AT4G17750

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003700 DNA-binding transcription factor activity	IBA GO_REF:0000033	ACCEPT	Summary: HSFA1A is a transcriptional activator that binds specifically to heat shock elements (HSEs) in target gene promoters and activates transcription. The protein contains a conserved DNA-binding domain (DBD) with helix-turn-helix motif and an AHA transcriptional activation domain. IBA annotations are based on phylogenetic inference and are generally reliable. Reason: This annotation accurately captures HSFA1A's core function as a DNA-binding transcription factor. Evidence from PMID:7948881 demonstrates that recombinant ATHSF1 binds specifically to synthetic oligonucleotides containing heat shock elements. PMID:21931939 shows that HSFA1A functions as a main positive regulator in heat shock-responsive gene expression. The deep-research document confirms that HSFA1A directly binds HSE sequences and activates transcription of multiple target genes. This is a CORE function of the protein. Supporting Evidence: PMID:7948881 After expression in Escherichia coli the recombinant Athsf1 protein binds specifically to a synthetic oligonucleotide containing five heat shock elements. PMID:21931939 Arabidopsis HsfA1 transcription factors function as the main positive regulators in heat shock-responsive gene expression. file:ARATH/AT4G17750/AT4G17750-deep-research-perplexity.md HSFA1A functions as the master regulator of heat shock protein genes, directly controlling the expression of multiple heat shock protein families essential for cellular proteostasis file:ARATH/AT4G17750/AT4G17750-deep-research-falcon.md HSFA1A encodes a sequence-specific transcription factor that initiates and shapes the plant heat stress response (HSR) by binding heat-responsive promoter elements and inducing canonical protective programs (notably heat shock proteins, other HSFs, and additional stress TFs).
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: HSFA1A binds sequence-specifically to heat shock elements (HSEs) with the consensus sequence 5'-AGAAnnTTCT-3' in the promoter regions of target genes transcribed by RNA polymerase II. This is well-supported by experimental evidence showing specific binding to HSE-containing oligonucleotides. Reason: This annotation accurately describes the sequence-specific DNA-binding activity of HSFA1A. UniProt states that the protein "specifically binds DNA sequence 5'-AGAAnnTTCT-3' known as heat shock promoter elements (HSE)." PMID:7948881 demonstrates specific binding to HSE sequences. The deep-research document confirms that HSFA1A recognizes HSEs through a highly selective binding mechanism, with DAP-seq identifying 5034 putative binding sites genome-wide. This is a CORE molecular function. Supporting Evidence: UniProt:P41151 Transcriptional activator that specifically binds DNA sequence 5'-AGAAnnTTCT-3' known as heat shock promoter elements (HSE). PMID:7948881 After expression in Escherichia coli the recombinant Athsf1 protein binds specifically to a synthetic oligonucleotide containing five heat shock elements. file:ARATH/AT4G17750/AT4G17750-deep-research-perplexity.md HSFA1A specifically recognizes heat shock elements through a highly selective binding mechanism... DAP-seq identified 5034 putative HSFA1A binding sites in the Arabidopsis genome
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: HSFA1A localizes to the nucleus upon heat stress where it binds to target gene promoters and activates transcription. Under non-stress conditions, the protein is predominantly cytoplasmic but translocates to the nucleus in response to stress. IBA annotations are consistent with experimental evidence showing nuclear localization. Reason: Nuclear localization is well-documented and essential for HSFA1A function. UniProt lists both cytoplasm and nucleus as localization sites. PMID:21931939 reports nuclear accumulation of HsfA1 proteins under heat stress. The deep-research document states that HSFA1A exhibits dynamic subcellular localization, residing primarily in the cytoplasm under normal conditions and translocating to the nucleus upon heat stress. This is CORE to the protein's function as a transcription factor. Supporting Evidence: UniProt:P41151 Cytoplasm {ECO:0000305}. Nucleus. PMID:21931939 HsfA1 protein accumulation in the nucleus was negatively regulated by their interactions with HSP90, and other factors potentially strongly activate the HsfA1 proteins under HS stress. file:ARATH/AT4G17750/AT4G17750-deep-research-perplexity.md HSFA1A exhibits dynamic subcellular localization that responds to stress conditions, with the protein residing primarily in the cytoplasm under normal growth conditions and translocating to the nucleus upon heat stress
GO:0034605 cellular response to heat	IBA GO_REF:0000033	ACCEPT	Summary: HSFA1A is THE master regulator of the cellular response to heat in Arabidopsis, functioning as the primary transcriptional activator that initiates the heat shock response cascade. This is the most accurate biological process annotation for HSFA1A's CORE function. Reason: This annotation perfectly captures HSFA1A's primary biological role. PMID:21931939 demonstrates that HsfA1 transcription factors "function as the main positive regulators in heat shock-responsive gene expression" and that triple/quadruple mutants have drastically impaired heat stress responses. The deep-research document extensively documents HSFA1A as "the master regulator of heat shock response" and "primary master controller of the heat stress response." This is the CORE biological process for HSFA1A. Supporting Evidence: PMID:21931939 Arabidopsis HsfA1 transcription factors function as the main positive regulators in heat shock-responsive gene expression... HS-responsive gene expression, including that of molecular chaperones and transcription factors, was globally and drastically impaired in the hsfa1a/b/d triple mutant file:ARATH/AT4G17750/AT4G17750-deep-research-perplexity.md HSFA1A (Heat Shock Factor A-1a) represents a critical transcriptional regulator in plants, functioning as the primary master controller of the heat stress response in Arabidopsis thaliana file:ARATH/AT4G17750/AT4G17750-deep-research-falcon.md HSFA1 family members are widely described as the top tier (“master regulators”) in an HSF regulatory hierarchy.
GO:0003677 DNA binding	IEA GO_REF:0000043	ACCEPT	Summary: This is a valid but overly general annotation. HSFA1A does bind DNA, but the more specific terms (GO:0000978 for sequence-specific DNA binding and GO:0003700 for transcription factor activity) better capture its function. This IEA annotation is based on keyword mapping. Reason: While this annotation is technically correct (HSFA1A does bind DNA), it is quite general. However, it's acceptable as a broad parent term alongside the more specific annotations already present. The IEA evidence comes from UniProtKB keyword mapping which correctly identifies the DNA-binding domain. More specific child terms are also annotated, so this serves as an appropriate general classification. Supporting Evidence: PMID:7948881 Arabidopsis heat shock factor: isolation and characterization of the gene and the recombinant protein PMID:7948881 After expression in Escherichia coli the recombinant Athsf1 protein binds specifically to a synthetic oligonucleotide containing five heat shock elements.
GO:0003700 DNA-binding transcription factor activity	IEA GO_REF:0000002	ACCEPT	Summary: Duplicate of the IBA annotation for the same term. Both are correct and represent HSFA1A's CORE molecular function. IEA evidence is from InterPro domain mapping. Reason: This is a duplicate annotation of GO:0003700 which is already annotated with IBA evidence. Both annotations are correct and accurately describe HSFA1A's core function as a DNA-binding transcription factor. Having multiple lines of evidence (IBA and IEA) for the same term is acceptable and reinforces the confidence in the annotation. The IEA evidence comes from InterPro HSF domain recognition. Supporting Evidence: UniProt:P41151 Transcriptional activator that specifically binds DNA sequence 5'-AGAAnnTTCT-3' known as heat shock promoter elements (HSE).
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Duplicate of nucleus annotation already present with IBA evidence. IEA evidence is from subcellular location vocabulary mapping. Both are correct. Reason: This is a duplicate annotation for nuclear localization, already annotated with IBA evidence. The IEA evidence comes from UniProtKB subcellular location mapping. Nuclear localization is well-established and essential for HSFA1A function as a transcription factor. Multiple lines of evidence support this annotation. Supporting Evidence: UniProt:P41151 Cytoplasm {ECO:0000305}. Nucleus.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: HSFA1A is predominantly cytoplasmic under non-stress conditions, where it is held in an inactive state through interactions with HSP70/HSP90. Upon heat stress, it translocates to the nucleus. This annotation correctly captures the cytoplasmic localization state. Reason: This annotation is correct and represents an important aspect of HSFA1A regulation. UniProt lists cytoplasm as a subcellular location. The deep-research document extensively describes how HSFA1A "resides primarily in the cytoplasm under normal growth conditions" where it is maintained in an inactive state by HSP70/HSP90 binding. This cytoplasmic sequestration is a key regulatory mechanism. The falcon deep-research report refines this picture by noting that recent primary work (Toribio et al. 2024) reports AtHSFA1a is predominantly nuclear even under non-stress conditions, with HOP co-chaperones affecting protein stability rather than localization. The cytoplasm annotation remains valid (UniProt lists both compartments), but the simple inactive-cytoplasmic-sequestration model may be Arabidopsis-context dependent. Supporting Evidence: UniProt:P41151 Cytoplasm {ECO:0000305}. Nucleus. file:ARATH/AT4G17750/AT4G17750-deep-research-perplexity.md Under non-stressed conditions, HSP70 and HSP90 maintain HSFA1A in a monomeric, cytoplasmic state through direct protein-protein interactions that repress its DNA-binding capacity and transcriptional activity file:ARATH/AT4G17750/AT4G17750-deep-research-falcon.md A notable Arabidopsis-specific feature emphasized by recent primary work is that AtHSFA1a is predominantly nuclear even under non-stress conditions.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: This is a valid but very general biological process term. HSFA1A does regulate transcription, but this term is too broad and doesn't capture the specificity of heat stress response regulation. However, it's acceptable as a high-level parent term. Reason: This annotation is technically correct but quite general. HSFA1A is a transcriptional regulator, so this parent term is appropriate. The IEA evidence comes from InterPro domain recognition. More specific terms like "cellular response to heat" better capture HSFA1A's actual biological role, but this serves as an appropriate general classification in the GO hierarchy. Supporting Evidence: PMID:21931939 Arabidopsis HsfA1 transcription factors function as the main positive regulators in heat shock-responsive gene expression
GO:0043565 sequence-specific DNA binding	IEA GO_REF:0000002	ACCEPT	Summary: HSFA1A binds sequence-specifically to heat shock elements with the consensus 5'-AGAAnnTTCT-3'. This annotation correctly captures the sequence-specific nature of DNA binding. Similar to GO:0000978 but more general. Reason: This annotation accurately describes HSFA1A's sequence-specific DNA-binding capability. The protein recognizes a specific consensus sequence (HSE) and binds with high specificity. PMID:7948881 demonstrates specific binding. The IEA evidence comes from InterPro domain recognition of the HSF DNA-binding domain, which is known to confer sequence-specific binding. This is a CORE molecular function. Supporting Evidence: UniProt:P41151 Transcriptional activator that specifically binds DNA sequence 5'-AGAAnnTTCT-3' known as heat shock promoter elements (HSE). PMID:7948881 After expression in Escherichia coli the recombinant Athsf1 protein binds specifically to a synthetic oligonucleotide containing five heat shock elements.
GO:0005515 protein binding	IPI PMID:18466301 The calmodulin-binding protein kinase 3 is part of heat-shoc...	ACCEPT	Summary: HSFA1A interacts with CRK1 (calmodulin-binding protein kinase 3), which phosphorylates HSFA1A and is part of the heat shock signal transduction pathway. While the generic "protein binding" term is correct, a more specific annotation would be better. Reason: This IPI annotation is based on experimental evidence from PMID:18466301 showing direct interaction between HSFA1A and CRK1 via yeast two-hybrid and FRET. The paper states "AtCBK3 interacts with AtHSFA1a" and "purified recombinant AtCBK3 phosphorylated recombinant AtHSFA1a in vitro." While "protein binding" is generic, it is technically correct and supported by experimental data. The interaction with CRK1 is functionally important for HSFA1A phosphorylation and activation during heat stress. Supporting Evidence: PMID:18466301 Using a yeast two-hybrid assay, we found that AtCBK3 interacts with AtHSFA1a. Fluorescence resonance energy transfer was used to confirm the interaction between AtCBK3-YFP and AtHSFA1a-CFP. Furthermore, we demonstrate that purified recombinant AtCBK3 phosphorylated recombinant AtHSFA1a in vitro.
GO:0005515 protein binding	IPI PMID:9801140 Interaction between the Arabidopsis thaliana heat shock tran...	ACCEPT	Summary: HSFA1A interacts with TBP (TATA-binding protein), a core component of the basal transcription machinery. This interaction is essential for HSFA1A to promote RNA polymerase II-dependent transcription of heat shock genes. Reason: This IPI annotation is based on experimental evidence from PMID:9801140 showing direct interaction between HSFA1A and TBP via affinity chromatography, EMSA, and yeast two-hybrid. The paper states "Arabidopsis thaliana HSF1 interacts directly with TBP" and "HSF has to communicate with the basal transcription machinery." While "protein binding" is generic, the interaction with TBP is functionally critical for HSFA1A's role in transcriptional activation and is well-supported experimentally. Supporting Evidence: PMID:9801140 The Arabidopsis thaliana HSF1 interacts directly with TBP, the general TATA box binding transcription factor, as shown by affinity chromatography and electrophoretic mobility shift analyses in vitro. An in vivo interaction between AtHSF1 and AtTBP1 was suggested by results employing the yeast two-hybrid system.
GO:0005634 nucleus	ISM GO_REF:0000122	ACCEPT	Summary: Third annotation for nuclear localization, this time based on AtSubP analysis (ISM evidence). Consistent with IBA and IEA annotations for the same term. Reason: This is another duplicate annotation for nuclear localization based on ISM (Inferred from Sequence Model) evidence via AtSubP subcellular localization prediction. Nuclear localization is well-established for HSFA1A and supported by multiple lines of evidence including experimental data. All three annotations (IBA, IEA, ISM) converge on the same correct localization. Supporting Evidence: UniProt:P41151 Cytoplasm {ECO:0000305}. Nucleus.
GO:0005515 protein binding	IPI PMID:20388662 Cytosol-localized heat shock factor-binding protein, AtHSBP,...	ACCEPT	Summary: HSFA1A interacts with HSBP (heat shock factor-binding protein), a negative regulator that binds to HSFA1A and decreases its DNA-binding capacity, functioning in the attenuation of heat shock response during recovery from heat stress. Reason: This IPI annotation is based on experimental evidence from PMID:20388662 showing interaction between HSFA1A and AtHSBP via protoplast two-hybrid assay. The paper states "AtHSBP interacts with itself and with the HSFs, AtHSFA1a, AtHSFA1b, and AtHSFA2" and "AtHSBP decreased AtHSFA1b DNA-binding capacity in vitro." This interaction is functionally important for negative regulation of HSFA1A activity during recovery from heat stress. Supporting Evidence: PMID:20388662 Protoplast two-hybrid assay results confirmed that AtHSBP interacts with itself and with the HSFs, AtHSFA1a, AtHSFA1b, and AtHSFA2. AtHSBP also negatively affected AtHSFA1b DNA-binding capacity in vitro.
GO:0005515 protein binding	IPI PMID:20657173 AtHSBP functions in seed development and the motif is requir...	ACCEPT	Summary: This is a duplicate of the PMID:20388662 annotation, documenting the same HSFA1A-HSBP interaction. PMID:20657173 is a commentary/follow-up paper on the same work showing that the HR domains in AtHSBP are required for interaction with AtHSFs. Reason: This IPI annotation documents the same HSFA1A-AtHSBP interaction as PMID:20388662, based on a related publication from the same research group. PMID:20657173 states "The HR domains at the C terminus of AtHSBP are important for... interacting with AtHSFs, which negatively affects the DNA-binding capacity and transactivation activity of AtHSFs during the HSR." This confirms the interaction and provides additional mechanistic details. Having multiple publications supporting the same interaction strengthens confidence. Supporting Evidence: PMID:20657173 The HR domains at the C terminus of AtHSBP are important for retaining AtHSBP in the cytoplasm under normal growth conditions and for interacting with AtHSFs, which negatively affects the DNA-binding capacity and transactivation activity of AtHSFs during the HSR.
GO:0005634 nucleus	IDA PMID:21931939 Arabidopsis HsfA1 transcription factors function as the main...	ACCEPT	Summary: Fourth annotation for nuclear localization, this time with IDA (direct assay) evidence from the key paper showing HSFA1A as the main positive regulator of heat shock response. This represents direct experimental evidence of nuclear accumulation. Reason: This IDA annotation is based on direct experimental evidence from PMID:21931939, which reports "HsfA1 protein accumulation in the nucleus was negatively regulated by their interactions with HSP90." This is stronger evidence than IBA, IEA, or ISM as it represents direct experimental observation of nuclear localization. The paper is also the definitive genetic study establishing HSFA1A's role as the master heat stress regulator. Nuclear localization is essential for HSFA1A function. Supporting Evidence: PMID:21931939 HsfA1 protein accumulation in the nucleus was negatively regulated by their interactions with HSP90, and other factors potentially strongly activate the HsfA1 proteins under HS stress.
GO:0009408 response to heat	IEP PMID:20229063 Functional characterization of AtHsp90.3 in Saccharomyces ce...	ACCEPT	Summary: This annotation documents heat-induced expression pattern (IEP evidence). While correct, GO:0034605 "cellular response to heat" is more specific and appropriate for HSFA1A's function as a cellular transcription factor. GO:0009408 is a broader parent term that can apply to organismal-level responses. Reason: This IEP (Inferred from Expression Pattern) annotation is based on heat-induced expression documented in PMID:20229063. The annotation is technically correct - HSFA1A is involved in response to heat. However, GO:0034605 "cellular response to heat" is more precise since HSFA1A functions at the cellular level as a transcription factor activating genes. GO:0009408 is the parent term and is acceptable but less specific. Both annotations coexist appropriately in the GO hierarchy. Supporting Evidence: UniProt:P41151 INDUCTION: By heat stress PMID:7948881 The gene is constitutively expressed but the level of mRNA for Athsf1 increases two-fold upon heat shock.
GO:0005634 nucleus	IDA PMID:19945192 Detection of in vivo interactions between Arabidopsis class ...	ACCEPT	Summary: Fifth annotation for nuclear localization with IDA evidence from a study on HSFA1A interactions using BiFC (bimolecular fluorescence complementation). This provides additional direct experimental evidence of nuclear localization. Reason: This IDA annotation is based on direct experimental evidence from PMID:19945192 using BiFC to detect in vivo interactions between class A HSFs in the nucleus. Nuclear localization of HSFA1A is well-established through multiple independent experimental approaches (BiFC, fluorescence microscopy, immunolocalization). This adds to the already strong evidence from multiple annotations with different evidence codes. Supporting Evidence: UniProt:P41151 Cytoplasm {ECO:0000305}. Nucleus.
GO:0005515 protein binding	IPI PMID:11807141 Interaction between Arabidopsis heat shock transcription fac...	ACCEPT	Summary: HSFA1A interacts with HSP70-1 and HSP70-4, which function as negative regulators maintaining HSFA1A in an inactive state under normal conditions. Upon heat stress, HSP70 dissociates, allowing HSFA1A activation. This is a critical regulatory interaction. Reason: This IPI annotation is based on experimental evidence from PMID:11807141 showing interaction between HSFA1A and HSP70 proteins via EMSA and yeast two-hybrid. The paper states "interaction between HSF and HSP70" and "Subdomain mapping indicates an interaction of the activation domain and DNA-binding domain of HSF1 with HSP70." UniProt confirms "Interacts with HSP70-1 and HSP70-4." This interaction is functionally essential for regulating HSFA1A activity and represents a key mechanism of heat stress sensing. Supporting Evidence: PMID:11807141 The interaction between HSF and HSP70 is reported using electrophoretic mobility shift and yeast two-hybrid assays. Subdomain mapping indicates an interaction of the activation domain and DNA-binding domain of HSF1 with HSP70. UniProt:P41151 Interacts with HSP70-1 and HSP70-4 file:ARATH/AT4G17750/AT4G17750-deep-research-falcon.md A widely used model for plant HSFA1 activation is chaperone-mediated repression at ambient temperature: HSFA1 proteins can be held inactive through interactions with HSP70/HSP90, and heat-induced protein misfolding titrates chaperones away, permitting HSFA1 activation.
GO:0003677 DNA binding	IDA PMID:7948881 Arabidopsis heat shock factor: isolation and characterizatio...	ACCEPT	Summary: This is a duplicate of the IEA annotation for GO:0003677, but with stronger IDA (direct assay) evidence from the foundational paper characterizing HSFA1A. This provides direct experimental demonstration of DNA binding. Reason: This IDA annotation is based on direct experimental evidence from PMID:7948881, which states "After expression in Escherichia coli the recombinant Athsf1 protein binds specifically to a synthetic oligonucleotide containing five heat shock elements." This is the original paper characterizing HSFA1A and demonstrating its DNA-binding activity through EMSA. IDA evidence is stronger than IEA, and DNA binding is a CORE function of HSFA1A. Supporting Evidence: PMID:7948881 After expression in Escherichia coli the recombinant Athsf1 protein binds specifically to a synthetic oligonucleotide containing five heat shock elements.
GO:0009408 response to heat	IEP PMID:7948881 Arabidopsis heat shock factor: isolation and characterizatio...	ACCEPT	Summary: This is a duplicate of the PMID:20229063 annotation for GO:0009408, documenting heat-induced expression from the original HSFA1A characterization paper. Both IEP annotations support the same biological process. Reason: This IEP annotation is based on expression pattern evidence from PMID:7948881, the foundational paper that first characterized HSFA1A. The paper states "the gene is constitutively expressed but the level of mRNA for Athsf1 increases two-fold upon heat shock." This demonstrates heat-responsive expression. As with the other GO:0009408 annotation, GO:0034605 "cellular response to heat" would be more specific, but this parent term is acceptable. Having multiple papers supporting heat responsiveness strengthens the annotation. Supporting Evidence: PMID:7948881 The gene is constitutively expressed but the level of mRNA for Athsf1 increases two-fold upon heat shock.
GO:0003700 DNA-binding transcription factor activity	ISS PMID:11118137 Arabidopsis transcription factors: genome-wide comparative a...	ACCEPT	Summary: Third annotation for GO:0003700 DNA-binding transcription factor activity, this time with ISS (Inferred from Sequence Similarity) evidence from a genome-wide comparative analysis of Arabidopsis transcription factors. Reason: This ISS annotation is based on sequence similarity evidence from PMID:11118137, a comprehensive comparative analysis of Arabidopsis transcription factors across eukaryotes. This is the third annotation for the same term (along with IBA and IEA), all converging on the correct molecular function. ISS evidence from comparative genomics provides additional support for HSFA1A's transcription factor activity. The annotation accurately describes HSFA1A's CORE molecular function. Supporting Evidence: UniProt:P41151 Transcriptional activator that specifically binds DNA sequence 5'-AGAAnnTTCT-3' known as heat shock promoter elements (HSE).

Gene Description

Existing Annotations Review

Core Functions

Transcriptional activation of heat shock protein genes and stress-responsive genes by binding as homotrimer to heat shock elements in target promoters

References

Deep Research

Falcon

Perplexity

📚 Additional Documentation

Notes

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