Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000122 negative regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: file:human/HES1/HES1-deep-research-falcon.md model: Edison Scientific Literature
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0005634 nucleus	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0007219 Notch signaling pathway	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0009952 anterior/posterior pattern specification	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0045665 negative regulation of neuron differentiation	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0050767 regulation of neurogenesis	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0070888 E-box binding	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0071820 N-box binding	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0003677 DNA binding	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0005634 nucleus	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	PENDING	Summary: TODO: Review this GOA annotation
GO:0046983 protein dimerization activity	IEA GO_REF:0000002	PENDING	Summary: TODO: Review this GOA annotation
GO:0005515 protein binding	IPI PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH re...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression.
GO:0000122 negative regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0000785 chromatin	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0001217 DNA-binding transcription repressor activity	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0001222 transcription corepressor binding	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0003143 embryonic heart tube morphogenesis	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0003281 ventricular septum development	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0003682 chromatin binding	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0005737 cytoplasm	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0008432 JUN kinase binding	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0010628 positive regulation of gene expression	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0010629 negative regulation of gene expression	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0010977 negative regulation of neuron projection development	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0016363 nuclear matrix	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0021861 forebrain radial glial cell differentiation	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0030182 neuron differentiation	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0032991 protein-containing complex	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0035315 hair cell differentiation	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0035909 aorta morphogenesis	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0035910 ascending aorta morphogenesis	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0042802 identical protein binding	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0042803 protein homodimerization activity	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0043254 regulation of protein-containing complex assembly	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0043279 response to alkaloid	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0043398 HLH domain binding	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0043565 sequence-specific DNA binding	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0044877 protein-containing complex binding	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0045687 positive regulation of glial cell differentiation	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0045747 positive regulation of Notch signaling pathway	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0045892 negative regulation of DNA-templated transcription	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0045893 positive regulation of DNA-templated transcription	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0045977 positive regulation of mitotic cell cycle, embryonic	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0046425 regulation of receptor signaling pathway via JAK-STAT	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0048538 thymus development	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0048711 positive regulation of astrocyte differentiation	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0048715 negative regulation of oligodendrocyte differentiation	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0048844 artery morphogenesis	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0050768 negative regulation of neurogenesis	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0051087 protein-folding chaperone binding	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0060253 negative regulation of glial cell proliferation	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0060412 ventricular septum morphogenesis	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0060675 ureteric bud morphogenesis	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0060716 labyrinthine layer blood vessel development	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0061626 pharyngeal arch artery morphogenesis	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0065003 protein-containing complex assembly	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0070888 E-box binding	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0071347 cellular response to interleukin-1	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0071356 cellular response to tumor necrosis factor	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0071398 cellular response to fatty acid	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0071820 N-box binding	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:0072012 glomerulus vasculature development	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0072049 comma-shaped body morphogenesis	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0072050 S-shaped body morphogenesis	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0072141 renal interstitial fibroblast development	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0072282 metanephric nephron tubule morphogenesis	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0090281 negative regulation of calcium ion import	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0097066 response to thyroid hormone	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0097084 vascular associated smooth muscle cell development	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0097150 neuronal stem cell population maintenance	IEA GO_REF:0000120	PENDING	Summary: TODO: Review this GOA annotation
GO:1904010 response to Aroclor 1254	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:1990090 cellular response to nerve growth factor stimulus	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:2000978 negative regulation of forebrain neuron differentiation	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:2000981 negative regulation of inner ear receptor cell differentiation	IEA GO_REF:0000107	PENDING	Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm	IDA GO_REF:0000052	PENDING	Summary: TODO: Review this GOA annotation
GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:1990837 sequence-specific double-stranded DNA binding	IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:28473536 Impact of cytosine methylation on DNA binding specificities of human transcription factors.
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0070888 E-box binding	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0071820 N-box binding	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0061626 pharyngeal arch artery morphogenesis	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0003143 embryonic heart tube morphogenesis	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0035910 ascending aorta morphogenesis	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0045977 positive regulation of mitotic cell cycle, embryonic	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0060412 ventricular septum morphogenesis	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:2000978 negative regulation of forebrain neuron differentiation	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0097150 neuronal stem cell population maintenance	IEP PMID:19682396 Notch signaling is required for maintaining stem-cell featur...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:19682396 Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells.
GO:0007219 Notch signaling pathway	IMP PMID:19682396 Notch signaling is required for maintaining stem-cell featur...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:19682396 Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells.
GO:0021861 forebrain radial glial cell differentiation	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0042531 positive regulation of tyrosine phosphorylation of STAT protein	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0043388 positive regulation of DNA binding	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0043565 sequence-specific DNA binding	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0046425 regulation of receptor signaling pathway via JAK-STAT	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0065003 protein-containing complex assembly	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:2000737 negative regulation of stem cell differentiation	IMP PMID:19682396 Notch signaling is required for maintaining stem-cell featur...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:19682396 Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells.
GO:2000974 negative regulation of pro-B cell differentiation	IMP PMID:12032823 Overexpression of the Notch target genes Hes in vivo induces...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:12032823 Overexpression of the Notch target genes Hes in vivo induces lymphoid and myeloid alterations.
GO:0042803 protein homodimerization activity	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0000122 negative regulation of transcription by RNA polymerase II	IDA PMID:12032823 Overexpression of the Notch target genes Hes in vivo induces...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:12032823 Overexpression of the Notch target genes Hes in vivo induces lymphoid and myeloid alterations.
GO:0005634 nucleus	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0048711 positive regulation of astrocyte differentiation	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0048715 negative regulation of oligodendrocyte differentiation	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0060253 negative regulation of glial cell proliferation	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0003151 outflow tract morphogenesis	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0003281 ventricular septum development	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0008284 positive regulation of cell population proliferation	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0045944 positive regulation of transcription by RNA polymerase II	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0048538 thymus development	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0048844 artery morphogenesis	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0097084 vascular associated smooth muscle cell development	ISS GO_REF:0000024	PENDING	Summary: TODO: Review this GOA annotation
GO:0000122 negative regulation of transcription by RNA polymerase II	IDA PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH re...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression.
GO:0042826 histone deacetylase binding	IPI PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH re...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression.
GO:0045892 negative regulation of DNA-templated transcription	IDA PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH re...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:12535671 Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression.
GO:0007219 Notch signaling pathway	IDA PMID:16160079 Conservation of the Notch1 signaling pathway in gastrointest...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:16160079 Conservation of the Notch1 signaling pathway in gastrointestinal carcinoid cells.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-2220979	PENDING	Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8878243	PENDING	Summary: TODO: Review this GOA annotation
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9013711	PENDING	Summary: TODO: Review this GOA annotation
GO:0003677 DNA binding	TAS PMID:7906273 Structure, chromosomal locus, and promoter analysis of the g...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:7906273 Structure, chromosomal locus, and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-1.
GO:0007399 nervous system development	TAS PMID:8020957 Genomic cloning and chromosomal localization of HRY, the hum...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:8020957 Genomic cloning and chromosomal localization of HRY, the human homolog to the Drosophila segmentation gene, hairy.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:12032823

Overexpression of the Notch target genes Hes in vivo induces lymphoid and myeloid alterations.

PMID:12535671

Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression.

PMID:16160079

Conservation of the Notch1 signaling pathway in gastrointestinal carcinoid cells.

PMID:19682396

Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells.

PMID:28473536

Impact of cytosine methylation on DNA binding specificities of human transcription factors.

PMID:7906273

Structure, chromosomal locus, and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-1. Negative autoregulation through the multiple N box elements.

PMID:8020957

Genomic cloning and chromosomal localization of HRY, the human homolog to the Drosophila segmentation gene, hairy.

Reactome:R-HSA-2220979

NOTCH1 PEST domain mutants stimulate HES1 transcription

Reactome:R-HSA-8878243

HES1 gene transcription is inhibited by RUNX3

Reactome:R-HSA-9013711

HES1 gene expression is stimulated by NOTCH4

file:human/HES1/HES1-deep-research-falcon.md

Deep research report on HES1

📚 Additional Documentation

Deep Research Falcon

(HES1-deep-research-falcon.md)

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gene_id: HES1
gene_symbol: HES1
uniprot_accession: Q14469
protein_description: 'RecName: Full=Transcription factor HES-1; AltName: Full=Class
B basic helix-loop-helix protein 39; Short=bHLHb39; AltName: Full=Hairy and enhancer
of split 1; AltName: Full=Hairy homolog; AltName: Full=Hairy-like protein; Short=hHL;'
gene_info: Name=HES1; Synonyms=BHLHB39, HL, HRY;
organism_full: Homo sapiens (Human).
protein_family: Not specified in UniProt
protein_domains: bHLH_dom. (IPR011598); HES_HEY. (IPR050370); HLH_DNA-bd_sf. (IPR036638);
Orange_dom. (IPR003650); Hairy_orange (PF07527)
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q14469
Protein Description: RecName: Full=Transcription factor HES-1; AltName: Full=Class B basic helix-loop-helix protein 39; Short=bHLHb39; AltName: Full=Hairy and enhancer of split 1; AltName: Full=Hairy homolog; AltName: Full=Hairy-like protein; Short=hHL;
Gene Information: Name=HES1; Synonyms=BHLHB39, HL, HRY;
Organism (full): Homo sapiens (Human).
Protein Family: Not specified in UniProt
Key Domains: bHLH_dom. (IPR011598); HES_HEY. (IPR050370); HLH_DNA-bd_sf. (IPR036638); Orange_dom. (IPR003650); Hairy_orange (PF07527)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "HES1" matches the protein description above
Verify the organism is correct: Homo sapiens (Human).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'HES1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene HES1 (gene ID: HES1, UniProt: Q14469) in human.

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.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q14469
Protein Description: RecName: Full=Transcription factor HES-1; AltName: Full=Class B basic helix-loop-helix protein 39; Short=bHLHb39; AltName: Full=Hairy and enhancer of split 1; AltName: Full=Hairy homolog; AltName: Full=Hairy-like protein; Short=hHL;
Gene Information: Name=HES1; Synonyms=BHLHB39, HL, HRY;
Organism (full): Homo sapiens (Human).
Protein Family: Not specified in UniProt
Key Domains: bHLH_dom. (IPR011598); HES_HEY. (IPR050370); HLH_DNA-bd_sf. (IPR036638); Orange_dom. (IPR003650); Hairy_orange (PF07527)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "HES1" matches the protein description above
Verify the organism is correct: Homo sapiens (Human).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene HES1 (gene ID: HES1, UniProt: Q14469) in human.

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.

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.

Comprehensive Research Report: Human HES1 (UniProt: Q14469)

Executive verification of target identity
- Gene/protein: HES1 (Hairy and enhancer of split-1), a basic helix-loop-helix (bHLH) transcription factor in human. Protein architecture includes an N‑terminal bHLH domain (basic DNA-binding region plus HLH dimerization), a central Orange domain (partner selectivity), and a C‑terminal WRPW tetrapeptide that recruits TLE/Groucho corepressors; length ≈280 amino acids (~29.4 kDa) (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624, July 2025) (zhang2025hes1inmalignant pages 1-2).
- Organism: Homo sapiens. All evidence below is consistent with human HES1 or directly relevant conserved mechanisms.

1) Key concepts and definitions
- Molecular function and DNA recognition: HES1 is a transcriptional repressor that binds DNA as homo- or heterodimers, preferring N‑box (CACNAG) and class C (CACGCG) motifs. The WRPW motif engages TLE/Groucho family corepressors, enabling chromatin repression, frequently with HDACs. HES1 can also recruit SIRT1 for TLE-independent deacetylation and can inhibit transcription elongation by attenuating P‑TEFb/Pol II Ser2 phosphorylation (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 2-4, zhang2025hes1inmalignant pages 1-2).
- Mechanism of Notch-dependent activation: Canonical Notch ligand binding triggers ADAM/γ‑secretase cleavage of the receptor, releasing NICD, which translocates to the nucleus and binds CSL, recruiting MAML co-activators to activate hes1 transcription (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 4-5, zhang2025hes1inmalignant pages 2-4).
- Core features as an oscillator: HES1 binds its own promoter to generate negative feedback and ultradian oscillations. These dynamics coordinate progenitor maintenance and differentiation programs in development (reviewed; primary dynamics summarized below) (https://doi.org/10.1101/2024.03.30.586691) (zhang2025hes1inmalignant pages 4-5, azhar2024unravellingdifferentialhes1 pages 1-4).
- Subcellular localization: HES1 functions as a nuclear DNA-binding transcriptional repressor; its regulatory roles and domain architecture are defined in the context of nuclear transcription (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 2-4, zhang2025hes1inmalignant pages 1-2).

2) Recent developments and latest research (2023–2024 priority)
- Intestinal homeostasis via HES1 oscillation periods (2024): Using a Hes1-Achilles knock-in reporter with intravital imaging/organoids, NOTCH-driven HES1 oscillations were shown to pattern fate decisions along the crypt–villus axis. Oscillation period encodes fate: ~90-minute oscillations promote Paneth cells; ~130-minute oscillations bias other secretory subtypes; low-period oscillations support stemness and proliferation (preprint, Aug 2024) (https://doi.org/10.1101/2024.08.26.609553) (weterings2024notchdrivenoscillationscontrol pages 1-5).
- Differential HES1 dynamics during axis elongation (2024): Single-cell tracking of an endogenously tagged Hes1 reporter in mouse embryos showed synchronized, high-amplitude oscillations in presomitic mesoderm (PSM) versus low-amplitude oscillations in the preneural tube (pre‑NT); Notch inhibition perturbed dynamics in tissue-specific ways (preprint, Apr 2024) (https://doi.org/10.1101/2024.03.30.586691) (azhar2024unravellingdifferentialhes1 pages 1-4).
- Immuno-oncology (2024): Myeloid cell–specific deletion of Hes1 in tumor-associated macrophages (TAMs) reduced tumor growth, lowered Arg1 (a T‑cell-suppressive enzyme), increased intratumoral cytotoxic T‑cell infiltration/activation, and enhanced response to anti‑PD‑1 therapy in vivo (Dec 2024) (https://doi.org/10.1186/s40164-024-00588-2) (kim2024disruptingnotchsignaling pages 1-2).
- Post-translational crosstalk via HEY1–HES1 heterodimerization and SUMOylation (2024): In endothelium, HEY1 SUMOylation by TRIM28 promotes HEY1 homodimers with high‑fidelity E‑box binding and repression of angiogenic RTK programs. DeSUMOylation (e.g., by VEGF/hypoxia) favors HEY1–HES1 heterodimerization, shifts DNA motif preference, weakens DNA binding, and relieves repression—demonstrating functional interplay with HES1 (Jan 2024) (https://doi.org/10.1161/CIRCRESAHA.123.323398) (ren2024sumoylationfinetunesendothelial pages 1-3, ren2024sumoylationfinetunesendothelial pages 13-15).

3) Function, processes, localization, and pathways
- Transcriptional repression and co-repressors: HES1 represses target genes by (i) N‑box/class C motif binding as dimers; (ii) recruiting TLE/Groucho co-repressors via WRPW (often with HDACs); (iii) TLE-independent SIRT1 recruitment; and (iv) interfering with elongation (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 2-4, zhang2025hes1inmalignant pages 1-2).
- Pathway position: HES1 is a canonical downstream effector of NOTCH signaling (NICD–CSL–MAML → HES1 transcription). It integrates inputs from other pathways (e.g., Hedgehog/Gli, Wnt/β‑catenin, ERK/AKT), underscoring crosstalk at the level of hes1 promoter activation and target gene networks (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 4-5, zhang2025hes1inmalignant pages 2-4).
- Developmental dynamics and roles:
- Intestine: HES1 oscillation periods encode lineage bias and maintain the absorptive–secretory balance; NOTCH activation suppresses secretory differentiation, while loss of HES1 skews toward secretory lineages (Aug 2024 preprint) (https://doi.org/10.1101/2024.08.26.609553) (weterings2024notchdrivenoscillationscontrol pages 1-5).
- Somite segmentation and neurogenesis: HES1/Hes-family oscillators coordinate segmentation clock and neurogenic timing; tissue-specific dynamics revealed by single-cell live imaging (Apr 2024 preprint) (https://doi.org/10.1101/2024.03.30.586691) (azhar2024unravellingdifferentialhes1 pages 1-4), and reviewed (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 4-5).
- Nuclear site of action: HES1 functions as a nuclear transcriptional repressor (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 1-2, zhang2025hes1inmalignant pages 2-4).

4) Expert opinions and analysis from authoritative sources
- Comprehensive mechanistic review (2025): A state-of-the-art review synthesizes HES1 structure (bHLH/Orange/WRPW), repression mechanisms (TLE/Groucho via WRPW; SIRT1; elongation control), oscillatory regulation, pathway crosstalk (JAK/STAT, PI3K/AKT/mTOR, Wnt/β‑catenin), developmental roles, and oncologic relevance, while emphasizing the need for large-sample validation of HES1 as an independent biomarker and integrated multi-omics to resolve tumor/immune functions (Frontiers in Immunology, July 2025) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 1-2, zhang2025hes1inmalignant pages 15-16).
- Preclinical immuno-oncology insight (2024): Targeting HES1 in myeloid compartments (TAMs) reprograms the TME and augments checkpoint blockade, supporting HES1 as an immunomodulatory node downstream of NOTCH (Experimental Hematology & Oncology, Dec 2024) (https://doi.org/10.1186/s40164-024-00588-2) (kim2024disruptingnotchsignaling pages 1-2).
- Vascular signaling plasticity (2024): Endothelial HEY1 SUMOylation and context-dependent HEY1–HES1 heterodimerization reveal a dynamic post-translational layer integrating angiogenic stimuli with NOTCH effector function (Circulation Research, Jan 2024) (https://doi.org/10.1161/CIRCRESAHA.123.323398) (ren2024sumoylationfinetunesendothelial pages 1-3, ren2024sumoylationfinetunesendothelial pages 13-15).

5) Relevant statistics and data from recent studies
- Intestinal oscillation periods: In vivo/in vitro analyses mapped distinct HES1 periods associated with fate bias—~90 min promoting Paneth cells; ~130 min increasing other secretory subtypes; shorter periods supporting stemness/proliferation (preprint, 2024) (https://doi.org/10.1101/2024.08.26.609553) (weterings2024notchdrivenoscillationscontrol pages 1-5).
- TAM-targeted Hes1 deletion: Conditional Hes1 KO in TAMs led to decreased tumor growth and increased cytotoxic T-cell infiltration/activity; Arg1 levels were reduced, alleviating T-cell suppression; combination with anti‑PD‑1 further enhanced tumor growth inhibition (peer-reviewed, 2024). While the study reports robust effects, quantitative magnitudes are model-specific and not detailed in the excerpt here (https://doi.org/10.1186/s40164-024-00588-2) (kim2024disruptingnotchsignaling pages 1-2).

Mechanistic details: domains, motifs, and repression
- Domains: bHLH (basic DNA binding; HLH dimerization), Orange (partner selection/protein–protein interactions), WRPW (TLE/Groucho recruitment) (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 1-2).
- DNA motifs: HES-family proteins preferentially bind N‑box (CACNAG) and class C (CACGCG) motifs; HES1 autorepresses via N‑box elements in its promoter (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 1-2, zhang2025hes1inmalignant pages 15-16).
- Co-repressors and chromatin: WRPW engages TLE/Groucho and HDACs; HES1 can recruit SIRT1 for TLE-independent repression; HES1 can also limit P‑TEFb–dependent transcription elongation (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 2-4, zhang2025hes1inmalignant pages 1-2).

Network position and crosstalk
- Canonical NOTCH effector: NICD–CSL–MAML activation of hes1 transcription is a defining regulatory step (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 4-5, zhang2025hes1inmalignant pages 2-4).
- Crosstalk: HES1 can bind STAT3 and facilitate its phosphorylation via JAK2, illustrating Notch–JAK/STAT axis integration (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 2-4, zhang2025hes1inmalignant pages 15-16).

Applications and real-world implementations
- Immuno-oncology: Myeloid (TAM) HES1 targeting improves the tumor microenvironment and synergizes with PD‑1 blockade in vivo, nominating HES1 for compartment-specific therapeutic strategies (https://doi.org/10.1186/s40164-024-00588-2, 2024) (kim2024disruptingnotchsignaling pages 1-2).
- Angiogenesis and vascular remodeling: Endothelial NOTCH effectors (HEY1 and HES1) are post-translationally tuned; modulating SUMO pathways (e.g., TRIM28–SENP) alters HEY1/HES1 dimer states and angiogenic gene repression, suggesting actionable axes impacting tumor/ischemic angiogenesis (https://doi.org/10.1161/CIRCRESAHA.123.323398, 2024) (ren2024sumoylationfinetunesendothelial pages 1-3, ren2024sumoylationfinetunesendothelial pages 13-15).
- NOTCH pathway therapeutics and HES1 as readout: Reviews consolidate that γ‑secretase inhibitors (GSIs) and ligand/receptor-directed biologics regulate canonical NOTCH outputs including HES1; preclinical/clinical programs often monitor HES1 as a pharmacodynamic marker of NOTCH blockade or activation in diverse cancers (reviewed synthesis) (https://doi.org/10.3389/fimmu.2025.1585624, 2025) (zhang2025hes1inmalignant pages 15-16, zhang2025hes1inmalignant pages 1-2). Note: Specific trial-level statistics are context‑ and agent‑dependent and not detailed in the accessible excerpts here.

Limitations and open questions
- While HES1 expression correlates with malignant progression and therapy resistance across contexts, its value as an independent biomarker requires large-sample clinical validation (reviewed) (https://doi.org/10.3389/fimmu.2025.1585624) (zhang2025hes1inmalignant pages 15-16).
- Tissue- and context-specific oscillation decoding: Emerging work shows that HES1 dynamics rather than static levels encode fate; translation into clinical biomarkers or interventions needs further study (https://doi.org/10.1101/2024.08.26.609553, 2024; https://doi.org/10.1101/2024.03.30.586691, 2024) (weterings2024notchdrivenoscillationscontrol pages 1-5, azhar2024unravellingdifferentialhes1 pages 1-4).

Conclusions
Human HES1 (Q14469) is a nuclear bHLH/Orange/WRPW transcriptional repressor and canonical NOTCH effector that binds N‑box/class C motifs and recruits Groucho/TLE through WRPW to silence targets. HES1 generates self‑organized oscillations that regulate developmental fate choices in the intestine, segmentation clock, and neurogenesis. Recent advances (2023–2024) highlight (i) period‑specific intestinal oscillations encoding fate, (ii) tissue‑specific embryonic dynamics, (iii) immuno‑oncology efficacy by ablating HES1 in TAMs, and (iv) endothelial SUMOylation-switches that alter HEY1–HES1 dimer usage and angiogenic repression. HES1 remains a central readout and mediator of NOTCH pathway therapeutics and a promising node for targeted manipulation, with further clinical validation and quantitative pharmacodynamic frameworks needed for biomarker deployment (zhang2025hes1inmalignant pages 1-2, weterings2024notchdrivenoscillationscontrol pages 1-5, azhar2024unravellingdifferentialhes1 pages 1-4, kim2024disruptingnotchsignaling pages 1-2, ren2024sumoylationfinetunesendothelial pages 1-3).

Cited sources (URLs and dates)
- Zhang et al., Hes1 in malignant tumors: from molecular mechanism to therapeutic potential. Frontiers in Immunology. 2025-07. URL: https://doi.org/10.3389/fimmu.2025.1585624 (zhang2025hes1inmalignant pages 1-2, zhang2025hes1inmalignant pages 4-5, zhang2025hes1inmalignant pages 15-16, zhang2025hes1inmalignant pages 2-4).
- Weterings et al., NOTCH-driven oscillations control cell fate decisions during intestinal homeostasis. bioRxiv. 2024-08-26. URL: https://doi.org/10.1101/2024.08.26.609553 (weterings2024notchdrivenoscillationscontrol pages 1-5).
- el Azhar et al., Unravelling differential Hes1 dynamics during axis elongation of mouse embryos through single-cell tracking. bioRxiv. 2024-04-01. URL: https://doi.org/10.1101/2024.03.30.586691 (azhar2024unravellingdifferentialhes1 pages 1-4).
- Kim et al., Disrupting Notch signaling related HES1 in myeloid cells reinvigorates antitumor T cell responses. Experimental Hematology & Oncology. 2024-12. URL: https://doi.org/10.1186/s40164-024-00588-2 (kim2024disruptingnotchsignaling pages 1-2).
- Ren et al., SUMOylation Fine-Tunes Endothelial HEY1 in the Regulation of Angiogenesis. Circulation Research. 2024-01. URL: https://doi.org/10.1161/CIRCRESAHA.123.323398 (ren2024sumoylationfinetunesendothelial pages 1-3, ren2024sumoylationfinetunesendothelial pages 13-15).

References

(zhang2025hes1inmalignant pages 1-2): Liping Zhang, Qian Zhang, Cheng Guo, Zixin Ru, Zetian Yang, Yi Geng, Junjie Yang, Daigui Zhang, Zhenhuai Yang, and Shuicai Huang. Hes1 in malignant tumors: from molecular mechanism to therapeutic potential. Frontiers in Immunology, Jul 2025. URL: https://doi.org/10.3389/fimmu.2025.1585624, doi:10.3389/fimmu.2025.1585624. This article has 2 citations and is from a peer-reviewed journal.
(zhang2025hes1inmalignant pages 2-4): Liping Zhang, Qian Zhang, Cheng Guo, Zixin Ru, Zetian Yang, Yi Geng, Junjie Yang, Daigui Zhang, Zhenhuai Yang, and Shuicai Huang. Hes1 in malignant tumors: from molecular mechanism to therapeutic potential. Frontiers in Immunology, Jul 2025. URL: https://doi.org/10.3389/fimmu.2025.1585624, doi:10.3389/fimmu.2025.1585624. This article has 2 citations and is from a peer-reviewed journal.
(zhang2025hes1inmalignant pages 4-5): Liping Zhang, Qian Zhang, Cheng Guo, Zixin Ru, Zetian Yang, Yi Geng, Junjie Yang, Daigui Zhang, Zhenhuai Yang, and Shuicai Huang. Hes1 in malignant tumors: from molecular mechanism to therapeutic potential. Frontiers in Immunology, Jul 2025. URL: https://doi.org/10.3389/fimmu.2025.1585624, doi:10.3389/fimmu.2025.1585624. This article has 2 citations and is from a peer-reviewed journal.
(azhar2024unravellingdifferentialhes1 pages 1-4): Yasmine el Azhar, Pascal Schulthess, Marek J. van Oostrom, Wilke H.M. Meijer, Wouter M. Thomas, Marianne Bauer, and Katharina F. Sonnen. Unravelling differential hes1 dynamics during axis elongation of mouse embryos through single-cell tracking. bioRxiv, Apr 2024. URL: https://doi.org/10.1101/2024.03.30.586691, doi:10.1101/2024.03.30.586691. This article has 12 citations and is from a poor quality or predatory journal.
(weterings2024notchdrivenoscillationscontrol pages 1-5): Sonja D. C. Weterings, Hiromune Eto, Jan-Daniël de Leede, Amir Giladi, Mirjam E. Hoekstra, Wouter F. Beijk, Esther J. M. Liefting, Karen B. van den Anker, Jacco van Rheenen, Alexander van Oudenaarden, and Katharina F. Sonnen. Notch-driven oscillations control cell fate decisions during intestinal homeostasis. bioRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.08.26.609553, doi:10.1101/2024.08.26.609553. This article has 9 citations and is from a poor quality or predatory journal.
(kim2024disruptingnotchsignaling pages 1-2): Myung Sup Kim, Hyeokgu Kang, Jung-Hwan Baek, Moon-Gyu Cho, Eun Joo Chung, Seok-Jun Kim, Joon-Yong Chung, and Kyung-Hee Chun. Disrupting notch signaling related hes1 in myeloid cells reinvigorates antitumor t cell responses. Experimental Hematology & Oncology, Dec 2024. URL: https://doi.org/10.1186/s40164-024-00588-2, doi:10.1186/s40164-024-00588-2. This article has 7 citations and is from a peer-reviewed journal.
(ren2024sumoylationfinetunesendothelial pages 1-3): Ruizhe Ren, Sha Ding, Kefan Ma, Yuanqing Jiang, Yiran Wang, Junbo Chen, Yunyun Wang, Yaohui Kou, Xiao Fan, Xiaolong Zhu, Lingfeng Qin, Cong Qiu, Michael Simons, Xiyang Wei, and Luyang Yu. Sumoylation fine-tunes endothelial hey1 in the regulation of angiogenesis. Circulation Research, 134:203-222, Jan 2024. URL: https://doi.org/10.1161/circresaha.123.323398, doi:10.1161/circresaha.123.323398. This article has 18 citations and is from a highest quality peer-reviewed journal.
(ren2024sumoylationfinetunesendothelial pages 13-15): Ruizhe Ren, Sha Ding, Kefan Ma, Yuanqing Jiang, Yiran Wang, Junbo Chen, Yunyun Wang, Yaohui Kou, Xiao Fan, Xiaolong Zhu, Lingfeng Qin, Cong Qiu, Michael Simons, Xiyang Wei, and Luyang Yu. Sumoylation fine-tunes endothelial hey1 in the regulation of angiogenesis. Circulation Research, 134:203-222, Jan 2024. URL: https://doi.org/10.1161/circresaha.123.323398, doi:10.1161/circresaha.123.323398. This article has 18 citations and is from a highest quality peer-reviewed journal.
(zhang2025hes1inmalignant pages 15-16): Liping Zhang, Qian Zhang, Cheng Guo, Zixin Ru, Zetian Yang, Yi Geng, Junjie Yang, Daigui Zhang, Zhenhuai Yang, and Shuicai Huang. Hes1 in malignant tumors: from molecular mechanism to therapeutic potential. Frontiers in Immunology, Jul 2025. URL: https://doi.org/10.3389/fimmu.2025.1585624, doi:10.3389/fimmu.2025.1585624. This article has 2 citations and is from a peer-reviewed journal.

Citations

weterings2024notchdrivenoscillationscontrol pages 1-5
kim2024disruptingnotchsignaling pages 1-2
ren2024sumoylationfinetunesendothelial pages 1-3
ren2024sumoylationfinetunesendothelial pages 13-15
https://doi.org/10.3389/fimmu.2025.1585624,
https://doi.org/10.3389/fimmu.2025.1585624
https://doi.org/10.1101/2024.03.30.586691
https://doi.org/10.1101/2024.08.26.609553
https://doi.org/10.1186/s40164-024-00588-2
https://doi.org/10.1161/CIRCRESAHA.123.323398
https://doi.org/10.1186/s40164-024-00588-2,
https://doi.org/10.1161/CIRCRESAHA.123.323398,
https://doi.org/10.1101/2024.08.26.609553,
https://doi.org/10.1101/2024.03.30.586691,
https://doi.org/10.1161/circresaha.123.323398,

📄 View Raw YAML

id: Q14469
gene_symbol: HES1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: HES1 (Hairy and Enhancer of Split 1) is a Class B bHLH 
  transcriptional REPRESSOR that maintains neural progenitor cells by blocking 
  neuronal differentiation. It is a direct target gene of Notch signaling (via 
  RBPJ/CSL binding to the HES1 promoter). HES1 represses proneural genes (ASCL1,
  NEUROG1, NEUROG2) by binding to N-box (CACNAG) and E-box (CANNTG) elements and
  recruiting TLE/Groucho corepressors via its C-terminal WRPW motif. HES1 
  expression oscillates with ~2-hour periodicity due to negative autoregulation,
  and this oscillation is important for proper cell fate decisions. In neural 
  development, HES1 is essential for maintaining the neural stem cell pool and 
  preventing premature neuronal differentiation.
existing_annotations:
  - term:
      id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: file:human/HES1/HES1-deep-research-falcon.md
          supporting_text: 'model: Edison Scientific Literature'
  - term:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0007219
      label: Notch signaling pathway
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0009952
      label: anterior/posterior pattern specification
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0045665
      label: negative regulation of neuron differentiation
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0050767
      label: regulation of neurogenesis
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0070888
      label: E-box binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0071820
      label: N-box binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0003677
      label: DNA binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0006355
      label: regulation of DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0046983
      label: protein dimerization activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:12535671
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:12535671
          supporting_text: Human Sir2-related protein SIRT1 associates with the 
            bHLH repressors HES1 and HEY2 and is involved in HES1- and 
            HEY2-mediated transcriptional repression.
  - term:
      id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0000785
      label: chromatin
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0000981
      label: DNA-binding transcription factor activity, RNA polymerase 
        II-specific
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0001217
      label: DNA-binding transcription repressor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0001222
      label: transcription corepressor binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0001227
      label: DNA-binding transcription repressor activity, RNA polymerase 
        II-specific
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0003143
      label: embryonic heart tube morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0003281
      label: ventricular septum development
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0003682
      label: chromatin binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0008432
      label: JUN kinase binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0010628
      label: positive regulation of gene expression
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0010629
      label: negative regulation of gene expression
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0010977
      label: negative regulation of neuron projection development
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0016363
      label: nuclear matrix
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0021861
      label: forebrain radial glial cell differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0030182
      label: neuron differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0032991
      label: protein-containing complex
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0035315
      label: hair cell differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0035909
      label: aorta morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0035910
      label: ascending aorta morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0042802
      label: identical protein binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0042803
      label: protein homodimerization activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0043254
      label: regulation of protein-containing complex assembly
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0043279
      label: response to alkaloid
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0043398
      label: HLH domain binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0043565
      label: sequence-specific DNA binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0044877
      label: protein-containing complex binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0045687
      label: positive regulation of glial cell differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0045747
      label: positive regulation of Notch signaling pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0045892
      label: negative regulation of DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0045893
      label: positive regulation of DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0045977
      label: positive regulation of mitotic cell cycle, embryonic
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0046425
      label: regulation of receptor signaling pathway via JAK-STAT
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0046427
      label: positive regulation of receptor signaling pathway via JAK-STAT
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0048538
      label: thymus development
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0048711
      label: positive regulation of astrocyte differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0048715
      label: negative regulation of oligodendrocyte differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0048844
      label: artery morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0050768
      label: negative regulation of neurogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0051087
      label: protein-folding chaperone binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0060253
      label: negative regulation of glial cell proliferation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0060412
      label: ventricular septum morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0060675
      label: ureteric bud morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0060716
      label: labyrinthine layer blood vessel development
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0061626
      label: pharyngeal arch artery morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0061629
      label: RNA polymerase II-specific DNA-binding transcription factor binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0065003
      label: protein-containing complex assembly
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0070888
      label: E-box binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0071347
      label: cellular response to interleukin-1
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0071356
      label: cellular response to tumor necrosis factor
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0071398
      label: cellular response to fatty acid
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0071820
      label: N-box binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0072012
      label: glomerulus vasculature development
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0072049
      label: comma-shaped body morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0072050
      label: S-shaped body morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0072141
      label: renal interstitial fibroblast development
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0072282
      label: metanephric nephron tubule morphogenesis
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0090281
      label: negative regulation of calcium ion import
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0097066
      label: response to thyroid hormone
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0097084
      label: vascular associated smooth muscle cell development
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0097150
      label: neuronal stem cell population maintenance
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:1904010
      label: response to Aroclor 1254
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:1990090
      label: cellular response to nerve growth factor stimulus
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:2000978
      label: negative regulation of forebrain neuron differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:2000981
      label: negative regulation of inner ear receptor cell differentiation
    evidence_type: IEA
    original_reference_id: GO_REF:0000107
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: IDA
    original_reference_id: GO_REF:0000052
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0001227
      label: DNA-binding transcription repressor activity, RNA polymerase 
        II-specific
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:1990837
      label: sequence-specific double-stranded DNA binding
    evidence_type: IDA
    original_reference_id: PMID:28473536
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:28473536
          supporting_text: Impact of cytosine methylation on DNA binding 
            specificities of human transcription factors.
  - term:
      id: GO:0061629
      label: RNA polymerase II-specific DNA-binding transcription factor binding
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0070888
      label: E-box binding
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0071820
      label: N-box binding
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0061626
      label: pharyngeal arch artery morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0003143
      label: embryonic heart tube morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0035910
      label: ascending aorta morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0045977
      label: positive regulation of mitotic cell cycle, embryonic
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0060412
      label: ventricular septum morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:2000978
      label: negative regulation of forebrain neuron differentiation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0097150
      label: neuronal stem cell population maintenance
    evidence_type: IEP
    original_reference_id: PMID:19682396
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:19682396
          supporting_text: Notch signaling is required for maintaining stem-cell
            features of neuroprogenitor cells derived from human embryonic stem 
            cells.
  - term:
      id: GO:0007219
      label: Notch signaling pathway
    evidence_type: IMP
    original_reference_id: PMID:19682396
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:19682396
          supporting_text: Notch signaling is required for maintaining stem-cell
            features of neuroprogenitor cells derived from human embryonic stem 
            cells.
  - term:
      id: GO:0021861
      label: forebrain radial glial cell differentiation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0042531
      label: positive regulation of tyrosine phosphorylation of STAT protein
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0043388
      label: positive regulation of DNA binding
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0043565
      label: sequence-specific DNA binding
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0046425
      label: regulation of receptor signaling pathway via JAK-STAT
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0046427
      label: positive regulation of receptor signaling pathway via JAK-STAT
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0065003
      label: protein-containing complex assembly
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:2000737
      label: negative regulation of stem cell differentiation
    evidence_type: IMP
    original_reference_id: PMID:19682396
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:19682396
          supporting_text: Notch signaling is required for maintaining stem-cell
            features of neuroprogenitor cells derived from human embryonic stem 
            cells.
  - term:
      id: GO:2000974
      label: negative regulation of pro-B cell differentiation
    evidence_type: IMP
    original_reference_id: PMID:12032823
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:12032823
          supporting_text: Overexpression of the Notch target genes Hes in vivo 
            induces lymphoid and myeloid alterations.
  - term:
      id: GO:0042803
      label: protein homodimerization activity
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    evidence_type: IDA
    original_reference_id: PMID:12032823
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:12032823
          supporting_text: Overexpression of the Notch target genes Hes in vivo 
            induces lymphoid and myeloid alterations.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0048711
      label: positive regulation of astrocyte differentiation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0048715
      label: negative regulation of oligodendrocyte differentiation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0060253
      label: negative regulation of glial cell proliferation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0003151
      label: outflow tract morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0003281
      label: ventricular septum development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0008284
      label: positive regulation of cell population proliferation
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0048538
      label: thymus development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0048844
      label: artery morphogenesis
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0097084
      label: vascular associated smooth muscle cell development
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    evidence_type: IDA
    original_reference_id: PMID:12535671
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:12535671
          supporting_text: Human Sir2-related protein SIRT1 associates with the 
            bHLH repressors HES1 and HEY2 and is involved in HES1- and 
            HEY2-mediated transcriptional repression.
  - term:
      id: GO:0042826
      label: histone deacetylase binding
    evidence_type: IPI
    original_reference_id: PMID:12535671
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:12535671
          supporting_text: Human Sir2-related protein SIRT1 associates with the 
            bHLH repressors HES1 and HEY2 and is involved in HES1- and 
            HEY2-mediated transcriptional repression.
  - term:
      id: GO:0045892
      label: negative regulation of DNA-templated transcription
    evidence_type: IDA
    original_reference_id: PMID:12535671
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:12535671
          supporting_text: Human Sir2-related protein SIRT1 associates with the 
            bHLH repressors HES1 and HEY2 and is involved in HES1- and 
            HEY2-mediated transcriptional repression.
  - term:
      id: GO:0007219
      label: Notch signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:16160079
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:16160079
          supporting_text: Conservation of the Notch1 signaling pathway in 
            gastrointestinal carcinoid cells.
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-2220979
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8878243
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005654
      label: nucleoplasm
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9013711
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0003677
      label: DNA binding
    evidence_type: TAS
    original_reference_id: PMID:7906273
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:7906273
          supporting_text: Structure, chromosomal locus, and promoter analysis 
            of the gene encoding the mouse helix-loop-helix factor HES-1.
  - term:
      id: GO:0007399
      label: nervous system development
    evidence_type: TAS
    original_reference_id: PMID:8020957
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:8020957
          supporting_text: Genomic cloning and chromosomal localization of HRY, 
            the human homolog to the Drosophila segmentation gene, hairy.
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with
      GO terms
    findings: []
  - id: GO_REF:0000024
    title: Manual transfer of experimentally-verified manual GO annotation data 
      to orthologs by curator judgment of sequence similarity
    findings: []
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000052
    title: Gene Ontology annotation based on curation of immunofluorescence data
    findings: []
  - id: GO_REF:0000107
    title: Automatic transfer of experimentally verified manual GO annotation 
      data to orthologs using Ensembl Compara
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:12032823
    title: Overexpression of the Notch target genes Hes in vivo induces lymphoid
      and myeloid alterations.
    findings: []
  - id: PMID:12535671
    title: Human Sir2-related protein SIRT1 associates with the bHLH repressors 
      HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional 
      repression.
    findings: []
  - id: PMID:16160079
    title: Conservation of the Notch1 signaling pathway in gastrointestinal 
      carcinoid cells.
    findings: []
  - id: PMID:19682396
    title: Notch signaling is required for maintaining stem-cell features of 
      neuroprogenitor cells derived from human embryonic stem cells.
    findings: []
  - id: PMID:28473536
    title: Impact of cytosine methylation on DNA binding specificities of human 
      transcription factors.
    findings: []
  - id: PMID:7906273
    title: Structure, chromosomal locus, and promoter analysis of the gene 
      encoding the mouse helix-loop-helix factor HES-1. Negative autoregulation 
      through the multiple N box elements.
    findings: []
  - id: PMID:8020957
    title: Genomic cloning and chromosomal localization of HRY, the human 
      homolog to the Drosophila segmentation gene, hairy.
    findings: []
  - id: Reactome:R-HSA-2220979
    title: NOTCH1 PEST domain mutants stimulate HES1 transcription
    findings: []
  - id: Reactome:R-HSA-8878243
    title: HES1 gene transcription is inhibited by RUNX3
    findings: []
  - id: Reactome:R-HSA-9013711
    title: HES1 gene expression is stimulated by NOTCH4
    findings: []
  - id: file:human/HES1/HES1-deep-research-falcon.md
    title: Deep research report on HES1
    findings: []

HES1

Gene Description

Existing Annotations Review

References

📚 Additional Documentation

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Citations

📄 View Raw YAML