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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.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.
NCU01633 is not merely an uncharacterized “HXT13-like” open reading frame. Direct functional work identifies it as glt-1, encoding GLT-1, the major low-affinity, high-capacity glucose transporter (system I) of Neurospora crassa. Glucose is the only substrate established directly in the retrieved literature. Heterologous radiotracer assays yielded a glucose Kₘ of 18.42 ± 3.38 mM and a Vmax of 30.75 ± 1.34 mmol h⁻¹ g⁻¹ dry cell weight, consistent with uptake under glucose-replete conditions. GLT-1 complements the high-affinity HGT-1/HGT-2 system, but it should not be annotated as a demonstrated glucose-signaling “transceptor”: that evidence applies specifically to HGT-1 and HGT-2. (wang2017identificationandcharacterization pages 1-2, wang2017identificationandcharacterization pages 12-14, wang2017identificationandcharacterization pages 3-6)
The literature on this exact protein is limited. Searches recovered one decisive functional paper from 2017 and one earlier cellulose-response study from 2013, but no direct NCU01633-specific study from 2023–2024. Thus, the experimentally supportable annotation is narrower than the UniProt description might imply: low-affinity glucose transporter GLT-1, with other hexoses, precise native localization, and an autonomous signaling role still unproven.
The primary literature directly maps NCU01633 to GLT-1 in N. crassa. It distinguishes this locus from hgt-1/NCU10021 and hgt-2/NCU04963, which encode the two major high-affinity glucose transporters. This locus assignment is therefore internally consistent with the supplied UniProt accession Q1K4S3 and its broad “hexose transporter” description. (wang2017identificationandcharacterization pages 1-2, wang2017identificationandcharacterization pages 3-6)
The requested organism is Neurospora crassa, and all protein-specific conclusions below are restricted to that species. The supplied strain aliases—ATCC 24698, 74-OR23-1A, CBS 708.71, DSM 1257, and FGSC 987—were not independently enumerated in the retrieved articles; they should be treated as UniProt strain metadata rather than as independently verified claims from these papers.
The direct N. crassa functional literature calls the protein GLT-1, not HXT13. “Hexose transporter HXT13” is therefore best treated as the supplied database name rather than evidence that NCU01633 is functionally equivalent to an HXT13 protein from Saccharomyces, Candida, or another fungus. No results for similarly named proteins in other organisms were used to assign function here.
The supplied InterPro assignments—MFS_dom, MFS_sugar_transport-like, MFS_Sugar_Transporters, MFS_trans_sf, and Sugar/inositol_transpt—are compatible with the experimental paper’s treatment of GLT-1 as an MFS transmembrane sugar transporter and its use of a TMHMM-derived multipass membrane model. This supports an integral membrane-transporter architecture, although it does not by itself determine substrate selectivity or native subcellular location. (wang2017identificationandcharacterization pages 18-20, wang2017identificationandcharacterization pages 12-14)
GLT-1 restored glucose utilization in the Saccharomyces cerevisiae EBY.VW4000 strain, which lacks endogenous hexose transporters, and its activity was measured by radiolabeled-glucose uptake. These are direct functional data establishing glucose as a transported substrate. (wang2017identificationandcharacterization pages 3-6)
The measured glucose Kₘ was 18.42 ± 3.38 mM, placing GLT-1 in the classical low-affinity N. crassa system-I range of approximately 8–20 mM. By comparison, HGT-1 and HGT-2 exhibited glucose Kₘ values of 16.13 ± 0.95 µM and 98.97 ± 22.02 µM, respectively. GLT-1 therefore has roughly three orders of magnitude lower apparent affinity than the high-affinity transporters. (wang2017identificationandcharacterization pages 1-2, wang2017identificationandcharacterization pages 3-6)
GLT-1 is nevertheless a high-capacity transporter. Its reported Vmax was 30.75 ± 1.34 mmol h⁻¹ g⁻¹ dry cell weight, whereas HGT-1 and HGT-2 had values of 26.42 ± 0.38 and 78.11 ± 4.46 µmol h⁻¹ g⁻¹, respectively. This affinity–capacity trade-off fits a system in which GLT-1 supports rapid carbon assimilation when extracellular glucose is abundant, while highly expressed HGT proteins scavenge glucose during depletion. (wang2017identificationandcharacterization pages 12-14)
No systematic substrate panel was recovered for NCU01633. Consequently, transport of fructose, mannose, galactose, xylose, cellobiose, or cellodextrins should not be asserted from the generic term “hexose transporter” or from MFS-family membership. The best experimentally grounded substrate annotation is simply glucose.
The N. crassa low-affinity system I was described physiologically as a glucose-diffusion or facilitated-transport system, in contrast to the active H⁺-cotransport mechanism of high-affinity system II. Because GLT-1 was assigned as the principal system-I component, facilitated glucose transport is a reasonable mechanistic annotation. However, proton dependence and transport stoichiometry were not directly measured using purified GLT-1, so the mechanistic confidence is lower than that for substrate and affinity. (wang2017identificationandcharacterization pages 12-14)
| Question/feature | Best-supported conclusion | Evidence type/strength | Key quantitative result | Important caveat |
|---|---|---|---|---|
| Identity | NCU01633 encodes GLT-1, the low-affinity glucose transporter of Neurospora crassa; this matches the functional class assigned to UniProt Q1K4S3. (wang2017identificationandcharacterization pages 1-2) | Direct locus-to-protein assignment; strong | — | “HXT13” is the supplied UniProt description, but the direct N. crassa literature calls the protein GLT-1; unrelated HXT13 proteins must not be conflated with it. |
| Primary substrate | GLT-1 directly transports glucose, as demonstrated by complementation of a hexose-transporter-null Saccharomyces cerevisiae strain and radiolabeled-glucose uptake. (wang2017identificationandcharacterization pages 3-6) | Heterologous functional assay plus uptake kinetics; strong | Glucose uptake was directly measured. | A systematic substrate panel was not reported, so transport of other hexoses is unproven. |
| Affinity and system assignment | GLT-1 is the major low-affinity, system-I glucose transporter, distinct from high-affinity HGT-1/NCU10021 and HGT-2/NCU04963. (wang2017identificationandcharacterization pages 1-2, wang2017identificationandcharacterization pages 3-6) | Direct kinetic characterization and comparison with physiological systems; strong | Kₘ = 18.42 ± 3.38 mM for glucose; HGT-1 and HGT-2 had Kₘ values of 16.13 ± 0.95 and 98.97 ± 22.02 µM, respectively. | Kinetics were measured after expression in yeast rather than directly in native N. crassa membranes. |
| Transport capacity | GLT-1 is a high-capacity transporter adapted to glucose-replete conditions. (wang2017identificationandcharacterization pages 12-14) | Direct heterologous uptake kinetics; strong | Vmax = 30.75 ± 1.34 mmol h⁻¹ g⁻¹ dry cell weight, versus 26.42 ± 0.38 and 78.11 ± 4.46 µmol h⁻¹ g⁻¹ for HGT-1 and HGT-2. | The approximately three-orders-of-magnitude capacity contrast depends on the heterologous assay and expression context. |
| Transport mechanism | System I, represented by GLT-1, was interpreted as a glucose-diffusion/facilitated-transport system, unlike active H⁺ cotransport by system II. (wang2017identificationandcharacterization pages 12-14) | Physiological synthesis supported by GLT-1 assignment; moderate | System I and II span about a 1,000-fold affinity range. | Proton dependence or stoichiometry was not directly measured for purified GLT-1 in the cited study. |
| Expression regime | glt-1 is predominant under adequate/high glucose, supporting rapid uptake when preferred carbon is plentiful; transient induction also occurs after exposure to moderately low glucose. (wang2017identificationandcharacterization pages 3-6) | RNA-seq and qRT-PCR; strong | At high glucose, reported glt-1 expression was about 210 RPKM; transient induction occurred at 0.05% glucose after 1 h. | Expression is dosage- and time-dependent; GLT-1 is not simply constitutive under every condition. |
| Deletion and redundancy | Loss of glt-1 alone can be compensated by other transporters, especially HGT-1/HGT-2; removing all three major transporters produces a high-glucose growth lag. (wang2017identificationandcharacterization pages 3-6) | Targeted deletion, growth, uptake, and qRT-PCR studies; strong | In Δglt-1, hgt-1/-2 rose approximately 60-fold at 0.5% glucose. | Reports describe the single-mutant phenotype as absent or moderate depending on assay; redundancy makes GLT-1 nonessential under tested laboratory conditions. |
| Avicel/cellulose response | NCU01633/glt-1 is strongly induced in the Avicel transcriptional response and belongs to a transporter-containing expression cluster associated with plant-cell-wall deconstruction. (coradetti2013analysisofa pages 3-5, wang2017identificationandcharacterization pages 3-6) | RNA-seq expression association; moderate | The Avicel regulon required >4-fold induction at adjusted P < 0.05 in the 2013 analysis. | Induction does not show that GLT-1 transports cellulose-derived oligomers; direct evidence supports glucose, not cellodextrin, as its substrate. |
| Effect on lignocellulase production | Δglt-1 alone has only slight effects on Avicel phenotypes and does not reproduce the approximately twofold protein hyperproduction caused by deleting hgt-1/-2. (wang2017identificationandcharacterization pages 6-7) | Deletion and complementation studies; moderate-to-strong | Δhgt-1 Δhgt-2 produced nearly 2× wild-type extracellular protein on Avicel; adding Δglt-1 caused no comparable additional effect. | The major cellulose-signaling phenotype belongs to HGT-1/-2, not GLT-1. |
| Family and localization | Supplied InterPro annotations place Q1K4S3 in the MFS sugar-transporter family, making it an integral multipass membrane protein expected to function at the cell boundary; TMHMM models also treated GLT-1 as a transmembrane transporter. (wang2017identificationandcharacterization pages 18-20, wang2017identificationandcharacterization pages 12-14) | Domain/topology prediction plus transporter function; moderate for topology, low-to-moderate for exact native location | — | Direct, unambiguous native GLT-1 plasma-membrane localization was not recovered; localization should therefore be described as predicted rather than established. |
| Signaling and carbon catabolite repression | The dual-affinity glucose-transport system interfaces with CRE-1-mediated carbon catabolite repression and cAMP–PKA regulation, but direct transceptor evidence is specifically for HGT-1/HGT-2, not GLT-1. (wang2017identificationandcharacterization pages 14-17, wang2017identificationandcharacterization pages 12-14) | Point mutants, 2-deoxyglucose response, transcriptomics, and cAMP assays for HGT-1/-2; strong for HGTs, insufficient for GLT-1 | A nontransporting GLT-1(R167K) control did not transmit the HGT-like CCR phenotype. | It would be incorrect to annotate NCU01633 itself as a demonstrated glucose transceptor from these experiments. |
| Recent evidence (2023–2024) | No direct 2023–2024 publication specifically characterizing NCU01633/Q1K4S3 was found; the decisive functional study remains Wang et al. (January 2017), supplemented by Coradetti et al. (June 2013). (wang2017identificationandcharacterization pages 1-2, coradetti2013analysisofa pages 3-5) | Literature-search result; moderate, search-dependent | Direct literature located: one principal functional study and one earlier expression study. | Absence from the retrieved literature is not proof that no newer dataset or unpublished study exists. |
Table: Evidence-based conclusions for NCU01633/Q1K4S3, separating direct glucose-transport findings from family-level predictions and HGT-1/HGT-2-specific signaling results.
GLT-1 is an MFS multipass membrane transporter and was structurally modeled with TMHMM; its physiological role is uptake of extracellular glucose. Together these observations strongly imply operation at the fungal plasma membrane. Constructs containing eGFP-tagged GLT-1 were generated and confocal microscopy was among the reported methods, but the retrieved text did not provide an unambiguous, protein-specific native localization result. Plasma-membrane localization should therefore be labeled strongly predicted/physiologically inferred, rather than definitively demonstrated in native N. crassa. (wang2017identificationandcharacterization pages 18-20, wang2017identificationandcharacterization pages 12-14)
There is no evidence in the retrieved literature for secretion, extracellular matrix residence, or localization to mitochondria, vacuoles, peroxisomes, or nuclei.
GLT-1 is the system-I component of a dual-affinity uptake strategy. It is preferentially deployed when glucose is plentiful, whereas HGT-1 and HGT-2 dominate under glucose limitation or carbon deprivation. Across the three proteins, the system spans approximately a 1,000-fold affinity range, allowing N. crassa to maintain carbon uptake across large environmental fluctuations. (wang2017identificationandcharacterization pages 12-14)
RNA-seq showed that glt-1 was the only surveyed sugar-transporter gene consistently prominent at high glucose. A transient induction also occurred after one hour at 0.05% glucose, indicating time- and dose-dependent regulation rather than a simple constitutive on/off pattern. At high glucose, an example expression value was approximately 210 RPKM, while hgt-1 reached roughly 5,700 RPKM under derepressed low-glucose conditions. (wang2017identificationandcharacterization pages 12-14, wang2017identificationandcharacterization pages 3-6)
A glt-1 deletion had little or condition-dependent effect in several assays because system II and other sugar transporters compensated. At low glucose, Δglt-1 retained uptake comparable to wild type, showing that GLT-1 is dispensable during glucose limitation. At high glucose, removal of all three principal transporters—glt-1, hgt-1, and hgt-2—caused a growth lag, whereas Δglt-1 alone could be rescued by induction of alternative transporters. In Δglt-1 exposed to 0.5% glucose, hgt-1 and hgt-2 expression increased approximately 60-fold. (wang2017identificationandcharacterization pages 3-6)
These findings explain why a single-gene knockout is not an adequate test of whether GLT-1 transports glucose: the N. crassa transporter network is highly redundant.
NCU01633 was among genes strongly induced when N. crassa was shifted to crystalline cellulose (Avicel). In the 2013 comparative transcriptome, it occurred in a cluster strongly induced in N. crassa but expressed weakly in Aspergillus nidulans. The study defined the Avicel regulon using at least fourfold induction with an adjusted P value below 0.05. This places glt-1 within the transcriptional program accompanying plant-cell-wall deconstruction. (coradetti2013analysisofa pages 3-5)
That association does not establish transport of cellulose oligomers. A more conservative interpretation is that hydrolytic enzymes release glucose from cellulose and that GLT-1 can assimilate this product when local glucose becomes sufficiently abundant. Dedicated N. crassa cellodextrin transporters are separate proteins.
Deletion of glt-1 alone had only slight effects on Avicel phenotypes. By contrast, deleting hgt-1 and hgt-2 generated nearly twofold greater extracellular protein production on Avicel and derepressed CLR-2/CAZy-associated lignocellulase expression; adding a glt-1 deletion did not reproduce or substantially enhance that phenotype. Complementation with HGT-1 or HGT-2, but not GLT-1, restored the high-affinity-transporter phenotype. Thus, the strongest direct control over cellulase derepression belongs to HGT-1/HGT-2 rather than GLT-1. (wang2017identificationandcharacterization pages 6-7)
The dual-affinity transport system interfaces with CRE-1-mediated carbon catabolite repression and cAMP–PKA regulation. A working physiological model is that GLT-1-mediated uptake supports glucose assimilation and vegetative growth in carbon-replete conditions, where cellulase genes are repressed. This places GLT-1 upstream of central carbon metabolism and indirectly within the carbon-catabolite-repression context. (wang2017identificationandcharacterization pages 14-17)
However, direct “transceptor” evidence came from transport-defective HGT-1 and HGT-2 mutants that retained signaling activity. The corresponding GLT-1(R167K) control did not transmit the same CCR phenotype. NCU01633 should therefore not be annotated as a demonstrated glucose sensor or transceptor. (wang2017identificationandcharacterization pages 12-14)
The highest-confidence conclusions are:
Moderate-confidence conclusions are that GLT-1 functions at the plasma membrane and uses facilitated diffusion. These follow from transporter architecture, physiological uptake, and system-I behavior but lack the same direct protein-specific evidence as the glucose kinetics.
Unsupported or insufficiently supported annotations include broad hexose specificity, cellodextrin transport, a catalytic reaction, a direct CLR-2 regulatory relationship, organellar localization, and autonomous glucose-transceptor activity.
No 2023–2024 source directly characterizing NCU01633/Q1K4S3 was found. The decisive study remains Wang et al., published in January 2017, which the retrieved bibliographic record reports as having 87 citations. Its principal contribution was the first systematic gene-level assignment of the N. crassa dual-affinity glucose-transport machinery. The earlier Coradetti et al. paper, published in June 2013, independently placed NCU01633 in the Avicel-responsive transcriptome. (wang2017identificationandcharacterization pages 1-2, coradetti2013analysisofa pages 3-5)
The current expert interpretation should therefore emphasize that the locus is functionally characterized but incompletely annotated. The strongest unresolved questions are:
The main application is metabolic engineering of filamentous fungi for lignocellulose conversion. Manipulating glucose-transporter affinity, capacity, and regulation could alter glucose assimilation, carbon catabolite repression, cellulase production, and the balance between vegetative growth and sporulation. GLT-1 is particularly relevant as a high-capacity uptake module for glucose-rich phases, whereas HGT-1/HGT-2 are more relevant to glucose limitation and signaling. The 2017 authors disclosed a patent application covering GLT-1 and HGT-1/HGT-2 for potential biotechnology applications, demonstrating translational interest, although the retrieved source did not document a deployed commercial process. (wang2017identificationandcharacterization pages 20-21)
Potential implementations include transporter balancing in consolidated bioprocessing strains, improving sugar capture after enzymatic cellulose hydrolysis, and decoupling biomass-degrading-enzyme production from glucose repression. These remain engineering opportunities rather than established NCU01633-based commercial implementations.
NCU01633 / Q1K4S3 / GLT-1: Neurospora crassa major-facilitator-superfamily low-affinity, high-capacity glucose transporter, functioning as system I of the dual-affinity glucose-uptake network and preferentially supporting carbon assimilation under glucose-replete conditions. Probable native location: plasma membrane. Experimentally established substrate: glucose; Kₘ 18.42 ± 3.38 mM. Broader hexose specificity and a direct glucose-sensing/transceptor role are not established. (wang2017identificationandcharacterization pages 1-2, wang2017identificationandcharacterization pages 12-14, wang2017identificationandcharacterization pages 3-6)
References
(wang2017identificationandcharacterization pages 1-2): Bang Wang, Jingen Li, Jingfang Gao, Pengli Cai, Xiaoyun Han, and Chaoguang Tian. Identification and characterization of the glucose dual-affinity transport system in neurospora crassa: pleiotropic roles in nutrient transport, signaling, and carbon catabolite repression. Biotechnology for Biofuels, Jan 2017. URL: https://doi.org/10.1186/s13068-017-0705-4, doi:10.1186/s13068-017-0705-4. This article has 87 citations.
(wang2017identificationandcharacterization pages 12-14): Bang Wang, Jingen Li, Jingfang Gao, Pengli Cai, Xiaoyun Han, and Chaoguang Tian. Identification and characterization of the glucose dual-affinity transport system in neurospora crassa: pleiotropic roles in nutrient transport, signaling, and carbon catabolite repression. Biotechnology for Biofuels, Jan 2017. URL: https://doi.org/10.1186/s13068-017-0705-4, doi:10.1186/s13068-017-0705-4. This article has 87 citations.
(wang2017identificationandcharacterization pages 3-6): Bang Wang, Jingen Li, Jingfang Gao, Pengli Cai, Xiaoyun Han, and Chaoguang Tian. Identification and characterization of the glucose dual-affinity transport system in neurospora crassa: pleiotropic roles in nutrient transport, signaling, and carbon catabolite repression. Biotechnology for Biofuels, Jan 2017. URL: https://doi.org/10.1186/s13068-017-0705-4, doi:10.1186/s13068-017-0705-4. This article has 87 citations.
(wang2017identificationandcharacterization pages 18-20): Bang Wang, Jingen Li, Jingfang Gao, Pengli Cai, Xiaoyun Han, and Chaoguang Tian. Identification and characterization of the glucose dual-affinity transport system in neurospora crassa: pleiotropic roles in nutrient transport, signaling, and carbon catabolite repression. Biotechnology for Biofuels, Jan 2017. URL: https://doi.org/10.1186/s13068-017-0705-4, doi:10.1186/s13068-017-0705-4. This article has 87 citations.
(coradetti2013analysisofa pages 3-5): Samuel T. Coradetti, Yi Xiong, and N. Louise Glass. Analysis of a conserved cellulase transcriptional regulator reveals inducer-independent production of cellulolytic enzymes in neurospora crassa. MicrobiologyOpen, 2:595-609, Jun 2013. URL: https://doi.org/10.1002/mbo3.94, doi:10.1002/mbo3.94. This article has 168 citations and is from a peer-reviewed journal.
(wang2017identificationandcharacterization pages 6-7): Bang Wang, Jingen Li, Jingfang Gao, Pengli Cai, Xiaoyun Han, and Chaoguang Tian. Identification and characterization of the glucose dual-affinity transport system in neurospora crassa: pleiotropic roles in nutrient transport, signaling, and carbon catabolite repression. Biotechnology for Biofuels, Jan 2017. URL: https://doi.org/10.1186/s13068-017-0705-4, doi:10.1186/s13068-017-0705-4. This article has 87 citations.
(wang2017identificationandcharacterization pages 14-17): Bang Wang, Jingen Li, Jingfang Gao, Pengli Cai, Xiaoyun Han, and Chaoguang Tian. Identification and characterization of the glucose dual-affinity transport system in neurospora crassa: pleiotropic roles in nutrient transport, signaling, and carbon catabolite repression. Biotechnology for Biofuels, Jan 2017. URL: https://doi.org/10.1186/s13068-017-0705-4, doi:10.1186/s13068-017-0705-4. This article has 87 citations.
(wang2017identificationandcharacterization pages 20-21): Bang Wang, Jingen Li, Jingfang Gao, Pengli Cai, Xiaoyun Han, and Chaoguang Tian. Identification and characterization of the glucose dual-affinity transport system in neurospora crassa: pleiotropic roles in nutrient transport, signaling, and carbon catabolite repression. Biotechnology for Biofuels, Jan 2017. URL: https://doi.org/10.1186/s13068-017-0705-4, doi:10.1186/s13068-017-0705-4. This article has 87 citations.