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. Examined as a synthesis row (ORGANELLES, 2026-10-20) - the PAINT IBD at PTN007717897 (PTHR48228-paint.tsv, Bilateria) is seeded by rat Amacr (RGD:3048) and human AMACR itself, both of which have direct evidence for a mitochondrial pool, and the node sits on the AMACR orthologue clade rather than on a paralog without one; the same node carries the racemase activity. The seeds record only the organelle, so the node correctly carries the root term; the matrix sub-compartment is added alongside in the NEW GO:0005759 row rather than substituted here. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN007717897 · PTN007717897 SUPPORTS TRANSFER PAINT ancestral node (Bilateria) in PTHR48228, seeded by RGD:3048 and UniProtKB:Q9UHK6 for mitochondrion, racemase activity and bile acid metabolism. The seeds' own evidence is organelle-level (fractionation, GFP targeting), so the node carries the organelle and not the matrix. RGD:3048 · rat Amacr SUPPORTS TRANSFER Rat racemase is bimodally distributed to peroxisomes and mitochondria by subcellular fractionation (PMID:11060359). UniProtKB:Q9UHK6 · human AMACR (the target itself) SUPPORTS TRANSFER The target among the IBD seeds is expected and is not circular; it marks that the target has its own experimental grounding (PMID:11060344, PMID:11060359, PMID:7649182). Supporting Evidence: PMID:11060359 alpha-methylacyl-CoA racemase is bimodally distributed to both the peroxisome and the mitochondrion. PMID:10770938 Immunoelectron microscopy and subcellular fractionation located racemase to mitochondria and peroxisomes.
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. Examined as a synthesis row (ORGANELLES, 2026-10-20) - the source line is the curated SUBCELLULAR LOCATION "Mitochondrion" with ECO:0000269 evidence from three papers, which record only the organelle (SL-0173), so the mapping correctly yields the root term. The matrix sub-compartment is added in the NEW GO:0005759 row; the upstream fix would be SL-0170 (Mitochondrion matrix) on the UniProt entry. 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...	ACCEPT	Summary: High-throughput mitochondrial-proteome study. AMACR is not named in the cached abstract/text; the per-protein evidence is in large-scale supplementary data. Reason: The AMACR-specific call sits in the MitoCoP supplementary tables, which are not cached, so it is accepted in deference to the GOA curator rather than verified here. Its claim, a mitochondrial pool of AMACR, is the same claim the EXP, IDA, IBA and IEA rows on this term make and is independently well supported, so the rows on this term are kept consistent. Organelle proteomics resolves the organelle, not the sub-compartment; the matrix location is captured by the separate NEW GO:0005759 row. Supporting Evidence: PMID:34800366 defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)
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
GO:0005759 mitochondrial matrix	IC PMID:11060359 Subcellular localization and physiological role of alpha-met...	NEW	Summary: Proposed sub-compartment for the mitochondrial pool of AMACR. The mitochondrial enzyme acts in mitochondrial beta-oxidation of pristanic-acid breakdown products, a matrix pathway, and the protein is soluble; the existing annotations stop at the organelle. Reason: Several lines agree. (1) Function - the mitochondrial enzyme racemizes (2R,6)-dimethylheptanoyl-CoA in mitochondrial beta-oxidation of the breakdown products of pristanic acid (purified protein and patient fibroblasts, PMID:11060359); this acyl-CoA is an intermediate of mitochondrial beta-oxidation, which runs in the matrix, so the racemase must act where that pathway generates its substrate. (2) Solubility - AMACR is a soluble monomer (purified from human liver, PMID:7649182) and UniProt annotates no transmembrane or intramembrane segment, so there is no membrane anchor that would place it in a mitochondrial membrane. (3) Import - N-terminal residues 22-85 carry mitochondrial targeting information (PMID:11060344), i.e. an import signal rather than recruitment to the outer surface, and immunoelectron microscopy in mouse liver places the enzyme within mitochondria (PMID:10770938). One caveat is recorded rather than hidden: in mouse the N-terminal signal is not cleaved (both organelle pools have the same N-terminus), so the classical cleaved-presequence signature of a matrix protein is absent, and no sub-mitochondrial fractionation or protease-protection experiment was found; hence IC rather than IDA. The peroxisomal pool is already captured by GO:0005782 peroxisomal matrix. Supporting Evidence: PMID:11060359 the mitochondrial enzyme plays a crucial role in the mitochondrial beta-oxidation of the breakdown products of pristanic acid byconverting (2R,6)-dimethylheptanoyl-CoA to its (S)-stereoisomer. PMID:7649182 It is a monomer of 47 kDa PMID:11060344 mitochondrial targeting information is localized between amino acids 22 and 85 PMID:10770938 Immunoelectron microscopy and subcellular fractionation located racemase to mitochondria and peroxisomes. PMID:10770938 It is concluded that the noncleavable N-terminal sequence of the polypeptide acts as a weak mitochondrial and that the C-terminal sequence acts as a peroxisomal targeting signal.

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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