Details for: ACOX3

Gene ID: 8310

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: ACOX3

Ensembl ID: ENSG00000087008

Description: acyl-CoA oxidase 3, pristanoyl

Cell Significance Landscape

Associated with

Significant Cells

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

  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 7.44
    rCSI 9.02%
    PRS 67.56
  • epithelial cell CL0000066
    CSI 5.62
    rCSI 8.64%
    PRS 75.75
  • melanocyte CL0000148
    CSI 3.75
    rCSI 2.78%
    PRS 82.44
  • interneuron CL0000099
    CSI 3.62
    rCSI 7.27%
    PRS 79.82
  • lung ciliated cell CL1000271
    CSI 3.32
    rCSI 3.84%
    PRS 80.92
  • plasmacytoid dendritic cell, human CL0001058
    CSI 3.28
    rCSI 2.29%
    PRS 90.55
  • secretory cell CL0000151
    CSI 3.02
    rCSI 3.16%
    PRS 86.1
  • cerebral cortex endothelial cell CL1001602
    CSI 2.98
    rCSI 5.15%
    PRS 80.62
  • hepatic stellate cell CL0000632
    CSI 2.93
    rCSI 10.96%
    PRS 81.36
  • neural crest cell CL0011012
    CSI 2.9
    rCSI 2.29%
    PRS 78.56
  • multi-ciliated epithelial cell CL0005012
    CSI 2.77
    rCSI 2.76%
    PRS 81.45
  • choroid plexus epithelial cell CL0000706
    CSI 2.41
    rCSI 3.94%
    PRS 78.72
  • hepatocyte CL0000182
    CSI 2.37
    rCSI 4.25%
    PRS 86.23
  • ciliated epithelial cell CL0000067
    CSI 2.35
    rCSI 2.06%
    PRS 77.88
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.32
    rCSI 2.78%
    PRS 72.27
  • vascular leptomeningeal cell CL4023051
    CSI 2.26
    rCSI 3.96%
    PRS 82.5
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.02
    rCSI 2.87%
    PRS 84.48
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.01
    rCSI 2.5%
    PRS 69.92
  • extravillous trophoblast CL0008036
    CSI 1.92
    rCSI 2.37%
    PRS 85.58
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.83
    rCSI 2.36%
    PRS 73.27
  • basal cell of epidermis CL0002187
    CSI 1.75
    rCSI 3.11%
    PRS 57.29
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.69
    rCSI 3.78%
    PRS 72.84
  • regular atrial cardiac myocyte CL0002129
    CSI 1.48
    rCSI 4.77%
    PRS 83.95
  • cardiac muscle cell CL0000746
    CSI 1.48
    rCSI 2.12%
    PRS 78.41
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.47
    rCSI 2.6%
    PRS 71.58
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.45
    rCSI 2.33%
    PRS 73.3
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.41
    rCSI 2.37%
    PRS 72.12
  • placental villous trophoblast CL2000060
    CSI 1.27
    rCSI 1.96%
    PRS 85.82
  • fibroblast of cardiac tissue CL0002548
    CSI 1.26
    rCSI 6.04%
    PRS 87.6
  • retinal ganglion cell CL0000740
    CSI 1.17
    rCSI 2.58%
    PRS 75.07
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.16
    rCSI 2.94%
    PRS 79.56
  • GABAergic neuron CL0000617
    CSI 1.14
    rCSI 3.81%
    PRS 72.41
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.02
    rCSI 6.34%
    PRS 80.21
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.88
    rCSI 2.15%
    PRS 69.88
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.82
    rCSI 2.56%
    PRS 75.55
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.78
    rCSI 2.44%
    PRS 73.44
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.67
    rCSI 2.54%
    PRS 72.42
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.63
    rCSI 2.25%
    PRS 70.08
  • direct pathway medium spiny neuron CL4023026
    CSI 0.37
    rCSI 8.8%
    PRS 69.69
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.36
    rCSI 2.13%
    PRS 72.56
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.3
    rCSI 7.29%
    PRS 70.13

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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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • 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 [ACOX3](/details-gene/8310) encodes acyl-coenzyme A oxidase 3, a peroxisomal enzyme that plays a key role in the catabolism of specific branched-chain fatty acids. Its primary function is the beta-oxidation of pristanoyl-CoA, a critical step in lipid metabolism. Initial characterization confirmed the existence of this gene in humans and distinguished its activity from other acyl-CoA oxidases ([Link](https://doi.org/10.1042/bj3250593)). Expression data from the **Overall** context reveals a broad but significant presence across diverse cell lineages, with the highest Cell Significance Index (CSI) observed in `[CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203)`, followed by `[epithelial cell](/details-cell/CL0000066)`, `[melanocyte](/details-cell/CL0000148)`, and `[interneuron](/details-cell/CL0000099)`. This pattern suggests that while [ACOX3](/details-gene/8310) performs a fundamental metabolic function, its activity is particularly important for the homeostasis and function of specific cell types across the immune, epithelial, and nervous systems. ## Cellular Roles and Expression Landscape The expression profile of [ACOX3](/details-gene/8310) indicates a role as a crucial metabolic enzyme in a wide range of specialized cells. **Overall**, its highest significance is in the immune system, specifically in `[CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203)` (CSI: 7.44). This strong signal suggests a specialized metabolic requirement, possibly related to fatty acid oxidation for the long-term survival and maintenance of this memory T cell subset. Its notable presence in `[plasmacytoid dendritic cell, human](/details-cell/CL0001058)` (CSI: 3.28) further points to a role within immune cell metabolism. Beyond the immune system, [ACOX3](/details-gene/8310) demonstrates high significance in various structural and secretory cells. It is a key marker in `[epithelial cell](/details-cell/CL0000066)` (CSI: 5.62) generally, with specific importance in `[lung ciliated cell](/details-cell/CL1000271)` (CSI: 3.32) and `[choroid plexus epithelial cell](/details-cell/CL0000706)` (CSI: 2.41), suggesting a role in maintaining metabolic integrity in tissues with high turnover or specialized secretory functions. The gene is also significantly expressed in neural and hepatic lineages. Its relevance in `[interneuron](/details-cell/CL0000099)` (CSI: 3.62) and `[cerebral cortex endothelial cell](/details-cell/CL1001602)` (CSI: 2.98) suggests a role in managing lipid metabolism within the unique microenvironment of the brain. As expected for a lipid-metabolizing enzyme, it is also significant in `[hepatocyte](/details-cell/CL0000182)` (CSI: 2.37) and `[hepatic stellate cell](/details-cell/CL0000632)` (CSI: 2.93), cell types central to systemic lipid processing. The broad expression across functionally distinct cell types highlights its role as a fundamental housekeeping gene for processing specific lipid substrates. ## Pathways and Molecular Function Functional annotations for [ACOX3](/details-gene/8310) firmly place it within the domain of peroxisomal lipid metabolism. The gene product is localized to the `[peroxisome](/details-go/GO0005777)` and its matrix, where it executes its primary molecular function of `[pristanoyl-coa oxidase activity](/details-go/GO0016402)`. This activity is a key component of the `[Fatty acid beta-oxidation using acyl-coa oxidase](/details-go/GO0033540)` biological process. According to Reactome, [ACOX3](/details-gene/8310) is a central enzyme in the `[Beta-oxidation of pristanoyl-coa](/details-pathway/R-HSA-389887)` pathway. This pathway is essential for the breakdown of pristanic acid, a branched-chain fatty acid derived from dietary sources, particularly from the phytol side chain of chlorophyll. Its involvement in broader `[Peroxisomal lipid metabolism](/details-pathway/R-HSA-390918)` and `[Metabolism of lipids](/details-pathway/R-HSA-556833)` pathways underscores its importance in cellular lipid homeostasis. This function is consistent with its high expression in metabolically active cells like `[hepatocyte](/details-cell/CL0000182)`s, which are primary sites of lipid processing, and its high significance in memory T cells, which are known to rely on fatty acid oxidation for energy and survival. ## Research Directions The widespread yet specific expression pattern of [ACOX3](/details-gene/8310), particularly its prominence in memory T cells, opens several avenues for future investigation. **Proposed Testable Hypotheses:** 1. The high significance of [ACOX3](/details-gene/8310) in `[CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203)` suggests that peroxisomal beta-oxidation of branched-chain fatty acids is a critical metabolic pathway for the long-term maintenance and bioenergetic fitness of this immune memory subset. 2. In non-immune cells like `[interneuron](/details-cell/CL0000099)`s and `[melanocyte](/details-cell/CL0000148)`s, [ACOX3](/details-gene/8310) may serve a protective function by preventing the accumulation of cytotoxic branched-chain fatty acids, thereby contributing to cellular longevity and preventing lipotoxicity. **Suggested Experimental Approach:** To test the first hypothesis regarding the role of [ACOX3](/details-gene/8310) in T cell memory, a conditional knockout mouse model could be employed. Specifically, mice with a floxed *Acox3* allele could be crossed with CD4-Cre transgenic mice to achieve T cell-specific deletion. Following an acute viral infection (e.g., with Lymphocytic Choriomeningitis Virus, LCMV), the development, persistence, and recall capacity of memory CD8+ T cells would be quantified via flow cytometry and tetramer staining. It would be predicted that [ACOX3](/details-gene/8310)-deficient T cells would exhibit impaired formation or survival of the memory pool. Furthermore, metabolic analysis of isolated memory T cells using techniques like Seahorse XF analysis could directly assess their capacity for fatty acid oxidation. **Therapeutic Potential:** As an intracellular metabolic enzyme, [ACOX3](/details-gene/8310) presents a challenging therapeutic target. Direct inhibition could have widespread, off-target effects due to its expression in multiple essential cell types. However, in certain contexts, targeting this pathway could be beneficial. For instance, if specific cancers, such as T cell lymphomas, demonstrate a unique metabolic dependency on peroxisomal fatty acid oxidation, then a highly specific small molecule inhibitor of [ACOX3](/details-gene/8310) could represent a viable therapeutic strategy. Conversely, in rare metabolic disorders characterized by the accumulation of pristanic acid, developing strategies for gene augmentation or pharmacological activation of [ACOX3](/details-gene/8310) could be a potential therapeutic avenue, although this remains technically challenging.

Genular Protein ID: 3269634374

Symbol: ACOX3_HUMAN

Name: Peroxisomal acyl-coenzyme A oxidase 3

UniProtKB Accession Codes:

O15254 Q96AJ8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 21 ChEMBL 1 ChiTaRS 1 DNASU 1 DisGeNET 1 DrugCentral 1 EC 1 EMBL 2 Ensembl 3 ExpressionAtlas 1 GO 10 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIRSF 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 2 RefSeq 5 Rhea 10 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9271077

Title: Evidence for the existence of a pristanoyl-CoA oxidase gene in man.

PubMed ID: 9271077

DOI: 10.1042/bj3250593

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: 19369195

Title: Large-scale proteomics analysis of the human kinome.

PubMed ID: 19369195

DOI: 10.1074/mcp.m800588-mcp200

PubMed ID: 22223895

Title: Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features.

PubMed ID: 22223895

DOI: 10.1074/mcp.m111.015131

PubMed ID: 22814378

Title: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

PubMed ID: 22814378

DOI: 10.1073/pnas.1210303109

PubMed ID: 25944712

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

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

Sequence Information:

  • Length: 700
  • Mass: 77629
  • Checksum: 40D1CD3DC6A620C1
  • Sequence:
    • MASTVEGGDT ALLPEFPRGP LDAYRARASF SWKELALFTE GEGMLRFKKT IFSALENDPL 
FARSPGADLS LEKYRELNFL RCKRIFEYDF LSVEDMFKSP LKVPALIQCL GMYDSSLAAK 
YLLHSLVFGS AVYSSGSERH LTYIQKIFRM EIFGCFALTE LSHGSNTKAI RTTAHYDPAT 
EEFIIHSPDF EAAKFWVGNM GKTATHAVVF AKLCVPGDQC HGLHPFIVQI RDPKTLLPMP 
GVMVGDIGKK LGQNGLDNGF AMFHKVRVPR QSLLNRMGDV TPEGTYVSPF KDVRQRFGAS 
LGSLSSGRVS IVSLAILNLK LAVAIALRFS ATRRQFGPTE EEEIPVLEYP MQQWRLLPYL 
AAVYALDHFS KSLFLDLVEL QRGLASGDRS ARQAELGREI HALASASKPL ASWTTQQGIQ 
ECREACGGHG YLAMNRLGVL RDDNDPNCTY EGDNNILLQQ TSNYLLGLLA HQVHDGACFR 
SPLKSVDFLD AYPGILDQKF EVSSVADCLD SAVALAAYKW LVCYLLRETY QKLNQEKRSG 
SSDFEARNKC QVSHGRPLAL AFVELTVVQR FHEHVHQPSV PPSLRAVLGR LSALYALWSL 
SRHAALLYRG GYFSGEQAGE VLESAVLALC SQLKDDAVAL VDVIAPPDFV LDSPIGRADG 
ELYKNLWGAV LQESKVLERA SWWPEFSVNK PVIGSLKSKL