CDC14 (Saccharomyces cerevisiae, UniProt Q00684) - curation notes

Identity and biochemistry

Cdc14/Oaf3/YFR028C, 551 aa, protein-tyrosine phosphatase superfamily, Cdc14 subfamily. Catalytic Cys283
(phosphocysteine intermediate), Asp253 general acid/base; the C-terminal Asn/Ser-rich tail (375-551) is
dispensable for activity and for the essential function PMID:9295359.
Dual-specificity in vitro PMID:9295359, but every characterised physiological substrate is a
CDK pSer-Pro site; pThr and pTyr are poor substrates (deep research, Kataria 2018 / DeMarco 2020 summaries:
"Phosphothreonine is disfavored because its additional methyl group creates steric conflict in the active
site."). This is why the EC 3.1.3.48-derived IEA GO:0004725 row was graded MODIFY -> GO:0008138
(protein tyrosine/serine/threonine phosphatase activity) and the IBA GO:0004722 row is the core MF.
Phosphatase activity is required for the essential function PMID:9295359.
In vivo substrate landscape: 835 Cdc14-dependent dephosphorylation sites on 455 candidate substrates,
with Smc4 (condensin) and Bud3 validated PMID:24319056.

RENT = Net1 + Cdc14 + Sir2, nucleolar from G1 through anaphase; Net1 inhibits Cdc14; Tem1-dependent
dispersal in late anaphase triggers mitotic exit PMID:10219244.
Net1(1-600) is a direct competitive inhibitor, Ki 3 nM, measured with Swi5 and Sic1 as substrates
PMID:11274204. PP2A-Cdc55 keeps Net1 underphosphorylated until separase downregulates it
PMID:16713564.
Cdc5 (Polo) binds Cdc14 directly through its Polo-box domain and is required for release
PMID:18927509.
Tof2 (Net1 paralog) binds Cdc14 directly; reported both as a nucleolar activator supporting rDNA
segregation PMID:18595708 and as a brake that retains a nucleolar pool after FEAR for later MEN release
PMID:18923139. Both papers agree on direct binding; the functional interpretation differs.
FEAR release is nuclear-confined and dispensable for timely mitotic exit but needed for timely rDNA
segregation PMID:26090959. MEN drives export to the cytoplasm PMID:26090959.
Localisation: nucleolus (G1-metaphase), nucleus (FEAR), cytoplasm, SPBs (MEN-dependent; preferentially the
bud/new SPB), bud neck in telophase [PMID:12062061 "We observed Cdc14-5GFP at the SPB in addition to the
nucleolus."; PMID:36259662 "In telophase cells characterised by disassembled spindles, Cdc14 was localised
at the bud SPB, nucleoli and bud neck (Type 3)."].

Reverses Cdc28 phosphorylation of Cdh1, Sic1 and Swi5 (Visintin 1998, not cached; summarised in UniProt and
the deep research: "Cdc14 is essential for late-anaphase-to-G1 progression in budding yeast."). Ordered
dephosphorylation of CDK substrates is set by the phosphatase:kinase ratio PMID:22078879.
Graded core: GO:0007096 regulation of exit from mitosis (IBA, IEA, IMP), GO:0000278, GO:0004721/GO:0004722.

rDNA segregation requires Cdc14 because of array length and Pol I hypertranscription PMID:16769819;
Cdc14 inhibits Pol I in anaphase, phosphatase-dependently, and this permits condensin loading
PMID:19158678. GO:0007059 IMP row graded MODIFY -> GO:0000070 mitotic sister chromatid segregation.
Interphase, TORC1-inactivation-induced rDNA condensation needs Cdc14, Rpd3, Hmo1, CLIP, cohibin but not
condensin PMID:35477092.
Spindle: Fin1 is dephosphorylated by Cdc14 in anaphase and then stabilises the spindle
PMID:17173039; Ase1 is another midzone substrate (UniProt).
Top2: Cdc14 opposes Top2 phosphorylation and, with Cdc5, promotes catenane resolution
PMID:41533572. The IGI (with CDC5) to
GO:0071103 DNA conformation change is kept non-core: the conformation change is Top2's work, Cdc14 is a
regulator.
SPB duplication licensing: Cdc14 dephosphorylates C-Sfi1 PMID:24954044.
rDNA heterochromatin formation (NAS, PMID:12923057): the cited paper is about Net1/Sir2/Fob1; Cdc14 is a
RENT subunit but the silencing work is Sir2's. Graded MARK_AS_OVER_ANNOTATED.

Cdk downregulation plus Cdc14 activation controls furrow ingression, membrane resolution and cell
separation; nuclear-retained Cdc14-NLS cannot support cytokinesis; Inn1 dephosphorylation is required
PMID:25371407.
Iqg1: Cdc14 binds and dephosphorylates CHD-flanking Cdk sites; iqg1-4A rescues actin ring failure of
cdc14-1 PMID:26085509.
Cbk1 (RAM network kinase) binds Cdc14 PMID:17892321; Gic1 binds Cdc14 directly but does not displace Net1
PMID:14734533.

Meiosis I spindle disassembly and two consecutive segregation phases need Cdc14/Slk19/Spo12
PMID:12737806.
Meiotic anaphase I/II cytoplasmic Cdc14 dephosphorylates Atg13 to activate Atg1 and autophagy
PMID:35238874; after TORC1 inactivation Cdc14 is needed for Atg13 dephosphorylation and PAS formation
PMID:29694832; SGD also records mitophagy from that paper (full text not cached; deferred to curator).
NaCl response: cdc14-3 transcriptome defect overlaps the Hog1 program, Hog1 nuclear localisation aberrant,
no direct Cdc14-Hog1 interaction PMID:25411400.

48 rows. Kinase partners (Cdc5, Cbk1, Snf1, Ste7, Cka1, Cka2, Mck1, Swe1, Chk1, Sak1, Bck1, Vhs1, Fmp48)
-> MODIFY to GO:0019901 protein kinase binding; Clb3 -> GO:0030332 cyclin binding; Rsp5 -> GO:0031625
ubiquitin protein ligase binding. Most kinase rows derive from the KPI AP-MS network
PMID:20489023.
Net1, Sir2, Tof2 (RENT / nucleolar anchor network), Sic1 and the Cdk substrates Ask1, Sli15, Orc6, Fin1
(PMID:22078879), Hsp42 (two HTP surveys), Gic1, Boi1, Met14 (APS kinase, not a protein kinase) -> REMOVE
as uninformative; complex membership is captured by GO:0030869 RENT complex, substrate relations belong on
has_input. Removal does not claim the interactions are false.

Which phosphoproteomic candidates are direct PxL-docked substrates vs. relay/indirect targets?
Any physiological pTyr substrate? (None known; hence the GO:0004725 MODIFY.)
Direct substrate mediating the osmotic-stress coordination.