glyA

id: P50435
gene_symbol: glyA
product_type: PROTEIN
taxon:
  id: NCBITaxon:272630
  label: Methylorubrum extorquens AM1
description: "glyA encodes serine hydroxymethyltransferase (SHMT, EC 2.1.2.1), a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the reversible interconversion of serine and glycine with tetrahydrofolate (THF). This reaction is crucial for the serine cycle, the central assimilatory pathway in methylotrophy, where it serves as the major source of one-carbon groups required for biosynthesis of purines, thymidylate, methionine, and other biomolecules. The enzyme functions as a homodimer in the cytoplasm. SHMT catalyzes: L-serine + THF ⇌ glycine + 5,10-methylenetetrahydrofolate + H₂O. In methylotrophic metabolism, this enzyme is essential for converting C1 units from formaldehyde oxidation (via the H4MPT pathway) into the tetrahydrofolate pool, where they are used for serine biosynthesis from glycine, completing a key step in the serine cycle. The enzyme also exhibits THF-independent aldolase activity toward β-hydroxyamino acids. Genetic studies have confirmed glyA is essential
  for methylotrophic growth in M. extorquens AM1."
existing_annotations:
- term:
    id: GO:0004372
    label: glycine hydroxymethyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Correct - SHMT catalyzes the reversible interconversion of serine and glycine with THF [file:METEA/glyA/glyA-uniprot.txt, "Catalyzes the reversible interconversion of serine and glycine with tetrahydrofolate (THF) serving as the one-carbon carrier"].
    action: ACCEPT
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'Correct - SHMT is localized to the cytoplasm where it participates in the serine cycle [file:METEA/glyA/glyA-uniprot.txt, "SUBCELLULAR LOCATION: Cytoplasm"].'
    action: ACCEPT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000118
  review:
    summary: Correct - More specific than cytoplasm; SHMT operates in the cytosolic compartment [file:METEA/glyA/glyA-uniprot.txt, "Cytoplasm"].
    action: ACCEPT
- term:
    id: GO:0006730
    label: one-carbon metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Correct - SHMT is central to C1 metabolism, transferring C1 units between amino acids and THF [file:METEA/glyA/glyA-uniprot.txt, "One-carbon metabolism; tetrahydrofolate interconversion"].
    action: ACCEPT
- term:
    id: GO:0008652
    label: amino acid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Correct but too general - SHMT catalyzes both serine and glycine biosynthesis; more specific child terms are available (e.g., glycine biosynthetic process, serine family amino acid biosynthetic process).
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Correct but too general - SHMT is a transferase, but the specific term "glycine hydroxymethyltransferase activity" (GO:0004372) is more informative.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0019264
    label: glycine biosynthetic process from L-serine
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'Correct - SHMT catalyzes step 1/1 in glycine biosynthesis from L-serine [file:METEA/glyA/glyA-uniprot.txt, "Amino-acid biosynthesis; glycine biosynthesis; glycine from L-serine: step 1/1"].'
    action: ACCEPT
- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'Correct - SHMT requires pyridoxal 5''-phosphate (PLP) as cofactor; lysine 242 forms covalent linkage [file:METEA/glyA/glyA-uniprot.txt, "COFACTOR: Name=pyridoxal 5''-phosphate...MOD_RES 242 N6-(pyridoxal phosphate)lysine"].'
    action: ACCEPT
- term:
    id: GO:0035999
    label: tetrahydrofolate interconversion
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'Correct - SHMT interconverts THF and 5,10-methylenetetrahydrofolate, essential for C1 metabolism [file:METEA/glyA/glyA-uniprot.txt, "PATHWAY: One-carbon metabolism; tetrahydrofolate interconversion"].'
    action: ACCEPT
- term:
    id: GO:0046653
    label: tetrahydrofolate metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000118
  review:
    summary: Correct but redundant - More specific term "tetrahydrofolate interconversion" (GO:0035999) captures the same process more precisely.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0006545
    label: glycine biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  review:
    summary: 'Correct - SHMT catalyzes glycine biosynthesis from serine; parent term of GO:0019264 [file:METEA/glyA/glyA-uniprot.txt, "glycine biosynthesis; glycine from L-serine: step 1/1"].'
    action: ACCEPT
core_functions:
- description: "GlyA catalyzes the reversible, pyridoxal 5'-phosphate (PLP)-dependent interconversion of L-serine and glycine with tetrahydrofolate (THF) serving as the one-carbon carrier, producing 5,10-methylenetetrahydrofolate. This enzyme is the central node of the serine cycle in methylotrophic metabolism, where it integrates C1 units from formaldehyde oxidation (via the H4MPT pathway) into cellular biosynthesis. The reaction provides the major source of one-carbon units required for synthesis of purines, thymidylate, methionine, and other biomolecules. GlyA functions as a homodimer in the cytoplasm and is essential for methylotrophic growth on methanol. The enzyme also exhibits THF-independent aldolase activity toward β-hydroxyamino acids via a retro-aldol mechanism."
  molecular_function:
    id: GO:0004372
    label: glycine hydroxymethyltransferase activity
  directly_involved_in:
  - id: GO:0035999
    label: tetrahydrofolate interconversion
  - id: GO:0006730
    label: one-carbon metabolic process
  - id: GO:0019264
    label: glycine biosynthetic process from L-serine
  - id: GO:0006545
    label: glycine biosynthetic process
  locations:
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: file:METEA/glyA/glyA-uniprot.txt
    supporting_text: 'Catalyzes the reversible interconversion of serine and glycine with tetrahydrofolate (THF) serving as the one-carbon carrier...COFACTOR: Name=pyridoxal 5''-phosphate...Homodimer...Cytoplasm...Genetics of the serine cycle in Methylobacterium extorquens AM1'
references:
- id: file:METEA/glyA/glyA-uniprot.txt
  title: UniProt entry for glyA serine hydroxymethyltransferase
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping.
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000118
  title: TreeGrafter-generated GO annotations
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods.
  findings: []
status: COMPLETE
tags:
- metea