id: A0A9L0T876 gene_symbol: WDPCP product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9796 label: Equus caballus description: >- WDPCP (fritz homolog) is a non-enzymatic scaffold protein of the conserved fritz family (PANTHER PTHR13667, subfamily SF5), built from an N-terminal seven-bladed WD40 beta-propeller followed by an alpha-solenoid and a disordered C-terminal tail. In vertebrates it forms the CPLANE (ciliogenesis and planar polarity effector) complex with Inturned and Fuzzy. At the ciliary base CPLANE recruits the peripheral IFT-A subunits to the basal body, and WDPCP is needed for transition-zone localization of septin 2 and MKS/NPHP proteins, so it is required for cilium formation. Orthologs are also found along the ciliary axoneme, and a cytoplasmic pool on the cell cortex, actin filaments and focal adhesions recruits septin 2 and supports actin organization, cell polarity and directional migration. In mouse the last ~60 residues of the tail bind monophosphorylated phosphoinositides, preferring PI(3)P. The horse protein A0A9L0T876 (756 aa) is the product of the Ensembl canonical WDPCP transcript. It is identical to the full-length horse model A0A9L0R7M2 through residue 660 and so keeps the complete propeller and solenoid. Its last 96 residues come from an alternative terminal exon and replace the conserved end of the tail, including the mapped phosphoinositide-binding segment. No function has been tested experimentally for any horse WDPCP product; all functions here are inferred from orthologs in the same subfamily. 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: summary: >- Maps the UniProt "Cell membrane" location, which for this unreviewed entry rests only on an ARBA rule. The membrane-proximal pool observed for orthologs is cortical and cytoskeletal, not an integral plasma-membrane location. action: MODIFY reason: >- WDPCP has no transmembrane segment. The experimental observations behind the subfamily's peripheral localization are cortical concentration of Fritz-GFP in Xenopus (Q32NR9, PTHR13667:SF5; PMID:20671153) and localization of mouse Wdpcp (Q8C456, SF5) to actin filaments and focal adhesions (PMID:24302887). A plausible means of membrane association, the PI(3)P-binding C-terminal tail (PMID:35427153), is missing from this particular product (see the bioinformatics results), which weakens a membrane claim further. The PAINT node PTN001007408 that governs this subfamily carries no plasma membrane assertion. The claim is better expressed as cell cortex. This is a lateral correction, not a refinement, and it is an inference: no horse WDPCP product has been localized. 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__A0A9L0T876/WDPCP__A0A9L0T876-bioinformatics/RESULTS.md supporting_text: The node carries no plasma membrane, axoneme, cell cortex or phosphatidylinositol binding assertion. - 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: summary: >- Axonemal localization is observed directly for two SF5 orthologs, endogenous mouse Wdpcp in IMCD3 cells and Xenopus Fritz in multiciliated cells, as a pool distinct from the ring at the ciliary base. action: ACCEPT reason: >- The UniProt location statement is ARBA-derived, but independent experimental support exists in the same PANTHER subfamily: an antibody against endogenous mouse Wdpcp stains the axoneme as well as a ring at the ciliary base (PMID:24302887), and Xenopus Fritz is found along ciliary axonemes (PMID:20671153). A0A9L0T876 keeps the whole propeller and solenoid of the full-length protein; its divergence is confined to the disordered C-terminal tail. Which region targets WDPCP to the axoneme has not been mapped, so this transfer to the A0A9L0T876 product remains an inference. Consistent with the human WDPCP review, which also accepts axoneme. 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__A0A9L0T876/WDPCP__A0A9L0T876-bioinformatics/RESULTS.md supporting_text: UniProt places A0A9L0T876 in PANTHER PTHR13667:SF5, the subfamily that contains human O95876, mouse - term: id: GO:0007399 label: nervous system development evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - FB:FBgn0086698 - MGI:MGI:2144467 - PANTHER:PTN001007408 review: summary: >- PAINT placed this term at the Eumetazoa node PTN001007408 from fly fritz and mouse Wdpcp. Horse WDPCP descends from that node. The term describes an organismal outcome of WDPCP's cellular roles. action: KEEP_AS_NON_CORE reason: >- Horse WDPCP is in subfamily SF5 under PTN001007408, so the IBA follows from descent and there is no sign of divergence in the structured domains. The supporting mouse data are mutant phenotypes (neural tube and other developmental defects arising from defective cilium-dependent Hedgehog signaling), which show that WDPCP is needed for normal neural development rather than identifying a neural-specific activity. Kept as non-core, matching the human WDPCP review. supported_by: - reference_id: file:HORSE/WDPCP__A0A9L0T876/WDPCP__A0A9L0T876-bioinformatics/RESULTS.md supporting_text: A0A9L0T876 receives the four IBA annotations of PAINT node PTN001007408 (taxon 6072, Eumetazoa; - term: id: GO:0035091 label: phosphatidylinositol binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables supporting_entities: - UniProtKB:Q8C456 - ensembl:ENSMUSP00000020568 review: summary: >- Ensembl Compara transfer from mouse Wdpcp, whose phosphoinositide binding maps to its last 60 C-terminal residues. That segment is absent from A0A9L0T876. action: REMOVE reason: >- Mouse Wdpcp binds PI(3)P, PI(5)P and PI(4)P on its own, and the binding maps to the last 60 C-terminal residues (PMID:35427153). In A0A9L0T876 the colinear alignment with human WDPCP ends at human residue 692; only 6 of the 60 residues of the equivalent human window (687-746) are present, and the next 96 residues are encoded by an alternative terminal exon unrelated to the conserved tail. The ciliopathy residue S708, which lies in the PIP-binding tail and alters binding when mutated, has no counterpart. The binding module on which the mouse activity depends is therefore missing from this product, and the Compara transfer (which works at the gene level) does not hold for it. The PAINT curators did not place phosphatidylinositol binding on PTN001007408 either. The activity is likely for the full-length horse product A0A9L0R7M2, which keeps the conserved tail, but it does not apply to A0A9L0T876 and should not be transferred onward from it. Whether the novel tail binds lipids is unknown. supported_by: - reference_id: PMID:35427153 supporting_text: Wdpcp engages PIPs via the last 60 C-terminal residues - reference_id: file:HORSE/WDPCP__A0A9L0T876/WDPCP__A0A9L0T876-bioinformatics/RESULTS.md supporting_text: Only 6 of those 60 residues (687-692) lie inside the colinear block of A0A9L0T876, and the ciliopathy residue S708, which sits in the PIP-binding tail, has no counterpart. - term: id: GO:0042733 label: embryonic digit morphogenesis evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in supporting_entities: - UniProtKB:O95876 - ensembl:ENSP00000272321 review: summary: >- Ensembl Compara transfer of a human IMP based on a patient with postaxial polydactyly; Wdpcp mutant mice also have Y-shaped metacarpals. A developmental manifestation of the ciliary role. action: KEEP_AS_NON_CORE reason: >- The donor annotation rests on loss-of-function genetics in human and mouse (PMID:27158779). These establish that the gene is needed for normal digit patterning, through cilium-dependent Hedgehog signaling, not that WDPCP carries out a digit-specific morphogenetic step. The same term is kept as non-core in the human WDPCP review. There is no horse phenotype data. supported_by: - reference_id: PMID:27158779 supporting_text: We also observed Y-shaped metacarpals and defects in tongue and palate morphology in Wdpcp mutants - term: id: GO:0043587 label: tongue morphogenesis evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in supporting_entities: - UniProtKB:O95876 - ensembl:ENSP00000272321 review: summary: >- Ensembl Compara transfer of a human IMP based on an oral-facial-digital patient with tongue hamartoma, supported by tongue defects in Wdpcp mutant mice. action: KEEP_AS_NON_CORE reason: >- An organismal manifestation of the ciliary defect (PMID:27158779), not a separate WDPCP activity. Kept as non-core, consistent with the human review; no horse phenotype data exist. supported_by: - reference_id: PMID:27158779 supporting_text: We also observed Y-shaped metacarpals and defects in tongue and palate morphology in Wdpcp mutants - term: id: GO:0044782 label: cilium organization evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - MGI:MGI:2144467 - PANTHER:PTN001007408 - UniProtKB:Q32NR9 review: summary: >- PAINT placed cilium organization at PTN001007408 from mouse and Xenopus experimental data. WDPCP takes part directly, as the CPLANE scaffold that recruits IFT-A and transition-zone proteins to the ciliary base. action: ACCEPT reason: >- Horse A0A9L0T876 is in subfamily SF5 under PTN001007408 and keeps the propeller and solenoid that form the CPLANE interfaces; its divergence is confined to the disordered tail, which is unresolved in the CPLANE structures. In mouse, CPLANE recruits peripheral IFT-A to the basal body (PMID:27158779), and Wdpcp is required to recruit Sept2, Nphp1 and Mks1 to the transition zone (PMID:24302887). WDPCP therefore performs part of the process as a recruiting scaffold. Inferred for horse, not tested. 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: in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis - reference_id: file:HORSE/WDPCP__A0A9L0T876/WDPCP__A0A9L0T876-bioinformatics/RESULTS.md supporting_text: the seven-bladed WD40 beta-propeller and the alpha-solenoid that form the Inturned/Fuzzy interfaces are retained intact. - term: id: GO:0045184 label: establishment of protein localization evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - MGI:MGI:2144467 - PANTHER:PTN001007408 review: summary: >- PAINT IBA from mouse Wdpcp. WDPCP recruits several proteins to more than one destination: SEPT2 to actin filaments, SEPT2/NPHP1/MKS1 to the transition zone and, within CPLANE, peripheral IFT-A to the basal body. action: ACCEPT reason: >- WDPCP is the recruiting scaffold in each case, so it does part of the work of the process. The general term is kept because the evidence covers several cargoes and destinations, one of them (SEPT2 to actin) outside the cilium. The narrower protein localization to ciliary transition zone (GO:1904491) is not an is_a descendant of this term and would cover only part of the evidence. Inferred for horse by descent from PTN001007408; consistent with the human WDPCP review. supported_by: - reference_id: PMID:24302887 supporting_text: Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments - reference_id: PMID:27158779 supporting_text: These data suggest that CPLANE acts by recruiting peripheral IFT-A proteins to the basal body - term: id: GO:0060021 label: roof of mouth development evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in supporting_entities: - UniProtKB:O95876 - ensembl:ENSP00000272321 review: summary: >- Ensembl Compara transfer of a human IMP based on a patient with a high arched palate; Wdpcp mutant mice also show palate defects. action: KEEP_AS_NON_CORE reason: >- As for tongue morphogenesis, this is a developmental manifestation of the ciliary role (PMID:27158779), not a distinct activity. Kept as non-core, consistent with the human review. supported_by: - reference_id: PMID:27158779 supporting_text: We also observed Y-shaped metacarpals and defects in tongue and palate morphology in Wdpcp mutants - term: id: GO:0097541 label: axonemal basal plate evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - MGI:MGI:2144467 - PANTHER:PTN001007408 review: summary: >- PAINT IBA from the MGI transition-zone localization of mouse Wdpcp. The basal plate lies at the distal end of the transition zone. action: ACCEPT reason: >- Mouse Wdpcp localizes to the ciliary transition zone (PMID:24302887); light microscopy cannot resolve the basal plate from the rest of the transition zone, but the PAINT and MGI curators chose this term and there is no evidence against it. Horse WDPCP descends from PTN001007408 within SF5. Accepted, as in the human review; inferred for horse. supported_by: - reference_id: PMID:24302887 supporting_text: We observed Wdpcp is localized to the transition zone - reference_id: file:HORSE/WDPCP__A0A9L0T876/WDPCP__A0A9L0T876-bioinformatics/RESULTS.md supporting_text: A0A9L0T876 receives the four IBA annotations of PAINT node PTN001007408 (taxon 6072, Eumetazoa; - term: id: GO:0097541 label: axonemal basal plate evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in supporting_entities: - UniProtKB:Q8C456 - ensembl:ENSMUSP00000020568 review: summary: Ensembl Compara transfer of the same mouse localization as the IBA row. action: ACCEPT reason: Same claim as the IBA row; accepted for consistency. supported_by: - reference_id: PMID:24302887 supporting_text: We observed Wdpcp is localized to the transition zone references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - 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: GO_REF:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara 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. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Mouse Wdpcp (Q8C456, PTHR13667:SF5) study with full text cached. Establishes the axonemal, transition-zone, actin and focal-adhesion pools and SEPT2/NPHP1/MKS1 recruitment. - 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, SF5); full text cached. Source of the cortical and axonemal localizations. Morphant phenotypes are not used as process evidence. - 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 and its basal-body IFT-A recruitment role; full text cached. Mouse and patient craniofacial/digit phenotypes are used only for the non-core developmental rows. - 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 the last 60 residues and shows the C-terminal ~100 residues are unresolved. Used to interpret the A0A9L0T876 tail. - id: file:HORSE/WDPCP__A0A9L0T876/WDPCP__A0A9L0T876-bioinformatics/RESULTS.md title: HORSE/WDPCP__A0A9L0T876/WDPCP__A0A9L0T876-bioinformatics/RESULTS.md findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Reproducible comparison of A0A9L0T876 with horse A0A9L0R7M2, human O95876 and mouse Q8C456, plus Ensembl exon structure and PAINT context; computed by analyze_canonical_model.py. core_functions: - description: >- Scaffold subunit of the CPLANE complex (with Inturned and Fuzzy) at the ciliary base that recruits peripheral IFT-A to the basal body and septin and MKS/NPHP proteins to the transition zone during cilium organization. Inferred from mouse and Xenopus orthologs in the same PANTHER subfamily and from PAINT node PTN001007408; not tested in horse. directly_involved_in: - id: GO:0044782 label: cilium organization - id: GO:0045184 label: establishment of protein localization 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__A0A9L0T876/WDPCP__A0A9L0T876-bioinformatics/RESULTS.md supporting_text: UniProt places A0A9L0T876 in PANTHER PTHR13667:SF5, the subfamily that contains human O95876, mouse suggested_questions: - question: >- Is the ENSECAT00000134648 transcript, with its alternative terminal exon inside an intron of the full-length model, translated in horse tissues, or is A0A9L0R7M2 the main WDPCP product? - question: >- Should GO annotations transferred at the gene level (Ensembl Compara, PAINT) be checked against the domain content of each UniProt product, given that this canonical product lacks the PIP-binding tail? suggested_experiments: - description: >- Compare phosphoinositide binding of the A0A9L0T876 and A0A9L0R7M2 C-terminal segments on PIP strips or liposomes, as done for mouse Wdpcp, and test whether the A0A9L0T876 product still assembles with Inturned and Fuzzy and reaches the ciliary base.