| Aspect | Key findings | Evidence/notes with specific numeric values where available | Primary citation context IDs |
|---|---|---|---|
| Enzyme activity | Zebrafish **fads2** encodes a **bifunctional front-end desaturase** with **Δ6 and Δ5** activities; later in vivo work supports an **alternative Δ8 route** consistent with trifunctional behavior in pathway context. | In yeast, zebrafish Fads2 converted C18 PUFA by **Δ6** desaturation and C20 PUFA by **Δ5** desaturation; crispant data support diversion through a **Δ8 bypass** when Δ6 function is impaired. Reviews place zebrafish among teleosts where Fads2 diversified after loss of canonical teleost **fads1**. (pqac-00000012, pqac-00000000, pqac-00000019, pqac-00000024) | (pqac-00000012, pqac-00000000, pqac-00000019, pqac-00000024) |
| Substrates/products (Δ6) | Primary Δ6 substrates are **18:2n-6 (LA)** and **18:3n-3 (ALA)**, yielding **18:3n-6 (GLA)** and **18:4n-3 (SDA)**. | Hastings et al. showed **18:2n-6 → 18:3n-6** at **11.7%** conversion and **18:3n-3 → 18:4n-3** at **29.4%** conversion in yeast, indicating stronger activity toward the n-3 substrate. Δ6 desaturation is described as the first/rate-limiting step in LC-PUFA biosynthesis. (pqac-00000012, pqac-00000010, pqac-00000019, pqac-00000024) | (pqac-00000012, pqac-00000010, pqac-00000019, pqac-00000024) |
| Substrates/products (Δ5) | Zebrafish Fads2 also desaturates C20 intermediates at the Δ5 position to generate **ARA** and **EPA**. | Hastings et al. measured **20:3n-6 → 20:4n-6 (ARA)** at **8.3%** conversion and **20:4n-3 → 20:5n-3 (EPA)** at **20.4%** conversion, again showing preference for n-3 substrate. (pqac-00000012, pqac-00000009) | (pqac-00000012, pqac-00000009) |
| C24 substrate activity / DHA route | Zebrafish Δ6Δ5 Fads2 can also act on **C24 PUFA**, supporting the **Sprecher pathway** for DHA biosynthesis. | In the Oboh et al. teleost survey, zebrafish DrΔ6Δ5Fads2 converted **24:4n-6 → 24:5n-6** at **10.4%** and **24:5n-3 → 24:6n-3** at **15.8%**; the **Δ24:5n-3/Δcontrol ratio was 1.33**, with **18:3n-3 control conversion 11.9%**. (pqac-00000014, pqac-00000022, pqac-00000026) | (pqac-00000014, pqac-00000022, pqac-00000026) |
| Δ8 pathway relevance | When fads2 function is partially disrupted in vivo, zebrafish LC-PUFA synthesis can be rerouted through an **alternative Δ8 pathway**. | Bláhová et al. interpret crispant egg lipid profiles as showing elongation of C18 precursors to **20:2n-6 (EDA)** and **20:3n-3 (ERA)** followed by Fads2-mediated **Δ8 desaturation**, bypassing the first Δ6 step. This supports the claim that zebrafish Fads2 behaves as **Δ6/Δ5/Δ8** in vivo pathway context. (pqac-00000000, pqac-00000001, pqac-00000002) | (pqac-00000000, pqac-00000001, pqac-00000002) |
| Pathway role | **fads2** is the key desaturase in endogenous **LC-PUFA biosynthesis**, linking dietary C18 essential fatty acids to **ARA, EPA, and DHA** production. | Reviews describe two major routes: **Δ6 pathway** (Δ6 desaturation → elongation → Δ5 desaturation) and **Δ8 pathway** (elongation → Δ8 desaturation → Δ5 desaturation). DHA can then be produced by the **Sprecher pathway** via **24:5n-3 → 24:6n-3** and peroxisomal β-oxidation, or by a direct Δ4 route in some other teleosts; zebrafish is aligned with the Sprecher-capable group. (pqac-00000019, pqac-00000022, pqac-00000025) | (pqac-00000019, pqac-00000022, pqac-00000025) |
| Localization | Zebrafish Fads2 is primarily associated with the **endoplasmic reticulum (ER)**, with additional evidence for **mitochondrial membrane** localization in transfected cells. | Chen et al. reported ER co-localization (with **ERp57**) and mitochondrial co-localization (with **COX IV**), plus Western-blot detection in the mitochondrial membrane fraction of HeLa cells expressing zebrafish Fads2. Reviews also describe Fads2 as an **ER membrane-bound** enzyme. (pqac-00000013, pqac-00000005, pqac-00000025, pqac-00000006) | (pqac-00000013, pqac-00000005, pqac-00000025, pqac-00000006) |
| Protein interactions | Fads2 functions within an ER lipid-biosynthetic complex with **CYB5R2/CYB5R3** and multiple **ELOVL** elongases. | Chen et al. measured donor-acceptor distances of **95 Å** to **CYB5R2** and **93 Å** to **CYB5R3**. Reported FRET efficiencies with elongases were **13 ± 1% (ELOVL2)**, **11 ± 0% (ELOVL4)**, and **7.8 ± 0.6% (ELOVL5)**; Fads2 was also in proximity to ELOVL7. (pqac-00000013, pqac-00000011) | (pqac-00000013, pqac-00000011) |
| Structure/domains | The protein architecture matches UniProt Q9DEX7: **N-terminal cytochrome b5-like domain**, conserved **HPGG** heme-binding motif, **three histidine boxes**, and multiple membrane-spanning helices. | Hastings reported a **1,590-bp ORF** encoding a **444-aa** protein. Reviews describe Fads2 as a modular, membrane-bound desaturase with a fused cytochrome b5-like domain and a C-terminal desaturase region containing **three conserved His-boxes**; topology models predict **up to four transmembrane α-helices** in ER membrane association. (pqac-00000009, pqac-00000004, pqac-00000006, pqac-00000023) | (pqac-00000009, pqac-00000004, pqac-00000006, pqac-00000023) |
| Catalytic mechanism | Fads2 is a **non-heme diiron front-end desaturase** that receives electrons through the cytochrome b5 system. | Mechanistic reviews describe electron transfer from **NADH → NADH-cytochrome b5 reductase → cytochrome b5 / fused cytochrome b5-like domain → diiron center**, with molecular oxygen used during double-bond insertion. Chen et al. likewise described zebrafish Fads2 as a **non-heme diiron desaturase** requiring the heme-binding cytochrome b5 motif. (pqac-00000021, pqac-00000023, pqac-00000005) | (pqac-00000021, pqac-00000023, pqac-00000005) |
| Phenotypes upon editing | Partial loss of fads2 impairs female reproductive output through altered egg LC-PUFA composition and poor egg quality. | Bláhová et al. generated **G0 CRISPR/Cas9 crispants with ~50–80% editing** and found impaired conversion of **LA→GLA** and **ALA→SDA**, altered egg LC-PUFA profiles, evidence of Δ8 bypass, and **bad-quality eggs** in edited females. Figure/table evidence in that paper centers on egg fatty-acid ratios and significant composition shifts. (pqac-00000000, pqac-00000001, pqac-00000015) | (pqac-00000000, pqac-00000001, pqac-00000015) |
| Key quantitative data summary | Available quantitative data show stronger activity toward **n-3 substrates** and measurable action on both **C18/C20** and **C24** PUFA. | Percent conversions reported: **11.7%** (18:2n-6→18:3n-6), **29.4%** (18:3n-3→18:4n-3), **8.3%** (20:3n-6→20:4n-6), **20.4%** (20:4n-3→20:5n-3), **10.4%** (24:4n-6→24:5n-6), **15.8%** (24:5n-3→24:6n-3), control **11.9%**, ratio **1.33**; editing efficiency in vivo **50–80%**. (pqac-00000012, pqac-00000014, pqac-00000000) | (pqac-00000012, pqac-00000014, pqac-00000000) |
| Applications / engineering | **fads2** is considered a promising **genome-editing target** for modifying fish fatty-acid composition and improving aquaculture value. | A 2024 review lists **fads2** and related Δ6 mutant alleles among targets affecting **fatty-acid composition in fish meat**. A broader review highlights promoter engineering, copy-number effects, and transgenesis, including evidence that heterologous **Δ5 Fads2** can function in zebrafish and that LC-PUFA biosynthesis can be increased by engineering pathway genes. (pqac-00000027, pqac-00000028, pqac-00000006) | (pqac-00000027, pqac-00000028, pqac-00000006) |


*Table: This table summarizes the functional annotation of zebrafish Danio rerio fads2 (UniProt Q9DEX7), including enzymatic activities, pathways, localization, structure, phenotypes, and engineering relevance. It compiles quantitative findings from primary studies and review-level context useful for gene function interpretation.*