Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes (By similarity).
Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
Evidence
1:
Inferred from Physical InteractionIntAct
ABL tyrosine kinase inhibitor (TKI) therapy induces clinical remission in chronic myeloid leukemia (CML) patients but early relapses and later emergence of TKI-resistant disease remain problematic. We recently demonstrated that the AHI-1 oncogene physically interacts with BCR-ABL and JAK2 and mediates cellular resistance to TKI in CML stem/progenitor cells. We now show that deletion of the SH3 domain of AHI-1 significantly enhances apoptotic response of BCR-ABL(+) cells to TKIs compared to cells expressing full-length AHI-1. We have also discovered a novel interaction between AHI-1 and Dynamin-2, a GTPase, through the AHI-1 SH3 domain. The crystal structure of the AHI-1 SH3 domain at 1.53-Å resolution reveals that it adopts canonical SH3 folding, with the exception of an unusual C-terminal α helix. PD1R peptide, known to interact with the PI3K SH3 domain, was used to model the binding pattern between the AHI-1 SH3 domain and its ligands. These studies showed that an "Arg-Arg-Trp" stack may form within the binding interface, providing a potential target site for designing specific drugs. The crystal structure of the AHI-1 SH3 domain thus provides a valuable tool for identification of key interaction sites in regulation of drug resistance and for the development of small molecule inhibitors for CML.
Evidence
2:
Inferred from Physical InteractionUniProtKB
Joubert syndrome and related disorders are autosomal recessive multisystem diseases characterized by cerebellar vermis aplasia/hypoplasia, retinal degeneration and cystic kidney disease. There are five known genes; mutations of which give rise to a spectrum of renal cystic diseases the most common of which is nephronophthisis, a disorder characterized by early loss of urinary concentrating ability, renal fibrosis, corticomedullary cyst formation and renal failure. Many of the proteins encoded by these genes interact with one another and are located at adherens junctions or the primary cilia and or basal bodies. Here we characterize Jouberin, a multi-domain protein encoded by the AHI1 gene. Immunohistochemistry with a novel antibody showed that endogenous Jouberin is expressed in brain, kidney and HEK293 cells. In the kidney, Jouberin co-localized with aquaporin-2 in the collecting ducts. 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. Jouberin is expressed at cell-cell junctions, primary cilia and basal body of mIMCD3 cells while a Jouberin-GFP construct localized to centrosomes in subconfluent and dividing MDCK cells. Our results suggest that Jouberin is a protein whose expression pattern supports both the adherens junction and the ciliary hypotheses for abnormalities leading to nephronophthisis.
Any process in which a protein is transported to, and/or maintained in, a specific location at the level of a cell. Localization at the cellular level encompasses movement within the cell, from within the cell to the cell surface, or from one location to another at the surface of a cell.
The process whose specific outcome is the progression of the central nervous system over time, from its formation to the mature structure. The central nervous system is the core nervous system that serves an integrating and coordinating function. In vertebrates it consists of the brain, spinal cord and spinal nerves. In those invertebrates with a central nervous system it typically consists of a brain, cerebral ganglia and a nerve cord.
The assembly of a cilium, a specialized eukaryotic organelle that consists of a filiform extrusion of the cell surface. Each cilium is bounded by an extrusion of the cytoplasmic membrane, and contains a regular longitudinal array of microtubules, anchored basally in a centriole.
The process whose specific outcome is the progression of the cloaca over time, from it's formation to the mature structure. The cloaca is the common chamber into which intestinal, genital and urinary canals open in vertebrates.
The characteristic morphogenetic movements where the primitive heart tube loops asymmetrically. This looping brings the primitive heart chambers into alignment preceding their future integration.
The process whose specific outcome is the progression of the hindbrain over time, from its formation to the mature structure. The hindbrain is the posterior of the three primary divisions of the developing chordate brain, or the corresponding part of the adult brain (in vertebrates, includes the cerebellum, pons, and medulla oblongata and controls the autonomic functions and equilibrium).
The progression of the Kupffer's vesicle over time from its initial formation until its mature state. The Kupffer's vesicle is a small but distinctive epithelial sac containing fluid, located midventrally posterior to the yolk cell or its extension, and transiently present during most of the segmentation period.
The establishment, maintenance and elaboration of the left/right axis. The left/right axis is defined by a line that runs orthogonal to both the anterior/posterior and dorsal/ventral axes. Each side is defined from the viewpoint of the organism rather of the observer (as per anatomical axes).
The morphogenetic process in which the anatomical structures of a polarized epithelium are generated and organized. A polarized epithelium is an epithelium where the epithelial sheet is oriented with respect to the planar axis.
The process whose specific outcome is the progression of the otic vesicle over time, from its formation to the mature structure. The otic vesicle is a transient embryonic structure formed during development of the vertebrate inner ear.
A process that is carried out at the cellular level and results in the assembly, arrangement of constituent parts, or disassembly of the outer segment of a photoreceptor cell, a sensory cell that reacts to the presence of light. The outer segment of the photoreceptor cell contains the light-absorbing materials.
The process in which the anatomical structures of the pronephric duct are generated and organized. The pronephric duct collects the filtrate from the pronephric tubules and opens to the exterior of the kidney.
The process in which the anatomical structures of a pronephric nephron tubule are generated and organized from an epithelium. A pronephric nephron tubule is an epithelial tube that is part of the pronephric nephron.
Any process that modulates the frequency, rate or extent of behavior, the specific actions or reactions of an organism in response to external or internal stimuli.
The process in which the vertebrate retina is organized into three laminae: the outer nuclear layer (ONL), which contains photoreceptor nuclei; the inner nuclear layer (INL), which contains amacrine, bipolar and horizontal cells; and the retinal ganglion cell (RGC) layer. Between the inner and outer nuclear layers, the outer plexiform layer (OPL) contains connections between the photoreceptors and bipolar and horizontal cells. The inner plexiform layer (IPL) is positioned between the INL and the ganglion cell layer and contains the dendrites of RGCs and processes of bipolar and amacrine cells. Spanning all layers of the retina are the radially oriented Mueller glia.
A series of molecular signals initiated by the binding of an extracellular ligand to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with regulation of a downstream cellular process, e.g. transcription.
A cellular transport process in which transported substances are moved in membrane-bounded vesicles; transported substances are enclosed in the vesicle lumen or located in the vesicle membrane. The process begins with a step that directs a substance to the forming vesicle, and includes vesicle budding and coating. Vesicles are then targeted to, and fuse with, an acceptor membrane.
Protein which is involved in the formation, organization, maintenance and degradation of the cilium, a cell surface projection found at the surface of a large proportion of eukaryotic. Their most prominent structural component is the axoneme which consists of nine doublet microtubules, with all motile cilia - except those at the embryonic node - containing an additional central pair of microtubules.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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