Amacr encodes alpha-methylacyl-CoA racemase, a peroxisomal and mitochondrial enzyme that interconverts stereoisomers of alpha-methyl-branched acyl-CoA esters, including pristanoyl-CoA and bile-acid intermediates. Only (2S)-methyl-branched acyl-CoAs can be degraded by beta-oxidation, so by converting (2R)-isomers to their (2S)-epimers the enzyme makes branched-chain fatty acids derived from phytanic and pristanic acid, and the C27 bile acid intermediates di- and trihydroxycholestanoyl-CoA, available to peroxisomal and mitochondrial beta-oxidation, the latter step being required for cholic and chenodeoxycholic acid synthesis. A single gene product carries both a C-terminal PTS1-like peroxisomal targeting signal and N-terminal mitochondrial targeting information, giving a bimodal peroxisomal/mitochondrial distribution (the rat liver enzyme is predominantly mitochondrial). It is also the 2-arylpropionyl-CoA epimerase that inverts (R)-ibuprofenoyl-CoA during the chiral inversion of ibuprofen.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: mitochondrion is retained for Amacr as supported contextual biology, but it is not the defining core function (IBA, GO_REF:0000033). Reason: This term describes the supported peroxisomal, mitochondrial, or cytoplasmic localization rather than the defining catalytic role. Supporting Evidence: UniProtKB:P70473 SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:11060359}. Mitochondrion {ECO:0000269|PubMed:11060359, ECO:0000269|PubMed:7649182}. |
| GO:0008111 alpha-methylacyl-CoA racemase activity | IBA GO_REF:0000033 | ACCEPT | Summary: alpha-methylacyl-CoA racemase activity is retained for Amacr because it matches the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033). Reason: This term is directly supported by Amacr alpha-methylacyl-CoA racemase activity on fatty-acid and bile-acid intermediates. Supporting Evidence: UniProtKB:P70473 FUNCTION: Catalyzes the interconversion of (R)- and (S)-stereoisomers of alpha-methyl-branched-chain fatty acyl-CoA esters (PubMed:8020470, PubMed:9106621). file:rat/Amacr/Amacr-deep-research-falcon.md AMACR is a **cofactor-independent racemase/epimerase** that catalyzes the **stereochemical inversion (racemization/epimerization) at C2 (Ξ±-carbon)** of **2-methyl-branched acyl-CoA thioesters**, converting **(2R) β (2S)** forms. |
| GO:0008206 bile acid metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: bile acid metabolic process is retained for Amacr because it matches the documented core molecular role or a direct pathway consequence (IBA, GO_REF:0000033). Reason: This term is directly supported by Amacr alpha-methylacyl-CoA racemase activity on fatty-acid and bile-acid intermediates. Supporting Evidence: UniProtKB:P70473 accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA, trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis) file:rat/Amacr/Amacr-deep-research-falcon.md AMACR also participates in metabolism/processing of **C27 bile-acid intermediates** (DHCA/THCA) during side-chain shortening steps that contribute to formation of mature bile acids. |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: catalytic activity captures part of Amacr biology, but a more specific or better-aspected GO term should replace it (IEA, GO_REF:0000002). Reason: Generic catalytic activity should be replaced with the specific alpha-methylacyl-CoA racemase activity supported for Amacr. Proposed replacements: alpha-methylacyl-CoA racemase activity Supporting Evidence: UniProtKB:P70473 FUNCTION: Catalyzes the interconversion of (R)- and (S)-stereoisomers of alpha-methyl-branched-chain fatty acyl-CoA esters (PubMed:8020470, PubMed:9106621). |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: mitochondrion is retained for Amacr as supported contextual biology, but it is not the defining core function (IEA, GO_REF:0000044). Reason: This term describes the supported peroxisomal, mitochondrial, or cytoplasmic localization rather than the defining catalytic role. Supporting Evidence: UniProtKB:P70473 SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:11060359}. Mitochondrion {ECO:0000269|PubMed:11060359, ECO:0000269|PubMed:7649182}. |
| GO:0005777 peroxisome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: peroxisome is retained for Amacr as supported contextual biology, but it is not the defining core function (IEA, GO_REF:0000044). Reason: This term describes the supported peroxisomal, mitochondrial, or cytoplasmic localization rather than the defining catalytic role. Supporting Evidence: UniProtKB:P70473 SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:11060359}. Mitochondrion {ECO:0000269|PubMed:11060359, ECO:0000269|PubMed:7649182}. |
| GO:0008111 alpha-methylacyl-CoA racemase activity | IEA GO_REF:0000120 | ACCEPT | Summary: alpha-methylacyl-CoA racemase activity is retained for Amacr because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000120). Reason: This term is directly supported by Amacr alpha-methylacyl-CoA racemase activity on fatty-acid and bile-acid intermediates. Supporting Evidence: UniProtKB:P70473 FUNCTION: Catalyzes the interconversion of (R)- and (S)-stereoisomers of alpha-methyl-branched-chain fatty acyl-CoA esters (PubMed:8020470, PubMed:9106621). |
| GO:0006631 fatty acid metabolic process | IEA GO_REF:0000041 | ACCEPT | Summary: fatty acid metabolic process is retained for Amacr because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000041). Reason: This term is directly supported by Amacr alpha-methylacyl-CoA racemase activity on fatty-acid and bile-acid intermediates. Supporting Evidence: UniProtKB:P70473 Acts only on coenzyme A thioesters, not on free fatty acids, and accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA file:rat/Amacr/Amacr-deep-research-falcon.md AMACR is positioned as a key node enabling catabolism of dietary or isoprenoid-derived **Ξ±-methyl-branched fatty acids**, particularly in the **phytanic β pristanic acid** metabolic axis, by converting the 2R-enantiomer to the 2S-enantiomer used by Ξ²-oxidation. |
| GO:0006699 bile acid biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: bile acid biosynthetic process is retained for Amacr because it matches the documented core molecular role or a direct pathway consequence (IEA, GO_REF:0000041). Reason: This term is directly supported by Amacr alpha-methylacyl-CoA racemase activity on fatty-acid and bile-acid intermediates. Supporting Evidence: UniProtKB:P70473 accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA, trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis) |
| GO:0008111 alpha-methylacyl-CoA racemase activity | ISO GO_REF:0000121 | ACCEPT | Summary: alpha-methylacyl-CoA racemase activity is retained for Amacr because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121). Reason: This term is directly supported by Amacr alpha-methylacyl-CoA racemase activity on fatty-acid and bile-acid intermediates. Supporting Evidence: UniProtKB:P70473 FUNCTION: Catalyzes the interconversion of (R)- and (S)-stereoisomers of alpha-methyl-branched-chain fatty acyl-CoA esters (PubMed:8020470, PubMed:9106621). |
| GO:0005739 mitochondrion | EXP PMID:11060359 Subcellular localization and physiological role of alpha-met... | KEEP AS NON CORE | Summary: mitochondrion is retained for Amacr as supported contextual biology, but it is not the defining core function (EXP, PMID:11060359). Reason: This term describes the supported peroxisomal, mitochondrial, or cytoplasmic localization rather than the defining catalytic role. Supporting Evidence: PMID:11060359 Subcellular localization and physiological role of alpha-methylacyl-CoA racemase. PMID:11060359 Subcellular fractionation experiments, however, revealed that both in humans and rats alpha-methylacyl-CoA racemase is bimodally distributed to both the peroxisome and the mitochondrion. |
| GO:0008111 alpha-methylacyl-CoA racemase activity | EXP PMID:9106621 Molecular cloning and expression of a 2-arylpropionyl-coenzy... | ACCEPT | Summary: alpha-methylacyl-CoA racemase activity is retained for Amacr because it matches the documented core molecular role or a direct pathway consequence (EXP, PMID:9106621). Reason: This term is directly supported by Amacr alpha-methylacyl-CoA racemase activity on fatty-acid and bile-acid intermediates. Supporting Evidence: PMID:9106621 Molecular cloning and expression of a 2-arylpropionyl-coenzyme A epimerase: a key enzyme in the inversion metabolism of ibuprofen. PMID:9106621 The expression of the epimerase was confirmed with Western blots using specific anti-epimerase antibodies and by measuring the rate of inversion of (R)-ibuprofenoyl-CoA. |
| GO:0005739 mitochondrion | IDA PMID:7649182 Purification and characterization of an alpha-methylacyl-CoA... | KEEP AS NON CORE | Summary: mitochondrion is retained for Amacr as supported contextual biology, but it is not the defining core function (IDA, PMID:7649182). Reason: This term describes the supported peroxisomal, mitochondrial, or cytoplasmic localization rather than the defining catalytic role. Supporting Evidence: PMID:7649182 Purification and characterization of an alpha-methylacyl-CoA racemase from human liver. PMID:7649182 the rat enzyme co-distributed exclusively with mitochondrial marker enzymes file:rat/Amacr/Amacr-deep-research-falcon.md Primary rat-focused evidence indicates AMACR/racemase activity occurs in **both peroxisomes and mitochondria**, and that AMACR was purified from **rat liver mitochondrial fractions** (monomeric protein ~45β47 kDa) despite peroxisomal targeting features in the sequence. |
| GO:0005777 peroxisome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: peroxisome is retained for Amacr as supported contextual biology, but it is not the defining core function (ISO, GO_REF:0000121). Reason: This term describes the supported peroxisomal, mitochondrial, or cytoplasmic localization rather than the defining catalytic role. Supporting Evidence: UniProtKB:P70473 SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:11060359}. Mitochondrion {ECO:0000269|PubMed:11060359, ECO:0000269|PubMed:7649182}. |
| GO:0005102 signaling receptor binding | ISO GO_REF:0000121 | REMOVE | Summary: signaling receptor binding misdescribes the only receptor interaction reported for AMACR, the binding of its C-terminal PTS1 to the peroxisomal import receptor Pex5p, which is a cargo-import receptor rather than a signaling receptor; the human source annotation is also no longer present in QuickGO (ISO, GO_REF:0000121). Reason: GO:0005102 is defined as binding to a receptor that combines with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function. The human AMACR evidence that most plausibly underlies this transfer is the in vitro interaction of recombinant racemase with the PTS1 receptor Pex5p (PMID:11060344), i.e. a targeting signal being recognised by the peroxisomal protein-import machinery. That is a property of the cargo's sorting signal, not a signaling-receptor-binding activity, and peroxisomal localization is already captured by the peroxisome annotations. A QuickGO query (2026-10-04) finds no GO:0005102 annotation on human AMACR (Q9UHK6 or Q9UHK6-1), so the donor annotation appears to have been withdrawn. Removal does not dispute the Pex5p interaction itself. Propagation Review Root cause: SOURCE STALE OR MISSING Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q9UHK6 Β· AMACR SOURCE STALE OR MISSING Human AMACR donor (cited as Q9UHK6 and isoform Q9UHK6-1). QuickGO no longer returns a GO:0005102 annotation for either identifier; the only receptor interaction in the human literature is PTS1 recognition by the Pex5p import receptor, which this term misdescribes. Supporting Evidence: PMID:11060344 From the in vitro interaction between recombinant racemase and recombinant human PTS1 receptor (Pex5p), and the peroxisomal localization of green fluorescent protein (GFP) fused to the N terminus of full-length racemase or its last six amino acids in tranfected Chinese hamster ovary (CHO) cells, we concluded that ASL is a new PTS1 variant. |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: mitochondrion is retained for Amacr as supported contextual biology, but it is not the defining core function (ISO, GO_REF:0000121). Reason: This term describes the supported peroxisomal, mitochondrial, or cytoplasmic localization rather than the defining catalytic role. Supporting Evidence: UniProtKB:P70473 SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:11060359}. Mitochondrion {ECO:0000269|PubMed:11060359, ECO:0000269|PubMed:7649182}. |
| GO:0005737 cytoplasm | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: cytoplasm is retained for Amacr as supported contextual biology, but it is not the defining core function (ISO, GO_REF:0000121). Reason: This term describes the supported peroxisomal, mitochondrial, or cytoplasmic localization rather than the defining catalytic role. Supporting Evidence: UniProtKB:P70473 SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:11060359}. Mitochondrion {ECO:0000269|PubMed:11060359, ECO:0000269|PubMed:7649182}. |
| GO:0008206 bile acid metabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: bile acid metabolic process is retained for Amacr because it matches the documented core molecular role or a direct pathway consequence (ISO, GO_REF:0000121). Reason: This term is directly supported by Amacr alpha-methylacyl-CoA racemase activity on fatty-acid and bile-acid intermediates. Supporting Evidence: UniProtKB:P70473 accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA, trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis) |
| GO:0005777 peroxisome | IDA PMID:14561759 Proteomic analysis of rat liver peroxisome: presence of pero... | KEEP AS NON CORE | Summary: peroxisome is retained for Amacr as supported contextual biology, but it is not the defining core function (IDA, PMID:14561759). Reason: This term describes the supported peroxisomal, mitochondrial, or cytoplasmic localization rather than the defining catalytic role. Supporting Evidence: PMID:14561759 Proteomic analysis of rat liver peroxisome: presence of peroxisome-specific isozyme of Lon protease. |
| GO:0005777 peroxisome | IDA PMID:11060359 Subcellular localization and physiological role of alpha-met... | KEEP AS NON CORE | Summary: peroxisome is retained for Amacr as supported contextual biology, but it is not the defining core function (IDA, PMID:11060359). Reason: This term describes the supported peroxisomal, mitochondrial, or cytoplasmic localization rather than the defining catalytic role. Supporting Evidence: PMID:11060359 Subcellular localization and physiological role of alpha-methylacyl-CoA racemase. PMID:11060359 Subcellular fractionation experiments, however, revealed that both in humans and rats alpha-methylacyl-CoA racemase is bimodally distributed to both the peroxisome and the mitochondrion. file:rat/Amacr/Amacr-deep-research-falcon.md Rat AMACR ends in the tetrapeptide **KANL**, described as a **PTS1-like** peroxisomal targeting signal. |
| GO:0006699 bile acid biosynthetic process | IDA PMID:11964182 The role of alpha-methylacyl-CoA racemase in bile acid synth... | ACCEPT | Summary: bile acid biosynthetic process is retained for Amacr because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:11964182). Reason: This term is directly supported by Amacr alpha-methylacyl-CoA racemase activity on fatty-acid and bile-acid intermediates. Supporting Evidence: PMID:11964182 The role of alpha-methylacyl-CoA racemase in bile acid synthesis. PMID:11964182 which after conversion by a alpha-methylacyl-CoA racemase into the (24S,25R) isomer can again be dehydrogenated by MFE-1 to 24-keto-3alpha,7alpha,12alpha-trihydroxycholestanoyl-CoA, a physiological intermediate in cholic acid synthesis. file:rat/Amacr/Amacr-deep-research-falcon.md AMACR also participates in metabolism/processing of **C27 bile-acid intermediates** (DHCA/THCA) during side-chain shortening steps that contribute to formation of mature bile acids. |
| GO:0008111 alpha-methylacyl-CoA racemase activity | IDA PMID:8020470 Purification and properties of an alpha-methylacyl-CoA racem... | ACCEPT | Summary: alpha-methylacyl-CoA racemase activity is retained for Amacr because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:8020470). Reason: This term is directly supported by Amacr alpha-methylacyl-CoA racemase activity on fatty-acid and bile-acid intermediates. Supporting Evidence: PMID:8020470 Purification and properties of an alpha-methylacyl-CoA racemase from rat liver. PMID:8020470 accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA and trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis) file:rat/Amacr/Amacr-deep-research-falcon.md AMACR is a **cofactor-independent racemase/epimerase** that catalyzes the **stereochemical inversion (racemization/epimerization) at C2 (Ξ±-carbon)** of **2-methyl-branched acyl-CoA thioesters**, converting **(2R) β (2S)** forms. |
| GO:0008206 bile acid metabolic process | IDA PMID:8020470 Purification and properties of an alpha-methylacyl-CoA racem... | ACCEPT | Summary: bile acid metabolic process is retained for Amacr because it matches the documented core molecular role or a direct pathway consequence (IDA, PMID:8020470). Reason: This term is directly supported by Amacr alpha-methylacyl-CoA racemase activity on fatty-acid and bile-acid intermediates. Supporting Evidence: PMID:8020470 Purification and properties of an alpha-methylacyl-CoA racemase from rat liver. PMID:8020470 accepts as substrates a wide range of alpha-methylacyl-CoAs, including pristanoyl-CoA and trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis) |
| GO:0005739 mitochondrion | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: mitochondrion transferred from human AMACR (Q9UHK6, isoform Q9UHK6-1) is consistent with direct rat evidence for mitochondrial racemase, kept as non-core localization context (ISO, GO_REF:0000121). Reason: Donor is human AMACR, cited at both the protein and canonical-isoform level; the human enzyme carries N-terminal mitochondrial targeting information and is found in mitochondria of liver and fibroblasts. Rat Amacr has its own fractionation evidence for a mitochondrial (in rat liver, predominantly mitochondrial) location. Duplicates the protein-level human-donor ISO row; localization is context for the racemase activity, not the core function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9UHK6-1 Β· AMACR SUPPORTS TRANSFER Human AMACR canonical isoform; mitochondrial localization of the human enzyme is experimentally established and matches rat data. Supporting Evidence: PMID:11060344 The enzyme activity is found not only in peroxisomes but also is present in mitochondria of human liver and fibroblasts. PMID:7649182 the rat enzyme co-distributed exclusively with mitochondrial marker enzymes |
| GO:0005777 peroxisome | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: peroxisome transferred from human AMACR (Q9UHK6, isoform Q9UHK6-1) is consistent with the rat PTS1-like C terminus and rat fractionation data, kept as non-core localization context (ISO, GO_REF:0000121). Reason: Donor is human AMACR, cited at both the protein and canonical-isoform level, whose C-terminal PTS1 variant is recognised by Pex5p and targets GFP fusions to peroxisomes. Rat Amacr ends in a PTS1-like KANL and is bimodally distributed to peroxisomes and mitochondria in rat liver fractionation. Duplicates the protein-level human-donor ISO row; localization is context for the racemase activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q9UHK6-1 Β· AMACR SUPPORTS TRANSFER Human AMACR canonical isoform; peroxisomal targeting via its PTS1 variant is experimentally established and the rat protein has a PTS1-like C terminus. Supporting Evidence: PMID:11060344 From the in vitro interaction between recombinant racemase and recombinant human PTS1 receptor (Pex5p), and the peroxisomal localization of green fluorescent protein (GFP) fused to the N terminus of full-length racemase or its last six amino acids in tranfected Chinese hamster ovary (CHO) cells, we concluded that ASL is a new PTS1 variant. PMID:11060359 Subcellular fractionation experiments, however, revealed that both in humans and rats alpha-methylacyl-CoA racemase is bimodally distributed to both the peroxisome and the mitochondrion. |
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