UniProt ID: Q6IVV8 |
FUNCTION: Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B. Can also form a functional, homotetrameric ion channel (By similarity). Functions as non-selective, voltage-gated cation channel (By similarity). Required for normal oscillation of Ca(2+) levels within cilia; these oscillations of the intraciliary Ca(2+) levels can trigger cytoplasmic Ca(2+) signaling cascades (PubMed:25660539). May contribute to the release of Ca(2+) stores from the endoplasmic reticulum (By similarity). Required for normal temporal variation of the intracellular Ca(2+) levels in the heart (PubMed:23376035). Plays a role in fluid-flow mechanosensation (By similarity). Required for normal specification of the body left-right axis during embryogenesis, most likely via its role in ciliary Ca(2+) oscillations in Kupffer's vesicle (PubMed:15269167, PubMed:16216239, PubMed:16943304, PubMed:17360770, PubMed:23376035, PubMed:25660539). {ECO:0000250|UniProtKB:O35245, ECO:0000250|UniProtKB:Q13563, ECO:0000269|PubMed:15269167, ECO:0000269|PubMed:16216239, ECO:0000269|PubMed:16943304, ECO:0000269|PubMed:17360770, ECO:0000269|PubMed:23376035, ECO:0000269|PubMed:25660539}. ACTIVITY REGULATION: Channel activity is regulated by phosphorylation. Channel activity is regulated by intracellular Ca(2+). {ECO:0000250|UniProtKB:Q13563}. SUBUNIT: Homotetramer (By similarity). Heterotetramer with pkd1, giving rise to a complex formed by one pkd1 chain and three pkd2 chains (By similarity). Interacts with pkd1l1 (By similarity). {ECO:0000250|UniProtKB:H2LRU7, ECO:0000250|UniProtKB:Q13563}. SUBCELLULAR LOCATION: Basolateral cell membrane {ECO:0000269|PubMed:16943304}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q13563}. Cell membrane, sarcolemma {ECO:0000269|PubMed:16943304}. Cytoplasm, myofibril, sarcomere {ECO:0000269|PubMed:16943304}. Sarcoplasmic reticulum membrane {ECO:0000269|PubMed:23376035}. Apical cell membrane {ECO:0000269|PubMed:16943304}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q13563}. Endoplasmic reticulum membrane {ECO:0000305|PubMed:26432887}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q13563}. Cell projection, cilium {ECO:0000269|PubMed:16943304, ECO:0000269|PubMed:26432887}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000269|PubMed:26432887}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:16943304}. Note=Detected at the basolateral cell membrane and on apical, lumenal cilia in anterior, proximal pronephric ducts, and in intracellular vesicles in the posterior part of the pronephric duct. Detected on apical cell membranes on epithelial cells in the ear. {ECO:0000269|PubMed:16943304}. TISSUE SPECIFICITY: Detected along cilia and at the cilium basal body in Kupffer's vesicle at the 10 somite stage (PubMed:26432887). Detected in heart at 48hpf (PubMed:23376035). Detected in muscle and pronephric kidney at 48 hpf (PubMed:16943304). Detected on trunk muscle sarcolemma and sarcomere, on ependymal cell cilia in brain, at the apical cell membrane in epithelial cells in the ear, at the lateral line organ and olfactory placode at 56 hpf (PubMed:16943304). Detected in adult kidney (at protein level) (PubMed:16943304). {ECO:0000269|PubMed:16943304, ECO:0000269|PubMed:26432887}. DEVELOPMENTAL STAGE: First detected at the onset of gastrulation in a band at the blastoderm margin (PubMed:16216239, PubMed:17360770). Ubiquitous during gastrulation, somatogenesis and at 48 hpf (PubMed:16943304). During gastrulation, detected at the hypoblast of the dorsal midline and in dorsal forerunner cells that form a ciliated Kupffer's vesicle later on (PubMed:16216239, PubMed:17360770, PubMed:26432887). Ubiquitous during early somite stages, with high levels of expression in Kupffer's vesicle (PubMed:16216239, PubMed:17360770). At subsequent stages, detected in pronephric duct primordia and neural floorplate (PubMed:16216239, PubMed:16943304, PubMed:17360770, PubMed:26432887). Highly expressed in brain at 24 hpf (PubMed:16216239). At 3 dpf, detected at pharyngeal arches and the pectoral fin bud (PubMed:16216239). {ECO:0000269|PubMed:16216239, ECO:0000269|PubMed:16943304, ECO:0000269|PubMed:17360770, ECO:0000269|PubMed:26432887}. DOMAIN: The C-terminal coiled-coil domain is involved in oligomerization. The coiled-coil domain binds calcium and undergoes a calcium-induced conformation change (in vitro). {ECO:0000250|UniProtKB:Q13563}. PTM: Phosphorylated. Phosphorylation is important for protein function; a mutant human construct that lacks the N-terminal phosphorylation sites cannot complement a zebrafish pkd2-deficient mutant. {ECO:0000269|PubMed:16551655}. PTM: N-glycosylated. The four subunits in a tetramer probably differ in the extent of glycosylation; simultaneous glycosylation of all experimentally validated sites would probably create steric hindrance. {ECO:0000250|UniProtKB:Q13563}. DISRUPTION PHENOTYPE: Morpholino knockdown of the protein impairs specification of the left-right axis during embryonic development and randomization of heart and gut looping, plus misexpression of left-side specific genes (PubMed:16216239, PubMed:16943304, PubMed:17360770, PubMed:26432887, PubMed:25660539). Morpholino knockdown of the protein causes body curvature, tail curling, hydrocephalus and kidney cysts (PubMed:15269167, PubMed:16216239, PubMed:16943304, PubMed:16551655, PubMed:17360770, PubMed:23376035, PubMed:26432887). Morpholino knockdown has no effect on number, length or motility of pronephric cilia, but the fluid flow through the pronephric ducts seems to be impaired due to physical obstruction of the ducts (PubMed:16943304). Likewise, morpholino knockdown of the protein has no effect on the motility of cilia in Kupffer's vesicle (PubMed:25660539). Morpholino knockdown of the protein leads to an increase of the volume of Kupffer's vesicle, without any change in the proliferation of the cells that line the vesicle (PubMed:26432887). Morpholino knockdown of the protein leads to impaired heart function, characterized by arrhytmia and frequently associated with pericardial and abdominal edema and atrioventricular block (PubMed:23376035). {ECO:0000269|PubMed:15269167, ECO:0000269|PubMed:16216239, ECO:0000269|PubMed:16551655, ECO:0000269|PubMed:16943304, ECO:0000269|PubMed:17360770, ECO:0000269|PubMed:23376035, ECO:0000269|PubMed:26432887}. SIMILARITY: Belongs to the polycystin family. {ECO:0000305}. |
UniProt ID: A0A8M6YVJ7 |
SUBCELLULAR LOCATION: Membrane {ECO:0000256|ARBA:ARBA00004141}; Multi- pass membrane protein {ECO:0000256|ARBA:ARBA00004141}. SIMILARITY: Belongs to the polycystin family. {ECO:0000256|ARBA:ARBA00007200}. |
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