YAR1 (P46683) — Transcription / MBF–SBF Membership Hypothesis: Focused Curation Report OpenScientist openscientist-autonomous 2 artifacts 2026-09-21T00:23:32.612026

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YAR1 (P46683) — Transcription / MBF–SBF Membership Hypothesis: Focused Curation Report

Gene: YAR1 / Saccharomyces cerevisiae (NCBITaxon:559292) · UniProt P46683 · 200 aa
Focus: function_assignment · slug transcriptional-regulation-and-mbf-sbf-membership
Seed hypothesis: Yar1 promotes RNA Pol II transcription or belongs to the MBF or SBF transcription complexes (to be adjudicated independently of DNA-binding transcription-activator activity and Rps3 chaperoning).

Executive Judgment

Verdict: REFUTED / OVER-ANNOTATED (for the transcription and MBF/SBF claims).

There is no primary experimental evidence that Yar1 promotes RNA Pol II transcription or is a subunit of the MBF (Mbp1–Swi6) or SBF (Swi4–Swi6) complexes. Every transcription-related GO annotation on P46683 carries evidence code IBA (Inferred from Biological Ancestor, GO_Central/PANTHER) — i.e., phylogenetically propagated, not observed. In contrast, all experimentally supported annotations (IDA/IMP/HDA) describe Yar1's role as a dedicated chaperone of ribosomal protein Rps3 in 40S small-subunit biogenesis and its nuclear import, backed by genetics, biochemistry, and a 2.8 Å co-crystal structure.

The source of the misannotation is traceable: since 1996 it has been noted that Yar1's ankyrin (ANK) repeats are most similar to those of the cell-cycle transcription factor Swi6. Yar1 and the SBF/MBF ankyrin proteins therefore fall into the same broad ankyrin-repeat PANTHER family (PTHR24198), and Swi6/SBF/MBF transcription terms propagate to Yar1 by IBA. Crucially, in Swi6/Swi4/Mbp1 DNA binding is conferred by the APSES (KilA-N/winged-helix) domain, not by the ANK repeats — and Yar1 possesses only ankyrin repeats, i.e., the generic protein–protein interaction module that does not bind DNA. Thus the seed's own Swi6/Cdc10 analogy, examined carefully, argues against the transcription claim rather than for it.

Most important caveat: absence of positive evidence is not proof of impossibility. A non-DNA-binding, sub-stoichiometric recruitment role cannot be formally excluded by the current data, but nothing in the primary literature or complex-composition datasets places Yar1 in MBF/SBF or at Pol II promoters. The parsimonious, evidence-based interpretation is a ribosome-biogenesis chaperone whose nuclear presence reflects Rps3 import, not transcription.

Evidence Matrix

Citation	Evidence type	Supports/Refutes/Qualifies	Claim tested	Key finding	Context	Confidence & limitations
PMID 24021814 (Holzer, Ban, Klinge 2013)	Structural (co-crystal, direct)	Refutes transcription; supports chaperone	Primary molecular function of Yar1	2.8 Å Rps3–Yar1 structure; Yar1 keeps Rps3 soluble and mediates its nuclear import	S. cerevisiae, in vitro/structural	High. Direct structural mechanism; defines the real function
PMID 15611164 (Loar et al 2004)	Mutant phenotype + interaction (direct)	Refutes transcription; supports 40S role	Whether Yar1 acts in transcription vs ribosome biogenesis	Yar1 binds Rps3 & Ltv1; Δyar1 has reduced 40S/excess free 60S; RPS3 overexpression rescues	S. cerevisiae genetics/biochem	High. Places Yar1 firmly in 40S production
PMID 8675027 (Lycan et al 1996)	Sequence/original characterization	Qualifies (explains the artifact)	Origin of Swi6/SBF link	Yar1 ANK repeats "most similar to…Swi6"; non-essential; slow-growth/cold-sensitive Δyar1; no essential TF phenotype	S. cerevisiae	High for the similarity claim; note authors did not demonstrate TF activity
PMID 16888326 (Seiser et al 2006)	Genetics/pathway (indirect)	Supports 40S/export context	Pathway context of Yar1 partners	Ltv1 (Yar1 partner) required for 40S nuclear export via Crm1	S. cerevisiae	Medium. Contextual, about Ltv1 not Yar1 directly
UniProt P46683 GO set (database)	Database/annotation provenance	Refutes direct transcription support	Evidence basis of TF/MBF/SBF terms	MBF complex, SBF complex, DNA-binding TF activator activity, +reg Pol II transcription are all IBA; all experimental terms are ribosome/localization	GO_Central/PANTHER	High. IBA = phylogenetic inference, not assay
InterPro/PANTHER (P46683) (computational)	Structural/evolutionary	Refutes DNA-binding capacity	Does Yar1 have a DNA-binding domain?	Only ANK signatures (IPR002110, Pfam PF12796, PANTHER PTHR24198); no APSES/KilA-N/winged-helix domain	Public bioinformatics	High. Lack of any DNA-binding fold
EBI Complex Portal CPX-946, CPX-950 (database, curated)	Interaction/complex composition	Refutes MBF/SBF membership	Is Yar1 a subunit of SBF or MBF?	SBF (CPX-946) = Swi4 + Swi6; MBF (CPX-950) = Mbp1 + Swi6; Yar1/P46683 absent from both	S. cerevisiae, manually curated	High. Authoritative complex definition
UniProt domain comparison (computational)	Structural/evolutionary	Refutes/qualifies	Does Yar1 share the DNA-binding module of SBF/MBF?	Swi4/Mbp1 carry APSES-type HTH + H-T-H DNA-binding motif; Yar1 (200 aa) has only 2 ANK repeats — the generic interaction module	Public bioinformatics	High. Yar1 lacks the DNA-contacting subunit's architecture
IntAct interactome (P46683) (database, interaction)	Interaction	Refutes transcription/complex link	Does Yar1 physically interact with SBF/MBF subunits?	15 records; partners = Rps3, Ltv1 + Hsp70/Hsp40 chaperones (Ssa1/2, Ssb1, Sse1, Sis1, Ydj1, Hsp78/26, Erj5, Ess1, Sfm1); no Swi4/Swi6/Mbp1	S. cerevisiae, curated PPIs	High. No interaction evidence for a transcription role

GO Curation Implications (leads requiring curator verification)

GO term	Aspect	Current evidence	Recommended action (lead)
GO:0001228 DNA-binding transcription activator activity, Pol II-specific	MF	IBA only; no APSES domain	Remove / do not propagate. Not supported; contradicted by domain architecture
GO:0030907 MBF transcription complex	CC	IBA only; no complex-composition data	Remove / mark NOT. No primary evidence Yar1 is an MBF subunit
GO:0033309 SBF transcription complex	CC	IBA only	Remove / mark NOT. No primary evidence Yar1 is an SBF subunit
GO:0045944 positive regulation of transcription by Pol II	BP	IBA only	Remove / treat as non-core. No direct evidence; any effect is downstream of ribosome biogenesis
GO:0042274 ribosomal small subunit biogenesis	BP	IMP (experimental)	Retain (core).
GO:0000056 ribosomal small subunit export from nucleus	BP	IMP	Retain.
GO:0005634 nucleus / GO:0005737 cytoplasm	CC	IDA/HDA	Retain. Nuclear signal reflects Rps3 import, not TF role
(candidate addition) protein chaperone / unfolded-protein binding on Rps3	MF	Direct structure PMID 24021814	Consider adding a chaperone MF term (e.g., unfolded/nascent-protein binding) — more informative than "protein binding"

Bottom line: The four IBA transcription terms are over-annotations and are the strongest candidates for removal or a NOT qualifier; the ribosome-biogenesis terms are the core, experimentally supported function.

Mechanistic Scope

Direct molecular activity: Yar1 is a small (200 aa) two-ANK-repeat protein that acts as a dedicated chaperone binding ribosomal protein Rps3, holding it in a soluble, import-competent state (co-crystal structure, PMID 24021814).
Cellular process: couples Rps3 folding/solubility to nuclear import and incorporation into the assembling 40S subunit (PMID 15611164, 16888326).
Downstream/indirect only: stress sensitivity, growth/cold-sensitivity of Δyar1, and any perturbation of gene-expression programs are secondary consequences of impaired 40S biogenesis, not evidence of a direct transcriptional function. Nuclear localization is expected for an Rps3 import chaperone and does not imply promoter association.

Complex Composition & Domain Comparison (computed, Iteration 2)

EBI Complex Portal (manually curated):

Complex	Accession	Subunits	Yar1 present?
SBF transcription complex	CPX-946	Swi4 (P25302) + Swi6 (P09959)	No
MBF ("MBP") transcription complex	CPX-950	Mbp1 (P39678) + Swi6 (P09959)	No

UniProt domain architecture:

Protein	Length	APSES/HTH DNA-binding domain	ANK repeats	Role
Yar1 (P46683)	200 aa	None	2	Rps3 chaperone (not a TF)
Swi6 (P09959)	803 aa	None	5	Shared regulatory subunit (SBF+MBF)
Swi4 (P25302)	1093 aa	APSES-HTH (37–147) + H-T-H (71–92)	2	SBF DNA-binding subunit
Mbp1 (P39678)	833 aa	APSES-HTH (5–111) + H-T-H (36–57)	2	MBF DNA-binding subunit

Interpretation: Yar1 is absent from both curated complexes. The seed's Swi6/Cdc10 precedent (a subunit lacking APSES) is technically real — Swi6 indeed has no APSES domain — but it does not transfer to Yar1: Swi6 is an 803-aa subunit with direct experimental complex-membership evidence, whereas Yar1 is a 200-aa protein with none. The only feature Yar1 shares with any SBF/MBF subunit is the generic ANK repeat, and Yar1's ANK repeats are structurally documented to bind Rps3 (PMID 24021814), not Swi4/Swi6/Mbp1. Shared ANK possession — the driver of the IBA propagation — is not evidence of shared complex membership.

Conflicts and Alternatives

Paralog/family confusion (primary artifact): Yar1 shares the ankyrin-repeat module with genuine SBF/MBF subunit Swi6. Broad PANTHER family PTHR24198 grouping drives IBA propagation of Swi6-derived transcription terms.
Domain-logic conflict: DNA binding in APSES transcription factors (Swi4/Mbp1) resides in the APSES/KilA-N domain, absent from Yar1; Swi6 itself contributes regulation via ANK-mediated protein interactions but is not the DNA-contacting subunit. So the "ANK repeats ≈ transcription factor" inference is unsound.
Alternative interpretation fully consistent with all data: Yar1 = ribosome-assembly chaperone; no competing primary dataset supports an MBF/SBF or Pol II role.
The seed's Swi6/Cdc10 precedent (non-DNA-binding complex membership) is a valid general caution but has no gene-specific support for Yar1.

Knowledge Gaps

Direct complex-composition/interaction test. Checked: Yar1 absent from curated MBF/SBF (Complex Portal); Yar1's full IntAct interactome (Rps3, Ltv1, Hsp70/Hsp40 chaperones) contains no Swi4/Swi6/Mbp1. Matters: IBA terms would need a real subunit assignment to stand; none exists. Status: largely resolved against the hypothesis. Further confirmation: Yar1-TAP MS would be expected to recover Rps3/Ltv1/chaperones, not SBF/MBF.
Promoter occupancy. Checked: none found. Matters: required for "positive regulation of Pol II transcription." Resolve: Yar1 ChIP-seq/ChIP-exo — expect no specific promoter binding.
Transcriptome specificity. Checked: Δyar1 phenotypes are ribosome-linked. Matters: distinguishes direct TF role from indirect ribosome-biogenesis effects. Resolve: nascent-transcription (4tU/GRO-seq) in Δyar1 vs 40S-biogenesis controls — expect shared, indirect signature.
Precise provenance of each IBA call. Checked: confirmed all four are IBA/GO_Central. Matters: pinpoints the ancestral node for a targeted GO_Central fix. Resolve: inspect the PTHR24198 reference tree annotation node.

Discriminating Tests

Yar1-TAP affinity-MS in exponentially growing cells: predicted interactors Rps3, Ltv1, import factors — not Swi4/Swi6/Mbp1.
Reciprocal SBF/MBF pulldowns (Swi6-, Swi4-, Mbp1-TAP): predicted absence of Yar1.
Yar1 ChIP-seq at cell-cycle (SCB/MCB) promoters: predicted no enrichment.
Domain rescue logic: Δyar1 growth defect is rescued by RPS3 overexpression (already shown, PMID 15611164) — a transcription-factor loss would not be rescued this way.
Sequence/structure: HHpred/InterProScan for an APSES domain in Yar1 — predicted none (consistent with our InterPro result).

Curation Leads (verify before applying)

Action: Downgrade/remove the four IBA transcription annotations (GO:0001228, GO:0030907, GO:0033309, GO:0045944) as phylogenetic over-annotation from a shared ankyrin-repeat family; consider NOT qualifiers if IBA cannot be locally suppressed.
Root-cause fix: Flag PANTHER PTHR24198 reference-tree node for GO_Central review — Swi6-derived transcription terms should not descend to the Yar1 chaperone lineage.
Retain as core: GO:0042274 (small-subunit biogenesis), GO:0000056 (small-subunit nuclear export), nucleus/cytoplasm CC.
Candidate addition (MF): a chaperone/unfolded-protein-binding term for Rps3 (avoid generic "protein binding"), supported by PMID 24021814.
Candidate references to cite in the review: PMID 24021814 (co-crystal, chaperone mechanism), PMID 15611164 (40S genetics/interactions), PMID 8675027 (origin of Swi6 similarity; explicitly note no TF activity was shown).
Suggested reviewer question: "Is there any dataset placing Yar1 in MBF/SBF or at Pol II promoters independent of its ankyrin-repeat homology to Swi6?" (Expected: no.)

Provenance

Computed evidence (executed code + outputs retained in the job log):
- Iter 1: (1) UniProt P46683 REST pull listing GO evidence codes — all transcription terms = IBA, all experimental terms = ribosome/localization; (2) InterPro/PANTHER signature pull for P46683 — ankyrin-repeat signatures only (IPR002110, PF12796, PTHR24198), no APSES/DNA-binding domain.
- Iter 2: (3) EBI Complex Portal search + composition of CPX-946 (SBF = Swi4+Swi6) and CPX-950 (MBF = Mbp1+Swi6) — Yar1/P46683 absent from both; (4) UniProt domain comparison Yar1 vs Swi6/Swi4/Mbp1 — Yar1 has only ANK repeats, Swi4/Mbp1 carry APSES-HTH + H-T-H DNA-binding motifs.
- Iter 3: (5) IntAct/PSICQUIC interactome of P46683 (15 records) — partners = Rps3, Ltv1 + Hsp70/Hsp40 chaperone network (Ssa1/2, Ssb1, Sse1, Sis1, Ydj1, Hsp78/26, Erj5, Ess1, Sfm1); no Swi4/Swi6/Mbp1.

Literature via PubMed (PMIDs 8675027, 15611164, 16888326, 24021814).