DZIP1L

Summary: DZIP1L associates with CBY2 in the human interactome screen.

Reason: Three positive human DZIP1L–CBY2 records include validated two-hybrid IM-23318-38645. Both listed participant sequences match their official records. CBY2/SPERT is the literal partner, not CBY1; the latter protein’s ciliary recruitment and transcriptional functions cannot be transferred simply from the chibby-family name. No evidence-backed informative binding class was established for CBY2, so retain this positive association as non-core.

Summary: DZIP1L binds the centrosomal protein CEP76.

Reason: Independent human CEP76 evidence identifies a centrosomal component that associates with CCP110 and CEP97 and limits centriole reduplication (UniProt Q8TAP6, with experimental provenance to PMID:19460342 and PMID:14654843). This supports membership in the microtubule cytoskeleton, rather than merely an unspecified visit to the centrosome. GO:0008092 includes binding to such a component and does not require a filament-forming partner. Human DZIP1L–CEP76 array, prey-pooling and validated two-hybrid records include IM-23318-38646 with matching participant reference sequences. The narrower term identifies the partner class; it does not assign CEP76 control of centriole duplication to DZIP1L or establish the native function of this pair.

Proposed replacements: cytoskeletal protein binding

Summary: DZIP1L associates with the 412-residue CBY2 product.

Reason: The literal partner is CBY2 product Q8NA61-2. The human centrosomal BFG-Y2H screen records this pair in IM-25015-290 and validated two-hybrid IM-25015-1224; both participant reference-sequence ROGIDs match the official sequences, including the 412-residue CBY2 product. Preserve the positive result without replacing CBY2 by CBY1 or transferring functions between them. No informative binding subclass is established for this partner.

Summary: DZIP1L binds the septin GTPase SEPTIN2.

Reason: Human SEPTIN2 association is supported by fragment yeast two-hybrid and endogenous reciprocal co-immunoprecipitation in PMID:28530676. SEPTIN2 is independently established as a filament-forming GTPase, so GTPase binding is an informative partner-class refinement. The N-terminal 165 residues of DZIP1L retain association, whereas residues 500–end do not. This does not assign GTP hydrolysis, GTPase regulation, purified binding affinity, or equal activity of both natural DZIP1L products to the target.

Proposed replacements: GTPase binding

Summary: The variant-interaction record retains positive DZIP1L–CEP76 binding.

Reason: Independent human CEP76 evidence identifies a centrosomal component that associates with CCP110 and CEP97 and limits centriole reduplication (UniProt Q8TAP6, with experimental provenance to PMID:19460342 and PMID:14654843). This supports membership in the microtubule cytoskeleton, rather than merely an unspecified visit to the centrosome. GO:0008092 includes binding to such a component and does not require a filament-forming partner. IntAct IM-27553-525 records positive human DZIP1L–CEP76 two-hybrid association and a mutation-with-no-effect feature at DZIP1L residue 643. The feature is neither on CEP76 nor a negative binding result. The incomplete article representation and failed challenge-page route do not establish its mutation mechanism. The exact positive curated pair is independently corroborated by PMID:25416956 and PMID:31515488; this supports the bounded binding-class assertion without pretending that the missing Methods/Results were read.

Proposed replacements: cytoskeletal protein binding

Summary: DZIP1L–CEP76 binding is retained in the tested variant records.

Reason: Independent human CEP76 evidence identifies a centrosomal component that associates with CCP110 and CEP97 and limits centriole reduplication (UniProt Q8TAP6, with experimental provenance to PMID:19460342 and PMID:14654843). This supports membership in the microtubule cytoskeleton, rather than merely an unspecified visit to the centrosome. GO:0008092 includes binding to such a component and does not require a filament-forming partner. Positive two-hybrid record IM-27438-30 places three mutation-with-no-effect features at DZIP1L positions 88, 595 and 625. These are not CEP76 changes or loss-of-binding observations. The source compares variant interactions with wild-type controls; no native function or disruptive variant mechanism is inferred for this pair.

Proposed replacements: cytoskeletal protein binding

Summary: DZIP1L associates with a C-terminal region of PRPF40A.

Reason: HuRI records a positive DZIP1L interaction with PRPF40A product O75400-2, including validated two-hybrid IM-25472-131281. The sufficient-binding-region feature is PRPF40A residues 716–930, not DZIP1L. Both listed reference sequences are authenticated. PRPF40A participates in splicing and cytoskeletal regulation, but these roles do not by themselves establish a specific binding subclass for this C-terminal fragment. Retain the association as non-core without assigning splicing or transcription activity to DZIP1L.

Summary: DZIP1L binds the E3 ubiquitin ligase TRIM37.

Reason: Positive human DZIP1L–TRIM37 HuRI records include validated two-hybrid IM-25472-122140. Independent UniProt functional curation establishes TRIM37 as an E3 ubiquitin-protein ligase. GO:0031625 explicitly denotes binding an E3 protein, so the positive pair and verified partner class support this refinement. No DZIP1L ubiquitin-transfer activity, substrate status, or control of TRIM37 catalysis is asserted.

Proposed replacements: ubiquitin protein ligase binding

Summary: HuRI independently supports DZIP1L association with CBY2.

Reason: The positive HuRI partner is CBY2 product Q8NA61-2, with validated record IM-25472-118276 and matching participant reference-sequence ROGIDs. CBY2 is not interchangeable with CBY1; no informative binding subclass is established from its current functional evidence. Preserve the supported association as non-core without borrowing the independent DZIP1L–CBY1 recruitment mechanism.

Summary: DZIP1L associates with an LRRN4 fragment.

Reason: Positive HuRI records, including IM-25472-124026, identify human LRRN4 residues 338–740 as sufficient for association with DZIP1L. This fragment annotation belongs to LRRN4 and both participant reference sequences match. LRRN4 is a leucine-rich-repeat membrane protein, but its record does not establish a sufficiently specific receptor or enzymatic class for an informative replacement. Retain binding as non-core without rejecting the measured fragment interaction because of native compartment differences.

Summary: DZIP1L associates with the AP-4 accessory protein TEPSIN.

Reason: Human DZIP1L–TEPSIN association is positive in three HuRI records, including validated two-hybrid IM-25472-147158. TEPSIN is an AP-4 accessory protein with direct AP4B1/AP4E1 contacts; binding TEPSIN is not equivalent to binding the heterotetrameric AP-4 complex, and the retrieved evidence does not establish TEPSIN itself as a signaling scaffold. Retain the positive generic association as non-core without assigning AP-4 cargo selection or vesicular transport activity to DZIP1L.

Summary: DZIP1L associates with PNMA5 in the human binary screen.

Reason: Human DZIP1L–PNMA5 association is recorded by array, prey-pooling and validated two-hybrid assays, including IM-25472-120573. Both listed sequences are authenticated. PNMA5’s current identity and nuclear annotation do not establish an informative enzyme, receptor, transcription-factor or cytoskeletal-component class for this binding assertion. Retain the positive association as non-core; its biological mechanism remains open.

Summary: DZIP1L binds the signaling scaffold AMOTL2.

Reason: AMOTL2 independently coordinates WWP1/Crumbs, LATS2 and YAP-pathway interactions in experimentally sourced human UniProt curation, supporting the signaling-scaffold class in GO:0097110. Its separate MAGI1/CDH5 scaffold description is by similarity and is not the sole basis for this classification. Positive human HuRI records include validated two-hybrid IM-25472-114743 and assign the sufficient-binding region to AMOTL2 residues 314–779. This refines the identity of the protein bound; it does not establish autonomous scaffold activity of that fragment or transfer Hippo-pathway regulation to DZIP1L.

Proposed replacements: scaffold protein binding

Summary: Human binary screening supports DZIP1L binding to CBY1.

Reason: CBY1 has independently documented human centriolar/basal-body localization and FAM92A recruitment associations, and the separate mouse study PMID:29487109 identifies Cby as a mother-centriolar appendage component. Together these support its cytoskeletal-component class. Human DZIP1L–CBY1 HuRI records include validated two-hybrid IM-25472-129202. The mouse Dzip1l-dependent Cby-positioning experiments remain distinct from this human binary screen; neither Wnt regulation nor CBY1 activity is transferred to DZIP1L.

Proposed replacements: cytoskeletal protein binding

Summary: Human affinity purification supports DZIP1L association with CBY1.

Reason: CBY1 is independently established as a centriolar/basal-body component, supported by human curated localization/recruitment evidence and the separate mouse appendage study PMID:29487109. BioPlex IM-29278-14305 identifies tagged human CBY1 as bait and DZIP1L as prey in anti-tag co-immunoprecipitation with spoke expansion. Cytoskeletal protein binding preserves that association scope. The independent human binary result in PMID:32296183 corroborates the pair, but does not convert this AP-MS record into purified binary affinity or prove a stable native DZIP1L complex.

Proposed replacements: cytoskeletal protein binding

Summary: Human localization supports centriolar and basal-body refinement of the broad inherited location.

Reason: The authentic PTN001469871 placement supports the broad cytoplasmic location; target-specific human microscopy resolves centriolar and basal-body pools. These provide a biological refinement rather than a claim that either has a formal cytoplasm ancestor in the current ontology. The replacement is not an exhaustive census of every DZIP1L molecule. HPA labels the additional cytosol observation Uncertain, so it does not establish a separate supported diffuse pool.

Proposed replacements: centriole ciliary basal body

Summary: Tagged human DZIP1L localizes near centrin at centrioles.

Reason: The human GFP-DZIP1L construct in PMID:19852954 localizes near centrin at centrioles and the ciliary basal body in hTERT-RPE1 cells. The named IMAGE4940443 archive has the long 767-residue architecture but three sequence differences from current Q8IYY4-1; the experiment is not an independently authenticated assay of every current natural product. The paper’s separate HeLa observation concerns DZIP1 and is not transferred to DZIP1L.

Summary: Endogenous human DZIP1L localizes to centrioles and distal basal bodies.

Reason: PMID:28530676 directly supports human DZIP1L localization at centrioles and distal basal bodies, including endogenous staining and proximity to transition-zone marker TCTN1 by 3D-SIM. Retain the centriolar pool alongside the basal-body pool rather than replacing one with the other or inferring that every fluorescent focus is a defined stable complex.

Summary: The UniProt centriole mapping agrees with human localization evidence.

Reason: The UniProt subcellular-location vocabulary maps SL-0046 explicitly to GO:0005814. DZIP1L carries this location with experimental provenance to PMID:28530676, independently consistent with the human localization assays. The mapping is therefore supported and is not a default localization inferred merely from protein sequence.

Summary: DZIP1L deficiency alters polycystin localization to cilia.

Reason: The operative human finding concerns altered PKD1/PC1 and PKD2/PC2 distribution to cilia in DZIP1L-deficient fibroblasts, while their cilia number and morphology remain largely normal. Refine broad regulation of protein localization to regulation of protein localization to cilium (GO:1903564), a verified descendant. This retains the measured cargo-localization role without asserting a direct transport motor, a universal ciliogenesis block, or loss of SEPT2 recruitment.

Proposed replacements: regulation of protein localization to cilium

Summary: The inherited basal-body location agrees with target-specific experiments.

Reason: The basal-body IBA descends from PTN000948208 on the verified DZIP1L tree path. Literal donor joins include human DZIP1L experimental basal-body annotations and mouse Dzip1l localization in PMID:29487109; target self-support is legitimate experimental grounding, not circularity. The inherited location agrees with independent human studies, without assuming all family proteins occupy identical additional compartments.

Summary: HPA supports basal-body localization at its individual-location confidence level.

Reason: The actual HPA target page classifies basal-body localization as Supported. Its antibody HPA030404 assay metadata includes the basal-body observation in RPTEC/TERT1 cells. Other HPA observations—microtubules, cytokinetic bridge, spindle, primary cilium, nucleoplasm and cytosol—are individually Uncertain; the overall score is not applied to them. Retain the specific supported basal-body assertion, which also agrees with targeted human studies.

Summary: Tagged human DZIP1L localizes at the base of primary cilia.

Reason: Human GFP-DZIP1L in the hTERT-RPE1 experiments of PMID:19852954 localizes at the base of primary cilia near the centrin-marked centriole. This supports basal-body localization. The named human IMAGE4940443 clone has a 767-residue architecture with three archived differences from current Q8IYY4-1; no exact all-product equivalence is inferred.

Summary: Endogenous human DZIP1L occupies the distal basal-body/transition-zone region.

Reason: PMID:28530676 supports endogenous human DZIP1L at the distal basal-body/transition-zone region, including 3D-SIM localization near TCTN1. This is a central compartment for its ciliary protein-organization role. Proximity and coassociation do not by themselves establish CPLANE membership or a purified multiprotein gate.

Summary: The cilium-assembly IBA is supported by the verified ancestral placement and experiments.

Reason: The cilium-assembly IBA is placed at PTN000948208, which is on the authenticated DZIP1L path. Current literal donor joins include human DZIP1L/DZIP1, mouse Dzip1l/Dzip1 and zebrafish dzip1l/dzip1 experimental assertions; they are not all relabelled direct human experiments. Human combined RNAi and mouse ciliary-bud/remodeling experiments support a conserved role despite context-dependent penetrance. Normal cilia number in one patient fibroblast line does not establish lineage-wide loss of this activity.

Summary: The target matches the cilium-assembly rule and independent biological evidence.

Reason: ARBA00027837 explicitly emits GO:0060271. DZIP1L satisfies its first alternative condition set: IPR013087 and IPR032714 are both present in the target record and its lineage includes Chordata. The condition match alone is not a mechanistic assay, but independent human and mouse studies support the assigned ciliogenesis role. No taxon mismatch or target-specific loss is established.

Summary: Combined human DZIP1/DZIP1L depletion reduces ciliogenesis.

Reason: PMID:19852954 supports a human ciliogenesis contribution through combined DZIP1 and DZIP1L RNAi in hTERT-RPE1 cells. It does not demonstrate that DZIP1L alone is universally indispensable. The positive combined-perturbation result, human basal-body localization and independent mouse ciliary-bud evidence support retaining the existing cilium-assembly assertion with this precise limitation; no autonomous catalytic mechanism is inferred.

Summary: DZIP1L contributes to ciliogenesis with organism and cell-context dependence.

Reason: The multi-organism experiments in PMID:28530676 support a ciliogenesis role with tissue and genotype dependence. The B155 human fibroblast result preserves cilia number and morphology while altering PC1/PC2 localization; mouse and zebrafish phenotypes must not be presented as that human cellular result. Retain the existing assembly assertion in the integrated evidence, including independent mouse ciliary-bud remodeling, without claiming universal cilia absence or assigning a new process merely from disease severity.

Summary: Endogenous human DZIP1L localizes to the ciliary transition-zone region.

Reason: PMID:28530676 reports DZIP1L colocalization with TCTN1 in ciliated human dermal fibroblasts and nearby DZIP1L/TCTN1 localization by 3D-SIM in human RPE-1 cells. These target-specific microscopy observations support the transition-zone compartment alongside the separately retained centriole and basal-body pools. The approximately 120-nm lateral imaging resolution does not establish molecular contact, exclusive residence or a defined gate complex. Current typed ancestry makes GO:0035869 nonredundant with GO:0005814 and GO:0036064. This is a measured cellular location, not a new process inferred from disease or loss-of-function necessity.