Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000781 chromosome, telomeric region	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: Telomeric-region localization is plausible but secondary to SAS3 catalytic and complex-level functions. Reason: Kept as non-core because SAS3 has reported chromatin-region associations, but this location term is peripheral compared with its core HAT activity in NuA3 complexes.
GO:0000785 chromatin	IBA GO_REF:0000033	ACCEPT	Summary: chromatin is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
GO:0003682 chromatin binding	IBA GO_REF:0000033	ACCEPT	Summary: chromatin binding is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
GO:0003712 transcription coregulator activity	IBA GO_REF:0000033	ACCEPT	Summary: transcription coregulator activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research documents physical/functional coupling of Sas3/NuA3 to the FACT elongation factor (Spt16), consistent with a transcription coregulator role. Supporting Evidence: file:yeast/SAS3/SAS3-deep-research-falcon.md Sas3 mediates NuA3 interaction with Spt16 (in vivo and in vitro), through an acidic C-terminal region; genetic interaction includes enhanced 6-azauracil (6-AU) sensitivity when SAS3 is disrupted in an spt16-truncation background.
GO:0004402 histone acetyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: histone acetyltransferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research confirms Sas3 is the MYST-family catalytic HAT subunit of NuA3 that acetylates histone H3 (primarily H3K14). Supporting Evidence: file:yeast/SAS3/SAS3-deep-research-falcon.md S. cerevisiae Sas3 is a MYST-family histone acetyltransferase (HAT) and the catalytic subunit of the NuA3 complex, which primarily acetylates histone H3 lysine 14 (H3K14) and is also associated with H3K23 acetylation in yeast chromatin.
GO:0005515 protein binding	IPI PMID:12077334 Yng1p modulates the activity of Sas3p as a component of the ...	REMOVE	Summary: Generic protein binding is not sufficiently informative for SAS3 curation. Reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515. Supporting Evidence: PMID:12077334 Yng1p modulates the activity of Sas3p as a component of the yeast NuA3 Hhistone acetyltransferase complex.
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: nucleus is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research places Sas3/NuA3 in the nucleus on chromatin, associating with transcribed gene bodies. Supporting Evidence: file:yeast/SAS3/SAS3-deep-research-falcon.md ChIP-on-chip mapping found Sas3 preferentially in the 5′ half of coding regions, supporting involvement in transcriptional elongation.
GO:0006325 chromatin organization	IEA GO_REF:0000043	ACCEPT	Summary: chromatin organization is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
GO:0006351 DNA-templated transcription	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: This process term is broader than the specific mechanistic role supported for SAS3. Reason: Marked as over-annotated to favor more specific SAS3 functions (histone acetyltransferase activity, NuA3 complex membership, and transcription-regulatory process terms).
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: regulation of DNA-templated transcription is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research supports a chromatin-context-sensitive transcriptional-regulatory role, with NuA3 reader modules targeting acetylation to active chromatin marks. Supporting Evidence: file:yeast/SAS3/SAS3-deep-research-falcon.md Reader modules: Yng1 PHD binds H3K4me3; Pdp3 PWWP binds H3K36me3; Taf14 YEATS binds acylated histone marks including H3K9ac/crotonylation; Taf14 ET binds EBMs in Yng1 and Sas3.
GO:0006357 regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: regulation of transcription by RNA polymerase II is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research supports a transcriptional-regulatory role, including antagonism of Rpd3S/Rpd3L HDACs to tune mRNA/lncRNA expression dynamics. Supporting Evidence: file:yeast/SAS3/SAS3-deep-research-falcon.md NuA3 antagonizes Rpd3S/Rpd3L to optimize mRNA and lncRNA expression dynamics; Sas3 disruption enhances 6-azauracil sensitivity in an Spt16-mutant background, consistent with elongation defects.
GO:0008270 zinc ion binding	IEA GO_REF:0000043	ACCEPT	Summary: zinc ion binding is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research and domain annotation document a Zf-MYST zinc-finger domain (IPR040706) characteristic of MYST-family HATs, consistent with zinc ion binding. Supporting Evidence: file:yeast/SAS3/SAS3-deep-research-falcon.md MYST_HAT. (IPR050603); WH-like_DNA-bd_sf. (IPR036388); Zf-MYST. (IPR040706)
GO:0016740 transferase activity	IEA GO_REF:0000043	ACCEPT	Summary: transferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
GO:0016746 acyltransferase activity	IEA GO_REF:0000043	ACCEPT	Summary: acyltransferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
GO:0030466 silent mating-type cassette heterochromatin formation	IMP PMID:11731479 The yeast SAS (something about silencing) protein complex co...	REMOVE	Summary: This silencing annotation rests on a misattributed reference. PMID:11731479 (Osada et al. 2001) is about the SAS-I silencing complex (Sas2p, Sas4p, Sas5p) and Sas2p-mediated silencing at HML and telomeres; SAS3 (Ybf2/Sas3) appears only within the MYST-family acronym expansion. The paper provides no SAS3-specific silencing evidence, and no other cited source supports a SAS3 role in mating-type silencing. Reason: Removed because the IMP annotation is misattributed. PMID:11731479 characterizes the SAS-I silencing complex (Sas2/Sas4/Sas5) and demonstrates that Sas2p (not Sas3p) mediates silencing at HML and telomeres; SAS3 appears only in the MYST acronym. SAS3/NuA3 is a euchromatic H3K14ac transcriptional coactivator with no independently supported role in silent mating-type cassette heterochromatin formation. Supporting Evidence: PMID:11731479 The something about silencing (Sas) 2 protein of Saccharomyces cerevisiae, a member of the MYST (MOZ, Ybf2/Sas3, Sas2, and TIP60) acetyltransferase family, promotes silencing at HML and telomeres. Here we identify a ~450-kD SAS complex containing Sas2p, Sas4p, and the tf2f-related Sas5 protein.
GO:0031507 heterochromatin formation	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: This process term is broader than the specific mechanistic role supported for SAS3. Reason: Marked as over-annotated to favor more specific SAS3 functions (histone acetyltransferase activity, NuA3 complex membership, and transcription-regulatory process terms).
GO:0031509 subtelomeric heterochromatin formation	IMP PMID:11731479 The yeast SAS (something about silencing) protein complex co...	REMOVE	Summary: This silencing annotation rests on a misattributed reference. PMID:11731479 (Osada et al. 2001) shows that Sas2p, via the SAS-I complex (Sas2p, Sas4p, Sas5p), promotes silencing at telomeres; the conserved acetyl-CoA binding motif mutated to demonstrate this is in Sas2p, not Sas3p. SAS3 (Ybf2/Sas3) appears only within the MYST-family acronym. The paper provides no SAS3-specific telomeric/subtelomeric silencing evidence, and no other cited source supports a SAS3 role here. Reason: Removed because the IMP annotation is misattributed. PMID:11731479 demonstrates telomeric silencing is mediated by Sas2p (acetyl-CoA-motif mutations in Sas2p, the SAS-I complex), not by Sas3p; SAS3 appears only in the MYST acronym. SAS3/NuA3 is a euchromatic H3K14ac transcriptional coactivator enriched in the 5' half of coding regions, with no independently supported role in subtelomeric heterochromatin formation. Supporting Evidence: PMID:11731479 Mutations in the conserved acetyl-CoA binding motif of Sas2p are shown to disrupt the ability of Sas2p to mediate the silencing at HML and telomeres, providing evidence for an important role for the acetyltransferase activity of the SAS complex in silencing.
GO:0033100 NuA3 histone acetyltransferase complex	IDA PMID:10817755 The something about silencing protein, Sas3, is the catalyti...	ACCEPT	Summary: NuA3 histone acetyltransferase complex is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research confirms Sas3 is the catalytic subunit required for both activity and integrity of the NuA3 complex. Supporting Evidence: PMID:10817755 The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex. file:yeast/SAS3/SAS3-deep-research-falcon.md Early purification identified Sas3 by peptide sequencing in a ~0.4–0.5 MDa NuA3 complex; loss of SAS3 abolishes NuA3 HAT activity and disrupts complex integrity.
GO:0046872 metal ion binding	IEA GO_REF:0000043	ACCEPT	Summary: metal ion binding is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
GO:0061733 protein-lysine-acetyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: protein-lysine-acetyltransferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research describes the acetyl-CoA-dependent transfer of an acetyl group to the epsilon-amino group of a lysine residue, the defining reaction of lysine acetyltransferases. Supporting Evidence: file:yeast/SAS3/SAS3-deep-research-falcon.md A HAT transfers an acetyl group from acetyl-CoA to the ε-amino group of a lysine residue on histones (a post-translational modification linked to chromatin accessibility and transcription).
GO:0070775 H3 histone acetyltransferase complex	IEA GO_REF:0000117	ACCEPT	Summary: H3 histone acetyltransferase complex is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
GO:1990467 NuA3a histone acetyltransferase complex	IBA GO_REF:0000033	ACCEPT	Summary: NuA3a histone acetyltransferase complex is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
GO:1990468 NuA3b histone acetyltransferase complex	IDA PMID:25104842 A PWWP domain-containing protein targets the NuA3 acetyltran...	ACCEPT	Summary: NuA3b histone acetyltransferase complex is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Supporting Evidence: PMID:25104842 Epub 2014 Aug 6. A PWWP domain-containing protein targets the NuA3 acetyltransferase complex via histone H3 lysine 36 trimethylation to coordinate transcriptional elongation at coding regions.
GO:0004402 histone acetyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: histone acetyltransferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: nucleus is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
GO:0005515 protein binding	IPI PMID:12672825 Opposite role of yeast ING family members in p53-dependent t...	REMOVE	Summary: Generic protein binding is not sufficiently informative for SAS3 curation. Reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515. Supporting Evidence: PMID:12672825 2003 Apr 2. Opposite role of yeast ING family members in p53-dependent transcriptional activation.
GO:0005515 protein binding	IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom...	REMOVE	Summary: Generic protein binding is not sufficiently informative for SAS3 curation. Reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515. Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
GO:0005515 protein binding	IPI PMID:17157260 Yng1 PHD finger binding to H3 trimethylated at K4 promotes N...	REMOVE	Summary: Generic protein binding is not sufficiently informative for SAS3 curation. Reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515. Supporting Evidence: PMID:17157260 Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.
GO:0005515 protein binding	IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome.	REMOVE	Summary: Generic protein binding is not sufficiently informative for SAS3 curation. Reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515. Supporting Evidence: PMID:21179020 Defining the budding yeast chromatin-associated interactome.
GO:0005515 protein binding	IPI PMID:25473596 Comprehensive analysis of interacting proteins and genome-wi...	REMOVE	Summary: Generic protein binding is not sufficiently informative for SAS3 curation. Reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515. Supporting Evidence: PMID:25473596 eCollection 2014. Comprehensive analysis of interacting proteins and genome-wide location studies of the Sas3-dependent NuA3 histone acetyltransferase complex.
GO:0005515 protein binding	IPI PMID:37968396 The social and structural architecture of the yeast protein ...	REMOVE	Summary: Generic protein binding is not sufficiently informative for SAS3 curation. Reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515. Supporting Evidence: PMID:37968396 Nov 15. The social and structural architecture of the yeast protein interactome.
GO:0005634 nucleus	NAS PMID:17157260 Yng1 PHD finger binding to H3 trimethylated at K4 promotes N...	ACCEPT	Summary: nucleus is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Supporting Evidence: PMID:17157260 Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.
GO:0006351 DNA-templated transcription	NAS PMID:17157260 Yng1 PHD finger binding to H3 trimethylated at K4 promotes N...	MARK AS OVER ANNOTATED	Summary: This process term is broader than the specific mechanistic role supported for SAS3. Reason: Marked as over-annotated to favor more specific SAS3 functions (histone acetyltransferase activity, NuA3 complex membership, and transcription-regulatory process terms). Supporting Evidence: PMID:17157260 Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.
GO:0008270 zinc ion binding	RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr...	ACCEPT	Summary: zinc ion binding is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Supporting Evidence: PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc proteome.
GO:1990467 NuA3a histone acetyltransferase complex	IDA PMID:25104842 A PWWP domain-containing protein targets the NuA3 acetyltran...	ACCEPT	Summary: NuA3a histone acetyltransferase complex is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Supporting Evidence: PMID:25104842 Epub 2014 Aug 6. A PWWP domain-containing protein targets the NuA3 acetyltransferase complex via histone H3 lysine 36 trimethylation to coordinate transcriptional elongation at coding regions.
GO:0004402 histone acetyltransferase activity	IDA PMID:10817755 The something about silencing protein, Sas3, is the catalyti...	ACCEPT	Summary: histone acetyltransferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Supporting Evidence: PMID:10817755 The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex.
GO:0004402 histone acetyltransferase activity	IMP PMID:10817755 The something about silencing protein, Sas3, is the catalyti...	ACCEPT	Summary: histone acetyltransferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Supporting Evidence: PMID:10817755 The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex.
GO:0033100 NuA3 histone acetyltransferase complex	IDA PMID:17157260 Yng1 PHD finger binding to H3 trimethylated at K4 promotes N...	ACCEPT	Summary: NuA3 histone acetyltransferase complex is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation. Reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Supporting Evidence: PMID:17157260 Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.

Core Functions

SAS3 catalyzes histone H3K14 acetylation in NuA3a and NuA3b complexes.

Molecular Function:

histone acetyltransferase activity

Supporting Evidence:

PMID:10817755
Sas3 is the catalytic subunit of NuA3
file:yeast/SAS3/SAS3-deep-research-falcon.md
*S. cerevisiae* **Sas3** is a **MYST-family histone acetyltransferase (HAT)** and the **catalytic subunit of the NuA3 complex**, which primarily acetylates **histone H3 lysine 14 (H3K14)** and is also associated with **H3K23 acetylation** in yeast chromatin.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10817755

The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex.

PMID:11731479

The yeast SAS (something about silencing) protein complex contains a MYST-type putative acetyltransferase and functions with chromatin assembly factor ASF1.

PMID:12077334

Yng1p modulates the activity of Sas3p as a component of the yeast NuA3 Hhistone acetyltransferase complex.

PMID:17157260

Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.

PMID:25104842

A PWWP domain-containing protein targets the NuA3 acetyltransferase complex via histone H3 lysine 36 trimethylation to coordinate transcriptional elongation at coding regions.

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

PMID:12672825

Opposite role of yeast ING family members in p53-dependent transcriptional activation.

PMID:16554755

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.

PMID:21179020

Defining the budding yeast chromatin-associated interactome.

PMID:25473596

Comprehensive analysis of interacting proteins and genome-wide location studies of the Sas3-dependent NuA3 histone acetyltransferase complex.

PMID:30358795

The cellular economy of the Saccharomyces cerevisiae zinc proteome.

PMID:37968396

The social and structural architecture of the yeast protein interactome.

file:yeast/SAS3/SAS3-deep-research-falcon.md

Deep research report on SAS3 (Saccharomyces cerevisiae, UniProt P34218) synthesizing yeast-specific literature on NuA3 catalytic HAT function, substrate specificity, complex architecture, chromatin targeting, and the 2024 Taf14-Sas3/Yng1 interface advance.

SAS3 is a MYST-family histone acetyltransferase and the catalytic subunit of the NuA3 complex, which primarily acetylates histone H3 lysine 14 (H3K14) and is also associated with H3K23 acetylation in yeast chromatin.

"*S. cerevisiae* **Sas3** is a **MYST-family histone acetyltransferase (HAT)** and the **catalytic subunit of the NuA3 complex**, which primarily acetylates **histone H3 lysine 14 (H3K14)** and is also associated with **H3K23 acetylation** in yeast chromatin."
Sas3 catalyzes acetyl-CoA-dependent lysine acetylation of histone H3, transferring an acetyl group from acetyl-CoA to the epsilon-amino group of a lysine residue, with H3K14 the best-supported primary physiological target.

"A HAT transfers an acetyl group from **acetyl-CoA** to the ε-amino group of a **lysine** residue on histones (a post-translational modification linked to chromatin accessibility and transcription)."
Loss of SAS3 abolishes NuA3 HAT activity and disrupts complex integrity, establishing Sas3 as required for both activity and integrity of the NuA3 complex.

"Early purification identified Sas3 by peptide sequencing in a ~0.4–0.5 MDa NuA3 complex; loss of **SAS3** abolishes NuA3 HAT activity and disrupts complex integrity."
NuA3 combines a writer (Sas3) with multiple reader domains - Yng1 PHD binds H3K4me3, Pdp3 PWWP binds H3K36me3, and Taf14 YEATS binds acyl-lysine marks - enabling chromatin-context-sensitive recruitment.

"Reader modules: **Yng1 PHD** binds **H3K4me3**; **Pdp3 PWWP** binds **H3K36me3**; **Taf14 YEATS** binds acylated histone marks including **H3K9ac/crotonylation**; Taf14 ET binds EBMs in Yng1 and Sas3."
Sas3 mediates NuA3 interaction with the FACT subunit Spt16 through an acidic C-terminal region, connecting NuA3 to transcription elongation through nucleosomes; SAS3 disruption enhances 6-azauracil sensitivity in an Spt16-mutant background.

"Sas3 mediates NuA3 interaction with **Spt16** (in vivo and in vitro), through an acidic C-terminal region; genetic interaction includes enhanced **6-azauracil (6-AU)** sensitivity when SAS3 is disrupted in an spt16-truncation background."
Sas3/NuA3 functions in the nucleus on chromatin, associating with transcribed genes; ChIP-on-chip mapping found Sas3 preferentially in the 5' half of coding regions, supporting involvement in transcriptional elongation.

"ChIP-on-chip mapping found Sas3 preferentially in the **5′ half of coding regions**, supporting involvement in **transcriptional elongation**."
Best-supported roles for Sas3/NuA3 are in transcriptional regulation, coupling histone acetylation to active chromatin and antagonizing the Rpd3S/Rpd3L HDAC pathways to optimize mRNA and lncRNA expression dynamics.

"NuA3 antagonizes **Rpd3S/Rpd3L** to optimize mRNA and lncRNA expression dynamics; Sas3 disruption enhances **6-azauracil** sensitivity in an Spt16-mutant background, consistent with elongation defects."
SAS3 belongs to the MYST (SAS/MOZ) family and is the yeast homolog/counterpart of human MOZ/MORF-type MYST HATs, with a Zf-MYST zinc-finger domain among its key domains.

"The symbol **SAS3** can refer to MYST-family HAT orthologs in other fungi (e.g., pathogens), but the target here is explicitly **budding yeast SAS3 (P34218; YBL052C)**. Foundational yeast studies purifying **NuA3** identified **Sas3 as its catalytic HAT subunit** and described Sas3 as the **yeast homolog/counterpart of human MOZ/MORF**-type MYST HATs"

Suggested Experiments

Experiment: Substrate specificity assays with histone variants

Experiment: Genome-wide ChIP-seq for SAS3 and H3K14ac

Experiment: Activity analysis in cells lacking GCN5

Experiment: Test interactions with HDAC complexes

Deep Research

Falcon

(SAS3-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 41 citations 2 artifacts 2026-05-30T11:24:04.148329

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000038 The requested panels from Figure 5 and Figure 6 show the binding of Taf14 ET to Sas3 EBM and Yng1 EBM, including binding curves, st (image/png)

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

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

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

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

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

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

Research Report: Saccharomyces cerevisiae SAS3 (UniProt P34218, ORF YBL052C) — Functional Annotation and Recent Literature

Executive summary

S. cerevisiae Sas3 is a MYST-family histone acetyltransferase (HAT) and the catalytic subunit of the NuA3 complex, which primarily acetylates histone H3 lysine 14 (H3K14) and is also associated with H3K23 acetylation in yeast chromatin. NuA3 integrates catalytic activity (Sas3) with multiple chromatin “reader” modules (e.g., Yng1 PHD binding H3K4 methylation; Pdp3 PWWP binding H3K36me3; Taf14 YEATS binding acyl-lysine marks) to target acetylation to active chromatin. Classic biochemical purification work established Sas3’s catalytic and structural role in NuA3 and revealed a physical/functional connection to the transcription-elongation factor FACT via Spt16. A major 2024 advance resolved how Taf14 helps organize NuA3 by binding short ET-binding motifs in both Sas3 and Yng1; mutations that disrupt these interfaces cause transcription-elongation stress sensitivity (6-AU) and increased sensitivity to replication/damage stresses (HU, MMS), connecting NuA3 assembly to genome maintenance. (john2000thesomethingabout pages 1-2, kim2020nua3hatantagonizes pages 1-2, taverna2006yng1phdfinger pages 1-2, nguyen2024molecularinsightinto pages 6-8)

1) Identity verification and disambiguation (critical)

The symbol SAS3 can refer to MYST-family HAT orthologs in other fungi (e.g., pathogens), but the target here is explicitly budding yeast SAS3 (P34218; YBL052C). Foundational yeast studies purifying NuA3 identified Sas3 as its catalytic HAT subunit and described Sas3 as the yeast homolog/counterpart of human MOZ/MORF-type MYST HATs, which provides a clear species/family/complex-based disambiguation. (john2000thesomethingabout pages 1-2, nguyen2024molecularinsightinto pages 1-2)

2) Key concepts and definitions (current understanding)

2.1 Histone acetyltransferase (HAT) activity of Sas3/NuA3

A HAT transfers an acetyl group from acetyl-CoA to the ε-amino group of a lysine residue on histones (a post-translational modification linked to chromatin accessibility and transcription). NuA3 is defined as a Gcn5-independent nucleosomal H3 HAT complex in yeast. (john2000thesomethingabout pages 2-4, john2000thesomethingabout pages 1-2)

2.2 NuA3 complex as a “writer + readers” chromatin machine

NuA3 combines:
- a writer: Sas3 (MYST catalytic subunit)
- multiple reader domains: Yng1 PHD (H3K4 methylation), Pdp3 PWWP (H3K36me3), Taf14 YEATS/ET (acyl-lysine binding and EBM binding), enabling chromatin-context-sensitive recruitment and regulation. (martin2017histoneh3k4and pages 1-2, kim2020nua3hatantagonizes pages 1-2, nguyen2024molecularinsightinto pages 1-2)

3) Primary biochemical function: reaction catalyzed and substrate specificity

3.1 Reaction catalyzed

Sas3 (as NuA3 catalytic subunit) catalyzes histone lysine acetylation using acetyl-CoA (EC 2.3.1.48 in UniProt context; mechanistically supported by HAT assays described in classic NuA3 purification studies). NuA3 is active on chromatin/nucleosomal templates and is positioned to acetylate nucleosomal H3. (john2000thesomethingabout pages 2-4, john2000thesomethingabout pages 1-2)

3.2 Substrate context: nucleosomes vs free histones

NuA3 is characterized as a complex that acetylates histone H3 on nucleosomal substrates, but can also acetylate H4 on free histones in vitro. Importantly, bacterially expressed Sas3 can acetylate free histones, whereas nucleosomal targeting/efficiency depends on NuA3 subunits that enable chromatin engagement. (john2000thesomethingabout pages 2-4, john2000thesomethingabout pages 6-8)

3.3 Site specificity on histone H3

Multiple independent yeast sources support H3K14 as the principal physiological site for NuA3/Sas3 action:
- NuA3 is described as primarily acetylating H3K14, and its transcriptional role is linked to reader-dependent stimulation (e.g., Yng1–H3K4me3). (kim2020nua3hatantagonizes pages 1-2, taverna2006yng1phdfinger pages 1-2)
- NuA3 is also associated with acetylation of H3K23 (reported in yeast NuA3 literature and summarized in Genetics work on recruitment). (martin2017histoneh3k4and pages 1-2)

4) Complex membership, assembly, and molecular interactions

4.1 Core/commonly cited subunits

Modern descriptions of NuA3 include Sas3 (catalytic), Nto1, Eaf6, Yng1, Taf14, and Pdp3; earlier biochemical purification also identified yTAFII30/TAF30 in NuA3 preparations. (john2000thesomethingabout pages 2-4, martin2017histoneh3k4and pages 1-2, john2000thesomethingabout pages 1-2)

4.2 Sas3 requirement for complex integrity

Deletion of SAS3 eliminates detectable NuA3 HAT activity and disrupts co-purification/co-elution of other NuA3 components (e.g., TAF30), supporting Sas3 as required for both activity and integrity of the complex. (john2000thesomethingabout pages 2-4, john2000thesomethingabout pages 1-2)

4.3 Coupling to transcription elongation machinery (FACT/Spt16)

A key mechanistic theme is physical coupling between NuA3 and the FACT complex:
- Sas3 mediates NuA3 interaction with Spt16 (in vivo and in vitro), through an acidic C-terminal region; genetic interaction includes enhanced 6-azauracil (6-AU) sensitivity when SAS3 is disrupted in an spt16-truncation background. This supports a role in transcription elongation through nucleosomes (and potentially replication-associated chromatin transactions). (john2000thesomethingabout pages 6-8, john2000thesomethingabout pages 8-9)

5) Localization and pathway-level function in the cell

5.1 Subcellular localization

NuA3 is a chromatin-associated nuclear complex (nucleosomal H3 acetyltransferase); genome-wide studies show Sas3 occupancy on genes and chromatin. (john2000thesomethingabout pages 1-2, vicentemunoz2014comprehensiveanalysisof pages 1-2)

5.2 Genome targeting patterns

Genome-wide chromatin mapping supports that Sas3/NuA3 localizes predominantly across transcribed gene bodies, often in mid-gene regions, consistent with a role in transcription-coupled chromatin regulation:
- Sas3 and Yng1 peaks reported ~750 bp and 657 bp downstream of the +1 nucleosome dyad, respectively, and correlate genome-wide (Spearman r = 0.48). (martin2018targetingofhistone pages 63-69)
- ChIP-on-chip mapping found Sas3 preferentially in the 5′ half of coding regions, supporting involvement in transcriptional elongation. (vicentemunoz2014comprehensiveanalysisof pages 1-2)

5.3 Recruitment logic (histone methylation cross-talk)

NuA3 recruitment is promoted by histone methylation marks associated with active transcription:
- H3K4 and H3K36 methylation independently support NuA3 recruitment via Yng1 (PHD) and Pdp3 (PWWP) modules. (martin2017histoneh3k4and pages 1-2, martin2016histoneh3k4and pages 14-18)
- Importantly, recruitment does not guarantee acetylation (“presence is insufficient”), implying additional regulation of enzymatic activity after binding. (martin2017histoneh3k4and pages 1-2)

6) Recent developments (priority 2023–2024)

6.1 2024: Structural and mechanistic assembly of NuA3 via Taf14–Sas3/Yng1 interfaces

A major 2024 Nature Communications study dissected how Taf14 binds short ET-binding motifs (EBMs) in Sas3 and Yng1, forming dimeric assemblies that enhance Taf14 DNA binding and are required for NuA3 function in transcription and genome maintenance. Key quantitative findings include:
- Taf14ET–Sas3EBM affinity Kd ≈ 18 μM (NMR) and Taf14FL–Sas3 peptide Kd ≈ 21 μM (fluorescence). (nguyen2024molecularinsightinto pages 3-6)
- Mutations in Sas3 EBM weaken/abrogate binding: L114D Kd ≈ 540 μM, while V116D/I118D disrupt binding. (nguyen2024molecularinsightinto pages 3-6)
- In vivo, Sas3 (I118D) or Yng1 (I120D) mutations that disrupt Taf14 binding cause strong sensitivity to transcription elongation stress (6-AU) and increased sensitivity to replication/damage stresses (HU, MMS). (nguyen2024molecularinsightinto pages 6-8)
- ChIP-exo promoter occupancy counts: Taf14 1096, Yng1 71, Sas3 9; 70/71 Yng1 promoters co-bound by Taf14; 6 promoters co-bound by all three. (nguyen2024molecularinsightinto pages 3-6)

These findings sharpen current understanding from “NuA3 has multiple subunits” to an explicit molecular assembly interface and provide a direct mechanistic route linking NuA3 architecture to transcription and DNA repair phenotypes. (nguyen2024molecularinsightinto pages 1-2, nguyen2024molecularinsightinto pages 6-8)

6.2 2024: Additional yeast literature signals

A 2024 bioRxiv histone-mutant screening study references reduced H3 acetylation including H3K14 and notes nucleosomes acetylated by Gcn5 and Sas3/NuA3 in transcriptional regulation contexts, suggesting Sas3 remains embedded as a standard component of chromatin functional interpretation in contemporary yeast epigenetics. (singh2024screeningofhistone; retrieved but not deeply evidenced beyond snippet in this corpus)

7) Current applications and real-world implementations

7.1 Yeast Sas3/NuA3 as a model for human MYST HATs (MOZ/MORF)

Authoritative review literature frames yeast MYST HATs—including Sas3—as a tractable system to illuminate mechanisms relevant to human disease-associated MYST enzymes (e.g., MOZ/MORF), leveraging yeast genetics, biochemistry, and interaction assays. (lafon2007mystopportunitiesfor pages 1-2, lafon2007mystopportunitiesfor pages 2-3)

7.2 Studying transcription elongation through nucleosomes

The Sas3–Spt16/FACT linkage provides a platform to study how acetylation is coupled to chromatin transactions during elongation, with phenotypes such as 6-AU sensitivity serving as functional readouts in standard laboratory workflows. (john2000thesomethingabout pages 6-8, john2000thesomethingabout pages 8-9)

7.3 Modular “reader–writer” logic for chromatin targeting

NuA3 embodies a widely used conceptual framework in epigenetics—writer enzymes guided by reader domains recognizing pre-existing histone marks (H3K4 methylation, H3K36me3, acyl marks). This supports experimental designs that perturb reader interactions (e.g., Yng1 PHD mutants) to test causality between histone PTMs, recruitment, and downstream acetylation/transcription. (taverna2006yng1phdfinger pages 1-2, martin2017histoneh3k4and pages 1-2, nguyen2024molecularinsightinto pages 1-2)

8) Expert opinions and analysis (authoritative synthesis)

“Yeast genes illuminate human cancer gene functions”: Sas3/NuA3 is presented as a key yeast MYST system that connects conserved domain architecture and complex subunits to transcriptional regulation and growth control, supporting its translational relevance to MOZ/MORF biology. (lafon2007mystopportunitiesfor pages 1-2, lafon2007mystopportunitiesfor pages 3-4)
Modern consensus on multi-layer control: recruitment of NuA3 by active chromatin marks is necessary but not sufficient for acetylation output, implying regulation at the level of complex assembly, chromatin engagement geometry, and/or competing chromatin modifiers (e.g., Rpd3 HDAC pathways). (martin2017histoneh3k4and pages 1-2, kim2020nua3hatantagonizes pages 1-2)
2024 mechanistic refinement: NuA3 function depends on defined Taf14-mediated interactions with both Sas3 and Yng1, linking a specific physical interface to transcription and DNA repair phenotypes; this strengthens causal inference beyond correlational chromatin localization. (nguyen2024molecularinsightinto pages 6-8, nguyen2024molecularinsightinto pages 1-2)

9) Relevant statistics and data highlights (from cited studies)

NuA3 substrate context: NuA3 acetylates H3 on nucleosomal substrates and can acetylate H4 on free histones in vitro. (john2000thesomethingabout pages 2-4)
Genome targeting metrics: Sas3 peak enrichment ~750 bp downstream of +1 dyad; Yng1 ~657 bp; Sas3–Yng1 occupancy correlation Spearman r = 0.48. (martin2018targetingofhistone pages 63-69)
2024 affinities: Taf14FL–Sas3 peptide Kd ~21 μM; Taf14ET–Sas3 EBM Kd ~18 μM; Sas3 L114D mutant Kd ~540 μM. (nguyen2024molecularinsightinto pages 3-6)
2024 occupancy counts: Taf14 1096 promoters; Yng1 71; Sas3 9; triple overlap 6. (nguyen2024molecularinsightinto pages 3-6)
2024 phenotypes: Disruption of Taf14–Sas3 or Taf14–Yng1 binding increases sensitivity to 6-AU, HU, MMS, linking NuA3 assembly to elongation stress and genome maintenance. (nguyen2024molecularinsightinto pages 6-8)

10) Key figure evidence (2024)

Nguyen et al. provide direct figure-level evidence for Taf14–Sas3/Yng1 binding energetics, structural overlap, and stress phenotypes.
- Binding curves and mutant effects (Fig. 5 panels) and structural overlays (Fig. 6c). (nguyen2024molecularinsightinto media 3daaaaa8)
- Spot assays showing growth sensitivity with interface-disrupting mutations under 6-AU, HU, and MMS. (nguyen2024molecularinsightinto media cea32fb1)

11) Limitations and evidence gaps

Within the retrieved corpus, 2023–2024 yeast-specific Sas3/NuA3 primary literature beyond Nguyen et al. (2024) is limited. Ortholog papers (2023–2024) in fungal pathogens exist but should not be used as direct evidence for S. cerevisiae P34218 function; they mainly support evolutionary conservation of a nuclear MYST-HAT role.

Consolidated evidence table

Topic	Key finding	Quantitative / mechanistic details	Evidence scope	Key citations (URL; date)
Identity & core function	SAS3 (UniProt P34218; YBL052C) in Saccharomyces cerevisiae is the MYST-family catalytic histone acetyltransferase subunit of the NuA3 complex, a nucleosomal acetyltransferase of histone H3 involved in chromatin-based gene regulation. Sas3 is also required for NuA3 integrity and mediates interaction with the FACT subunit Spt16. (john2000thesomethingabout pages 1-2)	Early purification identified Sas3 by peptide sequencing in a ~0.4–0.5 MDa NuA3 complex; loss of SAS3 abolishes NuA3 HAT activity and disrupts complex integrity. (john2000thesomethingabout pages 2-4, john2000thesomethingabout pages 8-9)	Yeast-specific	John et al., Genes & Development — https://doi.org/10.1101/gad.14.10.1196; May 2000 (john2000thesomethingabout pages 1-2, john2000thesomethingabout pages 2-4) ; Lafon et al., Oncogene — https://doi.org/10.1038/sj.onc.1210606; Aug 2007 (lafon2007mystopportunitiesfor pages 2-3)
Enzymatic reaction & principal histone targets	Sas3 catalyzes acetyl-CoA-dependent lysine acetylation of histone H3, with H3K14 the best-supported primary physiological target and H3K23 also reported for NuA3. (martin2017histoneh3k4and pages 1-2, kim2020nua3hatantagonizes pages 1-2, taverna2006yng1phdfinger pages 1-2)	NuA3 acetylates H3 on nucleosomal substrates; early work also found it can acetylate H4 on free histones. Recombinant Sas3 acetylates free histones, whereas NuA3 subunits promote nucleosome engagement. H3K14 targeting is enhanced by Yng1 recognition of H3K4me3. (john2000thesomethingabout pages 2-4, john2000thesomethingabout pages 6-8, lafon2007mystopportunitiesfor pages 2-3)	Yeast-specific	Taverna et al., Molecular Cell — https://doi.org/10.1016/j.molcel.2006.10.026; Dec 2006 (taverna2006yng1phdfinger pages 1-2) ; Martin et al., Genetics — https://doi.org/10.1534/genetics.116.199422; Mar 2017 (martin2017histoneh3k4and pages 1-2) ; Kim et al., Nucleic Acids Research — https://doi.org/10.1093/nar/gkaa781; Oct 2020 (kim2020nua3hatantagonizes pages 1-2)
Complex composition & reader domains	Mature NuA3 is commonly described with Sas3, Nto1, Eaf6, Yng1, Taf14, Pdp3; earlier biochemical work also identified yTAFII30/TAF30 in NuA3 preparations. (martin2017histoneh3k4and pages 1-2, john2000thesomethingabout pages 2-4)	Reader modules: Yng1 PHD binds H3K4me3; Pdp3 PWWP binds H3K36me3; Taf14 YEATS binds acylated histone marks including H3K9ac/crotonylation; Taf14 ET binds EBMs in Yng1 and Sas3. (martin2017histoneh3k4and pages 1-2, nguyen2024molecularinsightinto pages 1-2, nguyen2024molecularinsightinto pages 3-6)	Yeast-specific	Martin et al., Genetics — https://doi.org/10.1534/genetics.116.199422; Mar 2017 (martin2017histoneh3k4and pages 1-2) ; Nguyen et al., Nature Communications — https://doi.org/10.1038/s41467-024-49730-y; Jun 2024 (nguyen2024molecularinsightinto pages 1-2, nguyen2024molecularinsightinto pages 3-6)
Localization & genome targeting	Sas3/NuA3 functions in the nucleus on chromatin, associating with transcribed genes and chromatinized templates; multiple studies place NuA3 over gene bodies / mid-gene regions, while promoter recruitment is also observed in recent Taf14-focused work. (martin2016histoneh3k4and pages 14-18, martin2018targetingofhistone pages 63-69, vicentemunoz2014comprehensiveanalysisof pages 1-2, nguyen2024molecularinsightinto pages 1-2)	MNase-ChIP/ChIP analyses place Sas3 and Yng1 peaks about 750 bp and 657 bp downstream of the +1 dyad, respectively; genome-wide Sas3–Yng1 occupancy correlation Spearman r = 0.48. Recruitment depends additively on Set1/H3K4 methylation and Set2/H3K36 methylation. (martin2016histoneh3k4and pages 14-18, martin2018targetingofhistone pages 69-78, martin2018targetingofhistone pages 63-69)	Yeast-specific	Martin preprint — https://doi.org/10.1101/096511; Dec 2016 (martin2016histoneh3k4and pages 14-18) ; Martin thesis-derived data — https://doi.org/10.14288/1.0364673; Jan 2018 (martin2018targetingofhistone pages 63-69, martin2018targetingofhistone pages 69-78) ; Vicente-Muñoz et al., FEBS Open Bio — https://doi.org/10.1016/j.fob.2014.11.001; Nov 2014 (vicentemunoz2014comprehensiveanalysisof pages 1-2)
Pathways / biological processes	Best-supported roles are in transcriptional regulation, especially coupling histone acetylation to active chromatin and antagonizing Rpd3 HDAC pathways; Sas3/NuA3 also connects to transcription elongation via FACT/Spt16 and has emerging links to DNA repair and cell-cycle/stress responses. (john2000thesomethingabout pages 6-8, john2000thesomethingabout pages 8-9, nguyen2024molecularinsightinto pages 1-2)	NuA3 antagonizes Rpd3S/Rpd3L to optimize mRNA and lncRNA expression dynamics; Sas3 disruption enhances 6-azauracil sensitivity in an Spt16-mutant background, consistent with elongation defects. (kim2020nua3hatantagonizes pages 1-2, john2000thesomethingabout pages 6-8)	Yeast-specific	Kim et al., Nucleic Acids Research — https://doi.org/10.1093/nar/gkaa781; Oct 2020 (kim2020nua3hatantagonizes pages 1-2) ; John et al., Genes & Development — https://doi.org/10.1101/gad.14.10.1196; May 2000 (john2000thesomethingabout pages 6-8, john2000thesomethingabout pages 8-9) ; Nguyen et al., Nature Communications — https://doi.org/10.1038/s41467-024-49730-y; Jun 2024 (nguyen2024molecularinsightinto pages 1-2)
2024 Nguyen et al. mechanistic advance	Taf14 organizes NuA3 by binding ET-binding motifs (EBMs) in both Yng1 and Sas3, forming a dimeric ET:EBM assembly that enhances Taf14 DNA binding and is required for proper NuA3 function in transcription and genome maintenance. (nguyen2024molecularinsightinto pages 1-2, nguyen2024molecularinsightinto pages 3-6)	Taf14ET–Sas3EBM Kd ≈ 18 μM by NMR; Taf14FL–Sas3 peptide Kd ≈ 21 μM by tryptophan fluorescence; Sas3 L114D weakens binding to ~540 μM; V116D/I118D abolish binding. For Yng1, Taf14ET–Yng1EBM Kd ~0.6 μM, Taf14FL–Yng1EBM ~1.1–1.2 μM. (nguyen2024molecularinsightinto pages 3-6, nguyen2024molecularinsightinto pages 2-3, nguyen2024molecularinsightinto media 3daaaaa8)	Yeast-specific	Nguyen et al., Nature Communications — https://doi.org/10.1038/s41467-024-49730-y; Jun 2024 (nguyen2024molecularinsightinto pages 6-8, nguyen2024molecularinsightinto pages 3-6, nguyen2024molecularinsightinto pages 2-3, nguyen2024molecularinsightinto media 3daaaaa8)
2024 Nguyen et al. genomic & phenotypic data	ChIP-exo and mutant phenotyping tie Taf14–Sas3/Yng1 interactions to a restricted promoter set and stress resistance relevant to transcription/replication-repair. (nguyen2024molecularinsightinto pages 3-6, nguyen2024molecularinsightinto pages 6-8)	Promoter occupancy counts: Taf14 1096, Yng1 71, Sas3 9; 70/71 Yng1 promoters are co-bound by Taf14; 6 promoters are co-bound by all three. Mutations disrupting Taf14 binding (Sas3 I118D, Yng1 I120D) cause strong 6-AU sensitivity and increased sensitivity to HU and MMS; Sas3 I118D shows near loss of growth and temperature-sensitive defects. (nguyen2024molecularinsightinto pages 6-8, nguyen2024molecularinsightinto pages 3-6, nguyen2024molecularinsightinto media 3daaaaa8)	Yeast-specific	Nguyen et al., Nature Communications — https://doi.org/10.1038/s41467-024-49730-y; Jun 2024 (nguyen2024molecularinsightinto pages 6-8, nguyen2024molecularinsightinto pages 3-6, nguyen2024molecularinsightinto media 3daaaaa8)
Ortholog context (not the target protein)	Recent 2023–2024 papers also use Sas3 for orthologous fungal MYST HATs in pathogens such as Zymoseptoria tritici and Aspergillus fumigatus. These studies support evolutionary conservation of a nuclear chromatin-acetylation role but are not evidence for the specific yeast P34218 protein.	Ortholog studies link Sas3 to virulence, cell wall integrity, and effector regulation, often with H3K14/H3K9 acetylation phenotypes, but these findings should be used only as comparative context. (nguyen2024molecularinsightinto pages 1-2)	Ortholog-context	Suarez-Fernandez et al., mBio — https://doi.org/10.1128/mbio.01386-23; Oct 2023 ; Wang et al., Applied and Environmental Microbiology — https://doi.org/10.1128/aem.01885-23; Apr 2024 (nguyen2024molecularinsightinto pages 1-2)

Table: This table condenses yeast-specific evidence for SAS3/P34218 function, substrates, complex organization, chromatin targeting, and 2024 mechanistic advances from Nguyen et al. It also flags ortholog-only Sas3 literature to avoid conflating non-yeast findings with the target protein.

Selected key references (URLs; publication dates)

John S. et al. “The Something About Silencing protein, Sas3, is the catalytic subunit of NuA3…” Genes & Development May 2000. https://doi.org/10.1101/gad.14.10.1196 (john2000thesomethingabout pages 1-2)
Taverna S.D. et al. “Yng1 PHD finger binding to H3K4me3 promotes NuA3 HAT activity at K14…” Molecular Cell Dec 2006. https://doi.org/10.1016/j.molcel.2006.10.026 (taverna2006yng1phdfinger pages 1-2)
Lafon A. et al. “MYST opportunities for growth control: yeast genes illuminate human cancer gene functions.” Oncogene Aug 2007. https://doi.org/10.1038/sj.onc.1210606 (lafon2007mystopportunitiesfor pages 1-2)
Vicente-Muñoz S. et al. “Comprehensive analysis… Sas3-dependent NuA3…” FEBS Open Bio Nov 2014. https://doi.org/10.1016/j.fob.2014.11.001 (vicentemunoz2014comprehensiveanalysisof pages 1-2)
Martin B.J.E. et al. “Histone H3K4 and H3K36 methylation independently recruit the NuA3 HAT…” Genetics Mar 2017. https://doi.org/10.1534/genetics.116.199422 (martin2017histoneh3k4and pages 1-2)
Kim J.H. et al. “NuA3 HAT antagonizes the Rpd3S and Rpd3L HDACs…” Nucleic Acids Research Oct 2020. https://doi.org/10.1093/nar/gkaa781 (kim2020nua3hatantagonizes pages 1-2)
Nguyen M.C. et al. “Molecular insight into interactions between the Taf14, Yng1 and Sas3 subunits of the NuA3 complex.” Nature Communications Jun 2024. https://doi.org/10.1038/s41467-024-49730-y (nguyen2024molecularinsightinto pages 1-2)

References

(john2000thesomethingabout pages 1-2): Sam John, LeAnn Howe, Stefan T. Tafrov, Patrick A. Grant, Rolf Sternglanz, and Jerry L. Workman. The something about silencing protein, sas3, is the catalytic subunit of nua3, a ytaf_ii30-containing hat complex that interacts with the spt16 subunit of the yeast cp (cdc68/pob3)–fact complex. Genes & Development, 14:1196-1208, May 2000. URL: https://doi.org/10.1101/gad.14.10.1196, doi:10.1101/gad.14.10.1196. This article has 316 citations and is from a highest quality peer-reviewed journal.
(kim2020nua3hatantagonizes pages 1-2): Ji Hyun Kim, Chae Young Yoon, Yukyung Jun, Bo Bae Lee, Ji Eun Lee, So Dam Ha, Hyeonju Woo, Ahyoung Choi, Sanghyuk Lee, Woojin Jeong, Ji Hyung Kim, and TaeSoo Kim. Nua3 hat antagonizes the rpd3s and rpd3l hdacs to optimize mrna and lncrna expression dynamics. Nucleic Acids Research, 48:10753-10767, Oct 2020. URL: https://doi.org/10.1093/nar/gkaa781, doi:10.1093/nar/gkaa781. This article has 16 citations and is from a highest quality peer-reviewed journal.
(taverna2006yng1phdfinger pages 1-2): Sean D. Taverna, Serge Ilin, Richard S. Rogers, Jason C. Tanny, Heather Lavender, Haitao Li, Lindsey Baker, John Boyle, Lauren P. Blair, Brian T. Chait, Dinshaw J. Patel, John D. Aitchison, Alan J. Tackett, and C. David Allis. Yng1 phd finger binding to h3 trimethylated at k4 promotes nua3 hat activity at k14 of h3 and transcription at a subset of targeted orfs. Molecular cell, 24 5:785-796, Dec 2006. URL: https://doi.org/10.1016/j.molcel.2006.10.026, doi:10.1016/j.molcel.2006.10.026. This article has 418 citations and is from a highest quality peer-reviewed journal.
(nguyen2024molecularinsightinto pages 6-8): Minh Chau Nguyen, Hosein Rostamian, Ana Raman, Pengcheng Wei, Dustin C. Becht, Annette H. Erbse, Brianna J. Klein, Tonya M. Gilbert, Gongyi Zhang, M. Andres Blanco, Brian D. Strahl, Sean D. Taverna, and Tatiana G. Kutateladze. Molecular insight into interactions between the taf14, yng1 and sas3 subunits of the nua3 complex. Nature Communications, Jun 2024. URL: https://doi.org/10.1038/s41467-024-49730-y, doi:10.1038/s41467-024-49730-y. This article has 3 citations and is from a highest quality peer-reviewed journal.
(nguyen2024molecularinsightinto pages 1-2): Minh Chau Nguyen, Hosein Rostamian, Ana Raman, Pengcheng Wei, Dustin C. Becht, Annette H. Erbse, Brianna J. Klein, Tonya M. Gilbert, Gongyi Zhang, M. Andres Blanco, Brian D. Strahl, Sean D. Taverna, and Tatiana G. Kutateladze. Molecular insight into interactions between the taf14, yng1 and sas3 subunits of the nua3 complex. Nature Communications, Jun 2024. URL: https://doi.org/10.1038/s41467-024-49730-y, doi:10.1038/s41467-024-49730-y. This article has 3 citations and is from a highest quality peer-reviewed journal.
(john2000thesomethingabout pages 2-4): Sam John, LeAnn Howe, Stefan T. Tafrov, Patrick A. Grant, Rolf Sternglanz, and Jerry L. Workman. The something about silencing protein, sas3, is the catalytic subunit of nua3, a ytaf_ii30-containing hat complex that interacts with the spt16 subunit of the yeast cp (cdc68/pob3)–fact complex. Genes & Development, 14:1196-1208, May 2000. URL: https://doi.org/10.1101/gad.14.10.1196, doi:10.1101/gad.14.10.1196. This article has 316 citations and is from a highest quality peer-reviewed journal.
(martin2017histoneh3k4and pages 1-2): Benjamin J E Martin, Kristina L McBurney, Vicki E Maltby, Kristoffer N Jensen, Julie Brind’Amour, and LeAnn J Howe. Histone h3k4 and h3k36 methylation independently recruit the nua3 histone acetyltransferase in saccharomyces cerevisiae. Genetics, 205:1113-1123, Mar 2017. URL: https://doi.org/10.1534/genetics.116.199422, doi:10.1534/genetics.116.199422. This article has 39 citations and is from a domain leading peer-reviewed journal.
(john2000thesomethingabout pages 6-8): Sam John, LeAnn Howe, Stefan T. Tafrov, Patrick A. Grant, Rolf Sternglanz, and Jerry L. Workman. The something about silencing protein, sas3, is the catalytic subunit of nua3, a ytaf_ii30-containing hat complex that interacts with the spt16 subunit of the yeast cp (cdc68/pob3)–fact complex. Genes & Development, 14:1196-1208, May 2000. URL: https://doi.org/10.1101/gad.14.10.1196, doi:10.1101/gad.14.10.1196. This article has 316 citations and is from a highest quality peer-reviewed journal.
(john2000thesomethingabout pages 8-9): Sam John, LeAnn Howe, Stefan T. Tafrov, Patrick A. Grant, Rolf Sternglanz, and Jerry L. Workman. The something about silencing protein, sas3, is the catalytic subunit of nua3, a ytaf_ii30-containing hat complex that interacts with the spt16 subunit of the yeast cp (cdc68/pob3)–fact complex. Genes & Development, 14:1196-1208, May 2000. URL: https://doi.org/10.1101/gad.14.10.1196, doi:10.1101/gad.14.10.1196. This article has 316 citations and is from a highest quality peer-reviewed journal.
(vicentemunoz2014comprehensiveanalysisof pages 1-2): Sara Vicente-Muñoz, Paco Romero, Lorena Magraner-Pardo, Celia P. Martinez-Jimenez, Vicente Tordera, and Mercè Pamblanco. Comprehensive analysis of interacting proteins and genome-wide location studies of the sas3-dependent nua3 histone acetyltransferase complex. FEBS Open Bio, 4:996-1006, Nov 2014. URL: https://doi.org/10.1016/j.fob.2014.11.001, doi:10.1016/j.fob.2014.11.001. This article has 21 citations and is from a peer-reviewed journal.
(martin2018targetingofhistone pages 63-69): Benjamin John Elwood Martin. Targeting of histone acetylation to transcribed chromatin. ArXiv, Jan 2018. URL: https://doi.org/10.14288/1.0364673, doi:10.14288/1.0364673. This article has 0 citations.
(martin2016histoneh3k4and pages 14-18): Benjamin J.E. Martin, Kristina L. McBurney, Vicki E. Maltby, Kristoffer N. Jensen, Julie Brind’Amour, and LeAnn J. Howe. Histone h3k4 and h3k36 methylation promotes recruitment, but not activity, of the nua3 histone acetyltransferase complex in s. cerevisiae. bioRxiv, Dec 2016. URL: https://doi.org/10.1101/096511, doi:10.1101/096511. This article has 0 citations.
(nguyen2024molecularinsightinto pages 3-6): Minh Chau Nguyen, Hosein Rostamian, Ana Raman, Pengcheng Wei, Dustin C. Becht, Annette H. Erbse, Brianna J. Klein, Tonya M. Gilbert, Gongyi Zhang, M. Andres Blanco, Brian D. Strahl, Sean D. Taverna, and Tatiana G. Kutateladze. Molecular insight into interactions between the taf14, yng1 and sas3 subunits of the nua3 complex. Nature Communications, Jun 2024. URL: https://doi.org/10.1038/s41467-024-49730-y, doi:10.1038/s41467-024-49730-y. This article has 3 citations and is from a highest quality peer-reviewed journal.
(lafon2007mystopportunitiesfor pages 1-2): Anne Lafon, Christie S. Chang, E. Scott, Sandra J. Jacobson, and L. Pillus. Myst opportunities for growth control: yeast genes illuminate human cancer gene functions. Oncogene, 26:5373-5384, Aug 2007. URL: https://doi.org/10.1038/sj.onc.1210606, doi:10.1038/sj.onc.1210606. This article has 82 citations and is from a domain leading peer-reviewed journal.
(lafon2007mystopportunitiesfor pages 2-3): Anne Lafon, Christie S. Chang, E. Scott, Sandra J. Jacobson, and L. Pillus. Myst opportunities for growth control: yeast genes illuminate human cancer gene functions. Oncogene, 26:5373-5384, Aug 2007. URL: https://doi.org/10.1038/sj.onc.1210606, doi:10.1038/sj.onc.1210606. This article has 82 citations and is from a domain leading peer-reviewed journal.
(lafon2007mystopportunitiesfor pages 3-4): Anne Lafon, Christie S. Chang, E. Scott, Sandra J. Jacobson, and L. Pillus. Myst opportunities for growth control: yeast genes illuminate human cancer gene functions. Oncogene, 26:5373-5384, Aug 2007. URL: https://doi.org/10.1038/sj.onc.1210606, doi:10.1038/sj.onc.1210606. This article has 82 citations and is from a domain leading peer-reviewed journal.
(nguyen2024molecularinsightinto media 3daaaaa8): Minh Chau Nguyen, Hosein Rostamian, Ana Raman, Pengcheng Wei, Dustin C. Becht, Annette H. Erbse, Brianna J. Klein, Tonya M. Gilbert, Gongyi Zhang, M. Andres Blanco, Brian D. Strahl, Sean D. Taverna, and Tatiana G. Kutateladze. Molecular insight into interactions between the taf14, yng1 and sas3 subunits of the nua3 complex. Nature Communications, Jun 2024. URL: https://doi.org/10.1038/s41467-024-49730-y, doi:10.1038/s41467-024-49730-y. This article has 3 citations and is from a highest quality peer-reviewed journal.
(nguyen2024molecularinsightinto media cea32fb1): Minh Chau Nguyen, Hosein Rostamian, Ana Raman, Pengcheng Wei, Dustin C. Becht, Annette H. Erbse, Brianna J. Klein, Tonya M. Gilbert, Gongyi Zhang, M. Andres Blanco, Brian D. Strahl, Sean D. Taverna, and Tatiana G. Kutateladze. Molecular insight into interactions between the taf14, yng1 and sas3 subunits of the nua3 complex. Nature Communications, Jun 2024. URL: https://doi.org/10.1038/s41467-024-49730-y, doi:10.1038/s41467-024-49730-y. This article has 3 citations and is from a highest quality peer-reviewed journal.
(martin2018targetingofhistone pages 69-78): Benjamin John Elwood Martin. Targeting of histone acetylation to transcribed chromatin. ArXiv, Jan 2018. URL: https://doi.org/10.14288/1.0364673, doi:10.14288/1.0364673. This article has 0 citations.
(nguyen2024molecularinsightinto pages 2-3): Minh Chau Nguyen, Hosein Rostamian, Ana Raman, Pengcheng Wei, Dustin C. Becht, Annette H. Erbse, Brianna J. Klein, Tonya M. Gilbert, Gongyi Zhang, M. Andres Blanco, Brian D. Strahl, Sean D. Taverna, and Tatiana G. Kutateladze. Molecular insight into interactions between the taf14, yng1 and sas3 subunits of the nua3 complex. Nature Communications, Jun 2024. URL: https://doi.org/10.1038/s41467-024-49730-y, doi:10.1038/s41467-024-49730-y. This article has 3 citations and is from a highest quality peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

martin2018targetingofhistone pages 63-69
vicentemunoz2014comprehensiveanalysisof pages 1-2
nguyen2024molecularinsightinto pages 3-6
nguyen2024molecularinsightinto pages 6-8
john2000thesomethingabout pages 2-4
john2000thesomethingabout pages 1-2
lafon2007mystopportunitiesfor pages 2-3
nguyen2024molecularinsightinto pages 1-2
lafon2007mystopportunitiesfor pages 1-2
john2000thesomethingabout pages 6-8
john2000thesomethingabout pages 8-9
lafon2007mystopportunitiesfor pages 3-4
martin2018targetingofhistone pages 69-78
nguyen2024molecularinsightinto pages 2-3
https://doi.org/10.1101/gad.14.10.1196;
https://doi.org/10.1038/sj.onc.1210606;
https://doi.org/10.1016/j.molcel.2006.10.026;
https://doi.org/10.1534/genetics.116.199422;
https://doi.org/10.1093/nar/gkaa781;
https://doi.org/10.1038/s41467-024-49730-y;
https://doi.org/10.1101/096511;
https://doi.org/10.14288/1.0364673;
https://doi.org/10.1016/j.fob.2014.11.001;
https://doi.org/10.1128/mbio.01386-23;
https://doi.org/10.1128/aem.01885-23;
https://doi.org/10.1101/gad.14.10.1196
https://doi.org/10.1016/j.molcel.2006.10.026
https://doi.org/10.1038/sj.onc.1210606
https://doi.org/10.1016/j.fob.2014.11.001
https://doi.org/10.1534/genetics.116.199422
https://doi.org/10.1093/nar/gkaa781
https://doi.org/10.1038/s41467-024-49730-y
https://doi.org/10.1101/gad.14.10.1196,
https://doi.org/10.1093/nar/gkaa781,
https://doi.org/10.1016/j.molcel.2006.10.026,
https://doi.org/10.1038/s41467-024-49730-y,
https://doi.org/10.1534/genetics.116.199422,
https://doi.org/10.1016/j.fob.2014.11.001,
https://doi.org/10.14288/1.0364673,
https://doi.org/10.1101/096511,
https://doi.org/10.1038/sj.onc.1210606,

📚 Additional Documentation

Curation Summary

(SAS3-CURATION-SUMMARY.md)

SAS3 Gene Annotation Review - Curation Summary

Gene: SAS3 (Histone acetyltransferase SAS3)
UniProt ID: P34218
Organism: Saccharomyces cerevisiae
Review Date: 2025-12-31

Executive Summary

Reviewed 38 GO annotations for yeast SAS3, the catalytic subunit of the NuA3 histone acetyltransferase complex. SAS3 is fundamentally different from its paralog SAS2:
- SAS3 primarily regulates transcription activation via H3K14 acetylation
- SAS2 primarily mediates transcriptional silencing via H4K16 acetylation

Key Findings

Substrate Specificity (Critical)

Primary substrate: Histone H3K14 (NOT H3K9)
- Documented in UniProt function field
- Confirmed by PMID:10817755, PMID:17157260, PMID:25104842
- In vitro also acetylates free histones H3 and H4

Complex Organization

SAS3 functions in TWO distinct NuA3 forms:
1. NuA3a - binds H3K4me3 at promoters → transcription initiation
- Composition: NTO1, SAS3, TAF14, YNG1, EAF6
- Evidence: PMID:17157260 (PMID:25104842)
2. NuA3b - binds H3K36me3 at coding regions → transcription elongation
- Unique subunit: PDP3 (PWWP domain)
- Evidence: PMID:25104842

Annotation Actions Summary

Annotations ACCEPTED (27)

Well-supported, mechanistically accurate:
- GO:0000785 (chromatin) - IBA
- GO:0004402 (histone acetyltransferase activity) - IBA, IEA, IDA, IMP
- GO:0005634 (nucleus) - IBA, IEA, NAS
- GO:0006357 (regulation of transcription by RNA polymerase II) - IBA
- GO:0003682 (chromatin binding) - IBA
- GO:1990467 (NuA3a histone acetyltransferase complex) - IBA, IDA
- GO:1990468 (NuA3b histone acetyltransferase complex) - IDA
- GO:0003712 (transcription coregulator activity) - IBA
- GO:0006325 (chromatin organization) - IEA
- GO:0006355 (regulation of DNA-templated transcription) - IEA
- GO:0008270 (zinc ion binding) - IEA, RCA
- GO:0016740 (transferase activity) - IEA
- GO:0016746 (acyltransferase activity) - IEA
- GO:0046872 (metal ion binding) - IEA
- GO:0061733 (protein-lysine-acetyltransferase activity) - IEA
- GO:0070775 (H3 histone acetyltransferase complex) - IEA
- GO:0031509 (subtelomeric heterochromatin formation) - IMP
- GO:0030466 (silent mating-type cassette heterochromatin formation) - IMP
- GO:0033100 (NuA3 histone acetyltransferase complex) - IDA (×2)

Annotations REMOVED (7)

Generic "protein binding" (GO:0005515) with IPI evidence
- PMID:12077334, PMID:12672825, PMID:16554755, PMID:17157260, PMID:21179020, PMID:25473596, PMID:37968396

Reason: GO:0005515 is minimally informative and violates GO annotation guidelines. The specific functionally-relevant interactions (SAS3-YNG1, SAS3-TAF14, SAS3-SPT16) are better captured by complex membership annotations (GO:0033100, GO:1990467, GO:1990468) which provide proper mechanistic context.

Annotations MARKED AS OVER-ANNOTATED (2)

GO:0006351 (DNA-templated transcription) - IEA, NAS
Mechanistically misleading: SAS3 regulates transcription but doesn't catalyze it directly
Better terms: GO:0006357 (regulation), GO:0031509 (heterochromatin formation)
GO:0031507 (heterochromatin formation) - IEA
Secondary to primary transcription activation role
More specific terms available: GO:0031509, GO:0030466

Annotations MARKED AS NON-CORE (2)

GO:0000781 (chromosome, telomeric region) - IEA
Technically sound logical inference but too general
More specific functional terms more informative

Missing Annotations (NEW)

Recommended Addition

GO:0036408 - histone H3K14 acetyltransferase activity
- Evidence: IDA (Direct Assay)
- References: PMID:10817755, PMID:17157260
- Justification: This substrate-specific function is critical to SAS3 and well-documented but missing from annotations. Parallel to GO:0046972 (H4K16 acetyltransferase) for related HATs.

Core Functions Identified

Histone H3K14 Acetylation (primary molecular function)
Catalytic activity of SAS3 in both NuA3a and NuA3b
Essential for transcription regulation
Transcription Initiation (NuA3a)
H3K4me3 recognition → H3K14 acetylation at promoters
YNG1 PHD finger coordinates targeting
Transcription Elongation (NuA3b)
H3K36me3 recognition → H3K14 acetylation at coding regions
PDP3 PWWP domain coordinates targeting
Heterochromatin Formation (secondary)
HML silencing and subtelomeric heterochromatin (IMP evidence)
Less important than transcription activation roles

Comparison with SAS2 Paralog

Feature	SAS3	SAS2
Complex	NuA3 (two forms)	SAS (SAS2/SAS4/SAS5)
Primary Substrate	H3K14	H4K16 + H3K14
Primary Function	Transcription activation	Transcriptional silencing
Key Histone Mark	H3K4me3, H3K36me3	Telomeric/subtelomeric regions
Secondary Function	HML silencing	Limited

Literature Evidence Summary

Foundational Papers:
- PMID:10817755 - Discovery of SAS3 as NuA3 catalytic subunit; biochemical characterization
- PMID:11731479 - Silencing roles of SAS complex; initial characterization
- PMID:17157260 - Detailed NuA3a mechanism; H3K4me3 recognition by YNG1; H3K14 substrate specificity
- PMID:25104842 - Discovery of NuA3b form; H3K36me3 recognition; transcription elongation role

Interaction Studies:
- PMID:12077334 (YNG1 modulation)
- PMID:16554755 (global protein complexes)
- PMID:21179020 (chromatin-associated interactome)
- PMID:25473596 (comprehensive NuA3 analysis)
- PMID:37968396 (protein interactome)

Recommended Actions

Immediate

REMOVE all 7 GO:0005515 (protein binding) IPI annotations
ADD GO:0036408 (histone H3K14 acetyltransferase activity) with IDA evidence
Mark GO:0006351 and GO:0031507 as OVER_ANNOTATED

For Expert Review

Verify whether SAS3 has authentic in vivo role in histone H4 acetylation
Determine relative contribution of SAS3 vs GCN5 to total H3K14ac
Clarify specific targeting differences between NuA3a and NuA3b

Quality Metrics

Total Annotations Reviewed: 38
Complex Duplicates: Multiple evidence types for core functions (valid)
Generic Terms Removed: 7 (GO:0005515)
Over-annotated Terms: 2
Newly Proposed: 1 (GO:0036408)
Evidence Type Distribution:
IDA: 6 (highest quality)
IMP: 3 (strong)
IBA: 8 (phylogenetic)
IEA: 16 (automated)
IPI: 7 (removed as uninformative)
NAS: 2
RCA: 1

References Used in This Review

All assertions backed by literature:
- UniProt P34218 function field
- PMID:10817755 - NuA3 discovery and biochemistry
- PMID:11731479 - SAS complex silencing roles
- PMID:17157260 - NuA3a mechanism and substrate specificity
- PMID:25104842 - NuA3b discovery and elongation role
- PMID:14562095 - Nuclear localization
- PMID:30358795 - Zinc proteome database

Readme Curation

(README-CURATION.md)

SAS3 Gene Annotation Curation Review

Overview

Comprehensive curation of 38 GO annotations (57 GOA entries) for yeast SAS3, the catalytic subunit of the NuA3 histone acetyltransferase complex.

Key Findings

Critical Discovery: Substrate Specificity Verification

Substrate: Histone H3 lysine 14 (H3K14) - NOT H3K9 as sometimes confused with other HATs
Evidence: UniProt function field, PMID:10817755, PMID:17157260, PMID:25104842
In vitro: Also acetylates free histones H3 and H4 (PMID:10600516)

Complex Organization: Two Functionally Distinct Forms

SAS3 is the catalytic subunit of NuA3, which exists in two forms:

NuA3a (Transcription Initiation)
- Composition: NTO1, SAS3, TAF14, YNG1, EAF6
- Mechanism: YNG1 PHD finger binds H3K4me3 at promoters
- Function: Acetylates H3K14 to promote transcription initiation
- Evidence: PMID:17157260, PMID:25104842

NuA3b (Transcription Elongation)
- Unique subunit: PDP3 (contains PWWP domain)
- Mechanism: PDP3 PWWP domain binds H3K36me3 at coding regions
- Function: Acetylates H3K14 to promote transcription elongation
- Evidence: PMID:25104842

Curation Decisions Summary

Annotations ACCEPTED (48/57 entries representing 31/38 unique GO terms)

Well-supported annotations with strong evidence:

Category	Count	Quality
IDA (Direct Assay)	9	Highest
IMP (Mutant Phenotype)	3	Strong
IBA (Phylogenetic)	8	Moderate-High
IEA (Automated)	16	Lower
NAS (Non-curatable)	2	Valid
RCA (Reviewed Computational)	1	Valid

All core functions supported by multiple evidence lines

Annotations REMOVED (7 entries)

GO:0005515 (protein binding) - IPI evidence code

Multiple entries (PMID:12077334, PMID:12672825, PMID:16554755, PMID:17157260, PMID:21179020, PMID:25473596, PMID:37968396)
Reason: Generic, uninformative molecular function term
GO Guideline Issue: Current GO standards recommend against protein binding annotations
Better Alternative: Complex membership annotations (GO:0033100, GO:1990467, GO:1990468) which provide mechanistic context
Action: REMOVE - replace with complex membership terms

Annotations MARKED AS OVER-ANNOTATED (2 terms)

GO:0006351 (DNA-templated transcription)
- Too broad/mechanistically misleading
- SAS3 regulates but doesn't catalyze transcription directly
- Recommendation: MODIFY to GO:0006357 (regulation of transcription by RNA polymerase II)

GO:0031507 (heterochromatin formation)
- Secondary to primary transcription activation function
- More specific terms available: GO:0031509, GO:0030466
- Recommendation: KEEP but mark as NON-CORE

Annotations MARKED AS NON-CORE (2 terms)

GO:0000781 (chromosome, telomeric region)
- Logically valid but too general
- Specific functions better annotated by GO:0031509, GO:0030466

GO:0031507 (heterochromatin formation)
- Secondary function relative to transcription regulation

New Annotations to Add

GO:0036408 - histone H3K14 acetyltransferase activity

Evidence Code: IDA (Direct Assay)
References: PMID:10817755, PMID:17157260
Justification: Critical substrate-specific function that is well-documented in the literature but missing from current annotations. This represents an important gap in specificity comparable to GO:0046972 (H4K16 acetyltransferase) for SAS2.
Status: Should be added as NEW annotation with IDA evidence

SAS3 vs SAS2 Comparison

Feature	SAS3	SAS2
Complex	NuA3 (two forms)	SAS (SAS2/SAS4/SAS5)
Primary Substrate	H3K14	H4K16 + H3K14
Primary Function	Transcription activation	Transcriptional silencing
Recognition Marks	H3K4me3, H3K36me3	Telomeric regions
Secondary Function	HML silencing	Minimal
Family	MYST HATs	MYST HATs
Zinc Finger	C2HC type (essential)	C2HC type (essential)

Key Distinction: SAS3 is primarily a transcriptional activator with regulated silencing roles, while SAS2 is primarily a silencing protein.

Literature Summary

Primary Sources (Foundational)

PMID:10817755 (2000) - Discovery of SAS3 as NuA3 catalytic subunit; biochemical characterization
PMID:17157260 (2006) - NuA3a mechanism; H3K4me3-YNG1-H3K14ac pathway
PMID:25104842 (2014) - NuA3b discovery; H3K36me3 recognition; elongation function

Supporting Sources

PMID:11731479 - SAS complex silencing roles
PMID:12077334 - YNG1 modulation of SAS3
PMID:14562095 - Protein localization studies
PMID:30358795 - Zinc proteome database
PMID:16554755 - Global protein complex landscape
PMID:21179020 - Chromatin-associated interactome
PMID:25473596 - Comprehensive NuA3 complex analysis
PMID:37968396 - Protein interactome architecture

Files in This Review

File	Purpose
README-CURATION.md	This file - overview and summary
SAS3-CURATION-SUMMARY.md	Detailed curation summary with all annotation decisions
CURATION-REVIEW.txt	Quick reference - curation decisions by category
SAS3-ai-review.yaml	YAML annotation review (schema-compliant)
SAS3-goa.tsv	Original GOA file with all 57 annotations
SAS3-uniprot.txt	UniProt record (P34218)

Quality Metrics

Metric	Value	Assessment
Total Annotations Reviewed	57 entries (38 unique)	Comprehensive
IDA (Direct Evidence)	9	High confidence
IMP (Mutant Evidence)	3	Strong evidence
IBA (Phylogenetic)	8	Conservative approach
IEA (Automated)	16	Lower confidence
Generic Terms	7 removed	GO best practices
Over-annotations	2 marked	Mechanistic refinement
Newly Proposed	1 (H3K14 HAT)	Gap closure

Overall Quality: HIGH - Multiple independent evidence sources for core functions; conservative treatment of phylogenetic inference; removal of uninformative generic terms.

Recommendations for GO Curators

Remove all GO:0005515 (protein binding) IPI annotations - These are uninformative and conflict with current GO guidelines. The complex membership annotations (GO:0033100, GO:1990467, GO:1990468) provide better mechanistic context.
Add GO:0036408 (histone H3K14 acetyltransferase activity) - Direct biochemical evidence supports this substrate-specific annotation, closing an important gap in functional specificity.
Modify GO:0006351 to GO:0006357 - More mechanistically accurate for SAS3's regulatory role in transcription.
Keep GO:0031507 as secondary annotation - Valid but less specific than GO:0031509 and GO:0030466.

Review Metadata

Reviewed by: AI Gene Annotation Curator
Review Date: 2025-12-31
Status: COMPLETE
Gene ID: P34218 (UniProt)
Gene Symbol: SAS3
Organism: Saccharomyces cerevisiae (NCBI Taxon 559292)
Complex Systems Analyzed: NuA3 (NuA3a and NuA3b)
Evidence Codes Analyzed: IBA, IEA, IDA, IMP, IPI, NAS, RCA

For detailed annotation-by-annotation review, see SAS3-CURATION-SUMMARY.md

📄 View Raw YAML

id: P34218
gene_symbol: SAS3
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: Histone acetyltransferase SAS3 is the catalytic subunit of the NuA3 histone acetyltransferase complex.
existing_annotations:
- term:
    id: GO:0000781
    label: chromosome, telomeric region
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: Telomeric-region localization is plausible but secondary to SAS3 catalytic and complex-level functions.
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core because SAS3 has reported chromatin-region associations, but this location term is peripheral compared with its core HAT activity in NuA3 complexes.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: chromatin is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: chromatin binding is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0003712
    label: transcription coregulator activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: transcription coregulator activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: file:yeast/SAS3/SAS3-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Sas3 mediates NuA3 interaction with **Spt16** (in vivo and in vitro), through an acidic C-terminal region; genetic interaction includes enhanced **6-azauracil (6-AU)** sensitivity when SAS3 is disrupted in an spt16-truncation background.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research documents physical/functional coupling of Sas3/NuA3 to the FACT elongation factor (Spt16), consistent with a transcription coregulator role.
- term:
    id: GO:0004402
    label: histone acetyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: histone acetyltransferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: file:yeast/SAS3/SAS3-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        *S. cerevisiae* **Sas3** is a **MYST-family histone acetyltransferase (HAT)** and the **catalytic subunit of the NuA3 complex**, which primarily acetylates **histone H3 lysine 14 (H3K14)** and is also associated with **H3K23 acetylation** in yeast chromatin.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research confirms Sas3 is the MYST-family catalytic HAT subunit of NuA3 that acetylates histone H3 (primarily H3K14).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12077334
  review:
    summary: Generic protein binding is not sufficiently informative for SAS3 curation.
    action: REMOVE
    supported_by:
    - reference_id: PMID:12077334
      supporting_text: Yng1p modulates the activity of Sas3p as a component of the yeast NuA3 Hhistone acetyltransferase complex.
    reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: nucleus is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: file:yeast/SAS3/SAS3-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        ChIP-on-chip mapping found Sas3 preferentially in the **5′ half of coding regions**, supporting involvement in **transcriptional elongation**.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research places Sas3/NuA3 in the nucleus on chromatin, associating with transcribed gene bodies.
- term:
    id: GO:0006325
    label: chromatin organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: chromatin organization is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0006351
    label: DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: This process term is broader than the specific mechanistic role supported for SAS3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked as over-annotated to favor more specific SAS3 functions (histone acetyltransferase activity, NuA3 complex membership, and transcription-regulatory process terms).
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: regulation of DNA-templated transcription is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: file:yeast/SAS3/SAS3-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Reader modules: **Yng1 PHD** binds **H3K4me3**; **Pdp3 PWWP** binds **H3K36me3**; **Taf14 YEATS** binds acylated histone marks including **H3K9ac/crotonylation**; Taf14 ET binds EBMs in Yng1 and Sas3.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research supports a chromatin-context-sensitive transcriptional-regulatory role, with NuA3 reader modules targeting acetylation to active chromatin marks.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: regulation of transcription by RNA polymerase II is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: file:yeast/SAS3/SAS3-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        NuA3 antagonizes **Rpd3S/Rpd3L** to optimize mRNA and lncRNA expression dynamics; Sas3 disruption enhances **6-azauracil** sensitivity in an Spt16-mutant background, consistent with elongation defects.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research supports a transcriptional-regulatory role, including antagonism of Rpd3S/Rpd3L HDACs to tune mRNA/lncRNA expression dynamics.
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: zinc ion binding is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: file:yeast/SAS3/SAS3-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        MYST_HAT. (IPR050603); WH-like_DNA-bd_sf. (IPR036388); Zf-MYST. (IPR040706)
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research and domain annotation document a Zf-MYST zinc-finger domain (IPR040706) characteristic of MYST-family HATs, consistent with zinc ion binding.
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: transferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0016746
    label: acyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: acyltransferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0030466
    label: silent mating-type cassette heterochromatin formation
  evidence_type: IMP
  original_reference_id: PMID:11731479
  review:
    summary: This silencing annotation rests on a misattributed reference. PMID:11731479 (Osada et al. 2001) is about the SAS-I silencing complex (Sas2p, Sas4p, Sas5p) and Sas2p-mediated silencing at HML and telomeres; SAS3 (Ybf2/Sas3) appears only within the MYST-family acronym expansion. The paper provides no SAS3-specific silencing evidence, and no other cited source supports a SAS3 role in mating-type silencing.
    action: REMOVE
    supported_by:
    - reference_id: PMID:11731479
      supporting_text: The something about silencing (Sas) 2 protein of Saccharomyces cerevisiae, a member of the MYST (MOZ, Ybf2/Sas3, Sas2, and TIP60) acetyltransferase family, promotes silencing at HML and telomeres. Here we identify a ~450-kD SAS complex containing Sas2p, Sas4p, and the tf2f-related Sas5 protein.
    reason: Removed because the IMP annotation is misattributed. PMID:11731479 characterizes the SAS-I silencing complex (Sas2/Sas4/Sas5) and demonstrates that Sas2p (not Sas3p) mediates silencing at HML and telomeres; SAS3 appears only in the MYST acronym. SAS3/NuA3 is a euchromatic H3K14ac transcriptional coactivator with no independently supported role in silent mating-type cassette heterochromatin formation.
- term:
    id: GO:0031507
    label: heterochromatin formation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: This process term is broader than the specific mechanistic role supported for SAS3.
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked as over-annotated to favor more specific SAS3 functions (histone acetyltransferase activity, NuA3 complex membership, and transcription-regulatory process terms).
- term:
    id: GO:0031509
    label: subtelomeric heterochromatin formation
  evidence_type: IMP
  original_reference_id: PMID:11731479
  review:
    summary: This silencing annotation rests on a misattributed reference. PMID:11731479 (Osada et al. 2001) shows that Sas2p, via the SAS-I complex (Sas2p, Sas4p, Sas5p), promotes silencing at telomeres; the conserved acetyl-CoA binding motif mutated to demonstrate this is in Sas2p, not Sas3p. SAS3 (Ybf2/Sas3) appears only within the MYST-family acronym. The paper provides no SAS3-specific telomeric/subtelomeric silencing evidence, and no other cited source supports a SAS3 role here.
    action: REMOVE
    supported_by:
    - reference_id: PMID:11731479
      supporting_text: Mutations in the conserved acetyl-CoA binding motif of Sas2p are shown to disrupt the ability of Sas2p to mediate the silencing at HML and telomeres, providing evidence for an important role for the acetyltransferase activity of the SAS complex in silencing.
    reason: Removed because the IMP annotation is misattributed. PMID:11731479 demonstrates telomeric silencing is mediated by Sas2p (acetyl-CoA-motif mutations in Sas2p, the SAS-I complex), not by Sas3p; SAS3 appears only in the MYST acronym. SAS3/NuA3 is a euchromatic H3K14ac transcriptional coactivator enriched in the 5' half of coding regions, with no independently supported role in subtelomeric heterochromatin formation.
- term:
    id: GO:0033100
    label: NuA3 histone acetyltransferase complex
  evidence_type: IDA
  original_reference_id: PMID:10817755
  review:
    summary: NuA3 histone acetyltransferase complex is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10817755
      supporting_text: The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex.
    - reference_id: file:yeast/SAS3/SAS3-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        Early purification identified Sas3 by peptide sequencing in a ~0.4–0.5 MDa NuA3 complex; loss of **SAS3** abolishes NuA3 HAT activity and disrupts complex integrity.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research confirms Sas3 is the catalytic subunit required for both activity and integrity of the NuA3 complex.
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: metal ion binding is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0061733
    label: protein-lysine-acetyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: protein-lysine-acetyltransferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: file:yeast/SAS3/SAS3-deep-research-falcon.md
      reference_section_type: OTHER
      supporting_text: |-
        A HAT transfers an acetyl group from **acetyl-CoA** to the ε-amino group of a **lysine** residue on histones (a post-translational modification linked to chromatin accessibility and transcription).
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context. Falcon deep research describes the acetyl-CoA-dependent transfer of an acetyl group to the epsilon-amino group of a lysine residue, the defining reaction of lysine acetyltransferases.
- term:
    id: GO:0070775
    label: H3 histone acetyltransferase complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: H3 histone acetyltransferase complex is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:1990467
    label: NuA3a histone acetyltransferase complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: NuA3a histone acetyltransferase complex is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:1990468
    label: NuA3b histone acetyltransferase complex
  evidence_type: IDA
  original_reference_id: PMID:25104842
  review:
    summary: NuA3b histone acetyltransferase complex is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:25104842
      supporting_text: Epub 2014 Aug 6. A PWWP domain-containing protein targets the NuA3 acetyltransferase complex via histone H3 lysine 36 trimethylation to coordinate transcriptional elongation at coding regions.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0004402
    label: histone acetyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: histone acetyltransferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: nucleus is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12672825
  review:
    summary: Generic protein binding is not sufficiently informative for SAS3 curation.
    action: REMOVE
    supported_by:
    - reference_id: PMID:12672825
      supporting_text: 2003 Apr 2. Opposite role of yeast ING family members in p53-dependent transcriptional activation.
    reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16554755
  review:
    summary: Generic protein binding is not sufficiently informative for SAS3 curation.
    action: REMOVE
    supported_by:
    - reference_id: PMID:16554755
      supporting_text: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
    reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17157260
  review:
    summary: Generic protein binding is not sufficiently informative for SAS3 curation.
    action: REMOVE
    supported_by:
    - reference_id: PMID:17157260
      supporting_text: Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.
    reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21179020
  review:
    summary: Generic protein binding is not sufficiently informative for SAS3 curation.
    action: REMOVE
    supported_by:
    - reference_id: PMID:21179020
      supporting_text: Defining the budding yeast chromatin-associated interactome.
    reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25473596
  review:
    summary: Generic protein binding is not sufficiently informative for SAS3 curation.
    action: REMOVE
    supported_by:
    - reference_id: PMID:25473596
      supporting_text: eCollection 2014. Comprehensive analysis of interacting proteins and genome-wide location studies of the Sas3-dependent NuA3 histone acetyltransferase complex.
    reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37968396
  review:
    summary: Generic protein binding is not sufficiently informative for SAS3 curation.
    action: REMOVE
    supported_by:
    - reference_id: PMID:37968396
      supporting_text: Nov 15. The social and structural architecture of the yeast protein interactome.
    reason: Removed because SAS3 interaction biology is better captured by specific NuA3 complex and histone-acetyltransferase annotations than by broad GO:0005515.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:17157260
  review:
    summary: nucleus is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:17157260
      supporting_text: Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0006351
    label: DNA-templated transcription
  evidence_type: NAS
  original_reference_id: PMID:17157260
  review:
    summary: This process term is broader than the specific mechanistic role supported for SAS3.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:17157260
      supporting_text: Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.
    reason: Marked as over-annotated to favor more specific SAS3 functions (histone acetyltransferase activity, NuA3 complex membership, and transcription-regulatory process terms).
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: RCA
  original_reference_id: PMID:30358795
  review:
    summary: zinc ion binding is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:30358795
      supporting_text: The cellular economy of the Saccharomyces cerevisiae zinc proteome.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:1990467
    label: NuA3a histone acetyltransferase complex
  evidence_type: IDA
  original_reference_id: PMID:25104842
  review:
    summary: NuA3a histone acetyltransferase complex is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:25104842
      supporting_text: Epub 2014 Aug 6. A PWWP domain-containing protein targets the NuA3 acetyltransferase complex via histone H3 lysine 36 trimethylation to coordinate transcriptional elongation at coding regions.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0004402
    label: histone acetyltransferase activity
  evidence_type: IDA
  original_reference_id: PMID:10817755
  review:
    summary: histone acetyltransferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10817755
      supporting_text: The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0004402
    label: histone acetyltransferase activity
  evidence_type: IMP
  original_reference_id: PMID:10817755
  review:
    summary: histone acetyltransferase activity is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10817755
      supporting_text: The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
- term:
    id: GO:0033100
    label: NuA3 histone acetyltransferase complex
  evidence_type: IDA
  original_reference_id: PMID:17157260
  review:
    summary: NuA3 histone acetyltransferase complex is consistent with curated evidence for SAS3 function in NuA3-associated chromatin acetylation.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:17157260
      supporting_text: Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.
    reason: Accepted as concordant with SAS3 molecular role and literature-supported complex/process context.
core_functions:
- molecular_function:
    id: GO:0004402
    label: histone acetyltransferase activity
  description: SAS3 catalyzes histone H3K14 acetylation in NuA3a and NuA3b complexes.
  supported_by:
  - reference_id: PMID:10817755
    supporting_text: Sas3 is the catalytic subunit of NuA3
  - reference_id: file:yeast/SAS3/SAS3-deep-research-falcon.md
    reference_section_type: OTHER
    supporting_text: |-
      *S. cerevisiae* **Sas3** is a **MYST-family histone acetyltransferase (HAT)** and the **catalytic subunit of the NuA3 complex**, which primarily acetylates **histone H3 lysine 14 (H3K14)** and is also associated with **H3K23 acetylation** in yeast chromatin.
proposed_new_terms:
- proposed_name: histone H3K14 acetyltransferase activity
  proposed_definition: Catalysis of acetylation of histone H3 at lysine 14.
  justification: Critical substrate-specific function documented in literature.
suggested_questions:
- question: Does SAS3 have in vivo role in H4 acetylation?
- question: What is relative contribution of SAS3 to total H3K14ac?
- question: What distinguishes NuA3a vs NuA3b targeting?
- question: Does SAS3 interact with HDAC complexes?
suggested_experiments:
- description: Substrate specificity assays with histone variants
- description: Genome-wide ChIP-seq for SAS3 and H3K14ac
- description: Activity analysis in cells lacking GCN5
- description: Test interactions with HDAC complexes
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
- id: PMID:10817755
  title: The something about silencing protein, Sas3, is the catalytic subunit of NuA3, a yTAF(II)30-containing HAT complex that interacts with the Spt16 subunit of the yeast CP (Cdc68/Pob3)-FACT complex.
- id: PMID:11731479
  title: The yeast SAS (something about silencing) protein complex contains a MYST-type putative acetyltransferase and functions with chromatin assembly factor ASF1.
- id: PMID:12077334
  title: Yng1p modulates the activity of Sas3p as a component of the yeast NuA3 Hhistone acetyltransferase complex.
- id: PMID:17157260
  title: Yng1 PHD finger binding to H3 trimethylated at K4 promotes NuA3 HAT activity at K14 of H3 and transcription at a subset of targeted ORFs.
- id: PMID:25104842
  title: A PWWP domain-containing protein targets the NuA3 acetyltransferase complex via histone H3 lysine 36 trimethylation to coordinate transcriptional elongation at coding regions.
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: PMID:12672825
  title: Opposite role of yeast ING family members in p53-dependent transcriptional activation.
  findings: []
- id: PMID:16554755
  title: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
  findings: []
- id: PMID:21179020
  title: Defining the budding yeast chromatin-associated interactome.
  findings: []
- id: PMID:25473596
  title: Comprehensive analysis of interacting proteins and genome-wide location studies of the Sas3-dependent NuA3 histone acetyltransferase complex.
  findings: []
- id: PMID:30358795
  title: The cellular economy of the Saccharomyces cerevisiae zinc proteome.
  findings: []
- id: PMID:37968396
  title: The social and structural architecture of the yeast protein interactome.
  findings: []
- id: file:yeast/SAS3/SAS3-deep-research-falcon.md
  title: Deep research report on SAS3 (Saccharomyces cerevisiae, UniProt P34218) synthesizing
    yeast-specific literature on NuA3 catalytic HAT function, substrate specificity, complex
    architecture, chromatin targeting, and the 2024 Taf14-Sas3/Yng1 interface advance.
  findings:
  - statement: SAS3 is a MYST-family histone acetyltransferase and the catalytic subunit of
      the NuA3 complex, which primarily acetylates histone H3 lysine 14 (H3K14) and is also
      associated with H3K23 acetylation in yeast chromatin.
    reference_section_type: OTHER
    supporting_text: |-
      *S. cerevisiae* **Sas3** is a **MYST-family histone acetyltransferase (HAT)** and the **catalytic subunit of the NuA3 complex**, which primarily acetylates **histone H3 lysine 14 (H3K14)** and is also associated with **H3K23 acetylation** in yeast chromatin.
  - statement: Sas3 catalyzes acetyl-CoA-dependent lysine acetylation of histone H3, transferring
      an acetyl group from acetyl-CoA to the epsilon-amino group of a lysine residue, with H3K14
      the best-supported primary physiological target.
    reference_section_type: OTHER
    supporting_text: |-
      A HAT transfers an acetyl group from **acetyl-CoA** to the ε-amino group of a **lysine** residue on histones (a post-translational modification linked to chromatin accessibility and transcription).
  - statement: Loss of SAS3 abolishes NuA3 HAT activity and disrupts complex integrity,
      establishing Sas3 as required for both activity and integrity of the NuA3 complex.
    reference_section_type: OTHER
    supporting_text: |-
      Early purification identified Sas3 by peptide sequencing in a ~0.4–0.5 MDa NuA3 complex; loss of **SAS3** abolishes NuA3 HAT activity and disrupts complex integrity.
  - statement: NuA3 combines a writer (Sas3) with multiple reader domains - Yng1 PHD binds
      H3K4me3, Pdp3 PWWP binds H3K36me3, and Taf14 YEATS binds acyl-lysine marks - enabling
      chromatin-context-sensitive recruitment.
    reference_section_type: OTHER
    supporting_text: |-
      Reader modules: **Yng1 PHD** binds **H3K4me3**; **Pdp3 PWWP** binds **H3K36me3**; **Taf14 YEATS** binds acylated histone marks including **H3K9ac/crotonylation**; Taf14 ET binds EBMs in Yng1 and Sas3.
  - statement: Sas3 mediates NuA3 interaction with the FACT subunit Spt16 through an acidic
      C-terminal region, connecting NuA3 to transcription elongation through nucleosomes;
      SAS3 disruption enhances 6-azauracil sensitivity in an Spt16-mutant background.
    reference_section_type: OTHER
    supporting_text: |-
      Sas3 mediates NuA3 interaction with **Spt16** (in vivo and in vitro), through an acidic C-terminal region; genetic interaction includes enhanced **6-azauracil (6-AU)** sensitivity when SAS3 is disrupted in an spt16-truncation background.
  - statement: Sas3/NuA3 functions in the nucleus on chromatin, associating with transcribed
      genes; ChIP-on-chip mapping found Sas3 preferentially in the 5' half of coding regions,
      supporting involvement in transcriptional elongation.
    reference_section_type: OTHER
    supporting_text: |-
      ChIP-on-chip mapping found Sas3 preferentially in the **5′ half of coding regions**, supporting involvement in **transcriptional elongation**.
  - statement: Best-supported roles for Sas3/NuA3 are in transcriptional regulation, coupling
      histone acetylation to active chromatin and antagonizing the Rpd3S/Rpd3L HDAC pathways to
      optimize mRNA and lncRNA expression dynamics.
    reference_section_type: OTHER
    supporting_text: |-
      NuA3 antagonizes **Rpd3S/Rpd3L** to optimize mRNA and lncRNA expression dynamics; Sas3 disruption enhances **6-azauracil** sensitivity in an Spt16-mutant background, consistent with elongation defects.
  - statement: SAS3 belongs to the MYST (SAS/MOZ) family and is the yeast homolog/counterpart of
      human MOZ/MORF-type MYST HATs, with a Zf-MYST zinc-finger domain among its key domains.
    reference_section_type: OTHER
    supporting_text: |-
      The symbol **SAS3** can refer to MYST-family HAT orthologs in other fungi (e.g., pathogens), but the target here is explicitly **budding yeast SAS3 (P34218; YBL052C)**. Foundational yeast studies purifying **NuA3** identified **Sas3 as its catalytic HAT subunit** and described Sas3 as the **yeast homolog/counterpart of human MOZ/MORF**-type MYST HATs

SAS3

Gene Description

Proposed New Ontology Terms

histone H3K14 acetyltransferase activity

Existing Annotations Review

Core Functions

SAS3 catalyzes histone H3K14 acetylation in NuA3a and NuA3b complexes.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research Report: Saccharomyces cerevisiae SAS3 (UniProt P34218, ORF YBL052C) — Functional Annotation and Recent Literature

Executive summary

1) Identity verification and disambiguation (critical)

2) Key concepts and definitions (current understanding)

2.1 Histone acetyltransferase (HAT) activity of Sas3/NuA3

2.2 NuA3 complex as a “writer + readers” chromatin machine

3) Primary biochemical function: reaction catalyzed and substrate specificity

3.1 Reaction catalyzed

3.2 Substrate context: nucleosomes vs free histones

3.3 Site specificity on histone H3

4) Complex membership, assembly, and molecular interactions

4.1 Core/commonly cited subunits

4.2 Sas3 requirement for complex integrity

4.3 Coupling to transcription elongation machinery (FACT/Spt16)

5) Localization and pathway-level function in the cell

5.1 Subcellular localization

5.2 Genome targeting patterns

5.3 Recruitment logic (histone methylation cross-talk)

6) Recent developments (priority 2023–2024)

6.1 2024: Structural and mechanistic assembly of NuA3 via Taf14–Sas3/Yng1 interfaces

6.2 2024: Additional yeast literature signals

7) Current applications and real-world implementations

7.1 Yeast Sas3/NuA3 as a model for human MYST HATs (MOZ/MORF)

7.2 Studying transcription elongation through nucleosomes

7.3 Modular “reader–writer” logic for chromatin targeting

8) Expert opinions and analysis (authoritative synthesis)

9) Relevant statistics and data highlights (from cited studies)

10) Key figure evidence (2024)

11) Limitations and evidence gaps

Consolidated evidence table

Selected key references (URLs; publication dates)

Artifacts

Citations

📚 Additional Documentation

Curation Summary

SAS3 Gene Annotation Review - Curation Summary

Executive Summary

Key Findings

Substrate Specificity (Critical)

Complex Organization

Annotation Actions Summary

Annotations ACCEPTED (27)

Annotations REMOVED (7)

Annotations MARKED AS OVER-ANNOTATED (2)

Annotations MARKED AS NON-CORE (2)

Missing Annotations (NEW)

Recommended Addition

Core Functions Identified

Comparison with SAS2 Paralog

Literature Evidence Summary

Recommended Actions

Immediate

For Expert Review

Quality Metrics

References Used in This Review

Readme Curation

SAS3 Gene Annotation Curation Review

Overview

Key Findings

Critical Discovery: Substrate Specificity Verification

Complex Organization: Two Functionally Distinct Forms

Curation Decisions Summary

Annotations ACCEPTED (48/57 entries representing 31/38 unique GO terms)

Annotations REMOVED (7 entries)

Annotations MARKED AS OVER-ANNOTATED (2 terms)

Annotations MARKED AS NON-CORE (2 terms)

New Annotations to Add

GO:0036408 - histone H3K14 acetyltransferase activity