CLN1 (YMR199W, P20437) — curation notes

Saccharomyces cerevisiae S288C. Reviewed for the
Yeast Cell Cycle & Translation Control
project (issue #3960).

Automated deep research was unavailable in this run (no provider API keys were
configured, so just deep-research yeast CLN1 failed for every provider). These
notes are therefore hand-assembled from the cached publications in
publications/ plus the UniProt record, and are not a
-deep-research-<provider>.md file.

Identity and family

• 546 aa, single chain, no reported processing
  [file:yeast/CLN1/CLN1-uniprot.txt "SEQUENCE 546 AA; 62050 MW;"].
• Cyclin-box protein: Pfam PF00134 Cyclin_N, PROSITE PS00292 CYCLINS,
  PIRSF PIRSF001770 Cyclin_CLN, InterPro IPR014399 Cyclin_CLN, and the
  CDD model cd20559 CYCLIN_ScCLN_like
  [file:yeast/CLN1/CLN1-uniprot.txt "CDD; cd20559; CYCLIN_ScCLN_like; 1."].
  UniProt places it in the cyclin family
  [file:yeast/CLN1/CLN1-uniprot.txt "Belongs to the cyclin family."].
• The IPR014399/PIRSF001770 Cyclin_CLN signature is the Cln1/Cln2-type
  G1/S cyclin family, distinct from Cln3 and from the B-type Clb cyclins. Only
  one disordered region is annotated (residues 224-265, MobiDB-lite), i.e. the
  cyclin box is the only structured module; the long C-terminal half is the
  PEST-rich instability region characteristic of this family.
• A low-abundance protein: 319 molecules/cell in log-phase SD medium
  [file:yeast/CLN1/CLN1-uniprot.txt "Present with 319 molecules/cell in log phase SD medium."].

Discovery and genetics

• CLN1 and CLN2 were isolated together as dosage suppressors of a
  cdc28 temperature-sensitive allele, which is what first tied them to the
  Cdc28 kinase PMID:2569741. The two
  gene products are close paralogs PMID:2569741.
• The three CLN genes are mutually redundant for viability but collectively
  essential: loss of all three arrests cells in G1
  PMID:2147225, and any one
  suffices PMID:2574633.
• Conditional CLN1 expression was the experiment that localised the essential
  Cln requirement to G1 PMID:2574633. The arrest point is Start
  PMID:2147225.
  Those two papers are the WITH/FROM-paired IGI rows for
  GO:0007089 traversing start control point of mitotic cell cycle, with
  CLN3 (SGD:S000000038) and CLN2 (SGD:S000006177) as the interacting genes —
  exactly the redundancy design the IGI code is for. Watch the SGD ids here: CLN1
  is S000004812, CLN2 is S000006177 and CLN3 is S000000038, so the numbering does
  not follow the gene names, and the IBA WITH/FROM lists are easy to misread.
• The inferred mechanism from the outset was activation of Cdc28
  PMID:2574633.

Cln1 is in the abundant, cell-cycle-regulated tier of Cln proteins

Tyers et al. compared the three Cln proteins directly, and Cln1 falls on the
Cln2 side of every axis:

• Abundance and kinase activity: PMID:8387915 — i.e. Cln1-associated
  Cdc28 is a strong histone H1 kinase.
• Periodicity: PMID:8387915. Consistent with UniProt
  [file:yeast/CLN1/CLN1-uniprot.txt "CLN1 and CLN2 mRNAs fluctuate periodically in the"].
• Position in the circuit: Cln3 acts upstream and induces CLN1; Cln1 is a
  less potent activator of Start when expressed artificially
  PMID:8387915. So Cln1 is an output/feedback cyclin, not the cell-size sensor.
• CLN1 transcription is SBF-dependent late-G1 transcription
  PMID:10409718.

Direct Cln1 biochemistry: the Cln1-Cdc28 holoenzyme

The cleanest CLN1-specific molecular-function experiment is the Stb1 kinase
assay. Cyclin-tagged complexes were pulled from yeast and assayed:

• PMID:10409718
• PMID:10409718
• and the genetics assign the in vivo kinase to Cln1/Cln2 rather than Cln3
  PMID:10409718.

This is a Cln1-containing kinase complex, with Cln1 as the regulatory subunit —
the direct basis for both GO:0016538/GO:0061575 and
GO:0000307 cyclin-dependent protein kinase holoenzyme complex. ComplexPortal
curates the complex explicitly as CPX-1699 CLN1-CDC28 kinase complex
[file:yeast/CLN1/CLN1-uniprot.txt "ComplexPortal; CPX-1699; CLN1-CDC28 kinase complex."].

Cln1 also binds the second CDK Pho85, with two curated experiments
[file:yeast/CLN1/CLN1-uniprot.txt "P20437; P17157: PHO85; NbExp=2; IntAct=EBI-4479, EBI-13327;"].
The cited paper (PMID:9032248) is cached abstract-only and its abstract is about
the Pcl cyclins, so the Cln1-Pho85 affinity experiment itself is not visible in
our cache; the interaction is nonetheless recorded by IntAct and UniProt. Whether
a Cln1-Pho85 complex is physiologically meaningful is unresolved.

Localisation

Cln1-GFP is in both compartments, imaged side by side with Cln2-GFP:
PMID:11080155.
This is the IDA source for the GO:0005634 and GO:0005737 rows. Note that the
finer-grained localisation results in the Cln literature (nuclear exclusion driven
by C-terminal phosphorylation, concentration at sites of polarised growth) were
obtained with Cln2, not Cln1; for Cln1 the evidence resolves no further than
nucleus and cytoplasm.

Turnover

Cln1 and Cln2 are substrates of SCF(Grr1), not SCF(Cdc4)
PMID:11080155.
This is a review statement within the cited paper rather than a Cln1 experiment
in it, so it is recorded here as background, not as annotation support.

Where Cln1 differs from Cln3: post-Start execution and Cln1/2-specific substrates

• Division of labour: PMID:10409718.
  Overexpressed CLN1 is nonetheless able to substitute for the missing Start
  transcription in a stb1 cln3 strain
  PMID:10409718.
• Cln1 shares with Cln2 a cyclin-specific substrate repertoire reached through
  LP docking motifs. Direct Cln1 experiment:
  PMID:21945277,
  and these are described as a cyclin class property
  PMID:21945277.
  Ste5 and Ste20 are pheromone-pathway components, so Cln1-Cdc28 contributes to
  shutting off mating signalling after Start.
• The late-G1 cyclin-CDK burst that CLN1 contributes to is required for
  morphogenesis specifically, and not for replication
  PMID:14688790. This is a
  combined cln1 cln2 pcl1 pcl2 phenotype, not a cln1 phenotype, so it informs
  the description but does not by itself license a CLN1 morphogenesis annotation.

Annotation decisions and the one NEW I decided against

Actions mirror those taken on the paralog genes/yeast/CLN2, because CLN1's
annotation set is a strict subset of CLN2's and the same term-level arguments
apply:

• GO:0016538 (4 rows: IBA, IEA, IDA x2) -> MODIFY to
  GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity.
  Cln1 does not merely regulate Cdc28, it activates it; the regulator term is the
  parent and GO:0061575 is the supported descendant.
• GO:0005515 (7 IPI rows, 6 with CDC28 and 1 with PHO85) -> MODIFY to
  GO:0019901 protein kinase binding. Both partners are protein kinases, and the
  interaction-detection rows support binding; the activator activity is asserted
  separately from the IDA rows. Bare protein binding is uninformative and the
  policy forbids ACCEPT/KEEP_AS_NON_CORE on it.
• GO:2000045 and GO:1902806 (both unsigned "regulation of G1/S") -> MODIFY
  to GO:1900087 positive regulation of G1/S transition of mitotic cell cycle.
  A sign correction, not a redundancy claim.
• GO:0000082, GO:0000307, GO:0005634, GO:0005737, GO:0007089 ->
  ACCEPT.

Considered and rejected: a NEW
GO:0180040 negative regulation of pheromone response MAPK cascade row, on the
strength of the Cln1-specific Ste5/Ste20 phosphorylation above. The comparator
check argues against it. In budding yeast only PPQ1 and AKR1 carry GO:0180040
(QuickGO, taxon 559292/4932, queried 2026-10-23), and CLN2 — which has
considerably stronger Ste5 evidence than CLN1, including PMID:17289571 — does not
carry it either. What CLN2 carries instead is
GO:0000321 re-entry into mitotic cell cycle after pheromone arrest (IGI,
PMID:9927449). That is a convention about how SGD annotates the Cln-pheromone
relationship, not a twenty-year gap, so the point is raised in
suggested_questions rather than asserted. CLN1 has no GO:0000321 row of its
own and I did not propose one: the PMID:9927449 genetics behind CLN2's rows is
not in our cache and I cannot tell whether CLN1 was assayed.

Open questions

Recorded in suggested_questions / suggested_experiments of the review:
whether Cln1 and Cln2 are genuinely interchangeable or have private substrates;
whether the Cln1-Pho85 interaction is physiological; and what, if anything,
distinguishes Cln1's contribution to the morphogenesis burst from Cln2's.