Sus1 is a small (108 aa), noncatalytic protein of the ENY2/Sus1 family that is a subunit of the SAGA transcriptional coactivator complex. In fission yeast it co-purifies with SAGA and with the deubiquitinase Ubp8. Together with Ubp8, Sgf11 and Sgf73 it forms the SAGA deubiquitination (DUB) module, which removes ubiquitin from histone H2B; Sgf73 anchors this module to SAGA. In structural work on the orthologous budding-yeast module, Sus1 clamps the long N-terminal helix of Sgf11 onto the zinc-finger UBP domain of Ubp8, so it acts as an assembly scaffold rather than as an enzyme. Its orthologs in budding yeast and animals are also subunits of TREX-2, the nuclear-pore-associated mRNA export complex, where they help target TREX-2 to the nuclear basket and support export of polyadenylated mRNA. In fission yeast, the TREX-2 role is inferred from these orthologs and has not been tested directly. Sus1 is mainly nuclear; studies in budding yeast also report a minor, conditional pool in cytoplasmic granules.
Summary: SAGA membership is inherited from the ENY2/Sus1 ancestor (PTN000282153) and is directly shown for the fission yeast protein.
Reason: The PAINT node PTN000282153 covers fungal, animal and plant ENY2/Sus1 proteins, and the target sits inside it (PTHR12514; no subfamily split separates the target from the donors). The target's own experimental SAGA annotation, from fission yeast SAGA purification, is among the descendant evidence. This is expected and is not circular. Independent fission yeast data place Sus1 in the Sgf73-anchored DUB module of SAGA.
IDA PMID:19056896 The S. pombe SAGA complex controls the switch from prolifera...
ACCEPT
Summary: Direct fission yeast SAGA purification identifies Sus1 as a subunit.
Reason: In Helmlinger et al. 2008, SAGA purified from fission yeast had the same composition as budding yeast SAGA. UniProt credits this paper for the 19-subunit inventory that includes sus1. Later fission yeast purifications (Ubp8-TAP; SAGA from sgf73 deletion strains) confirm that Sus1 is a subunit of the DUB module.
Summary: The automated SAGA mapping agrees with the experimental and phylogenetic evidence.
Reason: This row comes from the IPR018783/UniRule family signature. It is consistent with the direct fission yeast SAGA purification and the IBA for the same term.
IPI PMID:19056896 The S. pombe SAGA complex controls the switch from prolifera...
ACCEPT
Summary: Co-purification with SAGA in fission yeast.
Reason: The same SAGA purification as the IDA row, recorded as an interaction. Only the abstract is cached; the subunit inventory credited to this paper in UniProt includes sus1. We defer to the curator, who read the full text.
IPI PMID:29079657 TORC1 and TORC2 converge to regulate the SAGA co-activator i...
ACCEPT
Summary: Co-purification with the SAGA subunit Hfi1/Ada1 (SPBC887.18c) in fission yeast.
Reason: The WITH entity SPBC887.18c is hfi1/ada1, a core SAGA subunit. Only the abstract of this fission yeast SAGA proteomics paper is cached, so the Sus1 co-purification cannot be read here. It matches the other fission yeast purifications, and we defer to the curator.
Summary: The P-body location comes from a HAMAP rule. In budding yeast it is seen only partially, conditionally and transiently, and it has not been tested in fission yeast.
Reason: In budding yeast, Sus1 enters P-bodies mainly when overexpressed or in stationary phase. The authors describe the association as partial and probably transient, and Sus1 is not needed to form P-bodies. The HAMAP rule extends this conditional, minor localisation to the whole ENY2 family. It is plausible for fission yeast, but it is peripheral to Sus1's nuclear roles and has not been tested in this species. It is retained as non-core.
Summary: The PAINT node assigns coactivator activity to the ENY2/Sus1 clade. For Sus1 this activity is exercised as a noncatalytic SAGA subunit.
Reason: Coactivator activity belongs to SAGA as a whole. Sus1 is a stable subunit that is needed to retain and assemble the DUB module, and budding-yeast Sus1 is recruited to SAGA-dependent promoters during activation. The PAINT curator placed the activity at the ENY2/Sus1 ancestor, and the target is inside that clade. The term is accepted as Sus1's share of SAGA's coactivator function. It does not mean that Sus1 alone binds activators or has catalytic activity.
Summary: Correct but general. The nucleoplasm and nuclear pore locations, which this gene already carries, are more informative.
Reason: Sus1 is nuclear, but its known sites are more specific. It acts at SAGA-bound chromatin in the nucleoplasm and, in orthologs, at the nuclear basket of the nuclear pore with TREX-2. Both descendant terms are already annotated to this gene (GO:0005654, GO:0005643), so the general term is refined to them.
Summary: Nuclear-pore association through TREX-2 is conserved in the ENY2/Sus1 family. In fission yeast it is inferred, not observed.
Reason: Budding-yeast Sus1 is concentrated at nuclear pores, and Sus1 mutants that lose Sac3 binding fail to target TREX-2 to nuclear pore complexes. Sequence comparison shows that S. pombe Sus1 keeps the residues needed for these interactions (the sus1-10, sus1-11 and sus1-12 positions are identical or conservatively substituted), and the target is in the same PAINT clade as the characterised orthologs. The location is accepted by homology. It is part of the TREX-2 core function.
Summary: As a SAGA subunit, Sus1 is in the nucleoplasm.
Reason: SAGA is a nucleoplasmic chromatin-associated complex, and fission yeast Sus1 is a stable SAGA DUB-module subunit. Budding-yeast Sus1 is a nuclear protein that also accumulates at pores.
Summary: There is a minor, conditional cytoplasmic pool in budding yeast. It is not established in fission yeast.
Reason: The same evidence and judgement as the P-body row. Budding-yeast Sus1 gathers in cytoplasmic granules in stationary phase or when overexpressed, but it is mostly nuclear. A cytoplasmic pool is plausible, peripheral to function, and untested in fission yeast.
Sus1 is a nuclear protein with a concentration at the nuclear pores.
GO:0006357 regulation of transcription by RNA polymerase II
EXP PMID:21642955 Tra1 has specific regulatory roles, rather than global funct...
ACCEPT
Summary: Fission yeast SAGA study (Tra1). Only the abstract is cached.
Reason: The cached abstract of Helmlinger et al. 2011 does not mention sus1. The full text, including the expression profiling of SAGA mutants, could not be retrieved (Europe PMC returned an error). We defer to the PomBase curator, who read the full text. The claim fits Sus1's established place in the SAGA coactivator. The general "regulation" term is kept rather than refined because fission yeast SAGA both activates and represses targets (for example, ste11).
chromatin immunoprecipitation showed that Sus1 is associated with the promoter of a SAGA-dependent gene during transcription activation
GO:0006357 regulation of transcription by RNA polymerase II
IBA GO_REF:0000033
ACCEPT
Summary: Inherited from the ENY2/Sus1 ancestral node. The target's own experimental annotation is among the descendant evidence.
Reason: The target is inside the PTN000282153 clade. Its appearance in its own WITH/FROM reflects its experimental grounding (PMID:21642955) and is not circular.
Purification of the S. pombe SAGA complex showed that its subunit composition is identical to that of Saccharomyces cerevisiae.
GO:0006368 transcription elongation by RNA polymerase II
IEA GO_REF:0000104
KEEP AS NON CORE
Summary: Budding-yeast Sus1 travels with elongating RNA polymerase II, and its loss impairs elongation. This is an accessory, ortholog-based association.
Reason: In budding yeast, Sus1 associates with Ser5/Ser2-phosphorylated RNA polymerase II, occupies coding regions in a transcription-dependent way, and is needed for normal elongation. This places Sus1 at the elongation complex, where it links SAGA and TREX-2 to the nascent mRNP. It is a supporting role, not part of the polymerase chemistry. It has not been examined in fission yeast and is not part of the PAINT clade-level assertions, so it is kept as non-core.
Here, we show that Sus1 is required during transcription elongation and is associated with the elongating form of RNA Polymerase II (RNAP II) phosphorylated on Ser5 and Ser2 of the C-terminal domain (CTD).
Summary: Correct but general. The IBA term poly(A)+ mRNA export from nucleus, which the gene already carries, is more specific.
Reason: The export role runs through TREX-2, which docks polyadenylated mRNPs at the nuclear basket. GO:0016973 is a descendant term already annotated to this gene by IBA, so the general term is refined to it.
Summary: The PAINT ancestral node assigns mRNA export to the ENY2/Sus1 clade. Fission yeast Sus1 is inside the clade and keeps the TREX-2 binding residues.
Reason: Budding-yeast, fly and human ENY2/Sus1 proteins all act in nuclear mRNA export through TREX-2. The PAINT curator placed this function at PTN000282153, and nothing points to a loss in the fission yeast branch. S. pombe Sus1 keeps the positions whose mutation in budding yeast uncouples Sus1 from Sac3. Sus1 contributes structure to the export step, because it helps target TREX-2 to the pore. Fission yeast export has not been assayed directly.
Summary: Curator inference from SAGA membership. Sus1 contributes through the DUB module's histone H2B deubiquitination.
Reason: GO:0045815 covers changes to nucleosomal histones made to allow gene expression. Sus1 does not catalyse the change itself, but it is a structural subunit that the DUB module needs for its activity. Sus1 clamps Sgf11 onto Ubp8, and Sus1 loss in budding yeast impairs SAGA-dependent H2B deubiquitination. This is the scaffold case of participation.
Purification of the S. pombe SAGA complex showed that its subunit composition is identical to that of Saccharomyces cerevisiae.
GO:0045893 positive regulation of DNA-templated transcription
IEA GO_REF:0000120
MODIFY
Summary: Correct but general. The RNA polymerase II-specific descendant, already annotated by ISO, is better.
Reason: SAGA is a coactivator of RNA polymerase II transcription. GO:0045944 is a descendant term already carried by this gene (ISO from budding yeast SUS1), so the general term is refined to it.
Purification of the S. pombe SAGA complex showed that its subunit composition is identical to that of Saccharomyces cerevisiae.
GO:0045944 positive regulation of transcription by RNA polymerase II
ISO GO_REF:0000024
ACCEPT
Summary: Transferred from budding yeast SUS1, an ortholog in the same PAINT clade.
Reason: Budding-yeast Sus1 is recruited to a SAGA-dependent promoter during activation and is needed for normal transcription of SAGA-dependent genes. Fission yeast Sus1 is a SAGA subunit. The positive-regulation claim fits SAGA's coactivator role.
Summary: TREX-2 membership is inherited from the ENY2/Sus1 ancestral node. The target keeps the Sac3-binding residues.
Reason: Budding-yeast, fly and human ENY2/Sus1 are all TREX-2 subunits, and the PAINT curator placed membership at PTN000282153. The residues that budding-yeast Sus1 uses to bind Sac3 (sus1-10, sus1-11 and sus1-12 positions) are conserved or conservatively substituted in S. pombe. TREX-2 membership has not been shown biochemically in fission yeast; that is a suggested experiment, not grounds for rejecting the inheritance.
Summary: DUB-module membership is inherited from the ENY2/Sus1 node and is directly supported in fission yeast.
Reason: The DUB module (Ubp8-Sgf11-Sus1-Sgf73) is conserved from Arabidopsis to human. In fission yeast, Ubp8 co-purifies with Sus1, and Sus1 leaves SAGA together with Ubp8 and Sgf11 when Sgf73 is deleted. Both results mark Sus1 as a DUB-module subunit. In the budding-yeast DUB module structure, Sus1 is the scaffold that clamps Sgf11 onto Ubp8.
Under our experimental conditions Ubp8 co-purified with four SAGA subunitsβSus1, Tra1, Sgf73, and Sgf29
Core Functions
Noncatalytic scaffold subunit of the SAGA histone H2B deubiquitination module. It holds Sgf11 onto the Ubp8 deubiquitinase and so supports SAGA's chromatin-modifying coactivator function at RNA polymerase II genes.
We demonstrate that Sus1 is involved in the SAGA-dependent histone H2B deubiquitinylation and maintenance of normal H3 methylation levels.
TREX-2 subunit, inherited from the ENY2/Sus1 ancestor, that helps dock polyadenylated mRNPs at the nuclear pore basket for export. In fission yeast this role is inferred by homology.
Q: Does fission yeast Sus1 assemble with the S. pombe Sac3 and Thp1 orthologs into a nuclear-pore-associated TREX-2 complex, as in budding yeast and animals?
Q: Is the extra C-terminal sequence of S. pombe Sus1 (about 10 residues beyond the budding-yeast and human proteins) functionally relevant, or a disordered tail?
Suggested Experiments
Experiment: Affinity-purify tagged Sac3 and Thp1 from fission yeast and test for Sus1 co-purification; image Sus1-GFP for nuclear-rim enrichment, and test sus1 deletion for poly(A)+ RNA nuclear retention by FISH.
Type: affinity purification mass spectrometry; fluorescence microscopy; RNA FISH
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
Sus1 contributes to SAGA chromatin regulation and TREX-2-mediated nuclear mRNA export. Both predictions are supported but broader than the established chromatin-remodeling and polyadenylated-mRNA-export roles.
Review rationale: Mutant, localization and biochemical experiments in characterized budding yeast Sus1 establish an mRNA-export role through Sac3-Thp1/TREX-2. The fission yeast protein belongs to the conserved Sus1/ENY2 family, and curated phylogenetic and orthology annotations support the same complex role. GOA already records the more specific poly(A)+ mRNA export from nucleus (GO:0016973). The prediction is biologically supported through that justified comparative inference, with less transcript specificity.
Supporting Evidence:
PMID:14718168: "Biochemical analyses show that Sus1 interacts with SAGA, a large intranuclear histone acetylase complex involved in transcription initiation, and with the Sac3-Thp1 complex, which functions in mRNA export with specific nuclear pore proteins at the nuclear basket."
PMID:14718168: "Finally, mRNA export is impaired in sus1 mutants."
Review rationale: Fission yeast purification places Sus1 in SAGA, and characterized budding yeast Sus1 mutants establish participation in histone H2B deubiquitination and maintenance of histone H3 methylation. Transfer is justified by conserved Sus1 family identity and SAGA/DUB-module context; this is a noncatalytic contribution to chromatin regulation. GOA already specifies transcription initiation-coupled chromatin remodeling (GO:0045815). Generic chromatin organization is therefore supported but less precise.
Supporting Evidence:
PMID:19056896: "Purification of the S. pombe SAGA complex showed that its subunit composition is identical to that of Saccharomyces cerevisiae."
PMID:16855026: "We demonstrate that Sus1 is involved in the SAGA-dependent histone H2B deubiquitinylation and maintenance of normal H3 methylation levels."