Ano1
Developmental stage
In the developing respiratory system, expressed in epithelium of trachea and lung at 12.5 dpc and 14.5 dpc but not detected in distal epithelial tips. Expressed in the mesenchyme adjacent to the proximal conducting airway epithelium at 14.5 dpc but not at 16.5 dpc. Epithelial expression persists at 16.5 dpc. At 18.5 dpc, high levels detected only in epithelial cells of terminal sacules. In the developing gastrointestinal tract, expressed in the esophageal mesenchyme and epithelium of posterior stomach and intestine. In the developing skeleton, expressed in the perichondria of the neural arch of developing vertebrae at 14.5 dpc and 16.5 dpc. In developing skin, expression is restricted to basal layers of the epidermis at 16.5 dpc.
Domain
The region spanning the fifth and sixth transmembrane domains probably forms the pore-forming region.
Function
Calcium-activated chloride channel (CaCC) (PubMed:18724360, PubMed:22002868, PubMed:22634729, PubMed:23840801, PubMed:24913262, PubMed:25779870, PubMed:28561733, PubMed:28963502, PubMed:29236684, PubMed:29236691, PubMed:31147466, PubMed:34089532, PubMed:34433575, PubMed:35135993). Plays a role in transepithelial anion transport and smooth muscle contraction (PubMed:28561733, PubMed:29236684, PubMed:29236691). Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development. Required for CFTR activation by enhancing endoplasmic reticulum Ca(2+) store release and is also required for CFTR membrane expression (By similarity). Required for basal and ATP-dependent mucus secretion in airways and intestine, probably by controlling exocytosis of mucus-filled granules by providing Ca(2+) to an apical signaling compartment (PubMed:30586313). Contributes to airway mucus expression induced by interleukins IL3 and IL8 and by the asthma-associated protein CLCA1 and is required for expression of mucin MUC5AC (By similarity). However, was shown in another study not to be required for MUC5AC expression (By similarity). Plays a role in the propagation of Ca(2+) waves in Kolliker's organ in the cochlea and contributes to the refinement of auditory brainstem circuitries prior to hearing onset (PubMed:35129434). In vomeronasal sensory neurons, modulates spontaneous firing patterns in the absence of stimuli as well as the firing pattern of pheromone-evoked activity (PubMed:34433575). Responsible for calcium-activated chloride channel activity in type I taste cells of the vallate papillae (PubMed:34089532). Acts as a heat sensor in nociceptive neurons (PubMed:22634729). In dorsal root ganglion neurons, plays a role in mediating non-histaminergic Mas-related G-protein coupled receptor (MRGPR)-dependent itching, acting as a downstream effector of MRGPRs (PubMed:35135993). In the developing brain, required for the Ca(2+)-dependent process extension of radial glial cells (PubMed:31147466).
Sequence Similarities
Belongs to the anoctamin family.
Tissue Specificity
Expressed at the apical surface of the vomeronasal epithelium (at protein level) (PubMed:25779870, PubMed:34433575). Expressed in the lateral and septal nasal glands (at protein level) (PubMed:25779870). Highly expressed in pulmonary bronchiole epithelial cells, pancreatic and submandibular gland acinar cells, kidney proximal tubule, all retinal cell layers, most sensory cells of dorsal root ganglia, Leydig cells and spermatocytes (at protein level). In the dorsal root ganglia, detected in small-diameter nociceptive neurons and in larger myelinated neurons (at protein level) (PubMed:22634729). In the dorsal root ganglia, expressed in MrgprA3-positive neurons (at protein level) (PubMed:35135993). In the developing brain, highly expressed in the ventricular zone and subventricular zone at 12.5 dpc and 14.5 dpc where it is detected in radial glial cells but not in neurons with expression dramatically decreased at P1 (at protein level) (PubMed:31147466). Highly expressed in the endometrial stroma (at protein level) (PubMed:31175367). In taste buds of the vallate papillae, expressed in the apical region of type I taste cells (at protein level) (PubMed:34089532). In the kidney, expressed in the collecting duct (at protein level) (PubMed:24913262). In the retina, strongly expressed in the outer and inner plexiform layers, weakly expressed in some somata in the inner nuclear layer and ganglion cell layer and not expressed in the outer nuclear layer (at protein level) (PubMed:23840801). Expressed in various retinal neurons including rod bipolar cells (at protein level) (PubMed:23840801). Expressed in eye, brain, myometrium and endometrium with higher levels in endometrium than myometrium in estrus and day 18 pregnant mice (PubMed:31175367). Not detected in uterine smooth muscle cells (PubMed:31175367). Expressed at high levels in the thyroid gland and gastrointestinal muscles.
Cellular localization
- Apical cell membrane
- Multi-pass membrane protein
- Presynapse
- In differentiating airway epithelial cells, predominantly intracellular at day 0 but is apically localized by day 30 (By similarity). Expressed in the presynapse of retinal neurons (PubMed:23840801).
Alternative names
Tmem16a, Anoctamin-1, Transmembrane protein 16A