PDZD7 encodes a multi-PDZ-domain cytoplasmic scaffold protein, a paralog of the Usher-network scaffolds harmonin (USH1C) and whirlin (WHRN). The long isoform carries a harmonin-N-like domain followed by two N-terminal PDZ domains, a central proline-rich and disordered region, and a third C-terminal PDZ domain; it has no catalytic activity. Its best-characterized site of action is the ankle-link region at the tapered base of developing cochlear hair-cell stereocilia, where PDZD7 is a component of the transient USH2 (ankle-link) complex together with the transmembrane adhesion proteins usherin (USH2A) and ADGRV1 and the scaffold whirlin. PDZD7 binds the short cytoplasmic PDZ-binding motifs of USH2A and ADGRV1 and heterodimerizes with whirlin through its PDZ domains; the whirlin-PDZD7 heterodimer bridges USH2A and ADGRV1, so that the four proteins assemble into a dynamic, non-obligate quaternary complex of variable stoichiometry that can further condense by multivalency-driven phase separation. PDZD7 also homodimerizes through its PDZ2 domain and associates with other Usher-network proteins including SANS (USH1G) and MYO7A. Loss of PDZD7 in mice disperses USH2A, ADGRV1 and whirlin from the ankle region, produces splayed and disorganized hair bundles with missing short-row stereocilia, reduces hair-cell mechanotransduction currents and causes profound congenital deafness; in humans, biallelic PDZD7 variants cause autosomal recessive nonsyndromic sensorineural hearing loss (DFNB57), and heterozygous variants can aggravate retinal disease in individuals carrying USH2A or ADGRV1 mutations. PDZD7 is additionally detected at the base of the photoreceptor connecting cilium and at the ciliary base of cultured retinal pigment epithelial cells, but photoreceptors of Pdzd7-null mice retain normal USH2-protein localization and normal early retinal function, indicating a more limited role in the retina than in the cochlea. Functionally, PDZD7 acts as a multivalent adaptor that recruits, positions and stabilizes membrane adhesion proteins and partner scaffolds at a defined subdomain of the developing stereocilium, thereby maintaining hair-bundle architecture required for normal hearing.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005929 cilium | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT node PTN000563297 groups PDZD7 with its paralogs harmonin and whirlin; the WITH/FROM donors are mouse and rat Ush1c (MGI:1919338, RGD:1303329), mouse and rat Whrn (MGI:2682003, RGD:631330) and human PDZD7 itself (UniProtKB:Q9H5P4, which carries its own IDA for cilium). All of these scaffolds are found at the photoreceptor periciliary/connecting-cilium region, and PDZD7 was directly localized to the ciliary base of cultured hTERT-RPE1 cells and to the base of the mouse photoreceptor connecting cilium. Reason: The ciliary association is genuine and experimentally grounded on the target itself, so the transfer is sound. It is not, however, the core function: the protein concentrates at the ciliary base rather than within the ciliary compartment, and Pdzd7-null mouse photoreceptors retain normal localization of USH2A, ADGRV1 and whirlin at the periciliary membrane complex, so the retinal/ciliary pool is contextual next to the hair-cell ankle-link role. Supporting Evidence: PMID:20440071 we detected the newly predicted C-terminal epitope of PDZD7 at the ciliary base of cultured human retinal pigment epithelial (RPE) cells PMID:20440071 strong labeling at the base of the photoreceptor connecting cilium PMID:25406310 knockout of Pdzd7 expression in mouse photoreceptors does not affect the localizations of the three USH2 proteins at the periciliary membrane complex |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Transferred from node PTN001136696 with mouse harmonin and mouse whirlin as donors. PDZD7 is a cytosolic multi-PDZ scaffold that is recruited to the cytoplasmic face of the stereociliary plasma membrane, where it binds the short cytoplasmic tails of the transmembrane proteins USH2A and ADGRV1; peripheral association with the plasma membrane is therefore correct. Reason: True but uninformative. The membrane pool that matters is the restricted ankle-link subdomain of the stereociliary membrane, which is already captured by the more specific GO:0002141 (stereocilia ankle link) and GO:0002142 (stereocilia ankle link complex) rows; this generic parent adds no functional content and should not be treated as a core localization. Supporting Evidence: PMID:20440071 the first and second PDZ domains of PDZD7 interact with USH2A by coimmunoprecipitation studies |
| GO:0002142 stereocilia ankle link complex | IBA GO_REF:0000033 | ACCEPT | Summary: Donors are mouse Whrn (MGI:2682003) and mouse Pdzd7 (MGI:3608325), i.e. the target's own ortholog with experimental evidence, on the PDZD7/whirlin/harmonin node PTN000563297. This is the central, best-supported claim about PDZD7: the four USH2 proteins (USH2A, ADGRV1, whirlin, PDZD7) colocalize at the ankle-link region of developing hair bundles, and reconstitution shows that both whirlin and PDZD7 are required to link USH2A and ADGRV1 into one complex. Reason: Core function and correct node placement. PDZD7 is a defining component of the ankle-link complex; its loss in mouse disperses the other three components from the ankle region. Supporting Evidence: PMID:25406310 In hair cells, proteins encoded by the four genes are colocalized at the ankle link region of the mechanosensitive structure, the hair bundle, during development PMID:25406310 both WHRN and PDZD7 are required for the complex formation with USH2A and GPR98 PMID:25406310 where PDZD7 is essential for the normal localizations of USH2A, GPR98, and WHRN |
| GO:0032426 stereocilium tip | IBA GO_REF:0000033 | REMOVE | Summary: The WITH/FROM donors of this row are mouse whirlin (MGI:2682003) and rat whirlin (RGD:631330) only - neither mouse Pdzd7 (MGI:3608325) nor human PDZD7 appears, in contrast to the ankle-link-complex row on the same node (PTN000563297), which is seeded by Pdzd7 itself. Whirlin is the canonical stereocilium-tip scaffold, acting in the row-1 tip elongation complex, whereas every immunolocalization of PDZD7 places it at the ankle region immediately above the tapered stereociliary base and explicitly distinguishes it from the tip/upper tip-link insertion site. Reason: Paralog-driven propagation across a subcompartment boundary. The tip localization is a whirlin-specific property that arose in a sister lineage of the same PDZ-scaffold family; there is no report of PDZD7 at stereocilia tips, and the functional evidence (loss of ankle links, mislocalization of USH2A/ADGRV1/whirlin from the ankle region) places PDZD7's site of action at the stereociliary base. The source annotations are correct for whirlin; it is the transfer to PDZD7 that fails. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: MGI:MGI:2682003 · mouse whirlin (Whrn/Dfnb31) SUPPORTS SOURCE BUT NOT TARGET Whirlin is a genuine stereocilium-tip protein of the row-1 elongation complex; the tip annotation is sound for whirlin but is a paralog-specific property, not a property of the ankle-link scaffold PDZD7. RGD:631330 · rat whirlin SUPPORTS SOURCE BUT NOT TARGET Same paralog as the mouse donor; adds no independent support for PDZD7. PANTHER:PTN000563297 · PANTHER ancestral node (harmonin/whirlin/PDZD7 scaffolds) NOT RELEVANT Not a gene product. The node is shared with the ankle-link rows, but those rows are seeded by Pdzd7 itself whereas this row is seeded only by whirlin, which is where the subcompartment mismatch enters. Supporting Evidence: PMID:25406310 In hair cells, proteins encoded by the four genes are colocalized at the ankle link region of the mechanosensitive structure, the hair bundle, during development file:human/PDZD7/PDZD7-deep-research-falcon.md Immunofluorescence and tagged-protein studies placed PDZD7 immediately above the tapered stereociliary base, peripheral to the actin core. It overlaps USH2A, ADGRV1 and WHRN but is distinct from the upper tip-link insertion site where MYO7A clusters. |
| GO:0007605 sensory perception of sound | IBA GO_REF:0000033 | ACCEPT | Summary: Seeded by mouse Pdzd7 (MGI:3608325) on node PTN002750487. Constitutive Pdzd7-null mice are congenitally and profoundly deaf, and biallelic human PDZD7 variants cause autosomal recessive nonsyndromic sensorineural hearing loss (DFNB57), first identified through a homozygous translocation disrupting the gene. Reason: Core biological process, supported independently in mouse (knockout deafness) and in humans (DFNB57), with the target's own ortholog as the donor. Supporting Evidence: PMID:19028668 [our data provide strong evidence that PDZD7 is a new autosomal-recessive] deafness-causing gene and also a prime candidate gene for Usher syndrome. file:human/PDZD7/PDZD7-deep-research-falcon.md -null mice show congenital profound deafness by auditory brainstem response |
| GO:0060088 auditory receptor cell stereocilium organization | IBA GO_REF:0000033 | ACCEPT | Summary: Also seeded by mouse Pdzd7 on node PTN002750487. This is the most precise statement of what PDZD7 does: it organizes the USH2/ankle-link complex during hair-bundle development, and its loss produces splayed, twisted, variably sized outer-hair-cell bundles with missing short-row stereocilia. Reason: Core function at the right level of specificity, with target-ortholog experimental grounding. Supporting Evidence: PMID:25406310 causes disorganization and gradual degeneration of hair bundles in mice file:human/PDZD7/PDZD7-deep-research-falcon.md PDZD7 loss disrupts or redistributes USH2A, ADGRV1 and WHRN in developing cochlear hair cells. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Automatic mapping of the UniProt SUBCELLULAR LOCATION line "Nucleus", which itself traces to PMID:20440071. In that paper the nuclear signal amounted to some labelling in cultured cells and in the zebrafish inner retina, and the authors concluded that the retinal nuclear label was nonspecific because it was undiminished after morpholino knockdown and inconsistent with their in situ data. Reason: The underlying observation is weak and partly retracted by its own authors, and no nuclear function has ever been ascribed to PDZD7. The protein has no recognizable NLS and its characterized partners (USH2A, ADGRV1, whirlin, SANS, MYO7A) are all membrane or cytoskeletal. Retained only as a low-confidence localization, not as a site of action. Supporting Evidence: PMID:20440071 We also noted some nuclear labeling in the inner retina PMID:20440071 we conclude that this label is nonspecific to Pdzd7a |
| GO:0005929 cilium | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Automatic mapping of the UniProt SUBCELLULAR LOCATION "Cell projection, cilium" (ECO:0000269|PubMed:20440071), the same underlying immunofluorescence that supports the IDA cilium row: PDZD7 at the ciliary base of RPE cells and at the base of the photoreceptor connecting cilium. Reason: Correct as a localization, but the protein sits at the ciliary base/periciliary region rather than in the cilium proper, and the retinal role is dispensable in mouse knockouts. Keep as a secondary localization rather than a core site of action. Supporting Evidence: PMID:20440071 we detected the newly predicted C-terminal epitope of PDZD7 at the ciliary base of cultured human retinal pigment epithelial (RPE) cells |
| GO:0032420 stereocilium | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automatic annotation drawing on the mouse ortholog (UniProtKB:E9Q9W7) and the UniProt subcellular-location vocabulary. Mouse and human PDZD7 localize to the ankle region of hair-cell stereocilia during bundle development. Reason: Correct and core. The stereocilium is where PDZD7 acts; more specific child terms (stereocilia ankle link, ankle link complex) are annotated separately and are consistent with this row. Supporting Evidence: file:human/PDZD7/PDZD7-uniprot.txt Note=Localizes at the ankle region of the stereocilia. |
| GO:0120025 plasma membrane bounded cell projection | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA machine-learning annotation to the general parent of stereocilium and cilium, both of which are separately annotated for PDZD7. Reason: Not wrong - stereocilia and the connecting cilium are plasma-membrane-bounded cell projections - but the term is a redundant parent that conveys no information beyond the more specific GO:0032420 and GO:0002141 rows. |
| GO:0005515 protein binding | IPI PMID:20440071 PDZD7 is a modifier of retinal disease and a contributor to ... | MODIFY | Summary: IntAct/UniProt rows recording binary interactions of PDZD7 with USH2A (UniProtKB:O75445) and ADGRV1/GPR98 (UniProtKB:Q8WXG9), demonstrated by yeast two-hybrid (PDZD7 PDZ2 with the ADGRV1 C-terminal intracellular domain, isolated eight times as prey) and by reciprocal coimmunoprecipitation (PDZD7 PDZ1 and PDZ2 with the USH2A intracellular domain; binding reduced when the USH2A PDZ-binding motif is deleted). These are the two membrane partners of the ankle-link complex. Reason: The interactions are real, specific and central to PDZD7's biology, but the bare "protein binding" term carries no functional information. The molecular function these assays demonstrate is adaptor/scaffold activity: PDZD7 uses its PDZ domains to hold the cytoplasmic PDZ-binding motifs of usherin and ADGRV1 together with whirlin in one complex. GO:0030674 (protein-macromolecule adaptor activity) captures this and is the informative replacement. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:20440071 revealed interaction of PDZD7 (PDZ2 domain) with the C-terminal intracellular domain of GPR98 PMID:20440071 the first and second PDZ domains of PDZD7 interact with USH2A by coimmunoprecipitation studies PMID:25406310 Interaction between WHRN and PDZD7 is the bridge between USH2A and GPR98. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MARK AS OVER ANNOTATED | Summary: These IntAct rows come from a proteome-scale PDZ-PBM "holdup" fragmentomics survey in which isolated PDZ domains (including those of PDZD7) were titrated against a library of 10-mer C-terminal peptides. More than thirty partners were imported into GOA from this one dataset, including viral proteins (multiple HPV E6 types, HTLV1 Tax) and human proteins with no shared expression or biology with a cochlear ankle-link scaffold (ABCC4, ASIC3, SLC15A5, SLCO1C1, KIR3DL3, DGKK, PBK, RPS6KA1 and others). Most measured PDZ-PBM affinities in this study lie in the high-micromolar range, at or near the assay quantification threshold. Reason: This is a systematic domain-peptide affinity matrix, not evidence that these complexes form in cells: the authors themselves note the transient and promiscuous nature of PDZ-PBM binding and that such approaches generate false positives. Importing each measured pair as an organism-level "protein binding" annotation inflates the PDZD7 interactome with pairs that share neither compartment nor tissue, and none of them adds functional information. The biologically meaningful PDZ interactions of PDZD7 (USH2A, ADGRV1, whirlin) are captured by dedicated rows and by the USH2 complex annotation. Supporting Evidence: PMID:36115835 PDZ-PBM interactions are rather transient and promiscuous PMID:36115835 interactomics using AP-MS from cell extracts may generate false negatives (potential preys that are too weakly expressed) as well as false positives (indirect interactions) |
| GO:0002141 stereocilia ankle link | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from the mouse ortholog (UniProtKB:E9Q9W7, ENSMUSP00000133273), whose ankle-link localization is experimentally established by immunofluorescence in developing cochlear hair cells. Reason: One-to-one ortholog transfer of the defining localization of this protein; consistent with the ISS row for the same term and with the UniProt annotation that PDZD7 localizes at the ankle region of the stereocilia. Supporting Evidence: file:human/PDZD7/PDZD7-uniprot.txt Note=Localizes at the ankle region of the stereocilia. |
| GO:0002142 stereocilia ankle link complex | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl ortholog transfer from mouse Pdzd7 for membership of the ankle-link complex; duplicates the IBA and ISS rows for the same term, which is expected and unproblematic. Reason: Core complex membership, independently supported by biochemical reconstitution showing that whirlin and PDZD7 together are required to assemble USH2A and ADGRV1 into one complex. Supporting Evidence: PMID:25406310 both WHRN and PDZD7 are required for the complex formation with USH2A and GPR98 |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog transfer of homodimerization from mouse Pdzd7. PDZD7 homodimerizes through its PDZ2 domain, shown by colocalization of differently tagged constructs and by reciprocal FLAG pull-downs in which full-length PDZD7 recovers itself and the PDZ2 fragment but not PDZ1 or PDZ3; UniProt records the same ("Homodimerizes (via PDZ2 domain)"). Reason: Unlike bare "protein binding", this term is informative: self-association through PDZ2 contributes the multivalency that drives higher-order assembly of the ankle-link complex, and it is directly demonstrated for the human protein's ortholog with a mapped domain. Supporting Evidence: PMID:25406310 PDZD7 is able to form homodimers through the interaction between its PDZ2 domains file:human/PDZD7/PDZD7-uniprot.txt Homodimerizes (via PDZ2 domain). Component of USH2 complex, |
| GO:1990696 USH2 complex | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl ortholog transfer of membership in the USH2 complex (USH2A, ADGRV1, whirlin, PDZD7), also recorded by ComplexPortal (CPX-2821). Reconstitution in HEK293 cells shows that ADGRV1 pulls down USH2A only when both whirlin and PDZD7 are present, with the whirlin PDZ1-PDZD7 PDZ2 heterodimer forming the bridge; the assembled complex has variable stoichiometry, consistent with a dynamic, non-obligate complex. Reason: Core complex membership and the single most informative cellular-component statement about this protein. Supporting Evidence: PMID:25406310 Interaction between WHRN and PDZD7 is the bridge between USH2A and GPR98. PMID:25406310 the USH2 quaternary complex has a variable stoichiometry |
| GO:0005929 cilium | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Human Protein Atlas immunofluorescence assigning PDZD7 to a ciliary compartment in cultured cells. This is concordant with the independent detection of PDZD7 at the ciliary base of hTERT-RPE1 cells with a different antibody. Reason: Antibody-based localization in cell lines that agrees with published RPE-cell data, so it is retained; but the ciliary pool is peripheral to PDZD7's core role at stereociliary ankle links, and mouse knockouts show the USH2 complex does not require PDZD7 for its periciliary localization in photoreceptors. Supporting Evidence: PMID:20440071 we detected the newly predicted C-terminal epitope of PDZD7 at the ciliary base of cultured human retinal pigment epithelial (RPE) cells PMID:25406310 knockout of Pdzd7 expression in mouse photoreceptors does not affect the localizations of the three USH2 proteins at the periciliary membrane complex |
| GO:0060113 inner ear receptor cell differentiation | NAS PMID:25406310 Whirlin and PDZ domain-containing 7 (PDZD7) proteins are bot... | MODIFY | Summary: ComplexPortal non-traceable author statement attached to the USH2 complex, citing the in vitro reconstitution paper. That paper is a biochemical study of complex assembly; the in vivo phenotype it summarizes for the four USH2 genes is disorganization and gradual degeneration of hair bundles, not a failure of hair-cell fate specification or of cell-type differentiation. Reason: The essence - a developmental role in inner-ear sensory hair cells - is right, but the term overshoots. Hair cells differentiate normally in Pdzd7 mutants; what fails is the organization and maintenance of the stereociliary bundle. GO:0060088 (auditory receptor cell stereocilium organization) states the same biology at the correct level and is already supported by IBA and ISS rows. Proposed replacements: auditory receptor cell stereocilium organization Supporting Evidence: PMID:25406310 causes disorganization and gradual degeneration of hair bundles in mice |
| GO:0002141 stereocilia ankle link | ISS GO_REF:0000024 | ACCEPT | Summary: Curator-judged sequence-similarity transfer from mouse Pdzd7 (UniProtKB:E9Q9W7), a one-to-one ortholog, for the ankle-link localization established by immunolabelling of developing cochlear hair bundles. Reason: Sound ortholog transfer of the defining subcellular site of PDZD7 action; duplicates the Ensembl IEA row for the same term, which is acceptable. Supporting Evidence: PMID:25406310 In hair cells, proteins encoded by the four genes are colocalized at the ankle link region of the mechanosensitive structure, the hair bundle, during development |
| GO:0045184 establishment of protein localization | ISS GO_REF:0000024 | MODIFY | Summary: Transfer from mouse Pdzd7 of the observation that PDZD7 is required for the correct positioning of the other USH2 proteins: in Pdzd7-null cochlear hair cells USH2A, ADGRV1 and whirlin are lost or redistributed from the ankle region, and conversely PDZD7 becomes abnormally distributed along stereocilia in Ush2a- or Adgrv1-null mice. Reason: The biology is right but the term is a very high-level parent that would fit almost any trafficking or scaffolding protein. What is demonstrated is retention of membrane partners at a defined peripheral membrane subdomain of the stereocilium. No GO term for protein localization to a stereocilium or ankle link exists, so GO:1990778 (protein localization to cell periphery) is the closest existing term that adds information; a more specific "protein localization to stereocilium" term would be preferable if created. Proposed replacements: protein localization to cell periphery Supporting Evidence: PMID:25406310 where PDZD7 is essential for the normal localizations of USH2A, GPR98, and WHRN file:human/PDZD7/PDZD7-deep-research-falcon.md PDZD7 loss disrupts or redistributes USH2A, ADGRV1 and WHRN in developing cochlear hair cells. |
| GO:0050910 detection of mechanical stimulus involved in sensory perception of sound | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Transferred from mouse Pdzd7, where knockout hair cells show reduced mechanotransduction currents and reduced cochlear microphonics. PDZD7 is not, however, a component of the mechanotransduction apparatus: it is absent from the tip-link insertion sites and has no described association with the MET channel complex (TMC1/TMC2, TMIE, LHFPL5, PCDH15). The ankle-link complex it builds is a transient structure of the developing bundle that has disassembled by the time mature transduction is established. Reason: The reduced transduction currents are a downstream consequence of splayed, disorganized bundles rather than a direct role in mechanoelectrical transduction. The acts_upstream_of_or_within qualifier makes the row defensible rather than false, so it is flagged as an over-annotation rather than removed; the informative statements are the bundle-organization and hearing terms. Supporting Evidence: file:human/PDZD7/PDZD7-deep-research-falcon.md It overlaps USH2A, ADGRV1 and WHRN but is distinct from the upper tip-link insertion site where MYO7A clusters. |
| GO:0060088 auditory receptor cell stereocilium organization | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog transfer from mouse Pdzd7 of the hair-bundle organization phenotype; duplicates the IBA row for the same term with an independent line of inference. Reason: Core function, correctly scoped to auditory hair cells, and the term to which the weaker GO:0060113 NAS row should be redirected. Supporting Evidence: PMID:25406310 causes disorganization and gradual degeneration of hair bundles in mice |
| GO:0060117 auditory receptor cell development | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog transfer capturing the developmental window of PDZD7 function: the protein and the ankle-link complex are present transiently in the first postnatal days of cochlear hair-cell maturation, and its loss causes progressive bundle disorganization and outer-hair-cell degeneration. Reason: Correct and central. PDZD7's requirement is developmental rather than in the mature bundle, so this term is a genuine part of the core description rather than a generic developmental add-on. Supporting Evidence: file:human/PDZD7/PDZD7-uniprot.txt In cochlear developing hair cells, essential in organizing |
| GO:0002142 stereocilia ankle link complex | ISS GO_REF:0000024 | ACCEPT | Summary: Curator sequence-similarity transfer from mouse Pdzd7 for ankle-link complex membership; a third independent inference route to the same, well-supported claim. Reason: Core complex membership; duplication across evidence codes is expected and fine. Supporting Evidence: PMID:25406310 both WHRN and PDZD7 are required for the complex formation with USH2A and GPR98 |
| GO:0032420 stereocilium | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog transfer of stereociliary localization from mouse Pdzd7; the parent of the ankle-link terms annotated on the same evidence. Reason: Correct and core, consistent with UniProt's note that PDZD7 localizes at the ankle region of the stereocilia. Supporting Evidence: file:human/PDZD7/PDZD7-uniprot.txt Note=Localizes at the ankle region of the stereocilia. |
| GO:0005576 extracellular region | HDA PMID:22664934 Comparison of tear protein levels in breast cancer patients ... | REMOVE | Summary: Derived from a single high-throughput MALDI-TOF-TOF de novo proteomic comparison of pooled tear fluid from 25 breast cancer patients and 25 controls, a study unrelated to PDZD7 in which the protein is not discussed. PDZD7 is an intracellular multi-PDZ scaffold with no signal peptide, no transmembrane segment and no reported secreted form; its entire characterized biology is on the cytoplasmic face of the stereociliary and periciliary membrane. Reason: Identification in a pooled body-fluid proteome by de novo peptide sequencing is a well-known source of spurious localization calls, and here it contradicts the protein's architecture and every targeted study of its localization. This is an artifact of a high-throughput screen rather than evidence of an extracellular pool. Supporting Evidence: PMID:22664934 MALDI-TOF-TOF-driven semi-quantitative comparison of tear protein levels file:human/PDZD7/PDZD7-uniprot.txt Note=Localizes at the ankle region of the stereocilia. |
| GO:0005515 protein binding | IPI PMID:19028668 Homozygous disruption of PDZD7 by reciprocal translocation i... | MODIFY | Summary: Records the interaction of PDZD7 with SANS/USH1G (UniProtKB:Q495M9), demonstrated in the paper that first linked PDZD7 to human deafness; the same work also recovered harmonin from retinal lysate with GST-PDZD7. UniProt cites this interaction directly (Interacts with USH1G, PubMed:19028668). Reason: A genuine interaction with a fellow Usher-network scaffold, but "protein binding" is uninformative. The molecular function demonstrated is the same adaptor/scaffold activity that underlies PDZD7's role in the USH2 complex, so GO:0030674 (protein-macromolecule adaptor activity) is the appropriate informative replacement. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:19028668 [Protein-protein interaction assays revealed the integration of] PDZD7 in the protein network related to the human Usher syndrome. |
| GO:0005634 nucleus | IDA PMID:20440071 PDZD7 is a modifier of retinal disease and a contributor to ... | MARK AS OVER ANNOTATED | Summary: The primary annotation behind the UniProt "Nucleus" location. The evidence is antibody labelling in the zebrafish inner retina plus perinuclear/nuclear signal in transfected cultured cells; the authors report that the inner-retina label persisted unchanged after pdzd7a knockdown and was inconsistent with their in situ hybridization data, and conclude it is nonspecific. Reason: Retained rather than removed because a curator saw the full paper and the cultured-cell signal is reported there, but the strongest statement the source makes about nuclear labelling is that it is nonspecific, and no nuclear function, partner or targeting signal has ever been described for PDZD7. It should not be treated as a site of action. Supporting Evidence: PMID:20440071 PDZD7 is also present in the perinuclear region PMID:20440071 we conclude that this label is nonspecific to Pdzd7a |
| GO:0005929 cilium | IDA PMID:20440071 PDZD7 is a modifier of retinal disease and a contributor to ... | KEEP AS NON CORE | Summary: Direct immunofluorescence with a newly raised anti-PDZD7 antibody placed the protein at the ciliary base of serum-starved hTERT-RPE1 cells and, with a zebrafish antibody, at the base of the connecting cilium in zebrafish and P10 mouse photoreceptors; pdzd7a knockdown reduced Adgrv1/Gpr98 at the connecting cilium region. Reason: Well-executed direct localization, and PDZD7 plausibly contributes to positioning ADGRV1 in the periciliary region. It is nevertheless not the core function: the protein is at the ciliary base rather than in the cilium, and in Pdzd7-null mice the USH2 proteins remain correctly localized at the photoreceptor periciliary membrane complex with normal early ERGs, in contrast to the severe cochlear phenotype. Supporting Evidence: PMID:20440071 we detected the newly predicted C-terminal epitope of PDZD7 at the ciliary base of cultured human retinal pigment epithelial (RPE) cells PMID:20440071 Pdzd7 apparently localizes Gpr98 in the connecting cilium region |
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