Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Jouberin localizes to collecting ducts and interacts with nephrocystin-1.
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The abstract reports junctional/ciliary-base localization in mIMCD3 and Jouberin-GFP centrosomal localization in MDCK; full construct provenance remains unresolved.
"Jouberin is expressed at cell-cell junctions, primary cilia and basal body of mIMCD3 cells"
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Endogenous and exogenous NPHP1 association was measured in HEK293 cells.
"We show that Jouberin interacts with nephrocystin-1 as determined by yeast-2-hybrid system and this was confirmed by exogenous and endogenous co-immunoprecipitation in HEK293 cells."
Ahi1, whose human ortholog is mutated in Joubert syndrome, is required for Rab8a localization, ciliogenesis and vesicle trafficking.
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Mouse Ahi1 localizes to the basal body of primary cilia.
"Ahi1 immunostaining mapped to the base of the primary non-motile cilium, specifically the basal body"
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Ahi1 depletion lowers Rab8a abundance and basal-body accumulation.
"In contrast, in Ahi1-knockdown cells, Rab8a expression was significantly lower, and it could not be detected at the basal body"
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The HEK293 interaction experiment uses mouse Ahi1 in a human host-cell background.
"Since our mouse Ahi1 antibody cannot recognize human AHI1 in HEK293 cells, we used this cell line for testing whether Ahi1 and Rab8a form a complex."
Impaired Wnt-beta-catenin signaling disrupts adult renal homeostasis and leads to cystic kidney ciliopathy.
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GFP-Jouberin co-immunoprecipitates endogenous beta-catenin in 293T cells; this is complex association, not purified binary binding.
"We subjected 293T cells transfected with GFP-tagged Jbn to immunoprecipitation with a GFP-specific antibody followed by immunoblotting for endogenous β-catenin. This method revealed an interaction between β-catenin and GFP-Jbn but not GFP empty vector"
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Jouberin alone does not activate the Wnt reporter in the tested cells.
"HEK293T cells transfected with this construct and Jbn alone did not show activation of the Wnt pathway, indicating that Jbn is not an activator of the pathway"
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Ciliogenesis is preserved in the knockout contexts examined in this study.
"We therefore concluded that Jbn is not necessary for proper ciliogenesis, suggesting alternative mechanisms for the defects in these mice."
AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis.
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Ahi1 loss disrupts mouse photoreceptor outer-segment formation and opsin localization.
"We show that Ahi1-null mice fail to form retinal outer segments and have abnormal distribution of opsin throughout their photoreceptors."
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Lowering opsin dosage delays photoreceptor death, supporting a cargo-dependent survival effect.
"Apoptotic cell death of photoreceptors occurs rapidly between 2 and 4 weeks of age in these mice and is significantly (P = 0.00175 and 0.00613) delayed by a reduced dosage of opsin."
Neuronal Abelson helper integration site-1 (Ahi1) deficiency in mice alters TrkB signaling with a depressive phenotype.
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Mouse neuronal Ahi1 deficiency alters TrkB trafficking/degradation and signaling; primary full Results additionally measure internalization, which is not described by this abstract quote alone.
"Ahi1 deficiency promotes the degradation of endocytic TrkB and reduces TrkB signaling in neuronal cells."
Defective Wnt-dependent cerebellar midline fusion in a mouse model of Joubert syndrome.
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Wild-type Jouberin potentiates a stimulated Wnt reporter in the tested cells.
"Overexpression of wild-type Jbn in these cells resulted in a 1.6-fold increase in reporter activity over vector control"
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The three tested disease-variant constructs fail to produce the wild-type increase.
"In contrast, none of the mutants exhibited significantly increased Wnt activity compared with control."
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V443D reduces beta-catenin co-recovery.
"V443D however exhibited a considerable decrease in pulldown of endogenous β-catenin."
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Cerebellar granule neurons retain cilia in this mouse knockout context.
"CGNs isolated from Ahi1 null and control littermates exhibited indistinguishable number of cilia and morphology"
Modelling a ciliopathy: Ahi1 knockdown in model systems reveals an essential role in brain, retinal, and renal development.
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The primary experimental systems are mouse IMCD3 knockdown and zebrafish morpholinos; independent human evidence supports the conserved biological role.
"Mouse inner medullary collecting duct (IMCD3) cells were cultured in DMEM/Ham’s F12 supplemented with 10% fetal calf serum (Sigma-Aldrich, UK)."
A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain.
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The cited perturbations include B9D1 and TMEM231 knockout; source-specific Ahi1 membership is supported by affinity recovery/co-fractionation, not by the knockout result quoted here.
"Mouse knockouts of B9D1 and TMEM231 have identical defects in Sonic hedgehog (Shh) signalling and ciliogenesis."
Molecular and structural characterization of the SH3 domain of AHI-1 in regulation of cellular resistance of BCR-ABL(+) chronic myeloid leukemia cells to tyrosine kinase inhibitors.
The Joubert syndrome-associated missense mutation (V443D) in the Abelson-helper integration site 1 (AHI1) protein alters its localization and protein-protein interactions.
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Human AHI1-mutant fibroblasts have reduced ciliation.
"Fibroblasts from individuals with JBTS showed an ∼50% decrease in primary cilia formation"
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Ciliary ARL13B is reduced in the remaining patient-fibroblast cilia.
"JBTS fibroblasts displayed a significant reduction in ARL13B ciliary localization in their remaining primary cilia as compared with ARL13B ciliary localization in normal fibroblasts"
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AHI1 and NPHP1 co-migrate in two complex-size ranges; the inferred stoichiometries are tentative.
"AHI1-WT and NPHP1 co-migrated in two different size complexes, corresponding to molecular masses of 430 and 210 kDa"
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HAP1 association maps to an AHI1 region outside the WD40 and SH3 domains.
"We determined that a smaller region of AHI1-F2, denoted as AHI1-F3 (141–434 aa), is still able to bind HAP1"
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Differently tagged human AHI1 proteins co-immunoprecipitate.
"These results demonstrate that AHI1 is capable of self-association"
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Human AHI1 constructs localize to basal bodies in transfected cells.
"These results showed that ∼80% of the cells expressing the wild type AHI1 (AHI1-WT) protein had AHI1 at the basal body of the primary cilium"
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The human and mouse proteins differ in their N-terminal architecture.
"human AHI1 possesses an N-terminal coiled-coil domain (∼140 aa) that does not exist in the mouse Ahi1 protein"
Preferred SH3 domain partners of ADAM metalloproteases include shared and ADAM-specific SH3 interactions.
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The isolated AHI1 SH3 domain is selected by an ADAM12 tail in the tested assay.
"Interestingly, ADAM12, a strong nephrocystin binder, also selected the SH3 domain of another ciliary disease-associated protein AHI1/Jouberin"
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AHI1 SH3 recognizes canonical proline-rich motifs also preferred by several other SH3 domains.
"a preference for canonical motifs typical for SFK was shared by many SH3 domains, such as nephrocystin, AHI1, OSTF1, intersectin1(III), and Grb2(II)."
Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis.
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Ahi1 knockout abolishes OTUD1–Tyk2 association in mouse primary macrophages.
"We noticed that AHI1 did not strongly affect OTUD1 protein levels (Fig. 4f) but affected the interaction between OTUD1 and Tyk2, as shown by the abolishment of the OTUD1-Tyk2 interaction upon AHI1 knockout in primary macrophages"
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OTUD1 deficiency has little effect on Ahi1–Tyk2 association.
"However, OTUD1 deficiency did not strongly affect the AHI1-Tyk2 interaction"
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The dependency assay compares Ahi1 wild-type and knockout mouse peritoneal macrophages.
"Immunoprecipitation analysis of the interaction between endogenous OTUD1 and Tyk2 in Ahi1+/+ and Ahi1−/− mouse peritoneal macrophages."
AHI-1 interacts with BCR-ABL and modulates BCR-ABL transforming activity and imatinib response of CML stem/progenitor cells.
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Endogenous AHI1 co-immunoprecipitates BCR-ABL from human K562 cells.
"We demonstrated a direct interaction between AHI-1 and BCR-ABL at endogenous levels by detection of BCR-ABL in human CML cells (K562) after IP with a human AHI-1 antibody"
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JAK2 is recovered in the same complex; this alone does not establish an AHI1-dependent bridge.
"We determined that JAK2 was associated with this protein interaction complex, as AHI-1 could be detected by an anti–AHI-1 antibody in K562 cells after IP with a specific antibody to JAK2"
Retinal degeneration and failure of photoreceptor outer segment formation in mice with targeted deletion of the Joubert syndrome gene, Ahi1.
Subcellular spatial regulation of canonical Wnt signalling at the primary cilium.
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Ciliary sequestration of Jouberin limits beta-catenin nuclear signaling.
"The cilium, through regulated intraflagellar transport, diverts Jouberin (Jbn), a ciliopathy protein and context-specific Wnt pathway regulator, away from the nucleus and limits β-catenin nuclear entry."
Ahi1 promotes Arl13b ciliary recruitment, regulates Arl13b stability and is required for normal cell migration.
The Transition Zone Protein AHI1 Regulates Neuronal Ciliary Trafficking of MCHR1 and Its Downstream Signaling Pathway.
Cby1 promotes Ahi1 recruitment to a ring-shaped domain at the centriole-cilium interface and facilitates proper cilium formation and function.
Affinage mechanistic annotation for AHI1 (human)
Ciliopathy-associated protein, CEP290, is required for ciliary necklace and outer segment membrane formation in retinal photoreceptors.
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In mouse retinal photoreceptors, CEP290 loss restricts AHI1 localization to the proximal connecting cilium. The experiment measures AHI1 as an affected component, not its recruitment of other transition-zone proteins.
"our results indicate that proper AHI1 localization in the CC depends on CEP290."
RAB3IP stimulates nucleotide exchange on RAB8A
Recruitment of transition zone proteins
CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body
The Ciliopathy Gene ahi1 Is Required for Zebrafish Cone Photoreceptor Outer Segment Morphogenesis and Survival.
Missense mutations in the WD40 domain of AHI1 cause non-syndromic retinitis pigmentosa.
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Sequence-validated full-length human AHI1 isoform 1 was expressed as an N-terminal mRFP fusion; human hTERT-RPE1 imaging showed cytoplasmic and ciliary-base localization. This is a tagged overexpression assay, not endogenous localization.
"Wild-type mRFP-AHI1 showed a diffused cytoplasmic localisation and a strong enrichment at the ciliary base of ciliated hTERT-RPE1 cells"
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The tested RP-associated variants reduced basal-body enrichment; tested Joubert-associated WD40 variants produced a similar reduction, so this localization phenotype does not distinguish the clinical groups.
"Although RP-associated mutant Jouberin was still able to localise to the ciliary base, we observed a significant decrease of this enrichment compared with the wild-type protein"
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Cilium frequency and length were not significantly altered in the RPE1 mutant-overexpression comparisons. A separate patient-fibroblast comparison also retained ciliation and cilium length.
"Neither ciliary frequency nor cilium length varied significantly"