Cdc42 is an essential Rho-family small GTPase, the master regulator of cell polarity and
polarized (tip) growth in fission yeast. It cycles between GDP- and GTP-bound states,
activated by GEFs Scd1 and Gef1, inactivated by GAPs (Rga4, etc.). GTP-Cdc42 binds
effectors (scaffold Scd2, PAK kinases Shk1/Pak1 and Shk2/Pak2, formin For3) to organize
actin, exocytosis, and polarity. It is geranylgeranylated at the C-terminal CAAX for
plasma-membrane/cell-tip localization.
Essential gene; null cells arrest as small round dense cells; site-specific mutants
(G12V, Q61L, D118A) give large misshapen cells -> controls polarized growth.
PMID:8289788
PMID:8289788
Fractionates to soluble and particulate pools (cytosolic + membrane).
PMID:8289788
GTP/GDP switch; intrinsic GTPase hydrolysis stimulated by GAP.
PMID:21849474
GTP-Cdc42 binds CRIB-domain effectors incl PAKs and WASp.
PMID:18328707
Active GTP-Cdc42 concentrated at growing cell tips (CRIB-GFP reporter); GAP Rga4 excluded
from tips; Pom1 ensures bipolar Cdc42 activation.
PMID:18328707
Cdc42-GTP gradient at cell tip plasma membrane sets cell width (GEF Scd1 at tips, GAP Rga4
at sides).
PMID:21849474
Functional Cdc42-mCherrySW localizes to cell tips, division site, nuclear membrane;
trafficked on exocytic vesicles.
PMID:25837586
PMID:25837586
Membrane targeting (CAAX prenylation) essential.
PMID:25837586
Cdc42-GTP slower mobility than GDP at membrane (positive-feedback accumulation).
Cytokinesis / division site: GFP-Cdc42p at medial cell-division site during cytokinesis,
dependent on actin and the actomyosin ring.
PMID:10961446
PMID:10961446
Two GEFs give a spatiotemporal Cdc42 activation pattern in cytokinesis (Gef1 before, Scd1 after ring constriction).
PMID:26941334
Cdc42 (via Pak1) prevents precocious Rho1 activation during cytokinesis.
PMID:37039135
Hob3p recruits/concentrates Cdc42 to division site.
PMID:17363901
Membrane traffic / exocytosis: cdc42L160S has secretion + vesicle/vacuole defects;
exocyst mislocalized.
PMID:21899677
Required for transport/recycling of glucan synthases Bgs1/Bgs4 to PM.
PMID:23060961
Mating / cell fusion: Cdc42 explores cell periphery for mate selection; dynamic active
zones with Scd1/Scd2.
PMID:23200991
Cdc42 required for cell-cell fusion; mating needs higher Cdc42 levels than mitotic growth.
PMID:41855172
PMID:41855172
Ras1-GTP hydrolysis coordinates Cdc42 into single growth zone during mating.
PMID:24147005
Effectors / complex: Scd1, Scd2, Cdc42, Ras1-GTP cooperatively form a complex.
PMID:7923372
Shk1/Pak1 PAK binds Cdc42 (Ras/Cdc42 signaling module).
PMID:7597098
Shk1/Cdc42/Skb1 ternary complex.
PMID:8943016
Pak2/Shk2 PAK binds Cdc42 (membrane localization via PBD + Cdc42).
PMID:9660818
PMID:9660817
GEFs: Gef1 binds inactive Cdc42, stimulates GDP-GTP exchange in vitro.
PMID:12529446
Gef1p/Scd1p form a ring at division site; recruit active Cdc42 to septation site.
PMID:12972551
Cdc42 acts as hub in GEF feedforward (recruits scaffold Scd2 -> Scd1).
PMID:31719163
Spatial regulation: Orb6 NDR kinase restricts Cdc42 to tips (loss -> Cdc42/For3/Gef1 to
cell sides).
PMID:19646873
Two-GEF coordination by microtubules/Tea1-Tea4-Pom1.
PMID:29930085
Invasive filaments: activated Cdc42 concentrated at single growing tip.
PMID:20870879
Heat-stress adaptation: thermal stress transiently decreases Cdc42 activity -> monopolar
growth (Cdc42 at lateral cortex).
PMID:24146635
GO:0003925 "G protein activity" (IEA, EC mapping): small GTPases are not heterotrimeric
G-protein subunits; this EC-based term is misapplied. The correct MF is GTPase activity
(GO:0003924). -> REMOVE.
GO:0003924 "GTPase activity" IDA from PMID:18793338 — that paper is about Rga2 as a Rho2
GAP and does not measure Cdc42 intrinsic GTPase activity directly; the annotation is
conceptually correct but the cited reference is weak. GTPase activity is well-established
for Cdc42 (RHO-family GTPase) and supported by the GEF/GAP cycle literature. ACCEPT the
function (core); rely on broader evidence.
GO:0032951 "regulation of beta-glucan biosynthetic process" IGI from PMID:8887550:
PMID:8887550 explicitly shows cdc42+ and constitutively active cdc42 do NOT activate
(1-3)beta-D-glucan synthase (Rho1 does). PMID:8887550. The IGI annotation is at best very indirect (Cdc42 affects
trafficking of Bgs glucan synthases per PMID:23060961). MARK_AS_OVER_ANNOTATED / KEEP non-core.
GO:0032955 "regulation of division septum assembly" IMP also cited to PMID:8887550 (a Rho1
paper). The PMID assignment is questionable, but Cdc42 does have well-documented roles in
cytokinesis/septation (Gef1/Scd1, Bgs1 recruitment). Keep as non-core.
bare "protein binding" (GO:0005515) annotations: uninformative; each represents a real
interaction (Gef1, Scd1, Hob3, Scd2, Shk1/Pak1, Shk2/Pak2, Skb1, Pob1). MARK_AS_OVER_ANNOTATED
in favor of more informative effector/complex terms.
GO:0101026 "mitotic nuclear membrane biogenesis" (ISO) is in UniProt DR lines but NOT in
the goa.tsv annotation set provided; not reviewed here.