WDPCP

UniProt ID: A0A3Q2KRK8
Organism: Equus caballus
Review Status: COMPLETE
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Gene Description

WDPCP (fritz homolog) is a WD40 beta-propeller plus alpha-solenoid scaffold protein of the conserved fritz family (PANTHER PTHR13667, subfamily SF5). In vertebrates it forms the CPLANE (ciliogenesis and planar polarity effector) complex with Inturned and Fuzzy, which associates with the Rsg1 GTPase and JBTS17/CPLANE1 at the basal body and recruits peripheral IFT-A subunits there, so that WDPCP is needed for cilium formation. Orthologs localize to the ciliary transition zone/base and along the axoneme, and a cytoplasmic pool associates with the actin cytoskeleton, focal adhesions and the cell cortex, where WDPCP interacts with septin 2 and supports septin and actin organization, cell shape and directional migration. The C-terminal tail of the mouse protein binds monophosphorylated phosphoinositides, preferentially PI(3)P. The horse protein A0A3Q2KRK8 (705 aa) is one of eight Ensembl transcript products of the horse WDPCP gene; it retains the full propeller and solenoid but ends in an alternative 12-residue C-terminus that lacks the conserved end of the phosphoinositide-binding tail.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005886 plasma membrane
IEA
GO_REF:0000044
MODIFY
Summary: The membrane-associated pool of fritz/WDPCP is cortical rather than a plasma membrane protein per se; the experimental observations are cortical concentration of Fritz-GFP in Xenopus and actin-cytoskeleton/focal-adhesion localization in mouse cells.
Reason: This row maps the UniProt "Cell membrane" subcellular location, which for this unreviewed entry rests only on an ARBA rule; for the reviewed Xenopus ortholog (same PANTHER subfamily SF5) it traces to Kim et al. 2010, whose text actually reports Fritz-GFP "concentrated at the cell cortex". WDPCP has no transmembrane segment, and its lipid-binding tail prefers PI(3)P, an endosomal rather than plasma-membrane phosphoinositide (PMID:35427153). Mouse Wdpcp is cytoplasmic on actin filaments and focal adhesions (PMID:24302887). The PAINT curators did not propagate plasma membrane from the PTHR13667 node PTN001007408, which carries only ciliary terms. The claim is better expressed as cell cortex (GO:0005938); this is a lateral correction, not a refinement.
Proposed replacements: cell cortex
Supporting Evidence:
PMID:20671153
both sept2 fused to green fluorescent protein (sept2-GFP) and Fritz-GFP were concentrated at the cell cortex during CE
PMID:24302887
We show Wdpcp is localized in the ciliary transition zone, and also in the actin cytoskeleton and focal adhesions.
file:HORSE/WDPCP/WDPCP-bioinformatics/rereview/RESULTS-rereview.md
The node does not carry plasma membrane, axoneme, phosphatidylinositol binding or septin cytoskeleton terms.
GO:0005930 axoneme
IEA
GO_REF:0000044
ACCEPT
Summary: Axonemal localization is observed directly for two subfamily SF5 orthologs: endogenous mouse Wdpcp in IMCD3 cells and Xenopus Fritz in multiciliated cells, in addition to the ciliary-base pool.
Reason: The previous UNDECIDED was too cautious: the cached full texts state that Wdpcp/Fritz is found along the axoneme as well as in a ring at the ciliary base, in mouse (antibody) and Xenopus. The PAINT node PTN001007408 places the more specific axonemal basal plate (part of axoneme) at the eumetazoan ancestor of the family, and horse WDPCP sits in the same subfamily (SF5) as both experimental orthologs. The horse isoform retains the whole propeller and solenoid that form the CPLANE interfaces. Axoneme is kept as stated rather than refined, because the shaft pool is reported separately from the basal pool. The basal plate localization is not added as a row here because GOA already carries it on the canonical horse WDPCP product (A0A9L0T876); it is recorded in core_functions.
Supporting Evidence:
PMID:24302887
Using an antibody raised to Wdpcp, we showed Wdpcp is localized to the ciliary axoneme and in a ring-like structure at the base of the cilia in IMCD3 cells
PMID:20671153
sept7 and Fritz were localized along ciliary axonemes and in distinct foci near basal bodies
file:HORSE/WDPCP/WDPCP-bioinformatics/rereview/RESULTS-rereview.md
UniProt places A0A3Q2KRK8 in PTHR13667:SF5, the same subfamily as human O95876, mouse Q8C456 and Xenopus Q32NR9

Core Functions

Scaffold subunit of the CPLANE complex (with Inturned and Fuzzy) at the ciliary base, contributing to basal-body recruitment of peripheral IFT-A and transition-zone recruitment of septin and MKS/NPHP proteins during cilium organization.

Directly Involved In:
Supporting Evidence:
  • PMID:27158779
    These data suggest that CPLANE acts by recruiting peripheral IFT-A proteins to the basal body
  • PMID:24302887
    We observed Wdpcp is localized to the transition zone
  • file:HORSE/WDPCP/WDPCP-bioinformatics/rereview/RESULTS-rereview.md
    UniProt places A0A3Q2KRK8 in PTHR13667:SF5, the same subfamily as human O95876, mouse Q8C456 and Xenopus Q32NR9

References

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Suggested Questions for Experts

Q: Is the horse A0A3Q2KRK8 transcript (alternative final exon, lacking the conserved GSLxMxHFxLV C-terminus) expressed as a protein, and does its truncated tail still bind PI(3)P?

Q: Should GOA propagate PAINT IBA annotations to every UniProt product of a gene rather than only to the gene-centric canonical entry, given that this isoform retains the domains the node assertions depend on?

Suggested Experiments

Experiment: Express the A0A3Q2KRK8 C-terminal segment alongside the canonical-like A0A9L0R7M2 tail and compare phosphoinositide binding on PIP strips or liposomes, as done for mouse Wdpcp.

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 Β· WDPCP-protnlm-predictions-review.yaml Β· Review status: COMPLETE

ProtNLM2 (UniProt API snapshot 2026-09-08) emitted four GO terms for horse WDPCP isoform A0A3Q2KRK8: cell projection organization, cytoplasm, cilium and cytoskeleton. All four are biologically correct for this CPLANE scaffold, which sits in PANTHER subfamily PTHR13667:SF5 with the experimentally characterized mouse, human and Xenopus orthologs and retains the full WD40 propeller and alpha-solenoid. All four are, however, ancestors of more specific annotations the horse gene already carries and that the gene reviews accept: axoneme (on this product) and axonemal basal plate and cilium organization (IBA, on the canonical horse product A0A9L0T876). Each prediction is therefore less precise (LSP).

Source documents: projects/PROTNLM_EVALUATION/mammal-benchmark/horse40-predictions.csv Β· projects/PROTNLM_EVALUATION/mammal-benchmark/predictions.jsonl.gz Β· projects/PROTNLM_EVALUATION/mammal-benchmark/paired-sequences/WDPCP.json Β· genes/HORSE/WDPCP/WDPCP-hypotheses/horse40-cell-projection-organization/openscientist.md Β· genes/HORSE/WDPCP/WDPCP-ai-review.yaml Β· genes/HORSE/WDPCP__A0A9L0T876/WDPCP__A0A9L0T876-ai-review.yaml

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

GO:0030030 cell projection organization GO_BP
LSP β€” Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-09-08
Review rationale: WDPCP is a CPLANE subunit required for cilium formation: mouse CPLANE recruits peripheral IFT-A to the basal body, and a mouse Wdpcp in-frame deletion abolishes ciliogenesis. Horse A0A3Q2KRK8 is in the same PANTHER subfamily (SF5) as these orthologs and descends from PAINT node PTN001007408, which carries cilium organization; the canonical horse WDPCP product A0A9L0T876 carries GO:0044782 cilium organization by IBA, accepted in its gene review. GO:0044782 is_a GO:0120036 is_a GO:0030030 (OLS4), so the prediction is correct but less specific than an annotation the gene already has. The OpenScientist synthesis reaches the same conclusion on term breadth. The actin protrusion and migration phenotypes are real but do not by themselves warrant a more specific process term here.
Supporting Evidence:
GO:0005737 cytoplasm GO_CC
LSP β€” Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-09-08
Review rationale: Mouse Wdpcp has a cytoplasmic pool on actin filaments and focal adhesions, and Xenopus Fritz concentrates at the cell cortex; both orthologs share PANTHER subfamily SF5 with horse A0A3Q2KRK8, which retains the full propeller and solenoid. The prediction is therefore correct. This product already carries GO:0005930 axoneme (IEA, accepted in the gene review on direct mouse and Xenopus axonemal localization), and axoneme is a descendant of cytoplasm via ciliary plasm (OLS4); the cortical pool is likewise better captured by cell cortex, the replacement the gene review proposes for plasma membrane. Cytoplasm is thus a less precise restatement of supported locations.
Supporting Evidence:
  • PMID:24302887: "Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions."
  • PMID:20671153: "both sept2 fused to green fluorescent protein (sept2-GFP) and Fritz-GFP were concentrated at the cell cortex during CE"
  • PMID:24302887: "Using an antibody raised to Wdpcp, we showed Wdpcp is localized to the ciliary axoneme and in a ring-like structure at the base of the cilia in IMCD3 cells"
  • file:HORSE/WDPCP/WDPCP-bioinformatics/rereview/RESULTS-rereview.md: "UniProt places A0A3Q2KRK8 in PTHR13667:SF5, the same subfamily as human O95876, mouse Q8C456 and Xenopus Q32NR9"
GO:0005929 cilium GO_CC
LSP β€” Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-09-08
Review rationale: Endogenous mouse Wdpcp is detected along the ciliary axoneme and in a ring at the ciliary base, and Xenopus Fritz localizes along axonemes and near basal bodies; horse A0A3Q2KRK8 is in the same PANTHER subfamily. Cilium is therefore correct. The gene already carries axoneme on this product and axonemal basal plate (IBA) on the canonical product A0A9L0T876, both accepted in the gene reviews, and both are descendants of GO:0005929 cilium (OLS4). The prediction is correct but less specific than existing supported annotations.
Supporting Evidence:
  • PMID:24302887: "Using an antibody raised to Wdpcp, we showed Wdpcp is localized to the ciliary axoneme and in a ring-like structure at the base of the cilia in IMCD3 cells"
  • PMID:20671153: "sept7 and Fritz were localized along ciliary axonemes and in distinct foci near basal bodies"
  • PMID:24302887: "Wdpcp is localized to the transition zone"
  • file:HORSE/WDPCP/WDPCP-bioinformatics/rereview/RESULTS-rereview.md: "UniProt places A0A3Q2KRK8 in PTHR13667:SF5, the same subfamily as human O95876, mouse Q8C456 and Xenopus Q32NR9"
GO:0005856 cytoskeleton GO_CC
LSP β€” Less precise than existing annotation Review score: 2/2
Prediction method: ProtNLM2 Β· Version: UniProt API snapshot 2026-09-08
Review rationale: Mouse Wdpcp localizes to the actin cytoskeleton and is required to recruit Sept2 to actin filaments, and in Xenopus it acts through septins and actomyosin at the cell cortex; this orthology-based transfer within PANTHER subfamily SF5 supports the term. GO:0005930 axoneme, already carried by this product and accepted in the gene review, is a descendant of GO:0005856 cytoskeleton (OLS4), so the prediction is less specific than an existing supported annotation. The actin-associated pool has no more specific annotation in GOA, but the term as predicted remains an ancestor of the accepted axoneme location.
Supporting Evidence:
  • PMID:24302887: "in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments."
  • PMID:25436430: "Wdpcp acts via septins and actomyosin to control cell cortex stability during epithelial homeostasis"
  • PMID:24302887: "Using an antibody raised to Wdpcp, we showed Wdpcp is localized to the ciliary axoneme and in a ring-like structure at the base of the cilia in IMCD3 cells"
  • file:HORSE/WDPCP/WDPCP-bioinformatics/rereview/RESULTS-rereview.md: "UniProt places A0A3Q2KRK8 in PTHR13667:SF5, the same subfamily as human O95876, mouse Q8C456 and Xenopus Q32NR9"

Deep Research

Cyberian

(WDPCP-deep-research-cyberian.md)

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OpenScientist

(WDPCP-hypotheses/horse40-cell-projection-organization/openscientist.md)

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πŸ“š Additional Documentation

Notes

(WDPCP-notes.md)

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Bioinformatics Results

(RESULTS.md)

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πŸ“„ View Raw YAML

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