AMACR

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) propagation of mitochondrial localization. AMACR is genuinely dual-localized to peroxisomes and mitochondria from a single transcript, and the mitochondrial pool has a demonstrated catalytic role in beta-oxidation of pristanic-acid breakdown products. Reason: Direct experimental evidence supports mitochondrial localization and a mitochondrial catalytic role, consistent with this IBA propagation. Supporting Evidence: PMID:11060359 alpha-methylacyl-CoA racemase is bimodally distributed to both the peroxisome and the mitochondrion.
GO:0008111 alpha-methylacyl-CoA racemase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) propagation of the defining molecular function, alpha-methylacyl-CoA racemase activity. This is the core, experimentally established function of AMACR. Reason: Matches multiple experimental annotations (purified human enzyme, disease IMP) and the UniProt-curated catalytic activity; represents the core function. Supporting Evidence: PMID:7649182 accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA and trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis)
GO:0008206 bile acid metabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) propagation placing AMACR in bile acid metabolism. AMACR racemizes the C27 bile-acid intermediate THCA-CoA/DHCA-CoA, a required step in bile-acid synthesis. Reason: Consistent with experimental substrate data and disease phenotype (accumulation of C27 bile-acid intermediates on AMACR deficiency); genuine biological process. Supporting Evidence: PMID:7649182 trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis)
GO:0003824 catalytic activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro2GO (IPR003673, CoA-transferase family III) maps to the generic root-level molecular function "catalytic activity". Reason: Not wrong, but uninformative - the specific molecular function GO:0008111 (alpha-methylacyl-CoA racemase activity), supported by experimental evidence, fully supersedes this generic parent term. Supporting Evidence: PMID:7649182 accepts as substrates a wide range of alpha-methylacyl-CoAs
GO:0005739 mitochondrion	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location keyword mapping (SL-0173, Mitochondrion) to GO. Consistent with the curated SUBCELLULAR LOCATION and with experimental evidence for a mitochondrial AMACR pool. Reason: AMACR carries an internal mitochondrial targeting signal and a mitochondrial catalytic role is experimentally established; the keyword mapping is correct. Supporting Evidence: PMID:11060344 mitochondrial targeting information is localized between amino acids 22 and 85
GO:0005777 peroxisome	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location keyword mapping (SL-0204, Peroxisome) to GO. Peroxisome is the major site of AMACR activity. Reason: Matches multiple experimental peroxisomal-localization annotations and the curated SUBCELLULAR LOCATION; the bulk of racemase activity is peroxisomal. Supporting Evidence: PMID:7649182 the bulk activity was located in peroxisomes
GO:0008111 alpha-methylacyl-CoA racemase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated (RHEA/EC 5.1.99.4) mapping to the defining racemase activity. Redundant with the experimental annotations of the same term but correct. Reason: The RHEA:12657 / EC 5.1.99.4 mapping correctly captures the core catalytic function, which is experimentally validated. Supporting Evidence: PMID:7649182 A specific racemase for alpha-methylacyl-CoAs
GO:0006699 bile acid biosynthetic process	TAS Reactome:R-HSA-193368	ACCEPT	Summary: Reactome pathway (synthesis of bile acids via 7alpha-hydroxycholesterol) places AMACR in bile-acid biosynthesis via racemization of the C27 intermediate. Reason: AMACR racemizes (25R)-THCA-CoA to the (25S) form required for peroxisomal side-chain shortening to C24 bile acids; core biosynthetic role. Supporting Evidence: PMID:10655068 This enzyme is responsible for the conversion of pristanoyl-CoA and C27-bile acyl-CoAs to their (S)-stereoisomers
GO:0006699 bile acid biosynthetic process	TAS Reactome:R-HSA-193775	ACCEPT	Summary: Reactome pathway (synthesis of bile acids via 24-hydroxycholesterol) places AMACR in bile-acid biosynthesis. Duplicate of the biosynthetic-process annotation from a parallel Reactome route. Reason: Same core biosynthetic role via racemization of C27 bile-acid intermediates; correct. Supporting Evidence: PMID:10655068 This enzyme is responsible for the conversion of pristanoyl-CoA and C27-bile acyl-CoAs to their (S)-stereoisomers
GO:0033540 fatty acid beta-oxidation using acyl-CoA oxidase	TAS Reactome:R-HSA-389887	ACCEPT	Summary: Reactome pathway (beta-oxidation of pristanoyl-CoA) places AMACR in peroxisomal branched-chain fatty acid beta-oxidation. AMACR produces the (S)-pristanoyl-CoA that the acyl-CoA oxidase step can act on. Reason: AMACR racemizes (2R)-pristanoyl-CoA to (2S)-pristanoyl-CoA, an obligatory step upstream of peroxisomal acyl-CoA-oxidase-dependent beta-oxidation of pristanic acid; core catabolic role. Supporting Evidence: PMID:11060344 is an auxiliary enzyme required for the peroxisomal beta-oxidative breakdown of (2R)-pristanic acid
GO:0006631 fatty acid metabolic process	IEA GO_REF:0000041	ACCEPT	Summary: UniPathway mapping (UPA00199, fatty acid metabolism) to the broad fatty acid metabolic process term. Reason: Correct though general; AMACR participates in branched-chain fatty acid (pristanic acid) metabolism. Retained as a broad parent of the more specific beta-oxidation role. Supporting Evidence: PMID:11060359 plays an important role in the beta-oxidation of branched-chain fatty acids and fatty acid derivatives
GO:0006699 bile acid biosynthetic process	IEA GO_REF:0000041	ACCEPT	Summary: UniPathway mapping (UPA00221, bile acid biosynthesis) to bile-acid biosynthetic process. Redundant with the Reactome TAS annotations of the same term. Reason: Correctly captures AMACR's role in bile-acid biosynthesis via C27 intermediate racemization. Supporting Evidence: PMID:10655068 elevated plasma concentrations of pristanic acid (a branched-chain fatty acid) and C27-bile-acid intermediates
GO:0008111 alpha-methylacyl-CoA racemase activity	EXP PMID:7649182 Purification and characterization of an alpha-methylacyl-CoA...	ACCEPT	Summary: Experimental characterization of the purified human liver enzyme demonstrating alpha-methylacyl-CoA racemase activity. Core, defining molecular function. Reason: Enzyme purified ~3600-fold from human liver and shown to racemize alpha-methylacyl-CoA substrates; direct experimental basis for the core function. Supporting Evidence: PMID:7649182 A specific racemase for alpha-methylacyl-CoAs, which had previously been studied in rat liver
GO:0008111 alpha-methylacyl-CoA racemase activity	TAS Reactome:R-HSA-192056	ACCEPT	Summary: Reactome (isomerization of 25(R) THCA-CoA to 25(S) THCA-CoA) asserts the racemase activity on a specific bile-acid intermediate substrate. Reason: Correctly captures the core racemase activity acting on the C27 bile-acid intermediate THCA-CoA. Supporting Evidence: PMID:7649182 trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis)
GO:0008111 alpha-methylacyl-CoA racemase activity	TAS Reactome:R-HSA-193452	ACCEPT	Summary: Reactome (isomerization of 25(R) DHCA-CoA to 25(S) DHCA-CoA) asserts the racemase activity on the DHCA-CoA bile-acid intermediate. Reason: Correctly captures the core racemase activity acting on a C27 bile-acid intermediate. Supporting Evidence: PMID:10655068 conversion of pristanoyl-CoA and C27-bile acyl-CoAs to their (S)-stereoisomers
GO:0008111 alpha-methylacyl-CoA racemase activity	TAS Reactome:R-HSA-193736	ACCEPT	Summary: Reactome (isomerization of 3,7,24-THCA-CoA) asserts racemase activity on a bile-acid intermediate. Duplicate assertion of the core function. Reason: Correctly captures the core racemase activity. Supporting Evidence: PMID:7649182 A specific racemase for alpha-methylacyl-CoAs
GO:0008111 alpha-methylacyl-CoA racemase activity	TAS Reactome:R-HSA-193763	ACCEPT	Summary: Reactome assertion of AMACR racemase activity within the bile-acid synthesis pathway. Duplicate assertion of the core function. Reason: Correctly captures the core racemase activity. Supporting Evidence: PMID:7649182 A specific racemase for alpha-methylacyl-CoAs
GO:0005777 peroxisome	IDA GO_REF:0000052	ACCEPT	Summary: Immunofluorescence (Human Protein Atlas) localizing AMACR to the peroxisome. Consistent with the major site of racemase activity. Reason: Peroxisomal localization is the dominant, experimentally supported location of AMACR; core. Supporting Evidence: PMID:7649182 the bulk activity was located in peroxisomes
GO:0005782 peroxisomal matrix	TAS Reactome:R-HSA-192056	ACCEPT	Summary: Reactome places AMACR in the peroxisomal matrix, the soluble compartment where matrix enzymes act after PTS1-mediated import. Reason: AMACR is a soluble matrix enzyme imported via its C-terminal PTS1 variant; peroxisomal matrix is the precise location. Supporting Evidence: PMID:11060344 ASL is a new PTS1 variant
GO:0005782 peroxisomal matrix	TAS Reactome:R-HSA-193452	ACCEPT	Summary: Reactome peroxisomal-matrix localization (DHCA-CoA isomerization context). Duplicate of the peroxisomal-matrix location. Reason: Consistent precise matrix localization for this soluble PTS1-imported enzyme. Supporting Evidence: PMID:11060344 ASL is a new PTS1 variant
GO:0005782 peroxisomal matrix	TAS Reactome:R-HSA-193736	ACCEPT	Summary: Reactome peroxisomal-matrix localization (3,7,24-THCA-CoA context). Duplicate of the peroxisomal-matrix location. Reason: Consistent precise matrix localization for this soluble PTS1-imported enzyme. Supporting Evidence: PMID:11060344 ASL is a new PTS1 variant
GO:0005782 peroxisomal matrix	TAS Reactome:R-HSA-193763	ACCEPT	Summary: Reactome peroxisomal-matrix localization. Duplicate of the peroxisomal-matrix location. Reason: Consistent precise matrix localization for this soluble PTS1-imported enzyme. Supporting Evidence: PMID:11060344 ASL is a new PTS1 variant
GO:0005782 peroxisomal matrix	TAS Reactome:R-HSA-389897	ACCEPT	Summary: Reactome peroxisomal-matrix localization (pristanoyl-CoA isomerization context). Duplicate of the peroxisomal-matrix location. Reason: Consistent precise matrix localization for this soluble PTS1-imported enzyme. Supporting Evidence: PMID:11060344 ASL is a new PTS1 variant
GO:0005782 peroxisomal matrix	TAS Reactome:R-HSA-9033235	ACCEPT	Summary: Reactome peroxisomal-matrix localization (peroxisomal import context). Duplicate of the peroxisomal-matrix location. Reason: Consistent precise matrix localization for this soluble PTS1-imported enzyme. Supporting Evidence: PMID:11060344 ASL is a new PTS1 variant
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	UNDECIDED	Summary: High-throughput mitochondrial-proteome study. AMACR is not named in the cached abstract/text; the supporting evidence would be in large-scale supplementary data that cannot be verified from the cache. Reason: Cannot verify the AMACR-specific evidence from the cached publication (large-scale HTP dataset, gene not mentioned in available text). Mitochondrial localization is independently well supported by the experimental IDA/EXP annotations, so this HTP hit is plausibly correct but is left UNDECIDED for lack of verifiable cached evidence.
GO:0005739 mitochondrion	EXP PMID:11060344 Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA ...	ACCEPT	Summary: Experimental study of AMACR targeting demonstrating an internal mitochondrial targeting signal (aa 22-85) and dual peroxisomal/mitochondrial localization from a single transcript. Reason: Direct experimental evidence for mitochondrial targeting and localization of AMACR. Supporting Evidence: PMID:11060344 a single transcript gives rise to a racemase protein containing two topogenic signals, explaining the dual cellular localization of the activity
GO:0005777 peroxisome	EXP PMID:11060344 Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA ...	ACCEPT	Summary: Experimental study demonstrating peroxisomal targeting of AMACR via a novel C-terminal PTS1 variant (ASL). Reason: Direct experimental evidence for peroxisomal targeting/localization; core location. Supporting Evidence: PMID:11060344 ASL is a new PTS1 variant
GO:0005739 mitochondrion	IDA PMID:11060359 Subcellular localization and physiological role of alpha-met...	ACCEPT	Summary: Direct assay evidence for bimodal peroxisomal/mitochondrial distribution of AMACR, with a demonstrated mitochondrial catalytic role. Reason: Experimentally established mitochondrial localization with a functional mitochondrial beta-oxidation role. Supporting Evidence: PMID:11060359 alpha-methylacyl-CoA racemase is bimodally distributed to both the peroxisome and the mitochondrion
GO:0005777 peroxisome	IDA PMID:11060359 Subcellular localization and physiological role of alpha-met...	ACCEPT	Summary: Direct assay evidence for peroxisomal localization of AMACR as part of its bimodal distribution. Reason: Experimentally established peroxisomal localization; core location. Supporting Evidence: PMID:11060359 alpha-methylacyl-CoA racemase is bimodally distributed to both the peroxisome and the mitochondrion
GO:0008111 alpha-methylacyl-CoA racemase activity	IDA PMID:11060359 Subcellular localization and physiological role of alpha-met...	ACCEPT	Summary: Direct assay of racemase activity, including demonstration that the mitochondrial enzyme racemizes (2R,6)-dimethylheptanoyl-CoA. Core molecular function. Reason: Direct experimental demonstration of alpha-methylacyl-CoA racemase activity. Supporting Evidence: PMID:11060359 converting (2R,6)-dimethylheptanoyl-CoA to its (S)-stereoisomer
GO:0005829 cytosol	TAS Reactome:R-HSA-9033235	MARK AS OVER ANNOTATED	Summary: Reactome "cytosol" localization arising from the peroxisomal protein-import reaction (cargo translocates from cytosol to peroxisomal matrix). This reflects a transient import intermediate, not a functional cytosolic pool. Reason: AMACR is a PTS1-targeted matrix enzyme; its appearance in the cytosol is the pre-import transit state modeled by Reactome's import pathway, not a site where the enzyme carries out its function. The functional locations are peroxisome and mitochondrion. Supporting Evidence: PMID:11060344 ASL is a new PTS1 variant
GO:0005829 cytosol	TAS Reactome:R-HSA-9033236	MARK AS OVER ANNOTATED	Summary: Reactome "cytosol" localization from the peroxisomal docking/translocation import step (PEX5:cargo binding the docking module). Transient import intermediate, not a functional cytosolic pool. Reason: Same as the other cytosol annotation - reflects the pre-import transit state modeled by the peroxisomal-import pathway rather than a functional cytosolic localization. Supporting Evidence: PMID:11060344 ASL is a new PTS1 variant
GO:0005739 mitochondrion	IDA PMID:20102405 How useful is alpha-methylacyl-CoA racemase (AMACR) immunohi...	ACCEPT	Summary: Immunohistochemistry-based localization in a kidney-cancer diagnostic context (a Comment/Letter). Mitochondrial localization is independently well established. Reason: Mitochondrial localization of AMACR is robustly supported by multiple experimental studies; this IHC-based annotation is consistent with the established dual localization. Supporting Evidence: PMID:11060359 alpha-methylacyl-CoA racemase is bimodally distributed to both the peroxisome and the mitochondrion
GO:0008111 alpha-methylacyl-CoA racemase activity	IMP PMID:10655068 Mutations in the gene encoding peroxisomal alpha-methylacyl-...	ACCEPT	Summary: Mutational (IMP) evidence - patients with AMACR deficiency accumulate pristanic acid and C27 bile-acid intermediates, and disease-causing variants (e.g. S52P) inactivate the enzyme, establishing that AMACR provides the racemase activity in vivo. Reason: Loss-of-function variants abolish racemization of pristanoyl-CoA and C27-bile acyl-CoAs, directly linking AMACR to alpha-methylacyl-CoA racemase activity; core function. Supporting Evidence: PMID:10655068 This enzyme is responsible for the conversion of pristanoyl-CoA and C27-bile acyl-CoAs to their (S)-stereoisomers
GO:0005737 cytoplasm	IDA PMID:15941950 Alpha-methylacyl-CoA racemase protein expression is associat...	MARK AS OVER ANNOTATED	Summary: Breast-cancer immunohistochemistry study reporting AMACR in cytoplasmic granules consistent with mitochondrial and peroxisomal localization. The generic "cytoplasm" term is a parent of the specific organelle locations. Reason: The study itself attributes the cytoplasmic-granule staining to peroxisomes/mitochondria; the specific organelle terms (peroxisome, mitochondrion) already capture this, so the generic cytoplasm term is an over-annotation. Supporting Evidence: PMID:15941950 AMACR was seen in cytoplasmic granules consistent with a mitochondrial and peroxisomal localization
GO:0008206 bile acid metabolic process	IDA PMID:10655068 Mutations in the gene encoding peroxisomal alpha-methylacyl-...	ACCEPT	Summary: Direct evidence linking AMACR to bile-acid metabolism - AMACR-deficient patients accumulate C27 bile-acid intermediates that are AMACR substrates. Reason: Establishes AMACR's role in bile-acid metabolism via racemization of C27 bile-acid intermediates required for their onward degradation to C24 bile acids. Supporting Evidence: PMID:10655068 elevated plasma concentrations of pristanic acid (a branched-chain fatty acid) and C27-bile-acid intermediates
GO:0005739 mitochondrion	IDA PMID:7649182 Purification and characterization of an alpha-methylacyl-CoA...	ACCEPT	Summary: Subcellular fractionation of human tissues showing 10-30% of racemase activity in mitochondria (with the bulk in peroxisomes). Reason: Direct fractionation evidence for a mitochondrial AMACR pool; consistent with the established dual localization. Supporting Evidence: PMID:7649182 only 10-30% of the activity was found in mitochondria
GO:0005777 peroxisome	IDA PMID:7649182 Purification and characterization of an alpha-methylacyl-CoA...	ACCEPT	Summary: Subcellular fractionation of human tissues showing the bulk of racemase activity in peroxisomes; peroxisomal form absent in Zellweger (peroxisome-assembly-deficient) cells. Reason: Direct fractionation evidence that peroxisome is the dominant AMACR localization; core location. Supporting Evidence: PMID:7649182 the bulk activity was located in peroxisomes
GO:0008111 alpha-methylacyl-CoA racemase activity	IDA PMID:7649182 Purification and characterization of an alpha-methylacyl-CoA...	ACCEPT	Summary: Purification and direct enzymatic characterization of AMACR from human liver, establishing alpha-methylacyl-CoA racemase activity on CoA thioesters. This is the primary experimental basis for the core function. Reason: Purified human enzyme directly shown to racemize alpha-methylacyl-CoA substrates; defining core molecular function. Supporting Evidence: PMID:7649182 It acts only on coenzyme A thioesters, not on free fatty acids, and accepts as substrates a wide range of alpha-methylacyl-CoAs

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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