 3; ASAD remains required between them. Both Arabidopsis isoforms are characterized by PMID:16216875, while PMID:12602885 concerns AKHSDH2 specifically. Fusion does not establish substrate channeling or identical regulation.

PMID:16216875
Identification of six novel allosteric effectors of Arabidopsis thaliana aspartate kinase-homoserine dehydrogenase isoforms. Physiological context sets the specificity.
Both Arabidopsis AKHSDH isoforms were assayed directly. Their kinase and dehydrogenase activities implement the first and third reactions; their regulation differs.
These two activities catalyze the first and the third steps toward the synthesis of the essential amino acids threonine, isoleucine, and methionine.
PMID:12602885
Transcriptional and biochemical regulation of a novel Arabidopsis thaliana bifunctional aspartate kinase-homoserine dehydrogenase gene isolated by functional complementation of a yeast hom6 mutant.
Specific complementation and biochemical evidence for AKHSDH2, not an exclusive assignment of these assays to AKHSDH1.
These results confirm that akthr2 encodes a threonine-sensitive bifunctional enzyme.
Part 2: 4-phospho-L-aspartate reduction
4-phospho-L-aspartate to L-aspartate 4-semialdehydeReactionaspartate_semialdehyde_dehydrogenase_step

Annotons

Aspartate-semialdehyde dehydrogenase
aspartate_semialdehyde_dehydrogenase_activity
Participant: Family: HOM2 / asd (aspartate-semialdehyde dehydrogenase)
Gene:
HOM2 / asd (aspartate-semialdehyde dehydrogenase)
Family:
aspartate-semialdehyde dehydrogenases Verified fungal, enterobacterial and plant ASAD subfamilies. These are homologous implementations of the same reaction, not additional compulsory reactions.
Representative Members: HOM2 (Saccharomyces cerevisiae)UniProtKB:P13663 hom2 (Schizosaccharomyces pombe)UniProtKB:P78780 asd (Escherichia coli K-12)UniProtKB:P0A9Q9 At1g14810 (Arabidopsis thaliana)UniProtKB:Q8VYI4

Function

aspartate-semialdehyde dehydrogenase (NADP+) activityGO:0004073
Substrates: 4-phospho-L-aspartate NADPH
Products: L-aspartate 4-semialdehyde NADP+ phosphate
PMID:11812229
Overproduction, purification, and characterization of recombinant aspartate semialdehyde dehydrogenase from Arabidopsis thaliana.
Recombinant Arabidopsis ASAD consumes NADPH and aspartyl phosphate. The locus At1g14810 is linked to this primary study by PMID:22303247; the primary abstract itself does not give the locus.
The plant enzyme exhibited a specific activity of 26 micromol NADPH oxidized min(-1) mg(-1) of protein with a K(M) value for NADPH of 92 microM.
Part 3: aspartate semialdehyde reduction to homoserine
L-aspartate 4-semialdehyde to L-homoserineReactionhomoserine_dehydrogenase_step
Variant set: Homoserine dehydrogenase architecture by enzyme architecture (One Or More)
Monofunctional homoserine dehydrogenaseReactionmonofunctional_homoserine_dehydrogenase

Annotons

Monofunctional homoserine dehydrogenase
monofunctional_homoserine_dehydrogenase_activity
Participant: Family: HOM6 / hom (monofunctional homoserine dehydrogenase)
Gene:
HOM6 / hom (monofunctional homoserine dehydrogenase)
Family:
monofunctional homoserine dehydrogenases Verified fungal Hom6 membership. This subfamily also includes plant AKHSDH2; the monofunctional architecture is an additional restriction, not an inference from the family name alone.
Representative Members: HOM6 (Saccharomyces cerevisiae)UniProtKB:P31116 hom6 (Schizosaccharomyces pombe)UniProtKB:O94671

Function

homoserine dehydrogenase activityGO:0004412
Substrates: L-aspartate 4-semialdehyde NADPH
Products: L-homoserine NADP+

NADPH-dependent formation of homoserine, matching GO:0004412. S. cerevisiae Hom6 additionally uses NADH in direct assays (PMID:11341914); this extra donor capability is not made universal or conflated with the NADP-specific GO definition.

PMID:11341914
Characterization of yeast homoserine dehydrogenase, an antifungal target: the invariant histidine 309 is important for enzyme integrity.
Purified S. cerevisiae Hom6 reduces aspartate semialdehyde to homoserine with NADPH or NADH; this measured donor range is not assigned to all homologues.
HSD efficiently reduces aspartate semialdehyde to homoserine (Hse) using either NADH or NADPH
Homoserine dehydrogenase domain of a bifunctional AK-HSDHReactionbifunctional_ak_hsdh_dehydrogenase

Annotons

AK-HSDH homoserine dehydrogenase domain
ak_hsdh_homoserine_dehydrogenase_activity
Participant: Family: thrA / metL / AK-HSDH (bifunctional aspartate kinase-homoserine dehydrogenase)
Gene:
thrA / metL / AK-HSDH (bifunctional aspartate kinase-homoserine dehydrogenase)
Family:
bifunctional aspartate kinase-homoserine dehydrogenases These verified subfamilies contain the exemplars, but PTHR43070:SF5 also contains monofunctional fungal homoserine dehydrogenases. The selector is restricted to proteins with the demonstrated AK-HSDH fusion architecture; membership alone does not confer aspartate kinase activity. Official family names are retained verbatim. For E. coli MetL, release-pinned PANTHER assigns PTHR21499:SF29 whereas UniProt assigns PTHR43070:SF3; the index preserves both. The selected SF3 placement is the verified UniProt alternative, not an invented correction, and the fusion architecture is independently established.
Representative Members: thrA (Escherichia coli K-12)UniProtKB:P00561 metL (Escherichia coli K-12)UniProtKB:P00562 AKHSDH1 (Arabidopsis thaliana)UniProtKB:Q9SA18 AKHSDH2 (Arabidopsis thaliana)UniProtKB:O81852

Function

homoserine dehydrogenase activityGO:0004412
Substrates: L-aspartate 4-semialdehyde NADPH
Products: L-homoserine NADP+

One of two catalytic domains of a verified AK-HSDH fusion. The same protein implements separated steps 1 and 3; ASAD remains required between them. Both Arabidopsis isoforms are characterized by PMID:16216875, while PMID:12602885 concerns AKHSDH2 specifically. Fusion does not establish substrate channeling or identical regulation.

PMID:16216875
Identification of six novel allosteric effectors of Arabidopsis thaliana aspartate kinase-homoserine dehydrogenase isoforms. Physiological context sets the specificity.
Both Arabidopsis AKHSDH isoforms were assayed directly. Their kinase and dehydrogenase activities implement the first and third reactions; their regulation differs.
These two activities catalyze the first and the third steps toward the synthesis of the essential amino acids threonine, isoleucine, and methionine.
PMID:12602885
Transcriptional and biochemical regulation of a novel Arabidopsis thaliana bifunctional aspartate kinase-homoserine dehydrogenase gene isolated by functional complementation of a yeast hom6 mutant.
Specific complementation and biochemical evidence for AKHSDH2, not an exclusive assignment of these assays to AKHSDH1.
These results confirm that akthr2 encodes a threonine-sensitive bifunctional enzyme.
Part 2: homoserine to threonine (threonine branch)
L-homoserine to L-threonineMetabolic Pathwaythreonine_branch

Connections

O-phospho-L-homoserine produced by either phosphorylation route is consumed by threonine synthase; the plant methionine branch competes for this intermediate.
PMID:8973190
Substrate specificity and identification of functional groups of homoserine kinase from Escherichia coli.
Direct E. coli ThrB homoserine phosphorylation.
Homoserine kinase, an enzyme in the aspartate pathway of amino acid biosynthesis in Escherichia coli, catalyzes the conversion of L-homoserine to L-homoserine phosphate.
PMID:14699121
The thrH gene product of Pseudomonas aeruginosa is a dual activity enzyme with a novel phosphoserine:homoserine phosphotransferase activity.
Direct HPLC assay distinguishes phosphoserine-to-homoserine phosphoryl transfer from ATP-dependent kinase activity.
ThrH is able to further transfer the phosphoryl group to homoserine using phosphoserine as the phosphoryl group donor, indicating that ThrH has a novel phosphoserine:homoserine phosphotransferase activity.
PMID:8082795
Biochemical evidence that the Saccharomyces cerevisiae THR4 gene encodes threonine synthetase.
Yeast THR4-dependent formation of threonine from O-phosphohomoserine was measured in crude extracts.
The method is based on the quantification by reverse-phase high-performance liquid chromatography, of the threonine formed from O-phosphohomoserine.
Part 1: homoserine phosphorylation
L-homoserine to O-phospho-L-homoserineReactionhomoserine_kinase_step

Either implementation supplies O-phospho-L-homoserine. ThrH requires phosphoserine supply, outside this aspartate-to-threonine boundary. This is substrate continuity, not an ATP-kinase alias.

Variant set: Homoserine phosphorylation donor by phosphate donor and catalytic implementation (One Or More)
ATP-dependent homoserine kinaseReactionatp_dependent_homoserine_phosphorylation

Annotons

Homoserine kinase
homoserine_kinase_activity
Participant: Family: THR1 / thrB (homoserine kinase)
Gene:
THR1 / thrB (homoserine kinase)
Family:
GHMP-family homoserine kinases
Representative Members: THR1 (Saccharomyces cerevisiae)UniProtKB:P17423 thr1 (Schizosaccharomyces pombe)UniProtKB:O43056 thrB (Escherichia coli K-12)UniProtKB:P00547 HSK/DMR1 (Arabidopsis thaliana)UniProtKB:Q8L7R2 thrB (Methanocaldococcus jannaschii)UniProtKB:Q58504

Function

homoserine kinase activityGO:0004413
Substrates: L-homoserine ATP
Products: O-phospho-L-homoserine ADP

ATP-dependent formation of O-phosphohomoserine. It feeds the threonine-specific branch in the represented yeasts and E. coli but the shared threonine/methionine branchpoint in plants. These exemplars do not establish that every bacterial methionine pathway branches before phosphorylation.

PMID:8973190
Substrate specificity and identification of functional groups of homoserine kinase from Escherichia coli.
Direct E. coli ThrB homoserine phosphorylation.
Homoserine kinase, an enzyme in the aspartate pathway of amino acid biosynthesis in Escherichia coli, catalyzes the conversion of L-homoserine to L-homoserine phosphate.
PMID:10562426
Identification of the gene encoding homoserine kinase from Arabidopsis thaliana and characterization of the recombinant enzyme derived from the gene.
Arabidopsis HSK uses MgATP and supplies the shared plant methionine/threonine intermediate. The primary identifies a chromosome II locus, consistent with At2g17265 rather than the erroneous chromosome IV locus in PMID:22303247.
Homoserine kinase (EC 2.7.1.39) catalyzes the formation of O-phospho-l-homoserine, a branch point intermediate in the pathways for Met and Thr in plants.
PMID:11535056
Structural basis for the catalysis and substrate specificity of homoserine kinase.
Direct substrate/ATP-analogue structures of archaeal ThrB support the GHMP kinase implementation.
The high-resolution structures of Methanococcus jannaschii HSK ternary complexes with its amino acid substrate and ATP analogues have been determined by X-ray crystallography.
Phosphoserine-dependent ThrH transferReactionphosphoserine_dependent_homoserine_phosphorylation

Annotons

Phosphoserine-dependent homoserine phosphorylation
phosphoserine_homoserine_phosphotransferase_activity
Participant: Family: thrH (phosphoserine:homoserine phosphotransferase)
Gene:
thrH (phosphoserine:homoserine phosphotransferase)
Family:
ThrH phosphoserine:homoserine phosphotransferases Official PHOSPHOSERINE PHOSPHATASE classification is retained; the represented ThrH additionally transfers phosphate to homoserine. This activity is not assigned to every HAD-family phosphatase.
Representative Members: thrH (Pseudomonas aeruginosa PAO1)UniProtKB:Q9I2Y2

Function

phosphoserine:homoserine phosphotransferase activityGO:0043899
Substrates: O-phospho-L-serine L-homoserine
Products: L-serine O-phospho-L-homoserine

Transfers phosphate from phosphoserine to homoserine via HAD-like chemistry. Its separate phosphoserine hydrolysis activity is not an obligatory upstream step of this module; hydrolysis and transfer are alternative outcomes, not a compulsory sequential pathway.

PMID:14699121
The thrH gene product of Pseudomonas aeruginosa is a dual activity enzyme with a novel phosphoserine:homoserine phosphotransferase activity.
Direct HPLC assay distinguishes phosphoserine-to-homoserine phosphoryl transfer from ATP-dependent kinase activity.
ThrH is able to further transfer the phosphoryl group to homoserine using phosphoserine as the phosphoryl group donor, indicating that ThrH has a novel phosphoserine:homoserine phosphotransferase activity.
PMID:10220164
ThrH, a homoserine kinase isozyme with in vivo phosphoserine phosphatase activity in Pseudomonas aeruginosa.
Native P. aeruginosa thrB/thrH double disruption produces threonine auxotrophy. This establishes substitution in vivo; the later biochemical study PMID:14699121 identifies the phosphate donor and distinguishes ThrH from an ATP kinase.
In P. aeruginosa, threonine auxotrophy is observed only when both thrB and thrH are simultaneously inactivated.
Part 2: O-phospho-L-homoserine to L-threonine
O-phospho-L-homoserine to L-threonineReactionthreonine_synthase_step
Variant set: Threonine synthase regulatory type by enzyme subfamily and allosteric regulation (One Or More)

Alternative characterized synthase implementations, not mutually exclusive genome-wide categories. Regulatory response is anchored to the representative assays; it is not inferred from plant or bacterial taxonomy alone.

ThrC-type threonine synthase (bacteria, fungi)Reactionthrc_type_threonine_synthase

Annotons

ThrC-type threonine synthase
thrc_type_threonine_synthase_activity
Participant: Family: THR4 / thrC (threonine synthase)
Gene:
THR4 / thrC (threonine synthase)
Family:
ThrC-type threonine synthases
Representative Members: THR4 (Saccharomyces cerevisiae)UniProtKB:P16120 SPAC9E9.06c (Schizosaccharomyces pombe)UniProtKB:Q42598 thrC (Escherichia coli K-12)UniProtKB:P00934

Function

threonine synthase activityGO:0004795
Substrates: O-phospho-L-homoserine water
Products: L-threonine phosphate
PMID:8082795
Biochemical evidence that the Saccharomyces cerevisiae THR4 gene encodes threonine synthetase.
Yeast THR4-dependent formation of threonine from O-phosphohomoserine was measured in crude extracts.
The method is based on the quantification by reverse-phase high-performance liquid chromatography, of the threonine formed from O-phosphohomoserine.
PMID:10429206
Characterization of recombinant Arabidopsis thaliana threonine synthase.
Arabidopsis TS1 catalyzes the PLP-dependent terminal reaction; the same study compares its regulation and assembly with E. coli and yeast enzymes.
Threonine synthase (TS) catalyses the last step in the biosynthesis of threonine, the pyridoxal 5'-phosphate dependent conversion of L-homoserine phosphate (HSerP) into L-threonine and inorganic phosphate.
S-adenosylmethionine-activated threonine synthase (plants)Reactionsam_activated_threonine_synthase

Annotons

Plant S-adenosylmethionine-activated threonine synthase
sam_activated_threonine_synthase_activity
Participant: Family: TS1/MTO2 (plant threonine synthase)
Gene:
TS1/MTO2 (plant threonine synthase)
Family:
plant-type threonine synthases The normal release-pinned member index resolves TS1 to this subfamily within the officially named CYSTATHIONINE BETA-SYNTHASE family PTHR10314; UniProt confirms the parent family. The surprising parent label is not a reason to omit valid membership. This narrower selector covers the characterized plant threonine-synthase branch; its SAM response is supported independently by biochemical assays.
Representative Members: TS1/MTO2 (Arabidopsis thaliana)UniProtKB:Q9S7B5

Function

threonine synthase activityGO:0004795
Substrates: O-phospho-L-homoserine water
Products: L-threonine phosphate

Arabidopsis TS1 uses PLP for the terminal reaction and is activated by noncovalently bound SAM. SAM is neither a methyl donor nor a consumed cofactor in this reaction. This regulation is not generalized to bacterial or fungal threonine synthases (PMID:9748328, PMID:10429206).

PMID:10429206
Characterization of recombinant Arabidopsis thaliana threonine synthase.
Arabidopsis TS1 catalyzes the PLP-dependent terminal reaction; the same study compares its regulation and assembly with E. coli and yeast enzymes.
Threonine synthase (TS) catalyses the last step in the biosynthesis of threonine, the pyridoxal 5'-phosphate dependent conversion of L-homoserine phosphate (HSerP) into L-threonine and inorganic phosphate.