Gamt

Existing Annotations Review

Gene Description

Existing Annotations Review

Core Functions

Gamt catalyzes the SAM-dependent methylation of guanidinoacetate to creatine, completing creatine biosynthesis.

References

Deep Research

Falcon

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GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: nucleus is an unsupported IBA pan-ancestor localization call for Gamt. GAMT is a soluble cytosolic metabolic enzyme; rat liver subcellular fractionation localizes GAMT activity to the cytosolic fraction, and there is no experimental evidence for a nuclear pool or nuclear function. Downgraded from non-core to over-annotated. Reason: This compartment is not supported by the rat evidence, which places GAMT in the cytosolic fraction of liver; the nucleus call derives solely from an IBA pan-ancestor inference with no direct support. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN001282244 · PANTHER:PTN001282244 SUPPORTS SOURCE BUT NOT TARGET Current PTHR32379 PAINT slice confirms the nucleus IBD at this deep eukaryote node (taxon 2759, 2017-02-28), seeded by the S. cerevisiae family member (SGD:S000002873). Nuclear localization may be genuine for the yeast seed, but it does not transfer across this node - direct rat data place GAMT in the liver cytosolic fraction (nucleus and cytosol are mutually exclusive compartments), and the same node separately asserts cytoplasm (IBD seeded by S. pombe and S. cerevisiae members), which is the compartment the target evidence supports. No IRD prunes the mammalian branch, so the leak is a node-placement issue, not a withdrawn assertion. Supporting Evidence: file:rat/Gamt/Gamt-deep-research-falcon.md In rat liver, GAMT is primarily localized to the cytosolic fraction.
GO:0005737 cytoplasm	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: cytoplasm is retained for Gamt as supported contextual biology, but it is not the defining core function (IBA, GO_REF:0000033). Rat liver subcellular fractionation localizes GAMT enzymatic activity to the cytosolic fraction, corroborating cytoplasmic localization for this soluble metabolic enzyme. Reason: This term describes localization or oligomeric/interaction context rather than the defining catalytic role. Supporting Evidence: UniProtKB:P10868 FUNCTION: Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor. file:rat/Gamt/Gamt-deep-research-falcon.md In rat liver, GAMT is primarily localized to the cytosolic fraction.
GO:0006601 creatine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: creatine biosynthetic process is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033). GAMT catalyzes the second/terminal step of the two-step endogenous creatine biosynthetic pathway. Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: UniProtKB:P10868 FUNCTION: Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor. file:rat/Gamt/Gamt-deep-research-falcon.md GAMT is the second/terminal enzyme in the 2-step endogenous creatine pathway.
GO:0030731 guanidinoacetate N-methyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: guanidinoacetate N-methyltransferase activity is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033). This is the defining catalytic activity of GAMT, transferring a methyl group from SAM to guanidinoacetate to yield creatine. Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: UniProtKB:P10868 FUNCTION: Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor. file:rat/Gamt/Gamt-deep-research-falcon.md GAMT transfers a methyl group from S-adenosylmethionine (SAM/AdoMet) to guanidinoacetate (GAA), yielding creatine.
GO:0030731 guanidinoacetate N-methyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: guanidinoacetate N-methyltransferase activity is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000120). Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: UniProtKB:P10868 FUNCTION: Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor.
GO:0006601 creatine biosynthetic process	IEA GO_REF:0000120	ACCEPT	Summary: creatine biosynthetic process is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000120). Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: UniProtKB:P10868 FUNCTION: Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor.
GO:1990402 embryonic liver development	IEP PMID:15918910 Creatine synthesis and transport during rat embryogenesis: s...	MARK AS OVER ANNOTATED	Summary: embryonic liver development is marked as over-annotated for Gamt; the evidence supports the gene's core activity or context, not this broader process claim (IEP, PMID:15918910). Reason: The available evidence supports creatine biosynthesis and expression in relevant tissues, not a direct role in this broad developmental or organismal-growth process. Supporting Evidence: PMID:15918910 Creatine synthesis and transport during rat embryogenesis: spatiotemporal expression of AGAT, GAMT and CT1.
GO:0006601 creatine biosynthetic process	ISO GO_REF:0000121	ACCEPT	Summary: creatine biosynthetic process is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121). Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: UniProtKB:P10868 FUNCTION: Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor.
GO:0030731 guanidinoacetate N-methyltransferase activity	ISS GO_REF:0000024	ACCEPT	Summary: guanidinoacetate N-methyltransferase activity is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (ISS, GO_REF:0000024). Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: UniProtKB:P10868 FUNCTION: Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor.
GO:0030731 guanidinoacetate N-methyltransferase activity	ISO GO_REF:0000121	ACCEPT	Summary: guanidinoacetate N-methyltransferase activity is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121). Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: UniProtKB:P10868 FUNCTION: Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor.
GO:0006601 creatine biosynthetic process	TAS PMID:12079381 Crystal structure of guanidinoacetate methyltransferase from...	ACCEPT	Summary: creatine biosynthetic process is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (TAS, PMID:12079381). Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: PMID:12079381 Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase.
GO:0042802 identical protein binding	IPI PMID:12079381 Crystal structure of guanidinoacetate methyltransferase from...	KEEP AS NON CORE	Summary: identical protein binding is retained for Gamt as supported contextual biology, but it is not the defining core function (IPI, PMID:12079381). Reason: This term describes localization or oligomeric/interaction context rather than the defining catalytic role. Supporting Evidence: PMID:12079381 Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase.
GO:0006601 creatine biosynthetic process	IDA PMID:15533043 Catalytic mechanism of guanidinoacetate methyltransferase: c...	ACCEPT	Summary: creatine biosynthetic process is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:15533043). Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: PMID:15533043 Catalytic mechanism of guanidinoacetate methyltransferase: crystal structures of guanidinoacetate methyltransferase ternary complexes.
GO:0008757 S-adenosylmethionine-dependent methyltransferase activity	IDA PMID:15533043 Catalytic mechanism of guanidinoacetate methyltransferase: c...	ACCEPT	Summary: S-adenosylmethionine-dependent methyltransferase activity is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:15533043). GAMT is a SAM-dependent methyltransferase that uses S-adenosylmethionine as the obligate methyl donor. Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: PMID:15533043 Catalytic mechanism of guanidinoacetate methyltransferase: crystal structures of guanidinoacetate methyltransferase ternary complexes. file:rat/Gamt/Gamt-deep-research-falcon.md Required methyl donor/cofactor: SAM; acceptor substrate: guanidinoacetate.
GO:0030731 guanidinoacetate N-methyltransferase activity	IDA PMID:12069495 Myocellular creatine and creatine transporter serine phospho...	ACCEPT	Summary: guanidinoacetate N-methyltransferase activity is retained for Gamt, but PMID:12069495 only measured GAMT activity as a secondary starvation-study assay. Reason: The term is correct for Gamt; however, this particular PMID is marginal support because it reports that GAMT activity was not significantly changed in starved gastrocnemius muscle, rather than directly characterizing the enzyme. Supporting Evidence: PMID:12069495 Myocellular creatine and creatine transporter serine phosphorylation after starvation.
GO:0030731 guanidinoacetate N-methyltransferase activity	IDA PMID:15533043 Catalytic mechanism of guanidinoacetate methyltransferase: c...	ACCEPT	Summary: guanidinoacetate N-methyltransferase activity is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:15533043). Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: PMID:15533043 Catalytic mechanism of guanidinoacetate methyltransferase: crystal structures of guanidinoacetate methyltransferase ternary complexes.
GO:0050843 S-adenosylmethionine catabolic process	IDA PMID:15533043 Catalytic mechanism of guanidinoacetate methyltransferase: c...	ACCEPT	Summary: S-adenosylmethionine catabolic process is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:15533043). The methyl-transfer reaction consumes SAM and releases S-adenosylhomocysteine (SAH) as the coproduct. Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: PMID:15533043 Catalytic mechanism of guanidinoacetate methyltransferase: crystal structures of guanidinoacetate methyltransferase ternary complexes. file:rat/Gamt/Gamt-deep-research-falcon.md Coproduct is S-adenosylhomocysteine (SAH/AdoHcy).
GO:0030731 guanidinoacetate N-methyltransferase activity	NAS PMID:3277179 Molecular cloning, sequence analysis, and expression in Esch...	ACCEPT	Summary: guanidinoacetate N-methyltransferase activity is retained for Gamt because it matches the documented core molecular role or a direct pathway consequence (NAS, PMID:3277179). Reason: This term is directly supported by Gamt conversion of guanidinoacetate to creatine using SAM as methyl donor. Supporting Evidence: PMID:3277179 Molecular cloning, sequence analysis, and expression in Escherichia coli of the cDNA for guanidinoacetate methyltransferase from rat liver.
GO:0007283 spermatogenesis	ISO GO_REF:0000121	MARK AS OVER ANNOTATED	Summary: spermatogenesis is marked as over-annotated for Gamt; the evidence supports the gene's core activity or context, not this broader process claim (ISO, GO_REF:0000121). Reason: The available evidence supports creatine biosynthesis and expression in relevant tissues, not a direct role in this broad developmental or organismal-growth process. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:1098221 · mouse Gamt SUPPORTS SOURCE BUT NOT TARGET Mouse donor annotation reflects organism-level consequences of creatine deficiency rather than a direct Gamt role in spermatogenesis; the transfer propagates phenotype as function. Supporting Evidence: UniProtKB:P10868 FUNCTION: Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor.
GO:0009887 animal organ morphogenesis	ISO GO_REF:0000121	MARK AS OVER ANNOTATED	Summary: animal organ morphogenesis is marked as over-annotated for Gamt; the evidence supports the gene's core activity or context, not this broader process claim (ISO, GO_REF:0000121). Reason: The available evidence supports creatine biosynthesis and expression in relevant tissues, not a direct role in this broad developmental or organismal-growth process. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:1098221 · mouse Gamt SUPPORTS SOURCE BUT NOT TARGET Mouse donor annotation reflects organism-level consequences of creatine deficiency rather than a direct Gamt role in organ morphogenesis; the transfer propagates phenotype as function. Supporting Evidence: UniProtKB:P10868 FUNCTION: Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor.
GO:0040014 regulation of multicellular organism growth	ISO GO_REF:0000121	MARK AS OVER ANNOTATED	Summary: regulation of multicellular organism growth is marked as over-annotated for Gamt; the evidence supports the gene's core activity or context, not this broader process claim (ISO, GO_REF:0000121). Reason: The available evidence supports creatine biosynthesis and expression in relevant tissues, not a direct role in this broad developmental or organismal-growth process. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: MGI:MGI:1098221 · mouse Gamt SUPPORTS SOURCE BUT NOT TARGET Mouse donor annotation reflects growth impairment downstream of creatine deficiency, not a direct Gamt role in growth regulation; the transfer propagates phenotype as function. Supporting Evidence: UniProtKB:P10868 FUNCTION: Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor.