METK1

GO Term	Evidence	Action	Reason
GO:0046872 metal ion binding	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: SPKW keyword-mapping annotation (GO_REF:0000043) derived from the UniProt "Metal-binding", "Magnesium", "Cobalt" and "Potassium" keywords; present in the Sept 2025 GOA snapshot but removed from the current GOA release after the keyword2GO pipeline was retired for cellular organisms. The assertion is biochemically correct - the enzyme binds two divalent metal ions (Mg2+, with Mn2+ or Co2+ usable in vitro) and one monovalent potassium ion per subunit, both of which coordinate the substrates during catalysis. However, "metal ion binding" is an uninformative grouping term that does not distinguish a catalytically essential cofactor requirement from incidental metal contacts. More specific terms (magnesium ion binding, GO:0000287; potassium ion binding, GO:0030955) precisely capture the documented cofactor requirement. GOA's removal pruned a true-but-coarse term rather than losing biologically meaningful information. Reason: The term is correct (METK1 binds divalent metal and K+ cofactors required for catalysis) but uninformative. It is a redundant, low-information SPKW grouping term; the specific cofactor identities are better represented by the proposed replacement terms. Its removal from current GOA is justified as pruning of coarse keyword-derived annotation. Proposed replacements: magnesium ion binding potassium ion binding Supporting Evidence: file:POPTR/METK1/METK1-uniprot.txt Note=Binds 2 divalent ions per subunit. The metal ions interact CC primarily with the substrate (By similarity). Can utilize magnesium, CC manganese or cobalt (in vitro) file:POPTR/METK1/METK1-uniprot.txt Note=Binds 1 potassium ion per subunit. The potassium ion interacts CC primarily with the substrate (By similarity). file:POPTR/METK1/METK1-deep-research-falcon.md MAT binds ATP and L-methionine (requires Mg2+ and K+) and proceeds via an SN2-type reaction where methionine sulfur attacks the 5′ carbon of the ATP ribose; the ATP β–γ bond is hydrolyzed producing PPi and Pi.
GO:0006730 one-carbon metabolic process	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: SPKW keyword-mapping annotation (GO_REF:0000043) derived from the UniProt "One-carbon metabolism" keyword; present in the Sept 2025 GOA snapshot but removed from the current GOA release after the keyword2GO pipeline was retired for cellular organisms. The annotation is biologically defensible - S-adenosylmethionine produced by METK1 is the universal activated methyl donor that supplies one-carbon (methyl) units to methyltransferase reactions across nucleic acid, protein, lipid and small-molecule metabolism. However, GO:0006730 is a broad parent process and is coarse relative to the precise child term S-adenosylmethionine biosynthetic process (GO:0006556), which is already annotated (IBA and IEA) and directly describes what METK1 does. The enzyme synthesizes the methyl-donor cofactor; it does not itself transfer one-carbon units. The term is therefore correct-but-broad and largely redundant with the more specific GO:0006556 annotation. Reason: One-carbon metabolic process is a true but broad parent of the gene's actual role; METK1 produces the SAM methyl donor that feeds one-carbon/methyl-transfer metabolism. It is retained as a non-core process annotation because the core function is more precisely captured by S-adenosylmethionine biosynthetic process (GO:0006556). Its removal from current GOA is a minor loss at most, since the specific child term remains annotated. Supporting Evidence: file:POPTR/METK1/METK1-uniprot.txt FUNCTION: Catalyzes the formation of S-adenosylmethionine from CC methionine and ATP. file:POPTR/METK1/METK1-uniprot.txt PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis; CC S-adenosyl-L-methionine from L-methionine: step 1/1. file:POPTR/METK1/METK1-deep-research-falcon.md The universal methyl donor for methyltransferases, including those involved in DNA/histone methylation and secondary metabolism.
GO:0006556 S-adenosylmethionine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: S-adenosylmethionine biosynthesis is the direct pathway for methionine adenosyltransferase. Reason: The enzyme forms S-adenosyl-L-methionine from L-methionine and ATP. Supporting Evidence: file:POPTR/METK1/METK1-uniprot.txt PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis file:POPTR/METK1/METK1-deep-research-falcon.md The primary function inferred for Populus METK1 is to make SAM, the central activated methyl donor and branch-point metabolite
GO:0004478 methionine adenosyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Methionine adenosyltransferase activity is the core molecular function. Reason: The UniProt entry assigns EC 2.5.1.6 and the reaction for SAM synthesis. Supporting Evidence: file:POPTR/METK1/METK1-uniprot.txt FUNCTION: Catalyzes the formation of S-adenosylmethionine from CC methionine and ATP. file:POPTR/METK1/METK1-uniprot.txt EC=2.5.1.6 file:POPTR/METK1/METK1-deep-research-falcon.md Plant MAT/SAMS catalyzes L-methionine + ATP → S-adenosyl-L-methionine (SAM/AdoMet) + PPi + Pi
GO:0005524 ATP binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: ATP binding is required for the reaction but is less informative than methionine adenosyltransferase activity. Reason: Retain as a co-substrate binding feature, not as the core function. Supporting Evidence: file:POPTR/METK1/METK1-uniprot.txt Reaction=L-methionine + ATP + H2O = S-adenosyl-L-methionine
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Cytoplasm/cytosol localization is appropriate for this soluble AdoMet synthase. Reason: UniProt places the enzyme in the cytoplasm. Supporting Evidence: file:POPTR/METK1/METK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm
GO:0006556 S-adenosylmethionine biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: S-adenosylmethionine biosynthesis is the direct pathway for methionine adenosyltransferase. Reason: The enzyme forms S-adenosyl-L-methionine from L-methionine and ATP. Supporting Evidence: file:POPTR/METK1/METK1-uniprot.txt PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis file:POPTR/METK1/METK1-deep-research-falcon.md The primary function inferred for Populus METK1 is to make SAM, the central activated methyl donor and branch-point metabolite
GO:0004478 methionine adenosyltransferase activity	ISS GO_REF:0000024	ACCEPT	Summary: Methionine adenosyltransferase activity is the core molecular function. Reason: The UniProt entry assigns EC 2.5.1.6 and the reaction for SAM synthesis. Supporting Evidence: file:POPTR/METK1/METK1-uniprot.txt FUNCTION: Catalyzes the formation of S-adenosylmethionine from CC methionine and ATP. file:POPTR/METK1/METK1-uniprot.txt EC=2.5.1.6 file:POPTR/METK1/METK1-deep-research-falcon.md Plant MAT/SAMS catalyzes L-methionine + ATP → S-adenosyl-L-methionine (SAM/AdoMet) + PPi + Pi

Deep Research

Falcon

(METK1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 27 citations 2 artifacts 2026-05-21T14:12:14.787593

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000013 The requested Table 3 and Figure 8 are both located on page 9 of the document. Table 3 presents the chemical composition of cell wa (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Functional annotation of METK1 (UniProt A9P822) from Populus trichocarpa

Executive summary (identity verification and evidence limits)

The target protein is S-adenosylmethionine synthase 1 (AdoMet/SAM synthase; methionine adenosyltransferase, EC 2.5.1.6), gene METK1, ORF POPTR_0014s11000g, from Populus trichocarpa (western balsam poplar). In the retrieved literature set, I did not find a primary paper that explicitly assays or localizes this specific Populus trichocarpa protein (UniProt A9P822) by accession/ORF name. Therefore, the functional annotation below is a high-confidence orthology/family-based inference grounded in plant SAMS/MAT literature, supplemented with direct poplar evidence that metK (SAMS) is transcriptionally responsive under stress and sits in the expected methionine→SAM→ethylene/methylation pathway. (chen2025theyangcycle pages 4-5, feng2022differencesindetoxification pages 6-9)

1) Key concepts and definitions (current understanding)

1.1 What METK1 encodes

METK1/SAMS/MAT enzymes catalyze formation of S-adenosyl-L-methionine (SAM; AdoMet) from L-methionine and ATP; SAM is the central activated methyl donor and a precursor for several plant pathways. (chen2025theyangcycle pages 2-3, jockmann2025chemoselectivityofoand pages 26-30)

1.2 Primary biochemical function: catalyzed reaction and substrate specificity

Reaction (canonical MAT/SAMS):
- L-methionine + ATP → S-adenosyl-L-methionine (SAM) + pyrophosphate (PPi) + orthophosphate (Pi). (jockmann2025chemoselectivityofoand pages 26-30)

Mechanistic understanding (general MAT chemistry, applicable to plant homologs):
- MAT binds ATP and L-methionine (requires Mg2+ and K+) and proceeds via an SN2-type reaction where methionine sulfur attacks the 5′ carbon of the ATP ribose; the ATP β–γ bond is hydrolyzed producing PPi and Pi. (jockmann2025chemoselectivityofoand pages 26-30)

Substrate specificity:
- The defining substrates are L-methionine and ATP; the principal product is SAM. (jockmann2025chemoselectivityofoand pages 26-30)

1.3 Why SAM matters in plants (pathway context)

SAM is described in plant-focused reviews as:
- The universal methyl donor for methyltransferases, including those involved in DNA/histone methylation and secondary metabolism. (watanabe2021metabolismandregulatory pages 3-5, chen2025theyangcycle pages 2-3)
- A key precursor feeding biosynthesis of ethylene and polyamines, and also nicotianamine/phytosiderophores. (watanabe2021metabolismandregulatory pages 3-5, chen2025theyangcycle pages 2-3)
- A metabolite whose compartmentalization and recycling (Yang cycle / MTA cycle) influences growth and development. (chen2025theyangcycle pages 4-5, watanabe2021metabolismandregulatory pages 3-5)

1.4 Subcellular localization and compartmentation

Plant SAMS is reported to localize primarily to the cytoplasm and nucleus. This supports annotating Populus METK1 as a cytosolic/nuclear enzyme generating SAM for cellular methylation capacity and for distribution to other compartments. (chen2025theyangcycle pages 4-5)

SAM is synthesized in the cytoplasm, while methylation reactions in organelles require SAM transport. In cotton/Arabidopsis-focused discussion, SAM transporters include plastid- and mitochondria-associated transporters (e.g., AtSAMC1 plastid; AtSAMC2 plastid+mitochondrial membranes). (yang2023rolesofsadenosylmethionine pages 9-11)

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 2024: Field-scale engineering of SAM pools to modify lignin and biomass processing

A major 2024 development relevant to METK1 functional context is field testing of SAM depletion (via heterologous SAM hydrolase “AdoMetase”) in sorghum. This work provides real-world evidence that SAM availability constrains methylation-dependent wall chemistry:
- Acid-insoluble lignin decreased 18% (Davis site) and 13% (KARE site) in the best engineered line. (tian2024engineeredreductionof pages 8-9, tian2024engineeredreductionof media dafe8723)
- Cell-wall glucuronic acid methylation was reduced (reported via changes in GlcA vs 4-O-MeGlcA), consistent with reduced SAM-dependent methylation capacity. (tian2024engineeredreductionof pages 8-9, tian2024engineeredreductionof media dafe8723)
- Biomass saccharification sugar release improved by roughly ~12–24% depending on site and pretreatment conditions (as shown in the saccharification figure). (tian2024engineeredreductionof pages 8-9, tian2024engineeredreductionof media 23ba5d32)
- However, there were large yield penalties (e.g., up to 69% biomass reduction in one line at one site), indicating that globally reducing SAM can have strong pleiotropic impacts. (tian2024engineeredreductionof pages 8-9)

Although this is not a poplar study and manipulates SAM downstream of SAMS rather than altering METK1 directly, it is among the clearest 2024 demonstrations that SAM supply is rate-limiting for lignin-related methylation and biomass-processing traits in crops—supporting METK1’s inferred importance upstream of these processes. (tian2024engineeredreductionof pages 8-9, tian2024engineeredreductionof media 23ba5d32)

2.2 2023: SAM in stress responses and precursor partitioning (ethylene vs polyamines)

A 2023 review focusing on salt tolerance emphasizes that ethylene and polyamines share SAM as a common precursor and discusses SAM synthesis in the cytoplasm with organellar dependence on import. (yang2023rolesofsadenosylmethionine pages 9-11)

2.3 2023–2025: Regulatory control of plant SAMS abundance and downstream outcomes

Recent plant synthesis highlights multiple layers of SAMS regulation (phosphorylation and proteasome-mediated turnover) and links SAMS perturbations to developmental outcomes and lignin deposition via regulation of methionine adenosyltransferases. (chen2025theyangcycle pages 5-5, chen2025theyangcycle pages 10-11)

3) Current applications and real-world implementations

3.1 Biomass/cell-wall engineering (bioenergy, pulp, and digestibility)

The 2024 sorghum field trial demonstrates that altering SAM pools can measurably reduce lignin and improve saccharification, a direct route to improved biomass processing; it also highlights the main risk: growth/yield penalties if SAM depletion is not spatially/temporally controlled. (tian2024engineeredreductionof pages 8-9, tian2024engineeredreductionof media 23ba5d32)

3.2 Stress physiology and environmental resilience in trees

In poplar varieties exposed to SO2, methionine→SAM metabolism is explicitly placed in the sulfur/methionine response network, and metK (SAMS) is reported as up-regulated (with ACS) under SO2 fumigation in a resistant cultivar (“Purui”). This supports a real-world role for SAM production capacity in stress-associated metabolic remodeling in poplar. (feng2022differencesindetoxification pages 6-9)

3.3 Epigenetic regulation during wood formation

A Populus trichocarpa methylome/transcriptome resource quantified global methylation patterns during the transition from primary to secondary growth, providing context for SAM-demanding methylation processes in developing stems and wood formation. (zhang2020dnamethylationand pages 1-2)

4) Expert opinions and analysis from authoritative sources (interpretation grounded in reviews)

4.1 METK1 is best annotated as a “central metabolic capacity” enzyme

Plant-focused reviews frame SAMS as a “well-studied” Yang-cycle enzyme whose perturbation leads to broad developmental phenotypes and impacts methylation and hormone-related pathways. This implies METK1 is less likely to be a pathway-specific regulator and more likely a central capacity enzyme affecting multiple downstream processes via SAM availability. (chen2025theyangcycle pages 4-5, chen2025theyangcycle pages 10-11)

4.2 Expected downstream pathways influenced by METK1-derived SAM

Based on synthesis across reviews, the most defensible downstream processes to connect to Populus METK1 are:
- Transmethylation reactions (DNA/histone and small-molecule methylation). (watanabe2021metabolismandregulatory pages 3-5, chen2025theyangcycle pages 2-3)
- Ethylene biosynthesis (SAM used to produce ACC; methionine salvage/Yang cycle coupled to ethylene-associated turnover). (chen2025theyangcycle pages 11-11, feng2022differencesindetoxification pages 6-9)
- Polyamine metabolism (SAM is a precursor in polyamine biosynthesis; shared precursor logic affects stress responses). (watanabe2021metabolismandregulatory pages 3-5, yang2023rolesofsadenosylmethionine pages 9-11)
- Lignin and cell-wall methylation chemistry, because lignin monomer methylation depends on SAM and SAM-dependent O-methyltransferases; perturbations in SAM metabolism can reduce lignin and alter wall methylation. (chen2025theyangcycle pages 2-3, tian2024engineeredreductionof pages 8-9)

4.3 Cellular localization: cytosolic production with nuclear adjacency

Because plant SAMS is reported in the cytoplasm and nucleus, METK1 can be functionally interpreted as supporting (i) cytosolic methylation-dependent metabolism and (ii) nuclear methylation capacity (chromatin-associated methylation) while indirectly supplying SAM to organelles via transporters. (chen2025theyangcycle pages 4-5, yang2023rolesofsadenosylmethionine pages 9-11)

5) Relevant statistics and data from recent studies

5.1 Populus trichocarpa stem methylation levels during development

During primary-to-secondary growth in P. trichocarpa stems, whole-genome bisulfite sequencing found average methylation levels of approximately:
- CG ~53.6%, CHG ~37.7%, and CHH ~8.5% (genome-wide averages), with statistically significant differences among developmental stages. (zhang2020dnamethylationand pages 1-2)

These data are relevant to METK1 because methylation marks (5mC) depend on SAM supply as methyl donor, linking methylome maintenance and remodeling to cellular methylation capacity. (watanabe2021metabolismandregulatory pages 3-5, zhang2020dnamethylationand pages 1-2)

5.2 Poplar stress physiology: SO2 responses connected to metK/SAMS

In Populus × euramericana varieties exposed to SO2, the resistant cultivar showed substantial increases in sulfur-assimilation enzyme activities (e.g., increases reported on the order of ~27–54% depending on enzyme) and increased Cys/GSH under fumigation, and the pathway schematic and results state that Met is partly converted into SAM by metK and that metK is up-regulated under SO2 fumigation (with ACS, linking SAM to ethylene precursor ACC). (feng2022differencesindetoxification pages 6-9)

5.3 2024 field trial manipulating SAM pools (quantitative wall chemistry and performance)

From the 2024 sorghum AdoMetase field trial:
- Acid-insoluble lignin reduced by 18% and 13% (best line, different sites). (tian2024engineeredreductionof pages 8-9, tian2024engineeredreductionof media dafe8723)
- Sugar release after pretreatment + enzymatic digestion increased by roughly ~12–24% depending on conditions (figure). (tian2024engineeredreductionof media 23ba5d32)
- Biomass yield penalties up to 69% (site/line dependent). (tian2024engineeredreductionof pages 8-9)

Functional annotation statement for Populus METK1 (UniProt A9P822)

Recommended primary function annotation: METK1 (UniProt A9P822) is a S-adenosyl-L-methionine synthase (methionine adenosyltransferase; EC 2.5.1.6) catalyzing L-methionine + ATP → SAM + PPi + Pi in the cytoplasm and nucleus, thereby supplying SAM for cellular transmethylation reactions and as a precursor feeding ethylene and polyamine biosynthesis; through SAM availability it can indirectly influence lignin/cell-wall methylation chemistry and methylation-associated regulation during wood formation and stress responses in poplar. (jockmann2025chemoselectivityofoand pages 26-30, chen2025theyangcycle pages 4-5, feng2022differencesindetoxification pages 6-9, tian2024engineeredreductionof pages 8-9)

Summary table

Topic	Key points (concise)	Evidence/source (include paper title + year + URL)	Notes/limits
Target identity / ambiguity check	UniProt A9P822 is annotated as S-adenosylmethionine synthase 1 / methionine adenosyltransferase 1 (EC 2.5.1.6) from Populus trichocarpa, gene METK1 / POPTR_0014s11000g. Literature directly naming this exact poplar gene is sparse; functional annotation therefore relies mainly on conserved plant SAMS/MAT biology.	The Yang cycle in plants: a journey of methionine recycling with fascinating metabolites and enzymes (2025), https://doi.org/10.48130/ph-0025-0007; Metabolism and Regulatory Functions of O-Acetylserine, S-Adenosylmethionine, Homocysteine, and Serine in Plant Development and Environmental Responses (2021), https://doi.org/10.3389/fpls.2021.643403 (chen2025theyangcycle pages 2-3, chen2025theyangcycle pages 4-5, watanabe2021metabolismandregulatory pages 3-5)	No Populus-specific biochemical paper for A9P822 was retrieved in the available evidence set; conclusions are inference-based but strongly supported by family conservation.
Enzyme reaction / substrates / products / mechanism	Plant MAT/SAMS catalyzes L-methionine + ATP → S-adenosyl-L-methionine (SAM/AdoMet) + PPi + Pi. Mechanistically, methionine sulfur attacks the 5′ carbon of ATP ribose in an SN2-type reaction; enzyme activity requires Mg2+ and K+, with active oligomers described as homo-dimer/tetramer and loop closure during catalysis.	Chemoselectivity of O- and N-Methyltransferases (2025), URL not clearly available in retrieved record; plant context in The Yang cycle in plants (2025), https://doi.org/10.48130/ph-0025-0007 (jockmann2025chemoselectivityofoand pages 26-30, chen2025theyangcycle pages 2-3)	Mechanistic detail comes from general MAT literature, not a Populus enzyme assay. Still appropriate for A9P822 because UniProt places it in the canonical AdoMet synthase family.
Primary biochemical function of METK1	The primary function inferred for Populus METK1 is to make SAM, the central activated methyl donor and branch-point metabolite feeding methylation chemistry plus ethylene/polyamine-related metabolism.	The Yang cycle in plants (2025), https://doi.org/10.48130/ph-0025-0007; Metabolism and Regulatory Functions of O-Acetylserine... (2021), https://doi.org/10.3389/fpls.2021.643403 (chen2025theyangcycle pages 2-3, watanabe2021metabolismandregulatory pages 3-5)	This is the most defensible direct annotation for A9P822.
SAM as methyl donor	SAM is the universal methyl donor for many plant methyltransferases, including reactions affecting DNA/histone methylation, RNA/protein methylation, and secondary metabolism. Thus METK1 likely supports epigenetic regulation and broad methylation capacity.	Metabolism and Regulatory Functions of O-Acetylserine... (2021), https://doi.org/10.3389/fpls.2021.643403; Roles of S-Adenosylmethionine and Its Derivatives in Salt Tolerance of Cotton (2023), https://doi.org/10.3390/ijms24119517; The Yang cycle in plants (2025), https://doi.org/10.48130/ph-0025-0007 (watanabe2021metabolismandregulatory pages 3-5, yang2023rolesofsadenosylmethionine pages 9-11, chen2025theyangcycle pages 2-3)	For Populus, this implies a likely role in chromatin methylation and methyl-dependent metabolism, but gene-specific methylome data were not retrieved.
Lignin-related role	SAM is required by O-methyltransferases in lignin biosynthesis; perturbing SAM/SAMS can reduce lignin. A cited Arabidopsis sams3 mutation decreased lignin, and proteolytic regulation of methionine adenosyltransferases can affect lignin deposition.	The Yang cycle in plants (2025), https://doi.org/10.48130/ph-0025-0007 (chen2025theyangcycle pages 10-11, chen2025theyangcycle pages 2-3)	This supports annotating Populus METK1 as an upstream contributor to wood-cell-wall methylation and lignification, but not as a lignin-pathway enzyme per se.
Ethylene pathway connection	SAM is the immediate precursor used to make ACC, the precursor of ethylene; therefore METK1 likely influences ethylene biosynthetic capacity indirectly by supplying SAM. MTA/Methionine salvage cycle coupling links SAM turnover to ethylene production.	The Yang cycle in plants (2025), https://doi.org/10.48130/ph-0025-0007; Roles of S-Adenosylmethionine and Its Derivatives in Salt Tolerance of Cotton (2023), https://doi.org/10.3390/ijms24119517 (chen2025theyangcycle pages 11-11, chen2025theyangcycle pages 5-5, yang2023rolesofsadenosylmethionine pages 9-11)	No direct Populus METK1–ethylene experiment was retrieved.
Polyamine pathway connection	SAM is also a precursor for polyamine biosynthesis (via decarboxylated SAM in downstream steps). Reviews note ethylene and polyamines share SAM as a common precursor, placing METK1 at a key metabolic branch point.	Metabolism and Regulatory Functions of O-Acetylserine... (2021), https://doi.org/10.3389/fpls.2021.643403; Roles of S-Adenosylmethionine and Its Derivatives in Salt Tolerance of Cotton (2023), https://doi.org/10.3390/ijms24119517 (watanabe2021metabolismandregulatory pages 3-5, yang2023rolesofsadenosylmethionine pages 9-11)	Annotation is pathway-level; substrate specificity of METK1 itself is methionine + ATP, not polyamines.
Other SAM-dependent pathways	SAM also feeds biosynthesis of nicotianamine/phytosiderophores and methylation of compounds such as flavonoids and cell-wall-associated metabolites.	The Yang cycle in plants (2025), https://doi.org/10.48130/ph-0025-0007; Metabolism and Regulatory Functions of O-Acetylserine... (2021), https://doi.org/10.3389/fpls.2021.643403 (chen2025theyangcycle pages 2-3, watanabe2021metabolismandregulatory pages 3-5)	Broad systems role; not evidence of unique specialization of METK1 over other SAMS paralogs.
Subcellular localization of SAMS/METK protein	Plant SAMS is reported to localize in the cytoplasm and nucleus. This is the best-supported localization inference for Populus METK1.	The Yang cycle in plants (2025), https://doi.org/10.48130/ph-0025-0007 (chen2025theyangcycle pages 4-5)	No Populus A9P822 localization experiment was retrieved; localization inferred from plant ortholog studies.
SAM transport / compartmentation	Although SAM is synthesized in the cytoplasm, organelles need imported SAM for methylation reactions. Arabidopsis AtSAMC1 localizes to plastids and AtSAMC2 to plastid + mitochondrial membranes; Golgi-localized SAM transporters also affect cell-wall architecture and morphology.	Roles of S-Adenosylmethionine and Its Derivatives in Salt Tolerance of Cotton (2023), https://doi.org/10.3390/ijms24119517; The Yang cycle in plants (2025), https://doi.org/10.48130/ph-0025-0007 (yang2023rolesofsadenosylmethionine pages 9-11, chen2025theyangcycle pages 2-3)	This does not mean METK1 itself is membrane-localized; rather, it supports the annotation that METK1-generated SAM is distributed to other compartments.
Biological process inference for Populus	By family function, Populus METK1 most plausibly participates in methionine/SAM metabolism, methylation-dependent regulation, and indirect control of ethylene, polyamine, and lignin-related processes, all central to growth, development, and stress responses in plants.	The Yang cycle in plants (2025), https://doi.org/10.48130/ph-0025-0007; Metabolism and Regulatory Functions of O-Acetylserine... (2021), https://doi.org/10.3389/fpls.2021.643403 (chen2025theyangcycle pages 4-5, chen2025theyangcycle pages 10-11, watanabe2021metabolismandregulatory pages 3-5)	Appropriate for functional annotation; should be labeled as inference unless Populus-specific validation becomes available.
Regulation (post-translational)	Plant SAMS proteins are post-translationally regulated, including phosphorylation and 26S proteasome-mediated degradation. Examples include regulation by CDPK/CPK kinases and proteins such as OsWAK112, OsLCD3, and OsFBK12, with consequences for ethylene/polyamine balance and development.	The Yang cycle in plants (2025), https://doi.org/10.48130/ph-0025-0007 (chen2025theyangcycle pages 5-5, chen2025theyangcycle pages 10-11)	Specific regulators are from rice/cucumber/tomato studies, not Populus.
Developmental / stress evidence from plants	Altering SAMS affects flowering, grain size, pollen tube growth, fruit ripening, and tolerance to cold/drought/salt in multiple plants. These phenotypes support the view that METK1 is a central metabolic control point rather than a pathway-specific enzyme.	The Yang cycle in plants (2025), https://doi.org/10.48130/ph-0025-0007 (chen2025theyangcycle pages 4-5, chen2025theyangcycle pages 10-11, chen2025theyangcycle pages 5-5)	Indirect evidence for poplar; useful for hypothesis generation in woody tissues and stress biology.
Quantitative engineering evidence when SAM is reduced (2024 sorghum AdoMetase study)	Lowering SAM in sorghum by expressing AdoMetase reduced acid-insoluble lignin by 18% and 13% in line #1 at two field sites; biomass saccharification improved by about ~12–24% depending on site/pretreatment; biomass yield penalties were substantial: 69% reduction for line #1 and 49% for line #3 at one site, and about 23% less biomass for both lines at the other site.	Engineered reduction of S-adenosylmethionine alters lignin in sorghum (2024), https://doi.org/10.1186/s13068-024-02572-8 (tian2024engineeredreductionof pages 8-9, tian2024engineeredreductionof pages 11-12, tian2024engineeredreductionof media dafe8723, tian2024engineeredreductionof media 23ba5d32)	Not a Populus study and it manipulates SAM levels downstream of SAMS rather than METK1 directly, but it gives strong real-world evidence that SAM supply strongly constrains lignin methylation and biomass processing traits.
Practical annotation statement for A9P822	Recommended functional annotation: cytosolic/nuclear S-adenosylmethionine synthase that converts methionine and ATP to SAM, thereby supplying methyl donor capacity and precursors for ethylene/polyamine-associated metabolism; likely important for methylation status, cell-wall/lignin methylation, and stress/developmental responses in Populus.	Synthesized from plant SAMS/MAT literature above (chen2025theyangcycle pages 2-3, chen2025theyangcycle pages 4-5, chen2025theyangcycle pages 10-11, jockmann2025chemoselectivityofoand pages 26-30, watanabe2021metabolismandregulatory pages 3-5, yang2023rolesofsadenosylmethionine pages 9-11)	Best current evidence supports a high-confidence enzyme-function annotation but only moderate confidence for Populus-specific biological specialization.

Table: This table summarizes the most defensible functional annotation for Populus trichocarpa METK1 (UniProt A9P822) based on conserved plant SAMS/MAT literature. It highlights catalytic function, localization, pathway context, regulation, and quantitative evidence showing how SAM perturbation affects lignin and biomass traits.

Key references (publication date, URL)

Feng J. et al. Sep 2022. Differences in detoxification mechanism and gene expression changes of sulfur metabolism in coping with the air pollutant SO2 between the resistant and ordinary poplar variety. Acta Physiologiae Plantarum. https://doi.org/10.1007/s11738-022-03442-2 (feng2022differencesindetoxification pages 6-9)
Zhang Y. et al. Jul 2020. DNA methylation and its effects on gene expression during primary to secondary growth in poplar stems. BMC Genomics. https://doi.org/10.1186/s12864-020-06902-6 (zhang2020dnamethylationand pages 1-2)
Watanabe M. et al. May 2021. Metabolism and Regulatory Functions of O-Acetylserine, S-Adenosylmethionine, Homocysteine, and Serine in Plant Development and Environmental Responses. Frontiers in Plant Science. https://doi.org/10.3389/fpls.2021.643403 (watanabe2021metabolismandregulatory pages 3-5)
Yang L. et al. May 2023. Roles of S-Adenosylmethionine and Its Derivatives in Salt Tolerance of Cotton. Int. J. Mol. Sci. https://doi.org/10.3390/ijms24119517 (yang2023rolesofsadenosylmethionine pages 9-11)
Tian Y. et al. Oct 2024. Engineered reduction of S-adenosylmethionine alters lignin in sorghum. Biotechnology for Biofuels and Bioproducts. https://doi.org/10.1186/s13068-024-02572-8 (tian2024engineeredreductionof pages 8-9)
Chen H. et al. Jan 2025. The Yang cycle in plants: a journey of methionine recycling with fascinating metabolites and enzymes. Plant Hormones. https://doi.org/10.48130/ph-0025-0007 (chen2025theyangcycle pages 4-5)

References

(chen2025theyangcycle pages 4-5): Huixin Chen, Ziyi Zhao, Jiawen Chen, Jana Mertens, Bram Van de Poel, Dongdong Li, and Kunsong Chen. The yang cycle in plants: a journey of methionine recycling with fascinating metabolites and enzymes. Plant Hormones, 1:0-0, Jan 2025. URL: https://doi.org/10.48130/ph-0025-0007, doi:10.48130/ph-0025-0007. This article has 8 citations.
(feng2022differencesindetoxification pages 6-9): Jinxia Feng, Luyi Wang, Wenxin Liu, Xianchong Wan, Zhicheng Chen, and Jiaping Zhao. Differences in detoxification mechanism and gene expression changes of sulfur metabolism in coping with the air pollutant so2 between the resistant and ordinary poplar variety. Acta Physiologiae Plantarum, Sep 2022. URL: https://doi.org/10.1007/s11738-022-03442-2, doi:10.1007/s11738-022-03442-2. This article has 2 citations and is from a peer-reviewed journal.
(chen2025theyangcycle pages 2-3): Huixin Chen, Ziyi Zhao, Jiawen Chen, Jana Mertens, Bram Van de Poel, Dongdong Li, and Kunsong Chen. The yang cycle in plants: a journey of methionine recycling with fascinating metabolites and enzymes. Plant Hormones, 1:0-0, Jan 2025. URL: https://doi.org/10.48130/ph-0025-0007, doi:10.48130/ph-0025-0007. This article has 8 citations.
(jockmann2025chemoselectivityofoand pages 26-30): E Jockmann. Chemoselectivity of o-and n-methyltransferases. Unknown journal, 2025.
(watanabe2021metabolismandregulatory pages 3-5): Mutsumi Watanabe, Yukako Chiba, and Masami Yokota Hirai. Metabolism and regulatory functions of o-acetylserine, s-adenosylmethionine, homocysteine, and serine in plant development and environmental responses. Frontiers in Plant Science, May 2021. URL: https://doi.org/10.3389/fpls.2021.643403, doi:10.3389/fpls.2021.643403. This article has 96 citations.
(yang2023rolesofsadenosylmethionine pages 9-11): Li Yang, Xingxing Wang, Fuyong Zhao, Xianliang Zhang, Wei Li, Junsen Huang, Xiaoyu Pei, Xiang Ren, Yangai Liu, Kunlun He, Fei Zhang, Xiongfeng Ma, and Daigang Yang. Roles of s-adenosylmethionine and its derivatives in salt tolerance of cotton. International Journal of Molecular Sciences, 24:9517, May 2023. URL: https://doi.org/10.3390/ijms24119517, doi:10.3390/ijms24119517. This article has 21 citations.
(tian2024engineeredreductionof pages 8-9): Yang Tian, Yu Gao, Halbay Turumtay, Emine Akyuz Turumtay, Yen Ning Chai, Hemant Choudhary, Joon-Hyun Park, Chuan-Yin Wu, Christopher M. De Ben, Jutta Dalton, Katherine B. Louie, Thomas Harwood, Dylan Chin, Khanh M. Vuu, Benjamin P. Bowen, Patrick M. Shih, Edward E. K. Baidoo, Trent R. Northen, Blake A. Simmons, Robert Hutmacher, Jackie Atim, Daniel H. Putnam, Corinne D. Scown, Jenny C. Mortimer, Henrik V. Scheller, and Aymerick Eudes. Engineered reduction of s-adenosylmethionine alters lignin in sorghum. Biotechnology for Biofuels and Bioproducts, Oct 2024. URL: https://doi.org/10.1186/s13068-024-02572-8, doi:10.1186/s13068-024-02572-8. This article has 7 citations and is from a domain leading peer-reviewed journal.
(tian2024engineeredreductionof media dafe8723): Yang Tian, Yu Gao, Halbay Turumtay, Emine Akyuz Turumtay, Yen Ning Chai, Hemant Choudhary, Joon-Hyun Park, Chuan-Yin Wu, Christopher M. De Ben, Jutta Dalton, Katherine B. Louie, Thomas Harwood, Dylan Chin, Khanh M. Vuu, Benjamin P. Bowen, Patrick M. Shih, Edward E. K. Baidoo, Trent R. Northen, Blake A. Simmons, Robert Hutmacher, Jackie Atim, Daniel H. Putnam, Corinne D. Scown, Jenny C. Mortimer, Henrik V. Scheller, and Aymerick Eudes. Engineered reduction of s-adenosylmethionine alters lignin in sorghum. Biotechnology for Biofuels and Bioproducts, Oct 2024. URL: https://doi.org/10.1186/s13068-024-02572-8, doi:10.1186/s13068-024-02572-8. This article has 7 citations and is from a domain leading peer-reviewed journal.
(tian2024engineeredreductionof media 23ba5d32): Yang Tian, Yu Gao, Halbay Turumtay, Emine Akyuz Turumtay, Yen Ning Chai, Hemant Choudhary, Joon-Hyun Park, Chuan-Yin Wu, Christopher M. De Ben, Jutta Dalton, Katherine B. Louie, Thomas Harwood, Dylan Chin, Khanh M. Vuu, Benjamin P. Bowen, Patrick M. Shih, Edward E. K. Baidoo, Trent R. Northen, Blake A. Simmons, Robert Hutmacher, Jackie Atim, Daniel H. Putnam, Corinne D. Scown, Jenny C. Mortimer, Henrik V. Scheller, and Aymerick Eudes. Engineered reduction of s-adenosylmethionine alters lignin in sorghum. Biotechnology for Biofuels and Bioproducts, Oct 2024. URL: https://doi.org/10.1186/s13068-024-02572-8, doi:10.1186/s13068-024-02572-8. This article has 7 citations and is from a domain leading peer-reviewed journal.
(chen2025theyangcycle pages 5-5): Huixin Chen, Ziyi Zhao, Jiawen Chen, Jana Mertens, Bram Van de Poel, Dongdong Li, and Kunsong Chen. The yang cycle in plants: a journey of methionine recycling with fascinating metabolites and enzymes. Plant Hormones, 1:0-0, Jan 2025. URL: https://doi.org/10.48130/ph-0025-0007, doi:10.48130/ph-0025-0007. This article has 8 citations.
(chen2025theyangcycle pages 10-11): Huixin Chen, Ziyi Zhao, Jiawen Chen, Jana Mertens, Bram Van de Poel, Dongdong Li, and Kunsong Chen. The yang cycle in plants: a journey of methionine recycling with fascinating metabolites and enzymes. Plant Hormones, 1:0-0, Jan 2025. URL: https://doi.org/10.48130/ph-0025-0007, doi:10.48130/ph-0025-0007. This article has 8 citations.
(zhang2020dnamethylationand pages 1-2): Yang Zhang, Cong Liu, He Cheng, Shuanghui Tian, Yingying Liu, Shuang Wang, Huaxin Zhang, Muhammad Saqib, Hairong Wei, and Zhigang Wei. Dna methylation and its effects on gene expression during primary to secondary growth in poplar stems. BMC Genomics, Jul 2020. URL: https://doi.org/10.1186/s12864-020-06902-6, doi:10.1186/s12864-020-06902-6. This article has 52 citations and is from a peer-reviewed journal.
(chen2025theyangcycle pages 11-11): Huixin Chen, Ziyi Zhao, Jiawen Chen, Jana Mertens, Bram Van de Poel, Dongdong Li, and Kunsong Chen. The yang cycle in plants: a journey of methionine recycling with fascinating metabolites and enzymes. Plant Hormones, 1:0-0, Jan 2025. URL: https://doi.org/10.48130/ph-0025-0007, doi:10.48130/ph-0025-0007. This article has 8 citations.
(tian2024engineeredreductionof pages 11-12): Yang Tian, Yu Gao, Halbay Turumtay, Emine Akyuz Turumtay, Yen Ning Chai, Hemant Choudhary, Joon-Hyun Park, Chuan-Yin Wu, Christopher M. De Ben, Jutta Dalton, Katherine B. Louie, Thomas Harwood, Dylan Chin, Khanh M. Vuu, Benjamin P. Bowen, Patrick M. Shih, Edward E. K. Baidoo, Trent R. Northen, Blake A. Simmons, Robert Hutmacher, Jackie Atim, Daniel H. Putnam, Corinne D. Scown, Jenny C. Mortimer, Henrik V. Scheller, and Aymerick Eudes. Engineered reduction of s-adenosylmethionine alters lignin in sorghum. Biotechnology for Biofuels and Bioproducts, Oct 2024. URL: https://doi.org/10.1186/s13068-024-02572-8, doi:10.1186/s13068-024-02572-8. This article has 7 citations and is from a domain leading peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

jockmann2025chemoselectivityofoand pages 26-30
chen2025theyangcycle pages 4-5
yang2023rolesofsadenosylmethionine pages 9-11
tian2024engineeredreductionof pages 8-9
feng2022differencesindetoxification pages 6-9
zhang2020dnamethylationand pages 1-2
watanabe2021metabolismandregulatory pages 3-5
chen2025theyangcycle pages 2-3
chen2025theyangcycle pages 5-5
chen2025theyangcycle pages 10-11
chen2025theyangcycle pages 11-11
tian2024engineeredreductionof pages 11-12
https://doi.org/10.48130/ph-0025-0007;
https://doi.org/10.3389/fpls.2021.643403
https://doi.org/10.48130/ph-0025-0007
https://doi.org/10.3389/fpls.2021.643403;
https://doi.org/10.3390/ijms24119517;
https://doi.org/10.3390/ijms24119517
https://doi.org/10.1186/s13068-024-02572-8
https://doi.org/10.1007/s11738-022-03442-2
https://doi.org/10.1186/s12864-020-06902-6
https://doi.org/10.48130/ph-0025-0007,
https://doi.org/10.1007/s11738-022-03442-2,
https://doi.org/10.3389/fpls.2021.643403,
https://doi.org/10.3390/ijms24119517,
https://doi.org/10.1186/s13068-024-02572-8,
https://doi.org/10.1186/s12864-020-06902-6,

📄 View Raw YAML

id: A9P822
gene_symbol: METK1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:3694
  label: Populus trichocarpa
description: Cytosolic S-adenosylmethionine synthase 1 (methionine adenosyltransferase,
  MAT; EC 2.5.1.6) from Populus trichocarpa. METK1 catalyzes the only known biosynthetic
  route to S-adenosyl-L-methionine (SAM/AdoMet), condensing L-methionine with ATP
  and releasing triphosphate, which the same enzyme then hydrolyzes to phosphate and
  diphosphate. The reaction requires two divalent metal ions per subunit (Mg2+; Mn2+
  or Co2+ usable in vitro) and one monovalent potassium ion that coordinate the substrates.
  The enzyme acts as a homotetramer in the cytoplasm. SAM is the universal activated
  methyl donor for methyltransferases acting on DNA, RNA, proteins, lipids and small
  molecules, and is also the precursor for polyamine and ethylene biosynthesis in plants,
  making METK1 a metabolic hub. METK1 is one of several SAM synthase paralogs in the
  poplar genome.
existing_annotations:
# --- SPKW keyword-mapping annotations (GO_REF:0000043) ---
# Present in the Sept 2025 goa_uniprot_gcrp snapshot (go-db plant.ddb); REMOVED
# from the current (2026) GOA release. Reviewed retrospectively; retired: true.
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  retired: true
  review:
    summary: SPKW keyword-mapping annotation (GO_REF:0000043) derived from the UniProt
      "Metal-binding", "Magnesium", "Cobalt" and "Potassium" keywords; present in the
      Sept 2025 GOA snapshot but removed from the current GOA release after the keyword2GO
      pipeline was retired for cellular organisms. The assertion is biochemically correct
      - the enzyme binds two divalent metal ions (Mg2+, with Mn2+ or Co2+ usable in
      vitro) and one monovalent potassium ion per subunit, both of which coordinate
      the substrates during catalysis. However, "metal ion binding" is an uninformative
      grouping term that does not distinguish a catalytically essential cofactor requirement
      from incidental metal contacts. More specific terms (magnesium ion binding, GO:0000287;
      potassium ion binding, GO:0030955) precisely capture the documented cofactor
      requirement. GOA's removal pruned a true-but-coarse term rather than losing biologically
      meaningful information.
    action: MARK_AS_OVER_ANNOTATED
    reason: The term is correct (METK1 binds divalent metal and K+ cofactors required
      for catalysis) but uninformative. It is a redundant, low-information SPKW grouping
      term; the specific cofactor identities are better represented by the proposed
      replacement terms. Its removal from current GOA is justified as pruning of coarse
      keyword-derived annotation.
    proposed_replacement_terms:
    - id: GO:0000287
      label: magnesium ion binding
    - id: GO:0030955
      label: potassium ion binding
    supported_by:
    - reference_id: file:POPTR/METK1/METK1-uniprot.txt
      supporting_text: Note=Binds 2 divalent ions per subunit. The metal ions interact
        CC primarily with the substrate (By similarity). Can utilize magnesium, CC
        manganese or cobalt (in vitro)
    - reference_id: file:POPTR/METK1/METK1-uniprot.txt
      supporting_text: Note=Binds 1 potassium ion per subunit. The potassium ion interacts
        CC primarily with the substrate (By similarity).
    - reference_id: file:POPTR/METK1/METK1-deep-research-falcon.md
      supporting_text: MAT binds ATP and L-methionine (requires **Mg2+** and **K+**)
        and proceeds via an **SN2-type** reaction where methionine sulfur attacks the
        **5′ carbon** of the ATP ribose; the ATP β–γ bond is hydrolyzed producing **PPi
        and Pi**.
- term:
    id: GO:0006730
    label: one-carbon metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  retired: true
  review:
    summary: SPKW keyword-mapping annotation (GO_REF:0000043) derived from the UniProt
      "One-carbon metabolism" keyword; present in the Sept 2025 GOA snapshot but removed
      from the current GOA release after the keyword2GO pipeline was retired for cellular
      organisms. The annotation is biologically defensible - S-adenosylmethionine produced
      by METK1 is the universal activated methyl donor that supplies one-carbon (methyl)
      units to methyltransferase reactions across nucleic acid, protein, lipid and
      small-molecule metabolism. However, GO:0006730 is a broad parent process and
      is coarse relative to the precise child term S-adenosylmethionine biosynthetic
      process (GO:0006556), which is already annotated (IBA and IEA) and directly describes
      what METK1 does. The enzyme synthesizes the methyl-donor cofactor; it does not
      itself transfer one-carbon units. The term is therefore correct-but-broad and
      largely redundant with the more specific GO:0006556 annotation.
    action: KEEP_AS_NON_CORE
    reason: One-carbon metabolic process is a true but broad parent of the gene's actual
      role; METK1 produces the SAM methyl donor that feeds one-carbon/methyl-transfer
      metabolism. It is retained as a non-core process annotation because the core
      function is more precisely captured by S-adenosylmethionine biosynthetic process
      (GO:0006556). Its removal from current GOA is a minor loss at most, since the
      specific child term remains annotated.
    supported_by:
    - reference_id: file:POPTR/METK1/METK1-uniprot.txt
      supporting_text: 'FUNCTION: Catalyzes the formation of S-adenosylmethionine from
        CC methionine and ATP.'
    - reference_id: file:POPTR/METK1/METK1-uniprot.txt
      supporting_text: 'PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis;
        CC S-adenosyl-L-methionine from L-methionine: step 1/1.'
    - reference_id: file:POPTR/METK1/METK1-deep-research-falcon.md
      supporting_text: The **universal methyl donor** for methyltransferases, including
        those involved in **DNA/histone methylation** and **secondary metabolism**.
# --- Current GOA annotations (2026 release) ---
- term:
    id: GO:0006556
    label: S-adenosylmethionine biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: S-adenosylmethionine biosynthesis is the direct pathway for methionine
      adenosyltransferase.
    action: ACCEPT
    reason: The enzyme forms S-adenosyl-L-methionine from L-methionine and ATP.
    supported_by:
    - reference_id: file:POPTR/METK1/METK1-uniprot.txt
      supporting_text: 'PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine
        biosynthesis'
    - reference_id: file:POPTR/METK1/METK1-deep-research-falcon.md
      supporting_text: The primary function inferred for Populus METK1 is to make
        **SAM**, the central activated methyl donor and branch-point metabolite
- term:
    id: GO:0004478
    label: methionine adenosyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Methionine adenosyltransferase activity is the core molecular function.
    action: ACCEPT
    reason: The UniProt entry assigns EC 2.5.1.6 and the reaction for SAM synthesis.
    supported_by:
    - reference_id: file:POPTR/METK1/METK1-uniprot.txt
      supporting_text: 'FUNCTION: Catalyzes the formation of S-adenosylmethionine
        from CC methionine and ATP.'
    - reference_id: file:POPTR/METK1/METK1-uniprot.txt
      supporting_text: EC=2.5.1.6
    - reference_id: file:POPTR/METK1/METK1-deep-research-falcon.md
      supporting_text: Plant MAT/SAMS catalyzes **L-methionine + ATP → S-adenosyl-L-methionine
        (SAM/AdoMet) + PPi + Pi**
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: ATP binding is required for the reaction but is less informative than
      methionine adenosyltransferase activity.
    action: KEEP_AS_NON_CORE
    reason: Retain as a co-substrate binding feature, not as the core function.
    supported_by:
    - reference_id: file:POPTR/METK1/METK1-uniprot.txt
      supporting_text: Reaction=L-methionine + ATP + H2O = S-adenosyl-L-methionine
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: Cytoplasm/cytosol localization is appropriate for this soluble AdoMet
      synthase.
    action: ACCEPT
    reason: UniProt places the enzyme in the cytoplasm.
    supported_by:
    - reference_id: file:POPTR/METK1/METK1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0006556
    label: S-adenosylmethionine biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: S-adenosylmethionine biosynthesis is the direct pathway for methionine
      adenosyltransferase.
    action: ACCEPT
    reason: The enzyme forms S-adenosyl-L-methionine from L-methionine and ATP.
    supported_by:
    - reference_id: file:POPTR/METK1/METK1-uniprot.txt
      supporting_text: 'PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine
        biosynthesis'
    - reference_id: file:POPTR/METK1/METK1-deep-research-falcon.md
      supporting_text: The primary function inferred for Populus METK1 is to make
        **SAM**, the central activated methyl donor and branch-point metabolite
- term:
    id: GO:0004478
    label: methionine adenosyltransferase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Methionine adenosyltransferase activity is the core molecular function.
    action: ACCEPT
    reason: The UniProt entry assigns EC 2.5.1.6 and the reaction for SAM synthesis.
    supported_by:
    - reference_id: file:POPTR/METK1/METK1-uniprot.txt
      supporting_text: 'FUNCTION: Catalyzes the formation of S-adenosylmethionine
        from CC methionine and ATP.'
    - reference_id: file:POPTR/METK1/METK1-uniprot.txt
      supporting_text: EC=2.5.1.6
    - reference_id: file:POPTR/METK1/METK1-deep-research-falcon.md
      supporting_text: Plant MAT/SAMS catalyzes **L-methionine + ATP → S-adenosyl-L-methionine
        (SAM/AdoMet) + PPi + Pi**
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings:
  - statement: GO_REF:0000002 supplied one or more source GOA annotations reviewed
      in this file.
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings:
  - statement: SwissProt keyword-derived (SPKW) annotations present in the Sept 2025
      goa_uniprot_gcrp snapshot but removed from the current GOA release after GOA
      retired the keyword2GO pipeline for cellular organisms.
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings:
  - statement: GO_REF:0000024 supplied one or more source GOA annotations reviewed
      in this file.
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings:
  - statement: GO_REF:0000033 supplied one or more source GOA annotations reviewed
      in this file.
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings:
  - statement: GO_REF:0000044 supplied one or more source GOA annotations reviewed
      in this file.
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings:
  - statement: GO_REF:0000120 supplied one or more source GOA annotations reviewed
      in this file.
- id: file:POPTR/METK1/METK1-uniprot.txt
  title: UniProtKB reviewed entry for METK1
  findings:
  - statement: UniProt identifies METK1 as methionine adenosyltransferase, catalyzing
      S-adenosyl-L-methionine formation from L-methionine, ATP, and water in the cytoplasm.
- id: file:POPTR/METK1/METK1-goa.tsv
  title: QuickGO GOA annotations for METK1
  findings:
  - statement: GOA rows supplied the existing_annotations reviewed in this file.
- id: file:POPTR/METK1/METK1-deep-research-falcon.md
  title: Falcon deep-research report on METK1 (Populus trichocarpa S-adenosylmethionine
    synthase 1, UniProt A9P822)
  findings:
  - statement: METK1/SAMS/MAT (EC 2.5.1.6) catalyzes formation of S-adenosyl-L-methionine
      (SAM/AdoMet) from L-methionine and ATP via an SN2-type reaction in which the
      methionine sulfur attacks the 5' carbon of the ATP ribose; the report confirms
      this is the most defensible high-confidence enzyme-function annotation for A9P822.
  - statement: The catalytic mechanism requires Mg2+ and K+ cofactors that coordinate
      the substrates, corroborating the metal ion binding (cofactor) requirement of
      the enzyme.
  - statement: SAM produced by METK1 is the universal activated methyl donor for methyltransferases
      acting on DNA, histones, RNA, proteins and small molecules, and is a branch-point
      precursor feeding ethylene and polyamine biosynthesis - placing METK1 as a central
      one-carbon/methyl-transfer metabolic capacity enzyme rather than a pathway-specific
      regulator.
  - statement: Plant SAMS is reported to localize to the cytoplasm and nucleus, with
      SAM synthesized in the cytoplasm and distributed to organelles by dedicated SAM
      transporters; this supports the cytosolic localization annotation for METK1.
  - statement: In poplar (Populus x euramericana) exposed to SO2, metK/SAMS is up-regulated
      together with ACS in a resistant cultivar, providing direct genus-level evidence
      that METK1-type SAM-synthesis capacity participates in stress-associated metabolic
      remodeling; no primary study assays the specific P. trichocarpa A9P822 protein,
      so functional annotation rests on orthology/family inference.
core_functions:
- description: Synthesizes S-adenosyl-L-methionine from L-methionine and ATP in the
    cytosol.
  molecular_function:
    id: GO:0004478
    label: methionine adenosyltransferase activity
  directly_involved_in:
  - id: GO:0006556
    label: S-adenosylmethionine biosynthetic process
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:POPTR/METK1/METK1-uniprot.txt
    supporting_text: 'FUNCTION: Catalyzes the formation of S-adenosylmethionine from
      CC methionine and ATP.'
  - reference_id: file:POPTR/METK1/METK1-uniprot.txt
    supporting_text: Reaction=L-methionine + ATP + H2O = S-adenosyl-L-methionine +
      phosphate
  - reference_id: file:POPTR/METK1/METK1-uniprot.txt
    supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
  - reference_id: file:POPTR/METK1/METK1-deep-research-falcon.md
    supporting_text: '**Recommended functional annotation:** cytosolic/nuclear **S-adenosylmethionine
      synthase** that converts methionine and ATP to SAM, thereby supplying methyl
      donor capacity and precursors for ethylene/polyamine-associated metabolism'
proposed_new_terms: []
suggested_questions:
- question: Are METK1 and the other Populus SAM synthase paralogs functionally redundant,
    or do they supply distinct methylation, polyamine and ethylene biosynthetic demands
    in specific tissues (e.g. xylem during lignification)?
- question: Is METK1 expression coordinated with lignin biosynthesis, given that SAM
    is the methyl donor for caffeic acid O-methyltransferase and related monolignol-pathway
    methyltransferases in poplar wood formation?
suggested_experiments:
- description: Generate METK1-specific knockdown/CRISPR lines and quantify SAM and
    S-adenosylhomocysteine pools, transmethylation flux, and methylation-dependent
    phenotypes (DNA methylation, lignin content/composition) relative to paralog-specific
    lines.
  experiment_type: targeted functional assay
- description: Recombinantly express and purify METK1 to confirm EC 2.5.1.6 activity
    and measure the kinetic dependence on Mg2+ and K+, validating the predicted metal
    cofactor requirements directly in the poplar enzyme.
  experiment_type: enzyme kinetics / biochemical characterization
- description: Profile METK1 transcript and protein abundance across tissues and developmental
    stages (especially developing xylem) to test coordination with lignin biosynthesis
    and other SAM-dependent pathways.
  experiment_type: expression profiling

Gene Description

Existing Annotations Review

Core Functions

Synthesizes S-adenosyl-L-methionine from L-methionine and ATP in the cytosol.