gcvP

UniProt ID: C5AUG0
Organism: Methylorubrum extorquens AM1
Review Status: COMPLETE
📝 Provide Detailed Feedback

Gene Description

gcvP encodes glycine dehydrogenase (decarboxylating) (EC 1.4.4.2), also known as glycine cleavage system P protein, which catalyzes the first step of the glycine cleavage system. The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor (at Lys-699), cleaves the C-C bond to release CO2, and transfers the remaining methylamine moiety to the lipoamide cofactor of the H protein (gcvH). This initiates the oxidative decarboxylation of glycine, which is then completed by the T and L proteins to produce 5,10-methylene-THF, CO2, and ammonia. The enzyme belongs to the GcvP family and functions as a component of the four-protein glycine cleavage complex (P, T, L, and H). In methylotrophs, the glycine cleavage system connects the serine cycle to the THF one-carbon pool: glycine (produced from serine by serA) is oxidatively cleaved by the GCV system, generating 5,10-methylene-THF that feeds into C1 metabolism. GcvP is a large protein (948 AA) with three characteristic domains: two N-terminal glycine cleavage system P-protein domains (residues 14-438 and 474-721) and a C-terminal domain (residues 766-887). The enzyme is essential for glycine catabolism and for recycling one-carbon units during methylotrophic growth.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004375 glycine dehydrogenase (decarboxylating) activity
IEA
GO_REF:0000120
ACCEPT
Summary: This is the primary and specific catalytic activity of GcvP - the oxidative decarboxylation of glycine. The P protein binds glycine through its pyridoxal phosphate cofactor, cleaves the C-C bond to release CO2, and transfers the methylamine moiety to the H protein. [file:METEA/gcvP/gcvP-uniprot.txt, "Glycine dehydrogenase (decarboxylating)"; "EC=1.4.4.2"; "N(6)-[(R)-lipoyl]-L-lysyl-[glycine-cleavage complex H protein] + glycine + H(+) = N(6)-[(R)-S(8)-aminomethyldihydrolipoyl]-L-lysyl-[glycine-cleavage complex H protein] + CO2"]
GO:0005829 cytosol
IEA
GO_REF:0000118
ACCEPT
Summary: GcvP functions in the cytosol as part of the glycine cleavage complex. While cytosol is more specific than cytoplasm, the primary location annotation should be the glycine cleavage complex. [file:METEA/gcvP/gcvP-uniprot.txt, "The glycine cleavage system is composed of four proteins: P, T, L and H"]
GO:0005960 glycine cleavage complex
IEA
GO_REF:0000118
ACCEPT
Summary: GcvP is a component of the glycine cleavage complex, working together with gcvT, gcvH, and gcvL to catalyze the oxidative cleavage of glycine. This is the primary cellular location for the enzyme. [file:METEA/gcvP/gcvP-uniprot.txt, "Glycine cleavage system P-protein"; "The glycine cleavage system is composed of four proteins: P, T, L and H"]
GO:0006544 glycine metabolic process
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: This is a general parent term for all glycine metabolism. While technically correct, the more specific term GO:0019464 (glycine decarboxylation via glycine cleavage system) provides better functional annotation.
GO:0006546 glycine catabolic process
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: GcvP catalyzes the first step of glycine catabolism via the glycine cleavage system, initiating the oxidative decarboxylation of glycine. While correct, the more specific term GO:0019464 provides better functional annotation.
GO:0016491 oxidoreductase activity
IEA
GO_REF:0000043
KEEP AS NON CORE
Summary: This is a very general parent term for all oxidoreductase enzymes. While technically correct (GcvP catalyzes an oxidative decarboxylation), the more specific term GO:0004375 (glycine dehydrogenase activity) provides much better functional annotation.
GO:0016594 glycine binding
IEA
GO_REF:0000118
ACCEPT
Summary: GcvP binds glycine as its substrate through the pyridoxal phosphate cofactor. This is an essential substrate binding function that precedes the catalytic decarboxylation step. [file:METEA/gcvP/gcvP-uniprot.txt, "The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor"]
GO:0019464 glycine decarboxylation via glycine cleavage system
IEA
GO_REF:0000120
ACCEPT
Summary: GcvP catalyzes the first step of glycine decarboxylation via the glycine cleavage system, initiating the oxidative cleavage of glycine by releasing CO2 and transferring the methylamine moiety to the H protein. This is the specific biological process that GcvP participates in. [file:METEA/gcvP/gcvP-uniprot.txt, "The glycine cleavage system catalyzes the degradation of glycine"]
GO:0030170 pyridoxal phosphate binding
IEA
GO_REF:0000118
ACCEPT
Summary: GcvP requires pyridoxal phosphate (PLP) as a cofactor, which is covalently bound at Lys-699. The PLP cofactor is essential for binding the alpha-amino group of glycine and facilitating the decarboxylation reaction. [file:METEA/gcvP/gcvP-uniprot.txt, "COFACTOR: Name=pyridoxal 5'-phosphate"; "N6-(pyridoxal phosphate)lysine" at position 699; "The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor"]

Core Functions

GcvP catalyzes the first and rate-limiting step of the glycine cleavage system: the oxidative decarboxylation of glycine via a pyridoxal phosphate-dependent mechanism. The P protein binds the alpha-amino group of glycine through its PLP cofactor (covalently attached at Lys-699), cleaves the C-C bond to release CO2, and transfers the resulting methylamine moiety to the lipoamide cofactor of the H protein carrier. This initiates the four-step glycine cleavage process that ultimately produces 5,10-methylene-THF, CO2, and ammonia. In methylotrophic bacteria like M. extorquens AM1, the glycine cleavage system connects the serine cycle to the THF one-carbon pool: glycine (produced from serine via serA) is oxidatively cleaved by the GCV system, generating 5,10-methylene-THF for downstream C1 metabolism. GcvP is a large, multi-domain protein (948 AA) that functions as part of the four-protein complex (P, T, L, H) in the cytosol. The enzyme is essential for glycine catabolism and for recycling one-carbon units during growth on C1 compounds.

Supporting Evidence:
  • file:METEA/gcvP/gcvP-uniprot.txt
    The P protein binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO2 is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein. The glycine cleavage system catalyzes the degradation of glycine.

References

Gene Ontology annotation through association of InterPro records with GO terms.
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
TreeGrafter-generated GO annotations
Combined Automated Annotation using Multiple IEA Methods.
file:METEA/gcvP/gcvP-uniprot.txt
UniProt record for gcvP (C5AUG0)

📄 View Raw YAML

---
id: C5AUG0
gene_symbol: gcvP
product_type: PROTEIN
taxon:
  id: NCBITaxon:272630
  label: Methylorubrum extorquens AM1
description: 'gcvP encodes glycine dehydrogenase (decarboxylating) (EC 1.4.4.2), also
  known as glycine cleavage system P protein, which catalyzes the first step of the
  glycine cleavage system. The P protein binds the alpha-amino group of glycine through
  its pyridoxal phosphate cofactor (at Lys-699), cleaves the C-C bond to release CO2,
  and transfers the remaining methylamine moiety to the lipoamide cofactor of the
  H protein (gcvH). This initiates the oxidative decarboxylation of glycine, which
  is then completed by the T and L proteins to produce 5,10-methylene-THF, CO2, and
  ammonia. The enzyme belongs to the GcvP family and functions as a component of the
  four-protein glycine cleavage complex (P, T, L, and H). In methylotrophs, the glycine
  cleavage system connects the serine cycle to the THF one-carbon pool: glycine (produced
  from serine by serA) is oxidatively cleaved by the GCV system, generating 5,10-methylene-THF
  that feeds into C1 metabolism. GcvP is a large protein (948 AA) with three characteristic
  domains: two N-terminal glycine cleavage system P-protein domains (residues 14-438
  and 474-721) and a C-terminal domain (residues 766-887). The enzyme is essential
  for glycine catabolism and for recycling one-carbon units during methylotrophic
  growth.'
existing_annotations:
  - term:
      id: GO:0004375
      label: glycine dehydrogenase (decarboxylating) activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: This is the primary and specific catalytic activity of GcvP - the oxidative
        decarboxylation of glycine. The P protein binds glycine through its pyridoxal
        phosphate cofactor, cleaves the C-C bond to release CO2, and transfers the
        methylamine moiety to the H protein. [file:METEA/gcvP/gcvP-uniprot.txt, "Glycine
        dehydrogenase (decarboxylating)"; "EC=1.4.4.2"; "N(6)-[(R)-lipoyl]-L-lysyl-[glycine-cleavage
        complex H protein] + glycine + H(+) = N(6)-[(R)-S(8)-aminomethyldihydrolipoyl]-L-lysyl-[glycine-cleavage
        complex H protein] + CO2"]
      action: ACCEPT
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IEA
    original_reference_id: GO_REF:0000118
    review:
      summary: 'GcvP functions in the cytosol as part of the glycine cleavage complex.
        While cytosol is more specific than cytoplasm, the primary location annotation
        should be the glycine cleavage complex. [file:METEA/gcvP/gcvP-uniprot.txt,
        "The glycine cleavage system is composed of four proteins: P, T, L and H"]'
      action: ACCEPT
  - term:
      id: GO:0005960
      label: glycine cleavage complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000118
    review:
      summary: 'GcvP is a component of the glycine cleavage complex, working together
        with gcvT, gcvH, and gcvL to catalyze the oxidative cleavage of glycine. This
        is the primary cellular location for the enzyme. [file:METEA/gcvP/gcvP-uniprot.txt,
        "Glycine cleavage system P-protein"; "The glycine cleavage system is composed
        of four proteins: P, T, L and H"]'
      action: ACCEPT
  - term:
      id: GO:0006544
      label: glycine metabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: This is a general parent term for all glycine metabolism. While technically
        correct, the more specific term GO:0019464 (glycine decarboxylation via glycine
        cleavage system) provides better functional annotation.
      action: KEEP_AS_NON_CORE
  - term:
      id: GO:0006546
      label: glycine catabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: GcvP catalyzes the first step of glycine catabolism via the glycine
        cleavage system, initiating the oxidative decarboxylation of glycine. While
        correct, the more specific term GO:0019464 provides better functional annotation.
      action: KEEP_AS_NON_CORE
  - term:
      id: GO:0016491
      label: oxidoreductase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: This is a very general parent term for all oxidoreductase enzymes.
        While technically correct (GcvP catalyzes an oxidative decarboxylation), the
        more specific term GO:0004375 (glycine dehydrogenase activity) provides much
        better functional annotation.
      action: KEEP_AS_NON_CORE
  - term:
      id: GO:0016594
      label: glycine binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000118
    review:
      summary: GcvP binds glycine as its substrate through the pyridoxal phosphate
        cofactor. This is an essential substrate binding function that precedes the
        catalytic decarboxylation step. [file:METEA/gcvP/gcvP-uniprot.txt, "The P
        protein binds the alpha-amino group of glycine through its pyridoxal phosphate
        cofactor"]
      action: ACCEPT
  - term:
      id: GO:0019464
      label: glycine decarboxylation via glycine cleavage system
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: GcvP catalyzes the first step of glycine decarboxylation via the glycine
        cleavage system, initiating the oxidative cleavage of glycine by releasing
        CO2 and transferring the methylamine moiety to the H protein. This is the
        specific biological process that GcvP participates in. [file:METEA/gcvP/gcvP-uniprot.txt,
        "The glycine cleavage system catalyzes the degradation of glycine"]
      action: ACCEPT
  - term:
      id: GO:0030170
      label: pyridoxal phosphate binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000118
    review:
      summary: "GcvP requires pyridoxal phosphate (PLP) as a cofactor, which is covalently\
        \ bound at Lys-699. The PLP cofactor is essential for binding the alpha-amino\
        \ group of glycine and facilitating the decarboxylation reaction. [file:METEA/gcvP/gcvP-uniprot.txt,\
        \ \"COFACTOR: Name=pyridoxal 5'-phosphate\"; \"N6-(pyridoxal phosphate)lysine\"\
        \ at position 699; \"The P protein binds the alpha-amino group of glycine\
        \ through its pyridoxal phosphate cofactor\"]"
      action: ACCEPT
core_functions:
  - description: 'GcvP catalyzes the first and rate-limiting step of the glycine cleavage
      system: the oxidative decarboxylation of glycine via a pyridoxal phosphate-dependent
      mechanism. The P protein binds the alpha-amino group of glycine through its
      PLP cofactor (covalently attached at Lys-699), cleaves the C-C bond to release
      CO2, and transfers the resulting methylamine moiety to the lipoamide cofactor
      of the H protein carrier. This initiates the four-step glycine cleavage process
      that ultimately produces 5,10-methylene-THF, CO2, and ammonia. In methylotrophic
      bacteria like M. extorquens AM1, the glycine cleavage system connects the serine
      cycle to the THF one-carbon pool: glycine (produced from serine via serA) is
      oxidatively cleaved by the GCV system, generating 5,10-methylene-THF for downstream
      C1 metabolism. GcvP is a large, multi-domain protein (948 AA) that functions
      as part of the four-protein complex (P, T, L, H) in the cytosol. The enzyme
      is essential for glycine catabolism and for recycling one-carbon units during
      growth on C1 compounds.'
    molecular_function:
      id: GO:0004375
      label: glycine dehydrogenase (decarboxylating) activity
    directly_involved_in:
      - id: GO:0019464
        label: glycine decarboxylation via glycine cleavage system
    locations:
      - id: GO:0005829
        label: cytosol
    supported_by:
      - reference_id: file:METEA/gcvP/gcvP-uniprot.txt
        supporting_text: The P protein binds the alpha-amino group of glycine through
          its pyridoxal phosphate cofactor; CO2 is released and the remaining methylamine
          moiety is then transferred to the lipoamide cofactor of the H protein. The
          glycine cleavage system catalyzes the degradation of glycine.
    in_complex:
      id: GO:0005960
      label: glycine cleavage complex
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with GO
      terms.
    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: []
  - id: file:METEA/gcvP/gcvP-uniprot.txt
    title: UniProt record for gcvP (C5AUG0)
    findings: []
status: COMPLETE