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
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Isoforms of the human PDZ-73 protein exhibit differential tissue expression.
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Anti-PDZ-73 (harmonin) antibodies show strong cytoplasmic and prominently apical staining in small intestinal epithelium; multiple isoforms with differential tissue expression were defined.
"Immunohistochemical staining with anti-PDZ 73 monoclonal antibodies showed strong cytoplasmic reactivity in epithelial cells of the small intestine, colon and kidney tubules, with a prominent apical staining pattern in cells of the small intestine."
A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.
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USH1C encodes harmonin; patient mutations cause USH1 (deafness, vestibular dysfunction, retinitis pigmentosa), and in the mouse inner ear harmonin is expressed specifically in sensory hair cells.
"We showed that, in the mouse inner ear, only the sensory hair cells express harmonin."
Interaction of MCC2, a novel homologue of MCC tumor suppressor, with PDZ-domain Protein AIE-75.
Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F.
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Reports PCDH15 mutations in USH1F families; USH1C is mentioned only as background in the introduction listing identified USH1 genes.
"Genes for three of these loci have been identified: Usher syndrome type 1B ( USH1B [MIM 276903 ]; Weil et al. 1995 ), Usher syndrome type 1C ( USH1C [MIM 276904 ]; Bitner-Glindzicz et al. 2000 ; Verpy et al. 2000 )"
Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.
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Harmonin b is an F-actin-bundling protein that binds cadherin 23 in growing stereocilia and interacts directly with myosin VIIa, anchoring the tip-link cadherin to the stereociliary actin core.
"we demonstrate that harmonin b is an F-actin-bundling protein, which is thus likely to anchor cadherin 23 to the stereocilia microfilaments, thereby identifying a novel anchorage mode of the cadherins to the actin cytoskeleton"
Expression of AIE-75 PDZ-domain protein induces G2/M cell cycle arrest in human colorectal adenocarcinoma SW480 cells.
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Ectopic overexpression of AIE-75/harmonin in SW480 cells suppresses growth via G2/M arrest with mitotic slippage; PP2A catalytic subunits bind its PDZ domains in yeast two-hybrid.
"Expression of AIE-75 suppressed growth of SW480 cells in vitro in correlation with the expression levels. It was due mainly to G2/M phase cell cycle arrest associated with mitotic slippage"
Scaffold protein harmonin (USH1C) provides molecular links between Usher syndrome type 1 and type 2.
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Harmonin PDZ1 binds the C-terminal PDZ-binding motifs of the USH2 proteins USH2A (usherin) and VLGR1 (ADGRV1), and the proteins are co-expressed in stereocilia and synaptic terminals of hair cells and photoreceptors, molecularly bridging the USH1 and USH2 networks.
"We pinpoint these interactions to interactions between the PDZ1 domain of harmonin and the PDZ-binding motifs at the C-termini of the USH2 proteins and NBC3."
An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the inner ear and binds to harmonin (USH1C).
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DOCK4-Ex49, a Rac GEF isoform present along stereocilia, binds harmonin in yeast two-hybrid, suggesting a possible Rac signaling link to stereociliary actin organization.
"we showed its localization in the inner ear within the hair bundles along the stereocilia"
The structure of the harmonin/sans complex reveals an unexpected interaction mode of the two Usher syndrome proteins.
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The harmonin N-domain plus PDZ1 form a supramodule that binds the SANS SAM domain and PDZ-binding motif, locking the two scaffolds into a highly stable complex; USH1 patient mutations destabilize it.
"We further show that the synergistic PDZ1/SAM and PDZ1/carboxyl PDZ binding-motif interactions, between harmonin and Sans, lock the two scaffold proteins into a highly stable complex."
Proteomic analysis of the enterocyte brush border.
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Harmonin is identified in the isolated enterocyte brush border proteome among actin-membrane linkers and validated by apical microvillar immunostaining in CACO-2 BBE cells.
"All three probes produced striking punctate staining at the apical surface, representative of microvillar labeling"
Myosin VIIa and sans localization at stereocilia upper tip-link density implicates these Usher syndrome proteins in mechanotransduction.
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MYO7A and SANS cluster at the stereocilia upper tip-link density, and MYO7A, SANS and harmonin-b form a tripartite complex constituting the core of the UTLD, in which MYO7A pulls on CDH23 to tension the tip-link.
"We propose that MYO7A, sans, and harmonin-b form the core components of the UTLD molecular complex. In this complex, MYO7A is likely the motor element that pulls on CDH23 to exert tension on the tip-link."
The giant spectrin βV couples the molecular motors to phototransduction and Usher syndrome type I proteins along their trafficking route.
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Spectrin betaV associates with harmonin (and SANS) and is proposed to couple USH1 proteins and opsin to actin- and microtubule-based motors in photoreceptors.
"We showed that spectrin βV also associates with two USH1 proteins, sans (USH1G) and harmonin (USH1C)."
Intestinal brush border assembly driven by protocadherin-based intermicrovillar adhesion.
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Harmonin binds the cytoplasmic domains of CDHR2/CDHR5 with myosin-7b, promotes their localization to microvillar tips, and harmonin-deficient mice show severe brush border defects.
"The cytoplasmic domains of microvillar protocadherins interact with the scaffolding protein, harmonin, and myosin-7b, which promote localization to microvillar tips."
A proteome-scale map of the human interactome network.
A massively parallel pipeline to clone DNA variants and examine molecular phenotypes of human disease mutations.
ANKS4B Is Essential for Intermicrovillar Adhesion Complex Formation.
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USH1C interacts with ANKS4B and MYO7B and must activate both before the tripartite IMAC cytoplasmic module can assemble, revealing a hierarchy with USH1C as the nucleating scaffold.
"However, a tripartite complex only forms if ANKS4B and MYO7B are first activated by USH1C."
An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.
Architecture of the human interactome defines protein communities and disease networks.
LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein interactions in mammalian cells.
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
The small EF-hand protein CALML4 functions as a critical myosin light chain within the intermicrovillar adhesion complex.
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USH1C is enriched at distal microvillar tips in native brush borders and CACO-2 BBE cells, and is genetically shared between the IMAC and the Usher complex via different splice isoforms.
"Importantly, the USH1C scaffold is shared genetically between the IMAC and Usher complex, although different splice isoforms are utilized between these two complexes"
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Quantitative fragmentomics allow affinity mapping of interactomes.
UniProt record for USH1C (Q9Y6N9)
Falcon deep research report for human USH1C/harmonin
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Synthesizes literature establishing harmonin as a multivalent PDZ scaffold acting at the stereociliary upper tip-link density, in the developing ankle-link/USH2 network, in retinal photoreceptors and Mueller glia, and in the intestinal intermicrovillar adhesion complex.