Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0015297 antiporter activity	IEA GO_REF:0000002	ACCEPT	Summary: Antiporter activity is an appropriate catalytic-family annotation for this MATE candidate. Reason: The current public evidence clearly supports a MATE-family antiporter even though the exact specialized substrate remains unresolved.
GO:0016020 membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Membrane localization is appropriate but secondary to the pathway interpretation. Reason: This is a multi-pass membrane transporter, but the central review issue is its pathway placement rather than generic localization. Supporting Evidence: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-uniprot.txt CC -!- SUBCELLULAR LOCATION: Membrane
GO:0042910 xenobiotic transmembrane transporter activity	IEA GO_REF:0000002	UNDECIDED	Summary: The xenobiotic-transport assignment remains unresolved until the transported substrate is tested. Reason: Current evidence points toward a specialized nicotine-module transporter role, but the exact transported metabolite remains experimentally unresolved. Because MATE transporters often move alkaloids and other secondary metabolites, the nicotine-pathway placement does not by itself falsify a xenobiotic transmembrane transporter annotation. Supporting Evidence: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-deep-research-falcon.md No primary publication directly characterizes A0A314KVN4 / DTX40_3; annotation rests on MATE family inference (multidrug and toxic compound extrusion antiporters that often transport plant secondary metabolites) plus the nicotine-pathway genomic and co-expression evidence.
GO:0055085 transmembrane transport	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: This broad process term is reasonable context but not the key curation outcome. Reason: Keep the transport process annotation while prioritizing the antiporter function and pathway-specific interpretation.
GO:1990961 xenobiotic detoxification by transmembrane export across the plasma membrane	IEA GO_REF:0000002	UNDECIDED	Summary: This detoxification-process annotation is unresolved without substrate and localization evidence. Reason: The reviewed evidence supports a pathway-associated metabolite transporter, but it does not identify the transported substrate or establish whether export across the plasma membrane is the relevant compartment. A nicotine- related substrate could still fit a xenobiotic-detoxification framing, so this process annotation should remain undecided pending direct transport and localization assays. Supporting Evidence: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-deep-research-falcon.md The exact transported metabolite (nicotine, nicotine glucoside, or another intermediate) and the precise membrane localization remain experimentally unresolved.
GO:0042179 nicotine biosynthetic process	TAS file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-notes.md	NEW	Summary: MATE1 should be added as a pathway-associated nicotine biosynthetic gene. Reason: The pathway paper keeps MATE1 in the core late module on the basis of gene clustering and coordinated expression, even though its exact transported substrate remains to be nailed down experimentally. Supporting Evidence: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-notes.md The glucosylation preprint identifies an A622-MATE1-beta-GD1 cluster, reports that these genes are root enriched and tightly co-expressed with nicotine biosynthesis genes, and keeps MATE1 in the core late-pathway module even though the exact transported metabolite remains unresolved.

Core Functions

DTX40_3 is the best current NICAT MATE1 candidate for the membrane transport step associated with the late nicotine biosynthetic module.

Molecular Function:

antiporter activity

Directly Involved In:

nicotine biosynthetic process

Supporting Evidence:

file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-notes.md
The glucosylation preprint identifies an A622-MATE1-beta-GD1 cluster, reports that these genes are root enriched and tightly co-expressed with nicotine biosynthesis genes, and keeps MATE1 in the core late-pathway module even though the exact transported metabolite remains unresolved.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-uniprot.txt

UniProt entry A0A314KVN4 for Nicotiana attenuata DTX40_3

DTX40_3 is a membrane-localized MATE-family antiporter

"CC -!- SIMILARITY: Belongs to the multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family."
UniProt places DTX40_3 in membrane and multi-pass membrane protein annotations

"CC -!- SUBCELLULAR LOCATION: Membrane"

file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-notes.md

NaMATE1 DTX40_3 candidate notes

MATE1 is genomically and expression-linked to the late nicotine pathway module

"The glucosylation preprint identifies an A622-MATE1-beta-GD1 cluster, reports that these genes are root enriched and tightly co-expressed with nicotine biosynthesis genes, and keeps MATE1 in the core late-pathway module even though the exact transported metabolite remains unresolved."
DTX40_3 is the best current sequence-backed NICAT ortholog to tobacco MATE1

"The 2026-04-05 mapping dive assigns NaMATE1 to DTX40_3 / A0A314KVN4 as the best current sequence-backed NICAT ortholog to tobacco MATE1."

file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-deep-research-falcon.md

Deep research report on NaMATE1/DTX40_3 (Falcon/Edison Scientific Literature)

No primary publication directly characterizes A0A314KVN4 / DTX40_3; annotation rests on MATE family inference (multidrug and toxic compound extrusion antiporters that often transport plant secondary metabolites) plus the nicotine-pathway genomic and co-expression evidence placing this candidate as the attenuata ortholog of tobacco MATE1 in the A622-MATE1-beta-GD1 late-pathway module - the exact transported metabolite (nicotine, nicotine glucoside, or another intermediate) and the precise membrane localization remain experimentally unresolved.

Suggested Experiments

Experiment: Express DTX40_3 in a heterologous transport system and test transport of nicotine, nicotine glucoside, and related late-pathway intermediates.

Hypothesis: DTX40_3 preferentially transports one or more late nicotine-pathway metabolites, and direct assays are needed to determine whether xenobiotic transport annotations also apply.

Type: transporter substrate-specificity assay

Experiment: Disrupt the primary MATE1 candidate and profile subcellular metabolite partitioning together with total nicotine output after induction.

Hypothesis: Loss of DTX40_3 will alter late-pathway metabolite partitioning and reduce efficient nicotine accumulation.

Type: genetics plus compartment-resolved metabolite profiling

Deep Research

Falcon

(NaMATE1_candidate_DTX40_3-deep-research-falcon.md)

Functional annotation research report: **DTX40_3 / NaMATE1_candidate_DTX40_3** (UniProt **A0A314KVN4**) in *Nicotiana attenuata* Falcon Edison Scientific Literature 32 citations 2 artifacts 2026-05-22T22:47:26.712101

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000010 The requested visual content was found in Figures 4 and 6 of the document. Figure 6 shows the subcellular localization of Nt-JAT2-G (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Functional annotation research report: DTX40_3 / NaMATE1_candidate_DTX40_3 (UniProt A0A314KVN4) in Nicotiana attenuata

Executive summary and verification

Target identity (as specified): UniProt A0A314KVN4, gene DTX40_3 (ORF A4A49_09978) from Nicotiana attenuata (coyote tobacco). UniProt describes this protein as “Protein detoxification / multidrug and toxic compound extrusion protein” and assigns it to the MATE (multidrug and toxic compound extrusion; DTX) transporter family with InterPro/Pfam MATE domains.

Critical limitation: In the retrieved, full‑text accessible literature set, no publication explicitly mentions N. attenuata gene symbol DTX40_3, UniProt A0A314KVN4, or ORF A4A49_09978. Therefore, gene-specific functional claims (substrate, localization, phenotype) cannot be stated as experimentally validated for this N. attenuata locus. All functional annotation below is constrained to (i) family/domain-level evidence and (ii) closest Nicotiana and plant MATE homolog precedents, clearly labeled as inference. (takanashi2014themultidrugand pages 1-3, shitan2016secondarymetabolitesin pages 3-6)

1) Key concepts and definitions (current understanding)

1.1 What are plant MATE/DTX transporters?

Plant MATE (DTX) proteins are secondary active transporters (cation antiporters) that use an electrochemical gradient (commonly H+ in many plant examples) to drive export or compartmentation of substrates. They are generally described as efflux transporters, moving substrates from the cytosol to the apoplast or into intracellular compartments such as the vacuole. (takanashi2014themultidrugand pages 1-3, shitan2016secondarymetabolitesin pages 3-6)

1.2 Typical topology and coupling

A widely cited property of plant MATEs is a predicted 12-transmembrane domain (12-TM) topology; they are “presumed to function as proton antiporters” in plants. (shitan2016secondarymetabolitesin pages 3-6)

1.3 Substrate scope and functional breadth

Plant MATEs transport chemically diverse substrates including secondary metabolites (alkaloids, flavonoids), organic acids (notably citrate), and hormone-related compounds (e.g., ABA/SA-related transport processes in some members). They contribute to:
- Detoxification and self-tolerance (sequestration/efflux of toxic metabolites or xenobiotics). (takanashi2014themultidrugand pages 1-3, shitan2016secondarymetabolitesin pages 3-6)
- Specialized metabolite storage, often in the vacuole (e.g., alkaloids/flavonoids). (takanashi2014themultidrugand pages 3-5, shitan2016secondarymetabolitesin pages 3-6)
- Metal homeostasis, such as citrate efflux for Fe translocation and Al3+ detoxification. (takanashi2014themultidrugand pages 7-9, takanashi2014themultidrugand pages 9-10)

2) Gene-centric functional annotation for N. attenuata DTX40_3 (A0A314KVN4)

2.1 Most defensible function statement (evidence-based)

Given UniProt’s description and the domain family assignment, DTX40_3 (A0A314KVN4) should be annotated as a MATE/DTX family secondary transporter likely involved in detoxification via efflux/compartmentation. This is consistent with plant MATE family roles as cation antiporters exporting substrates to the apoplast or vacuole. (takanashi2014themultidrugand pages 1-3, shitan2016secondarymetabolitesin pages 3-6)

2.2 Likely biological role in Nicotiana: vacuolar sequestration of defensive alkaloids (inference from closest Nicotiana homolog system)

Although not demonstrated for N. attenuata DTX40_3 specifically, the Nicotiana genus provides strong precedents that some MATEs function in alkaloid (nicotine) sequestration:
- The tobacco (N. tabacum) MATE Nt‑JAT2 is implicated in vacuolar sequestration of nicotine in leaves. It is methyl jasmonate (MeJA) inducible and leaf‑preferential, aligning with herbivory‑responsive defense deployment. (shitan2014involvementofthe pages 1-2, shitan2014involvementofthe pages 4-6)
- In yeast assays, Nt‑JAT2 expression lowered intracellular nicotine and also lowered anabasine and anatabine, supporting transport of multiple related alkaloids; it did not transport tested flavonoids in that assay. (shitan2014involvementofthe pages 3-4)
- Reviews of plant secondary metabolite transport similarly describe JAT1/JAT2 and MATE1/MATE2 as nicotine transporters that likely act as nicotine/H+ antiporters localized to the vacuolar membrane, with tissue specificity (leaf vs root vacuoles). (shitan2016secondarymetabolitesin pages 3-6, takanashi2014themultidrugand pages 3-5)

Gene-specific caution: The above is not proof that N. attenuata DTX40_3 transports nicotine; rather, it supports a plausible hypothesis that a Nicotiana MATE annotated for detoxification could participate in alkaloid compartmentation.

2.3 Subcellular localization: most likely tonoplast (inference)

For DTX40_3 itself, localization is unknown in the retrieved literature. However, multiple Nicotiana alkaloid MATEs are tonoplast-localized, consistent with a vacuolar sequestration mechanism. The Nt‑JAT2 paper provides direct imaging evidence that Nt‑JAT2‑GFP localizes to the tonoplast in plant cells, while heterologous yeast expression can show different membrane patterns. (shitan2014involvementofthe media eaf0b77f, shitan2014involvementofthe media a1b95952, shitan2014involvementofthe pages 1-2)

Thus, DTX40_3 is conservatively predicted to be an endomembrane MATE, plausibly tonoplast-localized, but this needs direct experimental confirmation (e.g., GFP fusion in N. attenuata). (shitan2016secondarymetabolitesin pages 3-6)

2.4 Pathway context: JA-regulated defense metabolism and long-distance nicotine allocation (inference)

In Nicotiana, nicotine biosynthesis and transport are strongly integrated with jasmonate signaling, coordinating expression of metabolic genes and transporters. JAT2 is explicitly described as jasmonate-inducible, linking MATE-mediated sequestration to defense signaling. (shitan2014involvementofthe pages 1-2, shitan2015translocationandaccumulation pages 2-3)

A 2024 authoritative tobacco review emphasizes that JA signaling activates transcriptional regulators coordinating downstream metabolic and transport genes needed for nicotine production and allocation. (shoji2024geneticregulationand pages 1-2)

For N. attenuata, DTX40_3 could plausibly function in the downstream transport/storage segment of JA-induced chemical defense, but again this is hypothesis without locus-specific expression data.

3) Recent developments (prioritizing 2023–2024)

3.1 2024: Quantitative demonstration of strict substrate specificity in a plant tonoplast MATE

A major 2024 advance for functional annotation is the detailed biochemical characterization of CrMATE1 (Catharanthus roseus), a tonoplast MATE shown to be a vacuolar importer with strict substrate specificity for secologanin. The study used Xenopus oocytes to show directionality and reported quantified transport: 1 mM secologanin translocated within 25 min. (li2024characterizationofa pages 1-2)

This is relevant to DTX40_3 because it demonstrates that plant MATEs can be highly substrate-specific gatekeepers of specialized metabolism flux, reinforcing that a “detoxification MATE” annotation does not imply promiscuity and that precise substrate identification requires direct transport assays. (li2024characterizationofa pages 2-3)

3.2 2024: Nicotine manipulation strategies and transporter context in tobacco

A 2024 Journal of Experimental Botany review synthesizes current nicotine biology and engineering strategies and reiterates that multiple MATE transporters (JAT1/JAT2/MATE1/MATE2) mediate vacuolar sequestration of nicotine as tonoplast proton antiporters. (shoji2024geneticregulationand pages 4-5)

The same review also provides application-oriented definitions used in the field: “low nicotine” and “ultra-low nicotine” are framed as <20% and 5% of wild-type nicotine levels, respectively. (shoji2024geneticregulationand pages 1-2)

3.3 2023: Broader functional diversification of DTX/MATE transporters

A 2023 review summarizes that DTX/MATE transporters participate in diverse processes beyond alkaloids, including:
- Seed vacuolar transport of flavonoid glycosides (e.g., DTX41/TT12). (zhang2023researchprogresson pages 8-11)
- Chloroplast envelope localization of some MATEs involved in salicylic acid-related processes (e.g., EDS5, referenced in plant MATE functional literature). (payne2016genediscoveryin pages 88-91)

For DTX40_3 annotation, this indicates that DTX naming does not uniquely specify substrate class, and that experimental localization/substrate testing is necessary.

4) Current applications and real-world implementations

4.1 Plant metabolic engineering and molecular breeding

In Nicotiana and other crops, transporters are increasingly viewed as engineering targets to alter metabolite accumulation in specific organs. The nicotine transporter literature explicitly discusses “transport engineering” concepts: coordinated manipulation of transporters can alter tissue allocation and final metabolite content. (shitan2014involvementofthe pages 6-8, shitan2015translocationandaccumulation pages 2-3)

4.2 Public-health driven nicotine reduction targets (tobacco)

The 2024 J Exp Bot review cites real-world regulatory goals and actions: WHO recommendation to reduce cigarette nicotine to 0.4 mg g−1 and the FDA’s proposed product standard (2022) to set a maximum nicotine level. While this is not N. attenuata biology per se, it is a major driver of transporter/biosynthesis research programs in Nicotiana. (shoji2024geneticregulationand pages 2-3)

4.3 Transporters as pathway flux “gatekeepers”

The CrMATE1 work highlights an emerging implementation theme: identifying transport steps that constrain pathway flux and using them to optimize production of valuable specialized metabolites. (li2024characterizationofa pages 1-2, li2024characterizationofa pages 2-3)

5) Expert synthesis and analysis (authoritative viewpoints)

5.1 The most likely functional hypothesis for DTX40_3

Given: (i) UniProt’s detoxification/MATE annotation and (ii) strong Nicotiana precedent for tonoplast MATE alkaloid sequestration, the most biologically coherent hypothesis is:

DTX40_3 encodes a 12‑TM MATE/DTX transporter that uses the proton motive force to sequester (export) toxic specialized metabolites—plausibly alkaloids—into the vacuole (tonoplast) to support self‑tolerance and defense deployment. (shitan2016secondarymetabolitesin pages 3-6, takanashi2014themultidrugand pages 3-5)

5.2 Alternative plausible roles (less supported without gene-specific data)

Because plant MATEs also include citrate exporters for Fe translocation and Al tolerance, and hormone-related transport functions, DTX40_3 could instead belong to a metal/hormone-related clade. Metal-handling MATEs (e.g., FRD3/FRDL-type) are phylogenetically distinct and are described as mediating citrate efflux into xylem or rhizosphere, supporting Fe mobilization and Al detoxification. (takanashi2014themultidrugand pages 7-9, takanashi2014themultidrugand pages 9-10)

Without sequence-phylogeny placement or expression context for A0A314KVN4, assigning DTX40_3 specifically to “nicotine” vs “citrate/Fe/Al” vs “ABA/SA” remains uncertain.

6) Statistics and quantitative data relevant to annotation

6.1 Gene family size and general properties

Arabidopsis contains 56 MATE genes (also described as “more than 50”). (shitan2016secondarymetabolitesin pages 3-6, takanashi2014themultidrugand pages 1-3)

6.2 Quantitative anchors from Nicotiana alkaloid transport literature

Nt‑JAT2 paper provides a physiological concentration gradient context: nicotine is approximately ~1 mM in xylem and can reach ~60 mM in leaf vacuoles, motivating tonoplast sequestration transport. (shitan2014involvementofthe pages 1-2)
MeJA induction kinetics for Nt‑JAT2 are described as rapid (within hours) with sustained induction over a day in the original study’s time course narrative. (shitan2014involvementofthe pages 2-3)

6.3 Quantitative functional data from a 2024 plant MATE study

CrMATE1 transports 1 mM secologanin within 25 min (oocyte assay). (li2024characterizationofa pages 1-2)
VIGS knockdown reduced transcript ~73–80%, increased secologanol 16–38×, and reduced downstream MIAs (e.g., catharanthine/vindoline). (li2024characterizationofa pages 2-3)

Visual evidence (for localization precedent)

The following figure panels document tonoplast localization of a Nicotiana MATE alkaloid transporter (Nt‑JAT2), supporting the plausibility of tonoplast targeting for related Nicotiana MATEs.

Nt‑JAT2‑GFP tonoplast localization in plant cells: (shitan2014involvementofthe media eaf0b77f)
Nt‑JAT2‑GFP localization patterns in yeast (heterologous expression): (shitan2014involvementofthe media a1b95952)

Summary table (evidence vs inference for DTX40_3)

Aspect	Evidence/notes	Best supporting citations (pqac ids)	External URL(s)/publication date(s)
Family/domain	Target identity verification: direct literature for Nicotiana attenuata DTX40_3 / UniProt A0A314KVN4 / ORF A4A49_09978 was not found in the retrieved corpus, so annotation should remain family-based and inferential. UniProt describes A0A314KVN4 as a plant MATE/DTX transporter with MATE_euk / MATE_fam / MatE domains. Broad plant MATE reviews describe this family as one of the largest transporter families in plants, involved in transport of secondary metabolites, organic acids, hormones, and xenobiotics.	(takanashi2014themultidrugand pages 1-3)	UniProt entry for A0A314KVN4: https://www.uniprot.org/uniprotkb/A0A314KVN4 ; Takanashi et al. 2014, Plant Biotechnology, Dec 2014: https://doi.org/10.5511/plantbiotechnology.14.0904a
Topology/energy coupling	Plant MATE transporters are typically predicted to have 12 transmembrane domains and commonly function as secondary antiporters, usually H+ coupled in plant examples. For Nicotiana alkaloid transporters, NtMATE1 shows H+/nicotine antiport activity in yeast; broader reviews state plant MATEs generally use Na+ or H+ electrochemical gradients, though proton coupling is the strongest inference for vacuolar alkaloid transporters. Thus, DTX40_3 is best annotated as a probable 12-TM H+-coupled antiporter unless direct data prove otherwise.	(shitan2016secondarymetabolitesin pages 3-6, takanashi2014themultidrugand pages 3-5, takanashi2014themultidrugand pages 1-3)	Shitan 2016, Biosci Biotechnol Biochem, Jul 2016: https://doi.org/10.1080/09168451.2016.1151344 ; Takanashi et al. 2014, Dec 2014: https://doi.org/10.5511/plantbiotechnology.14.0904a
Likely subcellular localization	Direct localization for DTX40_3 is unavailable. In Nicotiana tabacum, the closest functional precedents for alkaloid-associated MATEs (Nt-JAT1, Nt-JAT2, NtMATE1/2) localize primarily to the tonoplast/vacuolar membrane and mediate vacuolar sequestration. Nt-JAT2-GFP was localized to the tonoplast in BY-2 cells; yeast heterologous expression can show plasma-membrane signal, so plant-cell localization is more informative. Therefore DTX40_3 is most plausibly tonoplast-localized, though plasma membrane cannot be excluded without experiment.	(shitan2014involvementofthe pages 6-8, shitan2014involvementofthe pages 1-2, shitan2014involvementofthe pages 3-4, shitan2014involvementofthe media eaf0b77f, shitan2016secondarymetabolitesin pages 3-6)	Shitan et al. 2014, PLOS ONE, Sep 2014: https://doi.org/10.1371/journal.pone.0108789 ; Figure evidence for tonoplast localization in the same paper, Sep 2014
Likely substrates	No direct substrate assay for DTX40_3 was found. The strongest Nicotiana precedent is alkaloid transport, especially nicotine, plus related alkaloids anabasine and anatabine; Nt-JAT2 also handled berberine and scopolamine in yeast assays, but not tested flavonoids such as cyanidin 3-O-glucoside or rutin. Because A0A314KVN4 is annotated as a detoxification/MATE protein from Nicotiana attenuata, a species well known for inducible defensive alkaloid metabolism, the most conservative substrate prediction is specialized metabolite cation(s), likely pyridine alkaloids or other defense-related toxic metabolites, not a broad flavonoid transporter.	(shitan2014involvementofthe pages 6-8, shitan2014involvementofthe pages 1-2, shitan2014involvementofthe pages 3-4, takanashi2014themultidrugand pages 3-5)	Shitan et al. 2014, Sep 2014: https://doi.org/10.1371/journal.pone.0108789 ; Takanashi et al. 2014, Dec 2014: https://doi.org/10.5511/plantbiotechnology.14.0904a
Biological role/process	Best-supported inferred role is detoxification by compartmentation, i.e., moving specialized metabolites from the cytosol into the vacuole to reduce self-toxicity while enabling accumulation for defense. In Nicotiana homologs, this role is specifically vacuolar sequestration of nicotine/alkaloids after root-to-shoot transport. More generally, plant MATEs mediate xenobiotic efflux, alkaloid/flavonoid accumulation, citrate export, Fe homeostasis, and hormone transport; however, the Nicotiana homolog evidence points most strongly to alkaloid sequestration/detoxification rather than metal or hormone transport.	(takanashi2014themultidrugand pages 3-5, takanashi2014themultidrugand pages 1-3, shitan2014involvementofthe pages 3-4, shitan2016secondarymetabolitesin pages 3-6)	Takanashi et al. 2014, Dec 2014: https://doi.org/10.5511/plantbiotechnology.14.0904a ; Shitan 2016, Jul 2016: https://doi.org/10.1080/09168451.2016.1151344
Signaling/pathway context	Nicotiana MATE alkaloid transporters are closely linked to jasmonate (JA/MeJA)-responsive defense pathways. Nt-JAT2 is rapidly induced by methyl jasmonate, with strong leaf-preferential expression, supporting a role during herbivory-induced nicotine deployment. For DTX40_3 in N. attenuata, the most plausible pathway placement is therefore within JA-regulated defensive specialized metabolism, likely downstream of alkaloid biosynthesis and long-distance transport, where it would mediate final sequestration/storage. This remains an inference, not a gene-specific demonstration.	(shitan2014involvementofthe pages 6-8, shitan2014involvementofthe pages 2-3, shitan2014involvementofthe pages 4-6, payne2016genediscoveryin pages 93-97)	Shitan et al. 2014, Sep 2014: https://doi.org/10.1371/journal.pone.0108789 ; Shitan et al. 2015, Plant Signaling & Behavior, Jul 2015: https://doi.org/10.1080/15592324.2015.1035852
Key quantitative data	Family- and homolog-level quantitative anchors useful for annotation: Arabidopsis has >50 / 56 MATE genes; Nt-JAT2 is induced by MeJA within ~2 h and remains elevated for 24 h; Nt-JAT2 is a ~507 aa protein predicted to contain 12 TM helices; recent plant-MATE work showed another alkaloid-pathway transporter, CrMATE1, transports 1 mM secologanin within 25 min, and VIGS reduced transcript by ~73–80%, causing 16–38-fold secologanol accumulation and reduced downstream MIAs. These values do not measure DTX40_3 directly but illustrate realistic MATE family behavior and experimental expectations.	(takanashi2014themultidrugand pages 1-3, shitan2016secondarymetabolitesin pages 3-6, shitan2014involvementofthe pages 2-3, li2024characterizationofa pages 1-2, li2024characterizationofa pages 2-3)	Takanashi et al. 2014, Dec 2014: https://doi.org/10.5511/plantbiotechnology.14.0904a ; Shitan et al. 2014, Sep 2014: https://doi.org/10.1371/journal.pone.0108789 ; Li et al. 2024, Communications Biology, Aug 2024: https://doi.org/10.1038/s42003-024-06624-5
Confidence/limitations	High confidence: A0A314KVN4 is a plant MATE/DTX family transporter. Moderate confidence: it is a 12-TM, proton-coupled transporter. Moderate-to-low confidence: it is tonoplast-localized and transports nicotine/related alkaloids, because these are inferred from Nicotiana homologs rather than shown directly for DTX40_3. Low confidence for exact substrate specificity, tissue expression, and physiological phenotype until gene-specific localization, transport assays, and expression profiling are performed in N. attenuata.	(takanashi2014themultidrugand pages 1-3, shitan2014involvementofthe pages 1-2, shitan2016secondarymetabolitesin pages 3-6, takanashi2014themultidrugand pages 3-5)	Evidence synthesis based on cited sources above; no direct publication located for A0A314KVN4 / DTX40_3 in retrieved literature corpus

Table: This table summarizes the most defensible functional annotation for Nicotiana attenuata DTX40_3 (UniProt A0A314KVN4) using direct identity information plus experimentally characterized plant and Nicotiana MATE homologs. It is useful for separating high-confidence family-level facts from lower-confidence gene-specific inferences.

Conclusions

DTX40_3 (A0A314KVN4) is best annotated as a plant MATE/DTX secondary transporter involved in detoxification by efflux/compartmentation, consistent with MATE family definitions and plant MATE roles. (takanashi2014themultidrugand pages 1-3, shitan2016secondarymetabolitesin pages 3-6)
No gene-specific experimental literature was found for this exact N. attenuata locus in the retrieved corpus; thus substrate, localization, and pathway assignments remain hypotheses.
The strongest functional precedent in Nicotiana is tonoplast MATE-mediated vacuolar sequestration of nicotine and related alkaloids (Nt‑JAT2/JAT1/MATE1/2), making alkaloid transport a plausible candidate function for DTX40_3. (shitan2014involvementofthe pages 1-2, takanashi2014themultidrugand pages 3-5)
Recent 2024 work underscores that plant MATEs can be highly substrate-specific and quantitatively impactful on pathway flux, reinforcing the need for direct substrate tests for DTX40_3. (li2024characterizationofa pages 1-2, li2024characterizationofa pages 2-3)

Key references (with URLs and publication dates)

Shitan N. et al. 2014-09. PLOS ONE. “Nt‑JAT2… vacuolar sequestration of nicotine.” https://doi.org/10.1371/journal.pone.0108789 (shitan2014involvementofthe pages 1-2, shitan2014involvementofthe pages 3-4)
Takanashi K. et al. 2014-12. Plant Biotechnology. “The MATE family in plants.” https://doi.org/10.5511/plantbiotechnology.14.0904a (takanashi2014themultidrugand pages 1-3, takanashi2014themultidrugand pages 3-5)
Shitan N. 2016-07. Biosci Biotechnol Biochem. “Secondary metabolites… self‑tolerance mechanisms.” https://doi.org/10.1080/09168451.2016.1151344 (shitan2016secondarymetabolitesin pages 3-6)
Li F. et al. 2024-08. Communications Biology. “CrMATE1 vacuolar importer of secologanin.” https://doi.org/10.1038/s42003-024-06624-5 (li2024characterizationofa pages 1-2, li2024characterizationofa pages 2-3)
Shoji T. et al. 2024-08. Journal of Experimental Botany. “Genetic regulation and manipulation of nicotine biosynthesis…” https://doi.org/10.1093/jxb/erad341 (shoji2024geneticregulationand pages 4-5, shoji2024geneticregulationand pages 2-3, shoji2024geneticregulationand pages 1-2)

References

(takanashi2014themultidrugand pages 1-3): Kojiro Takanashi, Nobukazu Shitan, and Kazufumi Yazaki. The multidrug and toxic compound extrusion (mate) family in plants. Plant Biotechnology, 31:417-430, Dec 2014. URL: https://doi.org/10.5511/plantbiotechnology.14.0904a, doi:10.5511/plantbiotechnology.14.0904a. This article has 180 citations and is from a peer-reviewed journal.
(shitan2016secondarymetabolitesin pages 3-6): Nobukazu Shitan. Secondary metabolites in plants: transport and self-tolerance mechanisms. Bioscience, Biotechnology, and Biochemistry, 80:1283-1293, Jul 2016. URL: https://doi.org/10.1080/09168451.2016.1151344, doi:10.1080/09168451.2016.1151344. This article has 231 citations.
(takanashi2014themultidrugand pages 3-5): Kojiro Takanashi, Nobukazu Shitan, and Kazufumi Yazaki. The multidrug and toxic compound extrusion (mate) family in plants. Plant Biotechnology, 31:417-430, Dec 2014. URL: https://doi.org/10.5511/plantbiotechnology.14.0904a, doi:10.5511/plantbiotechnology.14.0904a. This article has 180 citations and is from a peer-reviewed journal.
(takanashi2014themultidrugand pages 7-9): Kojiro Takanashi, Nobukazu Shitan, and Kazufumi Yazaki. The multidrug and toxic compound extrusion (mate) family in plants. Plant Biotechnology, 31:417-430, Dec 2014. URL: https://doi.org/10.5511/plantbiotechnology.14.0904a, doi:10.5511/plantbiotechnology.14.0904a. This article has 180 citations and is from a peer-reviewed journal.
(takanashi2014themultidrugand pages 9-10): Kojiro Takanashi, Nobukazu Shitan, and Kazufumi Yazaki. The multidrug and toxic compound extrusion (mate) family in plants. Plant Biotechnology, 31:417-430, Dec 2014. URL: https://doi.org/10.5511/plantbiotechnology.14.0904a, doi:10.5511/plantbiotechnology.14.0904a. This article has 180 citations and is from a peer-reviewed journal.
(shitan2014involvementofthe pages 1-2): Nobukazu Shitan, Shota Minami, Masahiko Morita, Minaho Hayashida, Shingo Ito, Kojiro Takanashi, Hiroshi Omote, Yoshinori Moriyama, Akifumi Sugiyama, Alain Goossens, Masataka Moriyasu, and Kazufumi Yazaki. Involvement of the leaf-specific multidrug and toxic compound extrusion (mate) transporter nt-jat2 in vacuolar sequestration of nicotine in nicotiana tabacum. PLoS ONE, 9:e108789, Sep 2014. URL: https://doi.org/10.1371/journal.pone.0108789, doi:10.1371/journal.pone.0108789. This article has 112 citations and is from a peer-reviewed journal.
(shitan2014involvementofthe pages 4-6): Nobukazu Shitan, Shota Minami, Masahiko Morita, Minaho Hayashida, Shingo Ito, Kojiro Takanashi, Hiroshi Omote, Yoshinori Moriyama, Akifumi Sugiyama, Alain Goossens, Masataka Moriyasu, and Kazufumi Yazaki. Involvement of the leaf-specific multidrug and toxic compound extrusion (mate) transporter nt-jat2 in vacuolar sequestration of nicotine in nicotiana tabacum. PLoS ONE, 9:e108789, Sep 2014. URL: https://doi.org/10.1371/journal.pone.0108789, doi:10.1371/journal.pone.0108789. This article has 112 citations and is from a peer-reviewed journal.
(shitan2014involvementofthe pages 3-4): Nobukazu Shitan, Shota Minami, Masahiko Morita, Minaho Hayashida, Shingo Ito, Kojiro Takanashi, Hiroshi Omote, Yoshinori Moriyama, Akifumi Sugiyama, Alain Goossens, Masataka Moriyasu, and Kazufumi Yazaki. Involvement of the leaf-specific multidrug and toxic compound extrusion (mate) transporter nt-jat2 in vacuolar sequestration of nicotine in nicotiana tabacum. PLoS ONE, 9:e108789, Sep 2014. URL: https://doi.org/10.1371/journal.pone.0108789, doi:10.1371/journal.pone.0108789. This article has 112 citations and is from a peer-reviewed journal.
(shitan2014involvementofthe media eaf0b77f): Nobukazu Shitan, Shota Minami, Masahiko Morita, Minaho Hayashida, Shingo Ito, Kojiro Takanashi, Hiroshi Omote, Yoshinori Moriyama, Akifumi Sugiyama, Alain Goossens, Masataka Moriyasu, and Kazufumi Yazaki. Involvement of the leaf-specific multidrug and toxic compound extrusion (mate) transporter nt-jat2 in vacuolar sequestration of nicotine in nicotiana tabacum. PLoS ONE, 9:e108789, Sep 2014. URL: https://doi.org/10.1371/journal.pone.0108789, doi:10.1371/journal.pone.0108789. This article has 112 citations and is from a peer-reviewed journal.
(shitan2014involvementofthe media a1b95952): Nobukazu Shitan, Shota Minami, Masahiko Morita, Minaho Hayashida, Shingo Ito, Kojiro Takanashi, Hiroshi Omote, Yoshinori Moriyama, Akifumi Sugiyama, Alain Goossens, Masataka Moriyasu, and Kazufumi Yazaki. Involvement of the leaf-specific multidrug and toxic compound extrusion (mate) transporter nt-jat2 in vacuolar sequestration of nicotine in nicotiana tabacum. PLoS ONE, 9:e108789, Sep 2014. URL: https://doi.org/10.1371/journal.pone.0108789, doi:10.1371/journal.pone.0108789. This article has 112 citations and is from a peer-reviewed journal.
(shitan2015translocationandaccumulation pages 2-3): Nobukazu Shitan, Minaho Hayashida, and Kazufumi Yazaki. Translocation and accumulation of nicotine via distinct spatio-temporal regulation of nicotine transporters in nicotiana tabacum. Plant Signaling & Behavior, 10:e1035852, Jul 2015. URL: https://doi.org/10.1080/15592324.2015.1035852, doi:10.1080/15592324.2015.1035852. This article has 45 citations and is from a peer-reviewed journal.
(shoji2024geneticregulationand pages 1-2): Tsubasa Shoji, Takashi Hashimoto, and Kazuki Saito. Genetic regulation and manipulation of nicotine biosynthesis in tobacco: strategies to eliminate addictive alkaloids. Journal of Experimental Botany, 75:1741-1753, Aug 2024. URL: https://doi.org/10.1093/jxb/erad341, doi:10.1093/jxb/erad341. This article has 37 citations and is from a domain leading peer-reviewed journal.
(li2024characterizationofa pages 1-2): Fanfan Li, Mohammadamin Shahsavarani, Cody-Jordan Handy-Hart, Audrey Côté, Xavier Brasseur-Trottier, Victoria Montgomery, Robin N. Beech, Lan Liu, Stéphane Bayen, Yang Qu, Vincenzo De Luca, and Mehran Dastmalchi. Characterization of a vacuolar importer of secologanin in catharanthus roseus. Communications Biology, Aug 2024. URL: https://doi.org/10.1038/s42003-024-06624-5, doi:10.1038/s42003-024-06624-5. This article has 12 citations and is from a peer-reviewed journal.
(li2024characterizationofa pages 2-3): Fanfan Li, Mohammadamin Shahsavarani, Cody-Jordan Handy-Hart, Audrey Côté, Xavier Brasseur-Trottier, Victoria Montgomery, Robin N. Beech, Lan Liu, Stéphane Bayen, Yang Qu, Vincenzo De Luca, and Mehran Dastmalchi. Characterization of a vacuolar importer of secologanin in catharanthus roseus. Communications Biology, Aug 2024. URL: https://doi.org/10.1038/s42003-024-06624-5, doi:10.1038/s42003-024-06624-5. This article has 12 citations and is from a peer-reviewed journal.
(shoji2024geneticregulationand pages 4-5): Tsubasa Shoji, Takashi Hashimoto, and Kazuki Saito. Genetic regulation and manipulation of nicotine biosynthesis in tobacco: strategies to eliminate addictive alkaloids. Journal of Experimental Botany, 75:1741-1753, Aug 2024. URL: https://doi.org/10.1093/jxb/erad341, doi:10.1093/jxb/erad341. This article has 37 citations and is from a domain leading peer-reviewed journal.
(zhang2023researchprogresson pages 8-11): J Zhang, Q Li, C Li, Q Wang, and X Hou. Research progress on mate transporters in plants. Unknown journal, 2023.
(payne2016genediscoveryin pages 88-91): R Payne. Gene discovery in catharanthus roseus using virus induced gene silencing. Unknown journal, 2016.
(shitan2014involvementofthe pages 6-8): Nobukazu Shitan, Shota Minami, Masahiko Morita, Minaho Hayashida, Shingo Ito, Kojiro Takanashi, Hiroshi Omote, Yoshinori Moriyama, Akifumi Sugiyama, Alain Goossens, Masataka Moriyasu, and Kazufumi Yazaki. Involvement of the leaf-specific multidrug and toxic compound extrusion (mate) transporter nt-jat2 in vacuolar sequestration of nicotine in nicotiana tabacum. PLoS ONE, 9:e108789, Sep 2014. URL: https://doi.org/10.1371/journal.pone.0108789, doi:10.1371/journal.pone.0108789. This article has 112 citations and is from a peer-reviewed journal.
(shoji2024geneticregulationand pages 2-3): Tsubasa Shoji, Takashi Hashimoto, and Kazuki Saito. Genetic regulation and manipulation of nicotine biosynthesis in tobacco: strategies to eliminate addictive alkaloids. Journal of Experimental Botany, 75:1741-1753, Aug 2024. URL: https://doi.org/10.1093/jxb/erad341, doi:10.1093/jxb/erad341. This article has 37 citations and is from a domain leading peer-reviewed journal.
(shitan2014involvementofthe pages 2-3): Nobukazu Shitan, Shota Minami, Masahiko Morita, Minaho Hayashida, Shingo Ito, Kojiro Takanashi, Hiroshi Omote, Yoshinori Moriyama, Akifumi Sugiyama, Alain Goossens, Masataka Moriyasu, and Kazufumi Yazaki. Involvement of the leaf-specific multidrug and toxic compound extrusion (mate) transporter nt-jat2 in vacuolar sequestration of nicotine in nicotiana tabacum. PLoS ONE, 9:e108789, Sep 2014. URL: https://doi.org/10.1371/journal.pone.0108789, doi:10.1371/journal.pone.0108789. This article has 112 citations and is from a peer-reviewed journal.
(payne2016genediscoveryin pages 93-97): R Payne. Gene discovery in catharanthus roseus using virus induced gene silencing. Unknown journal, 2016.

Artifacts

Edison artifact artifact-00

Citations

shitan2016secondarymetabolitesin pages 3-6
shitan2014involvementofthe pages 3-4
shoji2024geneticregulationand pages 1-2
li2024characterizationofa pages 1-2
li2024characterizationofa pages 2-3
shoji2024geneticregulationand pages 4-5
zhang2023researchprogresson pages 8-11
payne2016genediscoveryin pages 88-91
shoji2024geneticregulationand pages 2-3
shitan2014involvementofthe pages 1-2
shitan2014involvementofthe pages 2-3
takanashi2014themultidrugand pages 1-3
takanashi2014themultidrugand pages 3-5
takanashi2014themultidrugand pages 7-9
takanashi2014themultidrugand pages 9-10
shitan2014involvementofthe pages 4-6
shitan2015translocationandaccumulation pages 2-3
shitan2014involvementofthe pages 6-8
payne2016genediscoveryin pages 93-97
https://www.uniprot.org/uniprotkb/A0A314KVN4
https://doi.org/10.5511/plantbiotechnology.14.0904a
https://doi.org/10.1080/09168451.2016.1151344
https://doi.org/10.1371/journal.pone.0108789
https://doi.org/10.1080/15592324.2015.1035852
https://doi.org/10.1038/s42003-024-06624-5
https://doi.org/10.1093/jxb/erad341
https://doi.org/10.5511/plantbiotechnology.14.0904a,
https://doi.org/10.1080/09168451.2016.1151344,
https://doi.org/10.1371/journal.pone.0108789,
https://doi.org/10.1080/15592324.2015.1035852,
https://doi.org/10.1093/jxb/erad341,
https://doi.org/10.1038/s42003-024-06624-5,

📚 Additional Documentation

Notes

(NaMATE1_candidate_DTX40_3-notes.md)

NaMATE1_candidate_DTX40_3 Notes

UniProt curates A0A314KVN4 as DTX40_3, a MATE-family multi-pass membrane antiporter. The current public entry is generic and detergent-like in naming, but it clearly places the candidate in the expected transporter family. [file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-uniprot.txt "DE RecName: Full=Protein DETOXIFICATION"; "DE AltName: Full=Multidrug and toxic compound extrusion protein"; "CC -!- SIMILARITY: Belongs to the multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family."; "CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein"]
The glucosylation preprint identifies an A622-MATE1-beta-GD1 cluster, reports that these genes are root enriched and tightly co-expressed with nicotine biosynthesis genes, and keeps MATE1 in the core late-pathway module even though the exact transported metabolite remains unresolved. [file:projects/NICOTINE_BIOSYNTHESIS/biorxiv-nicotine-glucosylation-notes.md "The paper identifies an A622-MATE1-beta-GD1 gene cluster in tobacco, plus a homeologous A622L-MATE2-beta-GD2 cluster; these clustered genes are root enriched and tightly co-expressed with known nicotine biosynthesis genes."; "MATE1 should remain in the core set because it is genomically and expression-linked to the late-pathway module."]
The 2026-04-05 mapping dive assigns NaMATE1 to DTX40_3 / A0A314KVN4 as the best current sequence-backed NICAT ortholog to tobacco MATE1. [file:projects/NICOTINE_BIOSYNTHESIS.md "NaMATE1 -> DTX40_3 / A0A314KVN4"; "Tobacco Nitab4.5_0000884g0030 (MATE1) maps cleanly to NIATv7_g09978, then to UniProt DTX40_3."]

📄 View Raw YAML

id: A0A314KVN4
gene_symbol: NaMATE1_candidate_DTX40_3
product_type: PROTEIN
status: DRAFT
aliases:
- DTX40_3
- NaMATE1
taxon:
  id: NCBITaxon:49451
  label: Nicotiana attenuata
description: >-
  NaMATE1_candidate_DTX40_3 is the best current NICAT mapping for the MATE1-like
  transporter genetically linked to the late nicotine-pathway module. The public
  record still describes a generic MATE detoxification transporter, but the
  pathway paper and mapping pass together support this accession as the leading
  attenuata candidate for the pathway-associated MATE transporter.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-uniprot.txt
  title: UniProt entry A0A314KVN4 for Nicotiana attenuata DTX40_3
  findings:
  - statement: DTX40_3 is a membrane-localized MATE-family antiporter
    supporting_text: 'CC   -!- SIMILARITY: Belongs to the multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family.'
    reference_section_type: DATABASE_ENTRY
  - statement: UniProt places DTX40_3 in membrane and multi-pass membrane protein annotations
    supporting_text: 'CC   -!- SUBCELLULAR LOCATION: Membrane'
    reference_section_type: DATABASE_ENTRY
- id: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-notes.md
  title: NaMATE1 DTX40_3 candidate notes
  findings:
  - statement: MATE1 is genomically and expression-linked to the late nicotine pathway module
    supporting_text: The glucosylation preprint identifies an A622-MATE1-beta-GD1 cluster, reports that these genes are root enriched and tightly co-expressed with nicotine biosynthesis genes, and keeps MATE1 in the core late-pathway module even though the exact transported metabolite remains unresolved.
    reference_section_type: LITERATURE_REVIEW
  - statement: DTX40_3 is the best current sequence-backed NICAT ortholog to tobacco MATE1
    supporting_text: The 2026-04-05 mapping dive assigns NaMATE1 to DTX40_3 / A0A314KVN4 as the best current sequence-backed NICAT ortholog to tobacco MATE1.
    reference_section_type: LITERATURE_REVIEW
- id: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-deep-research-falcon.md
  title: Deep research report on NaMATE1/DTX40_3 (Falcon/Edison Scientific Literature)
  findings:
  - statement: No primary publication directly characterizes A0A314KVN4 / DTX40_3;
      annotation rests on MATE family inference (multidrug and toxic compound extrusion
      antiporters that often transport plant secondary metabolites) plus the nicotine-pathway
      genomic and co-expression evidence placing this candidate as the attenuata
      ortholog of tobacco MATE1 in the A622-MATE1-beta-GD1 late-pathway module
      - the exact transported metabolite (nicotine, nicotine glucoside, or another
      intermediate) and the precise membrane localization remain experimentally
      unresolved.
existing_annotations:
- term:
    id: GO:0015297
    label: antiporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Antiporter activity is an appropriate catalytic-family annotation for this MATE candidate.
    action: ACCEPT
    reason: >-
      The current public evidence clearly supports a MATE-family antiporter even
      though the exact specialized substrate remains unresolved.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Membrane localization is appropriate but secondary to the pathway interpretation.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is a multi-pass membrane transporter, but the central review issue is
      its pathway placement rather than generic localization.
    supported_by:
    - reference_id: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-uniprot.txt
      supporting_text: 'CC   -!- SUBCELLULAR LOCATION: Membrane'
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0042910
    label: xenobiotic transmembrane transporter activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: The xenobiotic-transport assignment remains unresolved until the transported substrate is tested.
    action: UNDECIDED
    reason: >-
      Current evidence points toward a specialized nicotine-module transporter
      role, but the exact transported metabolite remains experimentally
      unresolved. Because MATE transporters often move alkaloids and other
      secondary metabolites, the nicotine-pathway placement does not by itself
      falsify a xenobiotic transmembrane transporter annotation.
    supported_by:
    - reference_id: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-deep-research-falcon.md
      supporting_text: >-
        No primary publication directly characterizes A0A314KVN4 / DTX40_3;
        annotation rests on MATE family inference (multidrug and toxic compound
        extrusion antiporters that often transport plant secondary metabolites)
        plus the nicotine-pathway genomic and co-expression evidence.
      reference_section_type: LITERATURE_REVIEW
- term:
    id: GO:0055085
    label: transmembrane transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: This broad process term is reasonable context but not the key curation outcome.
    action: KEEP_AS_NON_CORE
    reason: >-
      Keep the transport process annotation while prioritizing the antiporter
      function and pathway-specific interpretation.
- term:
    id: GO:1990961
    label: xenobiotic detoxification by transmembrane export across the plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: This detoxification-process annotation is unresolved without substrate and localization evidence.
    action: UNDECIDED
    reason: >-
      The reviewed evidence supports a pathway-associated metabolite transporter,
      but it does not identify the transported substrate or establish whether
      export across the plasma membrane is the relevant compartment. A nicotine-
      related substrate could still fit a xenobiotic-detoxification framing, so
      this process annotation should remain undecided pending direct transport
      and localization assays.
    supported_by:
    - reference_id: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-deep-research-falcon.md
      supporting_text: >-
        The exact transported metabolite (nicotine, nicotine glucoside, or
        another intermediate) and the precise membrane localization remain
        experimentally unresolved.
      reference_section_type: LITERATURE_REVIEW
- term:
    id: GO:0042179
    label: nicotine biosynthetic process
  evidence_type: TAS
  original_reference_id: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-notes.md
  review:
    summary: MATE1 should be added as a pathway-associated nicotine biosynthetic gene.
    action: NEW
    reason: >-
      The pathway paper keeps MATE1 in the core late module on the basis of gene
      clustering and coordinated expression, even though its exact transported
      substrate remains to be nailed down experimentally.
    supported_by:
    - reference_id: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-notes.md
      supporting_text: The glucosylation preprint identifies an A622-MATE1-beta-GD1 cluster, reports that these genes are root enriched and tightly co-expressed with nicotine biosynthesis genes, and keeps MATE1 in the core late-pathway module even though the exact transported metabolite remains unresolved.
      reference_section_type: LITERATURE_REVIEW
core_functions:
- molecular_function:
    id: GO:0015297
    label: antiporter activity
  directly_involved_in:
  - id: GO:0042179
    label: nicotine biosynthetic process
  description: >-
    DTX40_3 is the best current NICAT MATE1 candidate for the membrane transport
    step associated with the late nicotine biosynthetic module.
  supported_by:
  - reference_id: file:NICAT/NaMATE1_candidate_DTX40_3/NaMATE1_candidate_DTX40_3-notes.md
    supporting_text: The glucosylation preprint identifies an A622-MATE1-beta-GD1 cluster, reports that these genes are root enriched and tightly co-expressed with nicotine biosynthesis genes, and keeps MATE1 in the core late-pathway module even though the exact transported metabolite remains unresolved.
    reference_section_type: LITERATURE_REVIEW
proposed_new_terms: []
suggested_questions:
- question: >-
    What is the direct transported substrate of the attenuata MATE1 candidate:
    nicotine glucoside, nicotine, or another late-pathway intermediate?
- question: Is DTX40_3 localized to the vacuolar membrane, plasma membrane, or another endomembrane compartment in the nicotine pathway context?
suggested_experiments:
- description: Express DTX40_3 in a heterologous transport system and test transport of nicotine, nicotine glucoside, and related late-pathway intermediates.
  experiment_type: transporter substrate-specificity assay
  hypothesis: DTX40_3 preferentially transports one or more late nicotine-pathway metabolites, and direct assays are needed to determine whether xenobiotic transport annotations also apply.
- description: Disrupt the primary MATE1 candidate and profile subcellular metabolite partitioning together with total nicotine output after induction.
  experiment_type: genetics plus compartment-resolved metabolite profiling
  hypothesis: Loss of DTX40_3 will alter late-pathway metabolite partitioning and reduce efficient nicotine accumulation.

NaMATE1_candidate_DTX40_3

Gene Description

Existing Annotations Review

Core Functions

DTX40_3 is the best current NICAT MATE1 candidate for the membrane transport step associated with the late nicotine biosynthetic module.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Functional annotation research report: DTX40_3 / NaMATE1_candidate_DTX40_3 (UniProt A0A314KVN4) in Nicotiana attenuata

Executive summary and verification

1) Key concepts and definitions (current understanding)

1.1 What are plant MATE/DTX transporters?

1.2 Typical topology and coupling

1.3 Substrate scope and functional breadth

2) Gene-centric functional annotation for N. attenuata DTX40_3 (A0A314KVN4)

2.1 Most defensible function statement (evidence-based)

2.2 Likely biological role in Nicotiana: vacuolar sequestration of defensive alkaloids (inference from closest Nicotiana homolog system)

2.3 Subcellular localization: most likely tonoplast (inference)

2.4 Pathway context: JA-regulated defense metabolism and long-distance nicotine allocation (inference)

3) Recent developments (prioritizing 2023–2024)

3.1 2024: Quantitative demonstration of strict substrate specificity in a plant tonoplast MATE

3.2 2024: Nicotine manipulation strategies and transporter context in tobacco

3.3 2023: Broader functional diversification of DTX/MATE transporters

4) Current applications and real-world implementations

4.1 Plant metabolic engineering and molecular breeding

4.2 Public-health driven nicotine reduction targets (tobacco)

4.3 Transporters as pathway flux “gatekeepers”

5) Expert synthesis and analysis (authoritative viewpoints)

5.1 The most likely functional hypothesis for DTX40_3

5.2 Alternative plausible roles (less supported without gene-specific data)

6) Statistics and quantitative data relevant to annotation

6.1 Gene family size and general properties

6.2 Quantitative anchors from Nicotiana alkaloid transport literature

6.3 Quantitative functional data from a 2024 plant MATE study

Visual evidence (for localization precedent)

Summary table (evidence vs inference for DTX40_3)

Conclusions

Key references (with URLs and publication dates)

Artifacts

Citations

📚 Additional Documentation

Notes

NaMATE1_candidate_DTX40_3 Notes

📄 View Raw YAML