Details for: AMACR

Gene ID: 23600

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: AMACR

Ensembl ID: ENSG00000242110

Description: alpha-methylacyl-CoA racemase

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • pulmonary ionocyte CL0017000
    CSI 9.42
    rCSI 11.46%
    PRS 98.47
  • ionocyte CL0005006
    CSI 4.62
    rCSI 4.95%
    PRS 98.08
  • stem cell CL0000034
    CSI 3.99
    rCSI 3.85%
    PRS 96.65
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 3.49
    rCSI 4.95%
    PRS 97.08
  • epithelial cell of proximal tubule CL0002306
    CSI 3.28
    rCSI 8.01%
    PRS 94.38
  • Mueller cell CL0000636
    CSI 3.07
    rCSI 7.01%
    PRS 94.97
  • colon epithelial cell CL0011108
    CSI 2.93
    rCSI 3.07%
    PRS 96.86
  • intestinal epithelial cell CL0002563
    CSI 2.87
    rCSI 3%
    PRS 96.57
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 2.78
    rCSI 3.37%
    PRS 84.72
  • enteroendocrine cell CL0000164
    CSI 2.31
    rCSI 3.16%
    PRS 96.3
  • basal cell of epidermis CL0002187
    CSI 1.97
    rCSI 3.49%
    PRS 79.13
  • melanocyte of skin CL1000458
    CSI 1.26
    rCSI 1.71%
    PRS 80.23
  • helper T cell CL0000912
    CSI 1.15
    rCSI 1.63%
    PRS 93.4

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Alpha-methylacyl-CoA racemase, encoded by the gene [AMACR](/details-gene/23600), is a crucial enzyme in the metabolism of branched-chain fatty acids and bile acid intermediates. Functionally, it catalyzes the conversion of (R)- and (S)-stereoisomers of 2-methyl-branched-chain fatty acyl-CoA esters, a necessary step for their degradation via peroxisomal beta-oxidation. Research has localized this protein to both peroxisomes and mitochondria ([Link](https://pubmed.ncbi.nlm.nih.gov/11060344/)). Mutations in [AMACR](/details-gene/23600) are associated with adult-onset sensory motor neuropathy ([OMIM: 214950](https://omim.org/entry/214950)), and the gene is a well-established biomarker for prostate cancer ([Link](https://doi.org/10.1002/pros.20277)). Expression data indicates that **Overall**, [AMACR](/details-gene/23600) shows the highest significance in specialized, metabolically active epithelial cells, particularly [pulmonary ionocytes](/details-cell/CL0017000) and various kidney tubular cells, highlighting its fundamental role in tissues with high metabolic and transport demands. ## Cellular Roles and Expression Landscape The expression profile of [AMACR](/details-gene/23600) points to a primary function in specialized epithelial cells responsible for intensive metabolic and ion transport activities. **Overall**, the gene exhibits its highest significance in [pulmonary ionocytes](/details-cell/CL0017000) (CSI: 9.42) and other [ionocytes](/details-cell/CL0005006) (CSI: 4.62), cells known for their role in regulating ion and fluid balance across epithelial barriers. This pattern of high expression continues in other highly metabolic epithelial tissues, including the [kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111) (CSI: 3.49) and the [epithelial cell of proximal tubule](/details-cell/CL0002306) (CSI: 3.28), which are central to solute reabsorption and waste processing. Further evidence for its role in barrier tissues with high metabolic turnover is provided by its significant expression in [colon epithelial cells](/details-cell/CL0011108) and [basal cells of the epidermis](/details-cell/CL0002187). Its high significance in [stem cells](/details-cell/CL0000034) (CSI: 3.99) suggests a potential role in maintaining metabolic plasticity required for self-renewal and differentiation. Interestingly, [AMACR](/details-gene/23600) also shows moderate significance in adaptive immune cells, such as the [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203), which may indicate a role for fatty acid metabolism in supporting long-term immune memory. ## Pathways and Molecular Function The molecular functions of [AMACR](/details-gene/23600) are centered on lipid metabolism, which aligns with its expression in metabolically active cells. Gene Ontology annotations confirm its role in [alpha-methylacyl-coa racemase activity](/details-go/GO0008111), which is a key step in the [bile acid biosynthetic process](/details-go/GO0006699) and [fatty acid beta-oxidation using acyl-coa oxidase](/details-go/GO0033540). The enzyme's localization to the [cytoplasm](/details-go/GO0005737), [mitochondrion](/details-go/GO0005739), and [peroxisome](/details-go/GO0005777) is well-documented ([Link](https://pubmed.ncbi.nlm.nih.gov/11060359/)) and critical for its function, as it processes substrates for degradation in these organelles. Reactome pathway analysis further details its involvement in the [Beta-oxidation of pristanoyl-coa](/details-pathway/R-HSA-389887) and broader [Peroxisomal lipid metabolism](/details-pathway/R-HSA-390918). Its role in the [synthesis of bile acids and bile salts](/details-pathway/R-HSA-192105) is consistent with its high expression in liver and intestinal epithelial cells. The connection to the bile acid pathway is clinically significant, as defects can lead to liver disease due to the accumulation of toxic intermediates ([Link](https://doi.org/10.1053/gast.2003.50017)). ## Research Directions The established role of [AMACR](/details-gene/23600) in lipid metabolism and its association with pathology provide a strong foundation for further investigation, while its specific cellular expression patterns suggest novel functions. **Proposed Hypotheses:** 1. Given its exceptionally high significance in [pulmonary ionocytes](/details-cell/CL0017000), [AMACR](/details-gene/23600) may be essential for maintaining the unique lipid membrane composition required for the high-density expression and function of ion transporters like CFTR, thereby playing a critical role in airway surface liquid homeostasis. 2. The notable expression of [AMACR](/details-gene/23600) in [CD8-positive, alpha-beta memory T cells](/details-cell/CL0001203) suggests that fatty acid oxidation, mediated by [AMACR](/details-gene/23600), is a key metabolic pathway that fuels the long-term survival and rapid recall response of these immune cells. **Experimental Approach:** To test the hypothesis regarding the role of [AMACR](/details-gene/23600) in memory T cell function, a conditional knockout mouse model could be employed. Specifically, deleting *Amacr* in T cells (e.g., using a CD4-Cre driver) would allow for the study of its cell-intrinsic role. Following an acute viral infection (e.g., LCMV), the formation, maintenance, and recall response of memory CD8+ T cells could be quantified using flow cytometry and in vivo rechallenge experiments. Metabolic profiling of knockout versus wild-type memory T cells via Seahorse assays could directly assess the dependence on fatty acid oxidation. **Therapeutic Potential:** [AMACR](/details-gene/23600) is already a validated biomarker for prostate cancer, where its overexpression is associated with malignancy. This makes it a compelling therapeutic target. As an enzyme, it is amenable to small molecule inhibition. A specific inhibitor of [AMACR](/details-gene/23600) could selectively disrupt the metabolic pathways that fuel prostate cancer cell proliferation, potentially with fewer side effects than broad-acting chemotherapy. Furthermore, understanding its role in inherited metabolic neuropathies could inform therapeutic strategies aimed at either restoring its function or mitigating the accumulation of toxic lipid substrates.

Genular Protein ID: 1235075945

Symbol: AMACR_HUMAN

Name: Alpha-methylacyl-CoA racemase

UniProtKB Accession Codes:

Q9UHK6 A5YM47 B8Y916 B8Y918 F8W9N1 O43673 Q3KT79 Q96GH1 Q9Y3Q1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CTD 1 ChEBI 6 DMDM 1 DNASU 1 DisGeNET 1 EC 1 ELM 1 EMBL 12 Ensembl 4 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 Reactome 4 RefSeq 3 Rhea 8 SABIO-RK 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissLipids 1 SwissPalm 1 TreeFam 1 UCSC 1 UniPathway 2 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11060344

Title: Mitochondrial and peroxisomal targeting of 2-methylacyl-CoA racemase in humans.

PubMed ID: 11060344

PubMed ID: 10655068

Title: Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy.

PubMed ID: 10655068

DOI: 10.1038/72861

PubMed ID: 15880524

Title: A variant of the alpha-methyl-acyl-CoA racemase gene created by a deletion in exon 5 and its expression in prostate cancer.

PubMed ID: 15880524

DOI: 10.1002/pros.20277

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 7649182

Title: Purification and characterization of an alpha-methylacyl-CoA racemase from human liver.

PubMed ID: 7649182

DOI: 10.1111/j.1432-1033.1995.tb20766.x

PubMed ID: 11060359

Title: Subcellular localization and physiological role of alpha-methylacyl-CoA racemase.

PubMed ID: 11060359

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 12512044

Title: Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene mutation and effect of bile acid therapy.

PubMed ID: 12512044

DOI: 10.1053/gast.2003.50017

Sequence Information:

  • Length: 382
  • Mass: 42387
  • Checksum: E967D3221A90BEF8
  • Sequence:
    • MALQGISVVE LSGLAPGPFC AMVLADFGAR VVRVDRPGSR YDVSRLGRGK RSLVLDLKQP 
RGAAVLRRLC KRSDVLLEPF RRGVMEKLQL GPEILQRENP RLIYARLSGF GQSGSFCRLA 
GHDINYLALS GVLSKIGRSG ENPYAPLNLL ADFAGGGLMC ALGIIMALFD RTRTGKGQVI 
DANMVEGTAY LSSFLWKTQK LSLWEAPRGQ NMLDGGAPFY TTYRTADGEF MAVGAIEPQF 
YELLIKGLGL KSDELPNQMS MDDWPEMKKK FADVFAEKTK AEWCQIFDGT DACVTPVLTF 
EEVVHHDHNK ERGSFITSEE QDVSPRPAPL LLNTPAIPSF KRDPFIGEHT EEILEEFGFS 
REEIYQLNSD KIIESNKVKA SL