SIC1 (P38634) curation notes

Identity

Saccharomyces cerevisiae S288c, YLR079W, synonyms SDB25, "CDK inhibitor p40". 284 aa, ~32 kDa.
Domain: SIC1_C (IPR062579 / PF29958), matching the experimentally mapped C-terminal kinase-inhibitory
region (~residues 215-284). The N-terminal half (residues 1-89 in UniProt) is disordered and carries the
CDK phosphosites (Thr5, Thr33, Ser76 annotated in UniProt; Thr2/Thr5/Thr33/Thr45/Ser69/Ser76/Ser80 studied
by NMR). Thr173 is the Hog1 site, Ser201 the CK2 site.
Not related in sequence to metazoan Cip/Kip (p27/p21) or S. pombe Rum1; functional analogue only.
PMID:20417603
UniProt FUNCTION: "Substrate and inhibitor of the cyclin-dependent protein kinase CDC28"; interacts with
HOG1; IntAct interactions with CDC14, CDC4, HOG1.

Core biology

Discovery: p40 was purified as a Cdc28 substrate that bound tightly to Cdc28 and inhibited it
PMID:8421781.
Cyclin specificity and cell-cycle role: PMID:7954792;
PMID:7954792;
PMID:7954792.
IGI partners on the GO:0000082 rows: CDC4 (S000001885), CDC53 (S000002290), CDC34 (S000002461),
CLB5 (S000006324) — i.e. the SCF(Cdc4)-Cdc34 destruction machinery and the S-phase cyclin target.
Degradation mechanism: Cln1/2-Cdc28 (plus Pho85-Pcl1) multisite phosphorylation of the N-terminus creates
Cdc4 phosphodegrons; SCF(Cdc4) with Cdc34 ubiquitinates Sic1; proteasome degrades it.
PMID:19008353
PMID:19008353
PMID:19008353
PMID:18787112
Ultrasensitivity: PMID:19008353.
Transcription: Swi5-dependent SIC1 transcription in late M/early G1; SCF(Cdc4) degradation of Swi5
terminates SIC1 transcription so Sic1 can be cleared at late G1
PMID:18787112.
Mitotic exit / licensing (deep research, Philip et al. 2022 eLife, Venta et al. 2020):
[file:yeast/SIC1/SIC1-deep-research-falcon.md "Newly synthesized Sic1 contributes to the decline of mitotic Clb–Cdk1 activity and helps establish the low-CDK state required for mitotic exit and the next G1 phase."]
[file:yeast/SIC1/SIC1-deep-research-falcon.md "Sic1 releases Clb2–Cdk1–Cks1 from Cdc6, allowing Mcm2–7 loading onto chromatin after mitotic exit."]
Localisation: nuclear (functional Sic1-GFP), degraded by nuclear Cdc4
PMID:11080155;
both compartments PMID:11792824;
bipartite NLS and carbon-source modulation, Clb5 accumulates in cytoplasm when SIC1 is shut off
PMID:16294029.
Stress control: Hog1 binds and phosphorylates Sic1 (Thr173) to stabilise it and arrest G1 under osmostress
PMID:15448699;
T173A impairs arrest (UniProt MUTAGEN).
Cdc14 dephosphorylates Sic1 (in vitro substrate) PMID:11274204;
Cdc14-Sic1 also in AP-MS network [PMID:20489023 abstract only, no Sic1 text].
Autophagy: PMID:20417603;
Rim15 downstream PMID:20417603;
mechanism open PMID:20417603;
Pho85 cyclins Clg1/Pcl1/Pho80 destabilise Sic1 to promote autophagy.

Curation decisions

Term	Evidence	Action	Note
GO:0000082 G1/S transition (x4 IGI)	PMID:7954792	ACCEPT	Sic1 is the CKI that gates the switch; it performs the inhibition (participation test met). GO:2000134 used in core_functions for direction.
GO:0004861 CKI activity (x2 IDA)	PMID:7954792, PMID:8421781	ACCEPT	Core MF.
GO:0005515 with CDC14 (PMID:11274204, PMID:20489023)	IPI	REMOVE	Enzyme-substrate; uninformative bare term; interaction not disputed.
GO:0005515 with HOG1	IPI	REMOVE	Kinase-substrate; uninformative; biology recorded here.
GO:0005515 with CDC4 (x3)	IPI	MODIFY -> GO:1905761	Phosphodegron recognition by SCF substrate receptor; specific term already on gene.
GO:0005634 nucleus (3 IDA + IEA)		ACCEPT	Site of core function.
GO:0005737 cytoplasm (IDA + IEA)		ACCEPT	Real cytoplasmic pool, carbon-source modulated.
GO:0016242 neg. reg. macroautophagy	IMP	KEEP_AS_NON_CORE	Solid genetics, but secondary/lineage-specific, mechanism open.
GO:1905761 SCF binding (EXP + IDA)	PMID:19008353	KEEP_AS_NON_CORE	Direct and correct, but substrate-side (how Sic1 is regulated); mirrors p27 GO:0031625 handling.

Participation test applied: Sic1 does the inhibiting (activity), but for its own ubiquitination it is the
substrate, so no process term for its degradation is proposed and the SCF-binding MF is kept non-core.
Comparator: human CDKN1B carries GO:0031625 ubiquitin protein ligase binding (KEEP_AS_NON_CORE in that
review), and neither p27 nor Sic1 carries a ubiquitin-dependent catabolic process term as actor.

Not annotated / open

Cip/Kip-like escort of Clb5 into the nucleus (PMID:16294029) — single abstract-only report; raised in
suggested_questions rather than as a NEW cyclin binding / adaptor annotation.
Mitotic-exit role (GO:0010458) is used in core_functions on the strength of the deep-research
summary of Philip 2022 / Venta 2020 and the Schwob 1994 timing data; not proposed as NEW because the
primary papers are not in the publication cache.
CK2 Ser201, TORC1/Mpk1 stabilisation, Cks1 docking at pThr173 — from deep research only; notes only.