id: Q9UHK6
gene_symbol: AMACR
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'Alpha-methylacyl-CoA racemase (AMACR; EC 5.1.99.4) is an isomerase that
  interconverts the (R)- and (S)-epimers of 2-methyl-branched-chain fatty acyl-CoA
  esters. It acts only on coenzyme A thioesters (not free fatty acids) and accepts
  a wide range of alpha-methylacyl-CoA substrates including pristanoyl-CoA and the
  C27 bile-acid intermediates trihydroxycoprostanoyl-CoA (THCA-CoA) and DHCA-CoA,
  but not 3-methyl-branched or linear-chain acyl-CoAs. By converting (2R)-methyl-branched
  acyl-CoAs to their (S)-stereoisomers, AMACR generates the only stereoisomers that
  the peroxisomal beta-oxidation machinery can degrade, and is therefore essential
  for two catabolic routes; side-chain shortening of the C27 bile-acid intermediates
  (25R)-THCA-CoA and DHCA-CoA en route to the mature C24 bile acids, and degradation
  of the branched-chain fatty acid pristanic acid (the product of phytanic acid alpha-oxidation).
  The single AMACR transcript encodes a protein bearing two topogenic signals, a C-terminal
  PTS1 variant (KASL/ASL) and an internal mitochondrial targeting region, so the enzyme
  is dually localized to peroxisomes (bulk activity) and mitochondria, where a mitochondrial
  pool racemizes downstream pristanic-acid breakdown products. Loss-of-function variants
  cause AMACR deficiency, an adult-onset sensorimotor neuropathy and relapsing encephalopathy
  with elevated plasma pristanic acid and abnormal C27 bile-acid intermediates, and
  congenital bile acid synthesis defect type 4. AMACR is a member of the CoA-transferase
  III family and is a widely used immunohistochemical biomarker overexpressed in prostate
  and other carcinomas.'
alternative_products:
- name: '1'
  id: Q9UHK6-1
- name: 2 (IBLi)
  id: Q9UHK6-2
  sequence_note: VSP_037321, VSP_037326
- name: '3'
  id: Q9UHK6-4
  sequence_note: VSP_037323, VSP_037324
- name: '4'
  id: Q9UHK6-5
  sequence_note: VSP_044875
existing_annotations:
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: Direct experimental evidence supports mitochondrial localization and a
      mitochondrial catalytic role, consistent with this IBA propagation.
    supported_by:
    - reference_id: PMID:11060359
      supporting_text: alpha-methylacyl-CoA racemase is bimodally distributed to both
        the peroxisome and the mitochondrion.
- term:
    id: GO:0008111
    label: alpha-methylacyl-CoA racemase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic (IBA) propagation of the defining molecular function, alpha-methylacyl-CoA
      racemase activity. This is the core, experimentally established function of
      AMACR.
    action: ACCEPT
    reason: Matches multiple experimental annotations (purified human enzyme, disease
      IMP) and the UniProt-curated catalytic activity; represents the core function.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: accepts as substrates a wide range of alpha-methylacyl-CoAs,
        including pristanoyl-CoA and trihydroxycoprostanoyl-CoA (an intermediate in
        bile acid synthesis)
- term:
    id: GO:0008206
    label: bile acid metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Consistent with experimental substrate data and disease phenotype (accumulation
      of C27 bile-acid intermediates on AMACR deficiency); genuine biological process.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis)
- term:
    id: GO:0003824
    label: catalytic activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO (IPR003673, CoA-transferase family III) maps to the generic
      root-level molecular function "catalytic activity".
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: accepts as substrates a wide range of alpha-methylacyl-CoAs
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    reason: AMACR carries an internal mitochondrial targeting signal and a mitochondrial
      catalytic role is experimentally established; the keyword mapping is correct.
    supported_by:
    - reference_id: PMID:11060344
      supporting_text: mitochondrial targeting information is localized between amino
        acids 22 and 85
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: UniProt subcellular-location keyword mapping (SL-0204, Peroxisome) to
      GO. Peroxisome is the major site of AMACR activity.
    action: ACCEPT
    reason: Matches multiple experimental peroxisomal-localization annotations and
      the curated SUBCELLULAR LOCATION; the bulk of racemase activity is peroxisomal.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: the bulk activity was located in peroxisomes
- term:
    id: GO:0008111
    label: alpha-methylacyl-CoA racemase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: The RHEA:12657 / EC 5.1.99.4 mapping correctly captures the core catalytic
      function, which is experimentally validated.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: A specific racemase for alpha-methylacyl-CoAs
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193368
  qualifier: involved_in
  review:
    summary: Reactome pathway (synthesis of bile acids via 7alpha-hydroxycholesterol)
      places AMACR in bile-acid biosynthesis via racemization of the C27 intermediate.
    action: ACCEPT
    reason: AMACR racemizes (25R)-THCA-CoA to the (25S) form required for peroxisomal
      side-chain shortening to C24 bile acids; core biosynthetic role.
    supported_by:
    - reference_id: PMID:10655068
      supporting_text: This enzyme is responsible for the conversion of pristanoyl-CoA
        and C27-bile acyl-CoAs to their (S)-stereoisomers
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193775
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Same core biosynthetic role via racemization of C27 bile-acid intermediates;
      correct.
    supported_by:
    - reference_id: PMID:10655068
      supporting_text: This enzyme is responsible for the conversion of pristanoyl-CoA
        and C27-bile acyl-CoAs to their (S)-stereoisomers
- term:
    id: GO:0033540
    label: fatty acid beta-oxidation using acyl-CoA oxidase
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-389887
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:11060344
      supporting_text: is an auxiliary enzyme required for the peroxisomal beta-oxidative
        breakdown of (2R)-pristanic acid
- term:
    id: GO:0006631
    label: fatty acid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: UniPathway mapping (UPA00199, fatty acid metabolism) to the broad fatty
      acid metabolic process term.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:11060359
      supporting_text: plays an important role in the beta-oxidation of branched-chain
        fatty acids and fatty acid derivatives
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: UniPathway mapping (UPA00221, bile acid biosynthesis) to bile-acid biosynthetic
      process. Redundant with the Reactome TAS annotations of the same term.
    action: ACCEPT
    reason: Correctly captures AMACR's role in bile-acid biosynthesis via C27 intermediate
      racemization.
    supported_by:
    - reference_id: PMID:10655068
      supporting_text: elevated plasma concentrations of pristanic acid (a branched-chain
        fatty acid) and C27-bile-acid intermediates
- term:
    id: GO:0008111
    label: alpha-methylacyl-CoA racemase activity
  evidence_type: EXP
  original_reference_id: PMID:7649182
  qualifier: enables
  review:
    summary: Experimental characterization of the purified human liver enzyme demonstrating
      alpha-methylacyl-CoA racemase activity. Core, defining molecular function.
    action: ACCEPT
    reason: Enzyme purified ~3600-fold from human liver and shown to racemize alpha-methylacyl-CoA
      substrates; direct experimental basis for the core function.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: A specific racemase for alpha-methylacyl-CoAs, which had previously
        been studied in rat liver
- term:
    id: GO:0008111
    label: alpha-methylacyl-CoA racemase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192056
  qualifier: enables
  review:
    summary: Reactome (isomerization of 25(R) THCA-CoA to 25(S) THCA-CoA) asserts
      the racemase activity on a specific bile-acid intermediate substrate.
    action: ACCEPT
    reason: Correctly captures the core racemase activity acting on the C27 bile-acid
      intermediate THCA-CoA.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis)
- term:
    id: GO:0008111
    label: alpha-methylacyl-CoA racemase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193452
  qualifier: enables
  review:
    summary: Reactome (isomerization of 25(R) DHCA-CoA to 25(S) DHCA-CoA) asserts
      the racemase activity on the DHCA-CoA bile-acid intermediate.
    action: ACCEPT
    reason: Correctly captures the core racemase activity acting on a C27 bile-acid
      intermediate.
    supported_by:
    - reference_id: PMID:10655068
      supporting_text: conversion of pristanoyl-CoA and C27-bile acyl-CoAs to their
        (S)-stereoisomers
- term:
    id: GO:0008111
    label: alpha-methylacyl-CoA racemase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193736
  qualifier: enables
  review:
    summary: Reactome (isomerization of 3,7,24-THCA-CoA) asserts racemase activity
      on a bile-acid intermediate. Duplicate assertion of the core function.
    action: ACCEPT
    reason: Correctly captures the core racemase activity.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: A specific racemase for alpha-methylacyl-CoAs
- term:
    id: GO:0008111
    label: alpha-methylacyl-CoA racemase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193763
  qualifier: enables
  review:
    summary: Reactome assertion of AMACR racemase activity within the bile-acid synthesis
      pathway. Duplicate assertion of the core function.
    action: ACCEPT
    reason: Correctly captures the core racemase activity.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: A specific racemase for alpha-methylacyl-CoAs
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Immunofluorescence (Human Protein Atlas) localizing AMACR to the peroxisome.
      Consistent with the major site of racemase activity.
    action: ACCEPT
    reason: Peroxisomal localization is the dominant, experimentally supported location
      of AMACR; core.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: the bulk activity was located in peroxisomes
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-192056
  qualifier: located_in
  review:
    summary: Reactome places AMACR in the peroxisomal matrix, the soluble compartment
      where matrix enzymes act after PTS1-mediated import.
    action: ACCEPT
    reason: AMACR is a soluble matrix enzyme imported via its C-terminal PTS1 variant;
      peroxisomal matrix is the precise location.
    supported_by:
    - reference_id: PMID:11060344
      supporting_text: ASL is a new PTS1 variant
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193452
  qualifier: located_in
  review:
    summary: Reactome peroxisomal-matrix localization (DHCA-CoA isomerization context).
      Duplicate of the peroxisomal-matrix location.
    action: ACCEPT
    reason: Consistent precise matrix localization for this soluble PTS1-imported
      enzyme.
    supported_by:
    - reference_id: PMID:11060344
      supporting_text: ASL is a new PTS1 variant
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193736
  qualifier: located_in
  review:
    summary: Reactome peroxisomal-matrix localization (3,7,24-THCA-CoA context). Duplicate
      of the peroxisomal-matrix location.
    action: ACCEPT
    reason: Consistent precise matrix localization for this soluble PTS1-imported
      enzyme.
    supported_by:
    - reference_id: PMID:11060344
      supporting_text: ASL is a new PTS1 variant
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-193763
  qualifier: located_in
  review:
    summary: Reactome peroxisomal-matrix localization. Duplicate of the peroxisomal-matrix
      location.
    action: ACCEPT
    reason: Consistent precise matrix localization for this soluble PTS1-imported
      enzyme.
    supported_by:
    - reference_id: PMID:11060344
      supporting_text: ASL is a new PTS1 variant
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-389897
  qualifier: located_in
  review:
    summary: Reactome peroxisomal-matrix localization (pristanoyl-CoA isomerization
      context). Duplicate of the peroxisomal-matrix location.
    action: ACCEPT
    reason: Consistent precise matrix localization for this soluble PTS1-imported
      enzyme.
    supported_by:
    - reference_id: PMID:11060344
      supporting_text: ASL is a new PTS1 variant
- term:
    id: GO:0005782
    label: peroxisomal matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033235
  qualifier: located_in
  review:
    summary: Reactome peroxisomal-matrix localization (peroxisomal import context).
      Duplicate of the peroxisomal-matrix location.
    action: ACCEPT
    reason: Consistent precise matrix localization for this soluble PTS1-imported
      enzyme.
    supported_by:
    - reference_id: PMID:11060344
      supporting_text: ASL is a new PTS1 variant
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    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.
    action: UNDECIDED
    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.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: EXP
  original_reference_id: PMID:11060344
  qualifier: located_in
  review:
    summary: Experimental study of AMACR targeting demonstrating an internal mitochondrial
      targeting signal (aa 22-85) and dual peroxisomal/mitochondrial localization
      from a single transcript.
    action: ACCEPT
    reason: Direct experimental evidence for mitochondrial targeting and localization
      of AMACR.
    supported_by:
    - reference_id: PMID:11060344
      supporting_text: a single transcript gives rise to a racemase protein containing
        two topogenic signals, explaining the dual cellular localization of the activity
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: EXP
  original_reference_id: PMID:11060344
  qualifier: located_in
  review:
    summary: Experimental study demonstrating peroxisomal targeting of AMACR via a
      novel C-terminal PTS1 variant (ASL).
    action: ACCEPT
    reason: Direct experimental evidence for peroxisomal targeting/localization; core
      location.
    supported_by:
    - reference_id: PMID:11060344
      supporting_text: ASL is a new PTS1 variant
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:11060359
  qualifier: located_in
  review:
    summary: Direct assay evidence for bimodal peroxisomal/mitochondrial distribution
      of AMACR, with a demonstrated mitochondrial catalytic role.
    action: ACCEPT
    reason: Experimentally established mitochondrial localization with a functional
      mitochondrial beta-oxidation role.
    supported_by:
    - reference_id: PMID:11060359
      supporting_text: alpha-methylacyl-CoA racemase is bimodally distributed to both
        the peroxisome and the mitochondrion
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:11060359
  qualifier: located_in
  review:
    summary: Direct assay evidence for peroxisomal localization of AMACR as part of
      its bimodal distribution.
    action: ACCEPT
    reason: Experimentally established peroxisomal localization; core location.
    supported_by:
    - reference_id: PMID:11060359
      supporting_text: alpha-methylacyl-CoA racemase is bimodally distributed to both
        the peroxisome and the mitochondrion
- term:
    id: GO:0008111
    label: alpha-methylacyl-CoA racemase activity
  evidence_type: IDA
  original_reference_id: PMID:11060359
  qualifier: enables
  review:
    summary: Direct assay of racemase activity, including demonstration that the mitochondrial
      enzyme racemizes (2R,6)-dimethylheptanoyl-CoA. Core molecular function.
    action: ACCEPT
    reason: Direct experimental demonstration of alpha-methylacyl-CoA racemase activity.
    supported_by:
    - reference_id: PMID:11060359
      supporting_text: converting (2R,6)-dimethylheptanoyl-CoA to its (S)-stereoisomer
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033235
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:11060344
      supporting_text: ASL is a new PTS1 variant
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9033236
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:11060344
      supporting_text: ASL is a new PTS1 variant
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:20102405
  qualifier: located_in
  review:
    summary: Immunohistochemistry-based localization in a kidney-cancer diagnostic
      context (a Comment/Letter). Mitochondrial localization is independently well
      established.
    action: ACCEPT
    reason: Mitochondrial localization of AMACR is robustly supported by multiple
      experimental studies; this IHC-based annotation is consistent with the established
      dual localization.
    supported_by:
    - reference_id: PMID:11060359
      supporting_text: alpha-methylacyl-CoA racemase is bimodally distributed to both
        the peroxisome and the mitochondrion
- term:
    id: GO:0008111
    label: alpha-methylacyl-CoA racemase activity
  evidence_type: IMP
  original_reference_id: PMID:10655068
  qualifier: enables
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:10655068
      supporting_text: This enzyme is responsible for the conversion of pristanoyl-CoA
        and C27-bile acyl-CoAs to their (S)-stereoisomers
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:15941950
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:15941950
      supporting_text: AMACR was seen in cytoplasmic granules consistent with a mitochondrial
        and peroxisomal localization
- term:
    id: GO:0008206
    label: bile acid metabolic process
  evidence_type: IDA
  original_reference_id: PMID:10655068
  qualifier: involved_in
  review:
    summary: Direct evidence linking AMACR to bile-acid metabolism - AMACR-deficient
      patients accumulate C27 bile-acid intermediates that are AMACR substrates.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:10655068
      supporting_text: elevated plasma concentrations of pristanic acid (a branched-chain
        fatty acid) and C27-bile-acid intermediates
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:7649182
  qualifier: located_in
  review:
    summary: Subcellular fractionation of human tissues showing 10-30% of racemase
      activity in mitochondria (with the bulk in peroxisomes).
    action: ACCEPT
    reason: Direct fractionation evidence for a mitochondrial AMACR pool; consistent
      with the established dual localization.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: only 10-30% of the activity was found in mitochondria
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IDA
  original_reference_id: PMID:7649182
  qualifier: located_in
  review:
    summary: Subcellular fractionation of human tissues showing the bulk of racemase
      activity in peroxisomes; peroxisomal form absent in Zellweger (peroxisome-assembly-deficient)
      cells.
    action: ACCEPT
    reason: Direct fractionation evidence that peroxisome is the dominant AMACR localization;
      core location.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: the bulk activity was located in peroxisomes
- term:
    id: GO:0008111
    label: alpha-methylacyl-CoA racemase activity
  evidence_type: IDA
  original_reference_id: PMID:7649182
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Purified human enzyme directly shown to racemize alpha-methylacyl-CoA
      substrates; defining core molecular function.
    supported_by:
    - reference_id: PMID:7649182
      supporting_text: It acts only on coenzyme A thioesters, not on free fatty acids,
        and accepts as substrates a wide range of alpha-methylacyl-CoAs
core_functions:
- description: Interconverts the (R)- and (S)-epimers of 2-methyl-branched-chain acyl-CoA
    esters (alpha-methylacyl-CoA racemase, EC 5.1.99.4), converting (2R)-methyl-branched
    acyl-CoAs to the (S)-stereoisomers required by peroxisomal beta-oxidation. Essential
    for side-chain shortening of the C27 bile-acid intermediates (25R)-THCA-CoA/DHCA-CoA
    en route to C24 bile acids, and for degradation of the branched-chain fatty acid
    pristanic acid. Acts as a soluble matrix enzyme in the peroxisome (and a mitochondrial
    pool).
  molecular_function:
    id: GO:0008111
    label: alpha-methylacyl-CoA racemase activity
  directly_involved_in:
  - id: GO:0006699
    label: bile acid biosynthetic process
  - id: GO:0033540
    label: fatty acid beta-oxidation using acyl-CoA oxidase
  locations:
  - id: GO:0005782
    label: peroxisomal matrix
  - id: GO:0005739
    label: mitochondrion
  supported_by:
  - reference_id: PMID:7649182
    supporting_text: It 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
      and trihydroxycoprostanoyl-CoA (an intermediate in bile acid synthesis)
  - reference_id: PMID:10655068
    supporting_text: This enzyme is responsible for the conversion of pristanoyl-CoA
      and C27-bile acyl-CoAs to their (S)-stereoisomers, which are the only stereoisomers
      that can be degraded via peroxisomal beta-oxidation
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:human/AMACR/AMACR-uniprot.txt
  title: UniProtKB entry Q9UHK6 (AMACR_HUMAN)
  findings: []
- id: PMID:10655068
  title: Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase
    cause adult-onset sensory motor neuropathy.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Establishes AMACR racemase activity in vivo (loss-of-function
      variants), bile-acid and pristanic-acid substrate roles, and AMACR deficiency
      disease phenotype.
- id: PMID:11060344
  title: Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA racemase in humans.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Demonstrates dual peroxisomal (PTS1 variant ASL)
      and mitochondrial (aa 22-85) targeting from a single transcript.
- id: PMID:11060359
  title: Subcellular localization and physiological role of alpha-methylacyl-CoA racemase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Bimodal peroxisome/mitochondrion distribution and
      a functional mitochondrial racemase role on (2R,6)-dimethylheptanoyl-CoA.
- id: PMID:15941950
  title: Alpha-methylacyl-CoA racemase protein expression is associated with the degree
    of differentiation in breast cancer using quantitative image analysis.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified. Breast-cancer biomarker IHC; the cytoplasmic-granule
      staining is attributed to peroxisomes/mitochondria, so supports organelle rather
      than generic cytoplasm localization.
- id: PMID:20102405
  title: How useful is alpha-methylacyl-CoA racemase (AMACR) immunohistochemistry
    in the differential diagnosis of kidney cancers?
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified Comment/Letter on AMACR IHC in kidney-cancer diagnosis;
      diagnostic-biomarker context, tangential to core enzymatic function.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: Large-scale HTP mitochondrial-proteome study; AMACR is not named
      in the cached text, so the AMACR-specific evidence (supplementary data) could
      not be verified from the cache.
- id: PMID:7649182
  title: Purification and characterization of an alpha-methylacyl-CoA racemase from
    human liver.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified. Purification and enzymatic characterization of
      the human liver enzyme; substrate range, monomeric structure, and predominantly
      peroxisomal (10-30% mitochondrial) localization.
- id: Reactome:R-HSA-192056
  title: Isomerization of 25(R) THCA-CoA to 25(S) THCA-CoA
  findings: []
- id: Reactome:R-HSA-193368
  title: Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol
  findings: []
- id: Reactome:R-HSA-193452
  title: Isomerization of 25(R) DHCA-CoA to 25(S) DHCA-CoA
  findings: []
- id: Reactome:R-HSA-193736
  title: Isomerization of 3,7,24THCA-CoA to (24R, 25R) 3alpha,7alpha,24-trihydroxy-5beta-cholestanoyl-CoA
  findings: []
- id: Reactome:R-HSA-193763
  title: 'TODO: Fetch title'
  findings: []
- id: Reactome:R-HSA-193775
  title: Synthesis of bile acids and bile salts via 24-hydroxycholesterol
  findings: []
- id: Reactome:R-HSA-389887
  title: Beta-oxidation of pristanoyl-CoA
  findings: []
- id: Reactome:R-HSA-389897
  title: Isomerization of (2R)-pristanoyl-CoA to (2S)-pristanoyl-CoA
  findings: []
- id: Reactome:R-HSA-9033235
  title: Cargo of PEX5S,L translocates from the cytosol to the peroxisomal matrix
  findings: []
- id: Reactome:R-HSA-9033236
  title: PEX5S,L:Cargo binds PEX13:PEX14:PEX2:PEX10:PEX12 (Docking and Translocation
    Module)
  findings: []