id: A0A3Q2KRK8 gene_symbol: WDPCP product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9796 label: Equus caballus 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: - term: id: GO:0005886 label: plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0039 review: action: 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_replacement_terms: - id: GO:0005938 label: cell cortex supported_by: - reference_id: PMID:20671153 supporting_text: both sept2 fused to green fluorescent protein (sept2-GFP) and Fritz-GFP were concentrated at the cell cortex during CE - reference_id: PMID:24302887 supporting_text: We show Wdpcp is localized in the ciliary transition zone, and also in the actin cytoskeleton and focal adhesions. - reference_id: file:HORSE/WDPCP/WDPCP-bioinformatics/rereview/RESULTS-rereview.md supporting_text: The node does not carry plasma membrane, axoneme, phosphatidylinositol binding or septin cytoskeleton terms. - term: id: GO:0005930 label: axoneme evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0304 review: action: 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. supported_by: - reference_id: PMID:24302887 supporting_text: 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 - reference_id: PMID:20671153 supporting_text: sept7 and Fritz were localized along ciliary axonemes and in distinct foci near basal bodies - reference_id: file:HORSE/WDPCP/WDPCP-bioinformatics/rereview/RESULTS-rereview.md supporting_text: UniProt places A0A3Q2KRK8 in PTHR13667:SF5, the same subfamily as human O95876, mouse Q8C456 and Xenopus Q32NR9 references: - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: PMID:24302887 title: Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton. full_text_unavailable: false findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Mouse (Cys40 mutant, IMCD3/NIH-3T3/MEF) study; full text cached. Establishes axonemal, transition-zone, actin and focal-adhesion pools and the Sept2 interaction. Mouse Q8C456 is in the same PANTHER subfamily (SF5) as horse WDPCP. - id: PMID:20671153 title: Planar cell polarity acts through septins to control collective cell movement and ciliogenesis. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Xenopus Fritz (Q32NR9, subfamily SF5); full text cached. Source of the cortical and axonemal localization behind the UniProt Cell membrane/axoneme statements. Morphant phenotypes (gastrulation, cell elongation) are not used as process annotations. - id: PMID:27158779 title: The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Defines CPLANE (Intu, Fuz, Wdpcp) and its role in basal-body recruitment of peripheral IFT-A; full text cached. Mouse digit/palate phenotypes are organismal and not used. - id: PMID:35427153 title: Structure of the ciliogenesis-associated CPLANE complex. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cryo-EM of human and mouse CPLANE; maps mouse Wdpcp PIP binding to its C-terminal ~60 residues and notes the human-specific ~35-residue N-terminal extension. Used to interpret the horse isoform's altered C-terminus. - id: file:HORSE/WDPCP/WDPCP-bioinformatics/RESULTS.md title: HORSE/WDPCP/WDPCP-bioinformatics/RESULTS.md findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Earlier human-horse pairwise comparison (88.1% identity), retained but no longer cited as support. Its description of the C-terminal difference as a human 721-729 deletion is superseded by the re-review analysis, which shows that A0A3Q2KRK8 ends in an alternative 12-residue C-terminus and lacks the last ~24 human residues; the N-terminal difference is shared with mouse. - id: file:HORSE/WDPCP/WDPCP-bioinformatics/rereview/RESULTS-rereview.md title: HORSE/WDPCP/WDPCP-bioinformatics/rereview/RESULTS-rereview.md findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Reproducible comparison of all eight horse WDPCP gene-model products with human and mouse orthologs, with PANTHER subfamily and PAINT node context; computed by compare_gene_models_rereview.py. core_functions: - description: >- 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: - id: GO:0044782 label: cilium organization locations: - id: GO:0097541 label: axonemal basal plate - id: GO:0005930 label: axoneme supported_by: - reference_id: PMID:27158779 supporting_text: These data suggest that CPLANE acts by recruiting peripheral IFT-A proteins to the basal body - reference_id: PMID:24302887 supporting_text: We observed Wdpcp is localized to the transition zone - reference_id: file:HORSE/WDPCP/WDPCP-bioinformatics/rereview/RESULTS-rereview.md supporting_text: UniProt places A0A3Q2KRK8 in PTHR13667:SF5, the same subfamily as human O95876, mouse Q8C456 and Xenopus Q32NR9 suggested_questions: - question: >- 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? - question: >- 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: - description: >- 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.