NCU07379 encodes a 395-residue basic-leucine-zipper (bZIP) transcription factor of the fungal AP-1-like family (PANTHER PTHR40621:SF6). It has an N-terminal bZIP DNA-binding and dimerisation region and a less conserved C-terminal region. Within this subfamily it is the Neurospora crassa ortholog of the Aspergillus nidulans developmental regulator FlbB, not of the oxidative-stress regulator Yap1/NapA, whose N. crassa ortholog is NCU03905. As a bZIP factor it is expected to bind cis-regulatory DNA in the nucleus and activate RNA polymerase II transcription. A. nidulans FlbB activates flbD and brlA and is required for conidiation. The N. crassa deletion mutant, however, conidiates normally, and the genes that NCU07379 regulates in Neurospora are not known.
Existing Annotations Review
GO Term
Evidence
Action
Reason
GO:0000976 transcription cis-regulatory region binding
IBA GO_REF:0000033
ACCEPT
Summary: The PAINT inference from fungal node PTN008082960 is sound. NCU07379 descends from this node through the FlbB clade, and members of that clade, like the Yap1/Pap1 clade, have a conserved bZIP DNA-binding region.
Reason: The re-review tree places NCU07379 in the FlbB clade of PTHR40621:SF6 (100% bootstrap). This clade and the Yap1/Pap1 clade both descend from PTN008082960, the node where PAINT placed sequence-specific cis-regulatory DNA binding. A. nidulans FlbB, the characterised member of the target's own clade, has a conserved N-terminal bZIP domain and activates transcription of target promoters. Binding at a cis-regulatory region is therefore expected to be conserved. The Neurospora binding sites are not known.
flbB displays unique characteristics as a transcription factor, i.e., a highly conserved N-terminal bZIP domain
file:NEUCR/NCU07379/NCU07379-uniprot.txt
DR InterPro; IPR046347; bZIP_sf.
GO:0000976 transcription cis-regulatory region binding
IEA GO_REF:0000002
ACCEPT
Summary: The InterPro mapping from IPR050936 (AP-1-like) gives the same claim as the IBA row and is consistent with it.
Reason: This row makes the same claim as the accepted IBA row for GO:0000976, from AP-1-like family membership (IPR050936). The FlbB-clade placement does not change it, because both FlbB and Yap1 clade members are bZIP DNA-binding factors.
Summary: This is the core molecular function. The activator role is propagated from PTN008082960, and the characterised member of the target's own FlbB clade activates transcription of target genes.
Reason: The PAINT node PTN008082960 includes the FlbB clade, to which NCU07379 belongs. In A. nidulans, FlbB activates expression of flbD and, together with FlbD, of brlA. That is activator function in the target's own clade, so this is not only a transfer from the Yap1 clade. Fungal nuclear bZIP activators act on RNA polymerase II promoters. The targets of NCU07379 in N. crassa are unknown.
bZip transcription factor FlbB, which has been attributed to participate in transducing the aerial stimulus signal, activates the expression of c-Myb transcription factor FlbD
Summary: The term is correct but general. The more specific GO:0001228, which this review accepts from the IBA row, is supported.
Reason: The bZIP superfamily mapping (IPR046347) correctly identifies a DNA-binding transcription factor. The phylogenetic placement and the characterised FlbB clade member support the more specific activator term GO:0001228, which the gene already carries by IBA. Under the refinement rule, that descendant replaces this general term.
bZip transcription factor FlbB, which has been attributed to participate in transducing the aerial stimulus signal, activates the expression of c-Myb transcription factor FlbD
Summary: Nuclear location fits a bZIP transcription factor, and the FlbB ortholog has been seen in apical nuclei.
Reason: The UniProt subcellular-location line is an ARBA prediction, so it is not used as support. A DNA-binding transcription factor must act in the nucleus, and A. nidulans FlbB, in the same clade, has been observed in apical nuclei. FlbB also has a hyphal-tip pool, which PAINT did not propagate and which this review does not add. NCU07379 itself has not been localised.
FlbB accumulates at the hyphal apex during early vegetative growth but is later found in apical nuclei
GO:0006355 regulation of DNA-templated transcription
IEA GO_REF:0000002
MODIFY
Summary: The term is correct but general. The gene also carries the more specific GO:0045944, which is supported by the activator function.
Reason: The bZIP mapping supports a role in transcription regulation. The supported activator function (GO:0001228) implies the more specific descendant GO:0045944 (positive regulation of transcription by RNA polymerase II), which the gene already carries, so that term replaces this one.
bZip transcription factor FlbB, which has been attributed to participate in transducing the aerial stimulus signal, activates the expression of c-Myb transcription factor FlbD
GO:0045944 positive regulation of transcription by RNA polymerase II
IEA GO_REF:0000108
ACCEPT
Summary: This process follows logically from the accepted activator function GO:0001228.
Reason: The term is inferred from the accepted GO:0001228 activator activity, and FlbB-clade activation of target genes supports it. No specific developmental or stress process is attached. A. nidulans FlbB regulates conidiation, but the N. crassa NCU07379 deletion mutant conidiates normally. A conidiation process term would therefore be a transfer that the target's own phenotype contradicts.
bZip transcription factor FlbB, which has been attributed to participate in transducing the aerial stimulus signal, activates the expression of c-Myb transcription factor FlbD
The gross phenotype of a knockout of the FlbB ortholog in Ncras (NCU07379) was characterized by the Neurospora Genome Project (NGP)
GO:0090575 RNA polymerase II transcription regulator complex
IBA GO_REF:0000033
KEEP AS NON CORE
Summary: The term is plausible for a dimerising bZIP activator propagated from PTN008082960, but it is peripheral to the core activity and no partner has been identified.
Reason: bZIP factors bind DNA as homo- or heterodimers, and the PAINT node supports membership in a transcription regulator complex. For the FlbB clade, a heteromeric complex has only been proposed; no partner has been demonstrated, and no NCU07379 partner is known. The term is kept as non-core. It does not imply membership in core RNA polymerase II.
Like many bZIP proteins ( 45 ), FlbB may form a heteromeric complex.
Core Functions
Sequence-specific bZIP DNA-binding transcription activator (FlbB ortholog) that binds cis-regulatory DNA and activates RNA polymerase II transcription in the nucleus. Its N. crassa target genes are not known.
bZip transcription factor FlbB, which has been attributed to participate in transducing the aerial stimulus signal, activates the expression of c-Myb transcription factor FlbD
Q: Does NCU07379 share the hyphal-tip-to-nucleus relocalisation of A. nidulans FlbB, given that the N. crassa deletion has no reported conidiation defect?
Q: Which genes does NCU07379 regulate in N. crassa, given that the FlbB-FlbD-brlA conidiation branch of A. nidulans is not conserved there?
Suggested Experiments
Experiment: Tag NCU07379 with a fluorescent protein at its endogenous locus and image vegetative hyphae and conidiophores, to test whether it localises to the hyphal tip and to nuclei as A. nidulans FlbB does.
Experiment: Run ChIP-seq of tagged NCU07379 together with RNA-seq of the deletion strain under stress and developmental conditions, to identify direct targets and binding motifs.
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
NCU07379 is a bZIP transcription factor of the fungal AP-1-like family (PANTHER PTHR40621:SF6) that groups with the FlbB clade, not the Yap1/NapA clade. The single ProtNLM2 GO prediction, generic DNA-binding transcription factor activity, is correct but less precise than the RNA polymerase II-specific activator activity the gene already carries by PAINT, which the FlbB-clade evidence supports.
Review rationale: NCU07379 has a bZIP superfamily domain and is placed in the FlbB clade of the fungal AP-1-like subfamily PTHR40621:SF6. Aspergillus nidulans FlbB, the characterised member of that clade, is a bZIP factor that activates transcription of flbD and, with FlbD, of brlA. The prediction is therefore correct. The gene already carries GO:0003700 by InterPro mapping and the more specific descendant GO:0001228 (RNA polymerase II-specific activator activity) by PAINT, and the gene review accepts GO:0001228 as the core function, so the generic transcription-factor term is less precise than an existing supported annotation and is not novel. The N. crassa target genes are unknown.
PMID:17993569: "flbB displays unique characteristics as a transcription factor, i.e., a highly conserved N-terminal bZIP domain"
PMID:20132447: "bZip transcription factor FlbB, which has been attributed to participate in transducing the aerial stimulus signal, activates the expression of c-Myb transcription factor FlbD"