CycA

UniProt ID: M9NFR3
Organism: Drosophila melanogaster
Review Status: COMPLETE
📝 Provide Detailed Feedback

Gene Description

Cyclin A (CycA, CG5940) is the A-type cyclin of Drosophila and the only mitotic cyclin that is essential for mitosis in the fly embryo. It is a non-catalytic regulatory subunit of the cyclin-dependent kinase Cdk1 (Cdc2): through its N-terminal and C-terminal cyclin-box folds it binds and activates Cdk1, and its hydrophobic patch contributes to Cdk1 substrate recognition. CycA accumulates in the interphase cytoplasm, where it is kept by nuclear export, enters the nucleus in prophase and is degraded by APC/C-dependent proteolysis during mitosis. CycA-Cdk1 activity drives the G2/M transition, acting synergistically with cyclin B; its essential mitotic contribution in the embryo is to keep the APC/C activator Fizzy-related (Fzr) inactive in G2, so that mitotic cyclins are not destroyed before mitosis. When ectopically stabilized, CycA-Cdk1 can also promote S-phase entry, and loss of CycA converts mitotic cycles into endocycles. M9NFR3 is the 490-residue isoform C product, which differs from the reviewed 491-residue isoform A (P14785) only by the absence of one N-terminal glutamine and retains both cyclin-box folds.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000278 mitotic cell cycle
IEA
GO_REF:0000117 		MODIFY
Summary: Correct, but the fly genetics establish a more specific role in the G2/M transition of the mitotic cell cycle.
Reason: The ARBA term is true but general. Zygotic cycA mutant embryos fail to enter mitosis after the maternal supply is exhausted (Lehner and O'Farrell 1989, 1990), and cycA;cycB double mutants arrest in G2 before mitosis 15, a block rescued by either cyclin (Knoblich and Lehner 1993). CycA is the regulatory subunit of the Cdk1 kinase that performs this transition, so it participates in the process rather than being merely required for it. The specific supported descendant is GO:0000086 G2/M transition of mitotic cell cycle (is_a descendant of GO:0000278, verified in OLS). An S-phase-promoting capacity exists but was shown only by ectopic expression (Sprenger et al. 1997) and is not proposed here. Isoform C retains both cyclin folds (local alignment), so the gene-level evidence applies to this product.
Supporting Evidence:
PMID:8428595
demonstrate that cyclin A has a mitotic function and that it acts synergistically with cyclin B during the G2-M transition.
PMID:8428595
BrdU-labeling experiments indicate that cell cycle progression is blocked in G2 before entry into the fifteenth round of mitosis.
PMID:2139805
in mutant embryos deficient in cyclin A, cells that accumulate only cyclin B do not enter mitosis.
PMID:2564316
a functional cyclin A gene was required for continued division after exhaustion of maternally contributed cyclin A.
file:DROME/CycA/CycA-bioinformatics/RESULTS.md
The annotated cyclin domain 206–332 is fully retained and maps to target 205–331.
GO:0005634 nucleus
IEA
GO_REF:0000117 		KEEP AS NON CORE
Summary: CycA is nuclear in prophase, but it is cytoplasmic through interphase and nuclear accumulation is not required for its mitotic function.
Reason: Embryo immunostaining shows CycA relocating to the nuclear region early in prophase, and the reviewed isoform carries a nucleus IDA, so the location is real. It is transient, however: CycA is held in the interphase cytoplasm by Leptomycin B-sensitive nuclear export, and CycA tethered outside the nucleus, even at the membrane, still induces mitosis (Dienemann and Sprenger 2004). The term is as precise as the evidence warrants but is not the core site of function, so it is kept as non-core. Cytoplasm is proposed as a NEW location below. The PAINT node PTN000019791 also places nucleus at the cyclin ancestor, with FBgn0000404 among the donors.
Supporting Evidence:
PMID:2564316
cyclin A accumulates in the interphase cytoplasm of cellularized embryos, but relocates to the nuclear region early in prophase
PMID:15203007
Surprisingly, nuclear accumulation was not required, and even a membrane-tethered form of CycA was able to induce mitosis.
file:DROME/CycA/CycA-bioinformatics/RESULTS.md
The annotated cyclin domain 206–332 is fully retained and maps to target 205–331.
GO:0051301 cell division
IEA
GO_REF:0000117 		ACCEPT
Summary: CycA-Cdk1 drives entry into mitosis, which is required for continued cell divisions in the embryo.
Reason: Cyclin A is required for continued embryonic divisions after the maternal pool is exhausted, and its Cdk1 complex drives mitotic entry. Cell division is the standard process term for mitotic cyclins and is not entailed by the more specific G2/M transition term proposed above (that term sits under mitotic cell cycle, not under cell division), so it is retained rather than marked redundant.
Supporting Evidence:
PMID:2564316
a functional cyclin A gene was required for continued division after exhaustion of maternally contributed cyclin A.
PMID:2139805
in mutant embryos deficient in cyclin A, cells that accumulate only cyclin B do not enter mitosis.
GO:0000307 cyclin-dependent protein kinase holoenzyme complex
IPI
PMID:17431409
The Drosophila mitotic inhibitor Frühstart specifically bind... 		NEW
Summary: CycA functions as the cyclin subunit of a CycA-Cdk1 holoenzyme.
Reason: Not in GOA for M9NFR3. The reviewed isoform A is curated as a component of the Frs-CycA-Cdk1 complex (PMID:17431409), and fly cyclin A is reported to complex only with Cdk1/cdc2. The PAINT IBD for this complex at PTN000019791 includes vertebrate and yeast donors and covers the cyclin family. The more specific GO:0097124 cyclin A2-CDK2 complex (an IBA on P14785) is not proposed, because Drosophila CycA does not partner Cdk2.
Supporting Evidence:
file:DROME/CycA/CycA-reference-P14785-uniprot.txt
Component of the Frs-CycA-Cdk1 complex composed of CycA, Cdk1
PMID:9210381
In Drosophila , however, cyclin A only complexes with cdc2, so that both S and G2 roles are presumed to be carried out by cyclin A–cdc2

Core Functions

Regulatory (non-catalytic) subunit of Cdk1 that activates the kinase and directs substrate recognition through its hydrophobic patch; CycA-Cdk1 drives the G2/M transition, in part by keeping Fzr/APC-C inactive in G2.

Molecular Function:
cyclin-dependent protein serine/threonine kinase regulator activity
Directly Involved In:
G2/M transition of mitotic cell cycle
Cellular Locations:
cytoplasm
In Complex:
cyclin-dependent protein kinase holoenzyme complex
Supporting Evidence:
  • PMID:8428595
    demonstrate that cyclin A has a mitotic function and that it acts synergistically with cyclin B during the G2-M transition.
  • PMID:17431409
    We propose that binding of Frs to cyclins blocks the hydrophobic patch to interfere with Cdk1 substrate recognition.
  • PMID:15203007
    Rather, CycA-dependent kinase activity is required to inhibit one inhibitor of mitosis, the Fzr protein.
  • file:DROME/CycA/CycA-bioinformatics/RESULTS.md
    The annotated cyclin domain 206–332 is fully retained and maps to target 205–331.

References

Loading supporting content…

Download this section (compressed HTML)

Suggested Questions for Experts

Q: Which Cdk1 phosphorylation sites on Fzr (Cdh1) depend specifically on CycA rather than CycB or CycE, and is Fzr a direct CycA-Cdk1 substrate in G2 of cycle 16?

Q: The reviewed CycA isoform A (P14785) carries an IBA to GO:0097124 cyclin A2-CDK2 complex, but Drosophila CycA is reported to complex only with Cdk1. Should that IBA be excluded for the fly lineage?

Suggested Experiments

Experiment: Phosphoproteomics of cycA mutant versus wild-type embryos at cycle 16 with Rca1 co-expression, to separate CycA-Cdk1 substrates from the indirect consequence of premature APC/C-Fzr activation.

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM2 External predictions

View prediction review YAML · CycA-protnlm-predictions-review.yaml · Review status: COMPLETE

Both predictions are correct for Drosophila cyclin A, which retains the complete cyclin domain in this isoform C product. The CDK-regulator activity is already annotated on the canonical product P14785 by experimental evidence, and mitotic cell cycle phase transition is less specific than the G1/S and G2/M transition terms the gene already carries or is reviewed to carry.

Source documents: genes/DROME/CycA/CycA-protnlm-source.json · genes/DROME/CycA/CycA-bioinformatics/RESULTS.md

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity GO_MF
CNN — Correct but not novel Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08 · file:DROME/CycA/CycA-protnlm-source.json
Review rationale: The PC isoform preserves the complete cyclin domain of characterized Drosophila CycA. Primary work on the CycA–Cdk1 system demonstrates control of CDK substrate recognition through the cyclin hydrophobic patch. The one-residue N-terminal isoform difference lies outside that domain, supporting the regulator activity. The canonical product of the same gene, P14785, already carries this exact term in GOA by experimental evidence (accepted as its core function in the gene review), so the prediction is not novel and CNN applies; actual inclusion in the model training set is not established.
Supporting Evidence:
GO:0044772 mitotic cell cycle phase transition GO_BP
LSP — Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08 · file:DROME/CycA/CycA-protnlm-source.json
Review rationale: The term is correct for fly cyclin A but less specific than annotations the gene already carries. Mitotic cell cycle phase transition is the parent of both G2/M transition of mitotic cell cycle (GO:0000086) and G1/S transition of mitotic cell cycle (GO:0000082) (is_a, verified in OLS4). The canonical product P14785 already carries GO:0000082 (IBA and IMP, kept as non-core), and the re-reviewed gene identifies G2/M transition as the core process, supported by cycA mutant and cycA;cycB double-mutant phenotypes. Isoform C retains the complete cyclin domain, so the gene-level evidence applies to this product.
Supporting Evidence:
  • PMID:8428595: "demonstrate that cyclin A has a mitotic function and that it acts synergistically with cyclin B during the G2-M transition."
  • PMID:2564316: "a functional cyclin A gene was required for continued division after exhaustion of maternally contributed cyclin A."
  • PMID:9210381: "Cyclin A can drive the G1/S transition, but this function is suppressed by three types of control"
  • file:DROME/CycA/CycA-bioinformatics/RESULTS.md: "The annotated cyclin domain 206–332 is fully retained and maps to target 205–331."

Deep Research

Falcon

(CycA-deep-research-falcon.md)

Loading supporting content…

Download this section (compressed HTML)

FlyBase

(CycA-deep-research-flybase.md)
FlyBase gene description for CycA (DROME) FlyBase

FlyBase gene description for CycA (DROME)

Cyclin A (CycA) encodes a protein that binds to the product of Cdk1, thereby promoting Cdk1's protein kinase activity. The CycA-Cdk1 complex controls important aspects of progression through the cell cycle, including entry into mitosis. During the G2 phase, this complex is important for prevention of premature DNA re-replication. During mitosis and G1, the product of CycA is rapidly degraded (involving APC/C and the proteasome), resulting in inactivation of Cdk1 protein kinase activity.

📚 Additional Documentation

Notes

(CycA-notes.md)

Loading supporting content…

Download this section (compressed HTML)

Bioinformatics Results

(RESULTS.md)

Loading supporting content…

Download this section (compressed HTML)

Protnlm Function Review

(CycA-protnlm-function-review.md)

Loading supporting content…

Download this section (compressed HTML)

📄 View Raw YAML

Loading supporting content…

Download this section (compressed HTML)