| Function/Reaction | Substrates & products | Subcellular localization | Developmental roles/processes in zebrafish | Regulation/feedback | Recent applications (2024 studies) | Key evidence sources with DOI/URL and year |
|---|---|---|---|---|---|---|
| Retinoic-acid catabolic cytochrome P450; major RA-degrading enzyme during gastrulation that helps generate a robust hindbrain RA gradient (pqac-00000000, pqac-00000003) | Oxidizes all-trans RA to more polar metabolites; family products include 4-OH-RA, 4-oxo-RA, 18-OH-RA and other oxidized derivatives (pqac-00000014, pqac-00000015, pqac-00000017) | Membrane-anchored microsomal/ER cytochrome P450; heme-containing class II P450 inferred for zebrafish Cyp26a1 (pqac-00000015, pqac-00000019, pqac-00000020) | Establishes anterior RA-poor territory and posterior-to-anterior RA patterning; required for hindbrain AP patterning, rhombomere identity, and protection from excess RA; loss expands posterior hindbrain fates anteriorly (pqac-00000000, pqac-00000002, pqac-00000003) | Under complex feedback/feedforward control by RA and Fgf signaling; RA can induce cyp26a1 expression, creating adaptive buffering/homeostasis of RA availability (pqac-00000000, pqac-00000006) | Used conceptually as a readout of RA-pathway perturbation in zebrafish developmental studies and toxicology assays (pqac-00000008, pqac-00000009, pqac-00000013) | White 2007, PLoS Biol, doi:10.1371/journal.pbio.0050304, https://doi.org/10.1371/journal.pbio.0050304; Hernandez 2007, Development, doi:10.1242/dev.02706, https://doi.org/10.1242/dev.02706 |
| Enzymatic reaction detail: RA 4-hydroxylase/oxidase activity demonstrated in zebrafish microsomal assays (pqac-00000001, pqac-00000004, pqac-00000018) | Zebrafish Cyp26A1 microsomes mainly generate 4-OH-RA and 4-oxo-RA from all-trans RA; related CYP26 enzymes can also metabolize 9-cis RA and 13-cis RA, but not retinol/retinal in the cited assay system (pqac-00000014, pqac-00000016, pqac-00000018) | Activity assayed in microsomes from transfected cells, consistent with ER-derived membrane localization (pqac-00000016, pqac-00000018) | Restricts inappropriate RA signaling during somitogenesis and axial patterning; cyp26a1 overexpression reduces endogenous RA activity and alters hindbrain-somite patterning/asymmetric somites (pqac-00000001, pqac-00000004) | RA inducibility supports negative-feedback RA clearance; CYP26 enzymes act as RA sinks to sharpen signaling boundaries (pqac-00000005, pqac-00000006) | Supports use of cyp26a1 as a mechanistic biomarker for compounds or mutations that disturb RA metabolism/signaling (pqac-00000005, pqac-00000013) | Gu 2006, Mol Endocrinol, doi:10.1210/me.2005-0362, https://doi.org/10.1210/me.2005-0362; Thatcher & Isoherranen 2009, Expert Opin Drug Metab Toxicol, doi:10.1517/17425250903032681, https://doi.org/10.1517/17425250903032681 |
| Spatially restricted embryonic RA-clearance factor in anterior neural ectoderm/hindbrain field (pqac-00000002, pqac-00000003) | Functional effect is depletion of local RA available for receptor signaling rather than transport of another substrate (pqac-00000002, pqac-00000006) | Expressed in presumptive anterior neural ectoderm, then forebrain, midbrain, anterior hindbrain, and tailbud during early development (gene-expression territory rather than protein compartment) (pqac-00000002) | Creates RA-depleted anterior domains opposing posterior aldh1a2/raldh2 synthesis; essential for proper hindbrain segmentation and regional identity (pqac-00000002, pqac-00000003) | Integrated with transcriptional regulators such as zic factors that influence embryonic RA signaling territories (pqac-00000002) | Provides a developmental pathway node for dissecting hindbrain patterning and cranial motor-neuron specification mechanisms (pqac-00000002) | Drummond 2013, BMC Dev Biol, doi:10.1186/1471-213X-13-31, https://doi.org/10.1186/1471-213X-13-31 |
| General CYP26 biochemistry/current understanding: high-efficiency RA clearance enzyme family controlling RA homeostasis (pqac-00000006, pqac-00000015) | High catalytic activity toward all-trans RA; review cites Km < 100 nM and turnover ~1–10 pmol/min/pmol in transfected-cell systems for CYP26 enzymes; metabolites subsequently glucuronidated and eliminated (pqac-00000015) | ER/microsomal enzyme requiring POR-mediated electron transfer from NADPH via FAD and FMN; contains heme-binding domain (pqac-00000015, pqac-00000020) | Protects RA-sensitive tissues and helps establish local RA gradients across multiple developmental contexts; zebrafish hindbrain is a canonical example (pqac-00000006, pqac-00000000) | Negative feedback is a central systems-level property of CYP26-mediated RA homeostasis (pqac-00000006, pqac-00000015) | Basis for pharmacologic CYP26 inhibition/modulation concepts and for interpreting RA-pathway toxicity in zebrafish and other vertebrates (pqac-00000005, pqac-00000015) | Roberts 2020, J Dev Biol, doi:10.3390/jdb8010006, https://doi.org/10.3390/jdb8010006; Thatcher & Isoherranen 2009, doi:10.1517/17425250903032681, https://doi.org/10.1517/17425250903032681 |
| 2024 zebrafish toxicology application: cyp26a1 measured as an RA-pathway marker during environmentally relevant TPhP exposure (pqac-00000008, pqac-00000009, pqac-00000010) | Not a direct substrate study; cyp26a1 transcript assessed alongside raldh2 to test whether TPhP acts through RA/RXR signaling (pqac-00000009) | Whole-larva qPCR readout at 5 dpf; localization not the focus (pqac-00000010) | In this assay, no significant change in cyp26a1/raldh2 at 5 µg/L TPhP suggested the nM TPhP phenotype was not mediated by RXR/RA signaling; affected larvae were shorter and showed pericardial edema (0.14 mm decrease at 5 µg/L; 3.29 vs 3.14 mm; p=0.00012) (pqac-00000009) | Demonstrates utility of cyp26a1 as a pathway-discrimination marker distinguishing RA/RXR effects from tbx5a-associated cardiotoxicity (pqac-00000009) | Real-world implementation in developmental toxicology screening at environmentally relevant concentrations 0.5–5 µg/L (1.5–15 nM) (pqac-00000008, pqac-00000010) | Schmandt 2024, Toxics, doi:10.3390/toxics12050368, https://doi.org/10.3390/toxics12050368 |
| 2024 zebrafish disease/metabolism application: cyp26a1 upregulation marks disrupted RA metabolism in cobll1a mutants (pqac-00000012, pqac-00000013) | Not a direct enzymology study; cyp26a1 used as the RA-catabolism gene indicator within altered retinol/RA metabolic networks (pqac-00000012) | WISH detected expression of rdh10, aldh1a2, cyp26a1 and rbp4 in intestine or liver-associated territories in the study context (pqac-00000012) | cobll1a−/− embryos showed impaired digestive-organ development at 4 dpf, altered RA-pathway gene expression, increased lipid synthesis and reduced lipid catabolism; cyp26a1 was upregulated while aldh1a2/rdh10 and RAR genes were downregulated (pqac-00000012, pqac-00000013) | Shows cyp26a1 participates in broader RA-lipid homeostasis networks; RA catabolism shifts accompany hepatic/lipid phenotypes (pqac-00000012) | Application in metabolic disease modeling/NAFLD-related liver biology using CRISPR zebrafish mutants; lipid-pathway genes changed significantly (p < 0.01 for listed lipid-anabolism genes) (pqac-00000013, pqac-00000012) | Zeng 2024, Front Cell Dev Biol, doi:10.3389/fcell.2024.1381362, https://doi.org/10.3389/fcell.2024.1381362 |


*Table: This table summarizes the verified function, reaction chemistry, localization, developmental roles, regulation, and 2024 zebrafish applications of Danio rerio cyp26a1 (UniProt P79739). It is useful as a compact evidence-based functional annotation reference anchored to the cited source contexts.*