Recombinant Mouse Otopetrin-1 (Otop1) Protein

Function

Proton-selective ion channel (PubMed:29371428, PubMed:31160780, PubMed:31543453, PubMed:36596786, PubMed:37798269). Biphasically modulated by acid and alkali, mediating proton influx and efflux in response to extracellular acid and base stimulation, respectively (PubMed:36596786, PubMed:37798269). Sour taste receptor, which carries inward currents in response to extracellular acidification (PubMed:29371428, PubMed:31543264, PubMed:31543453, PubMed:37053086). Sensor for ammonium chloride (NH(4)Cl) in taste receptor cells. NH(4)Cl acts by increasing the intracellular pH, thereby generating a driving force for proton entry through OTOP1 channel (PubMed:37798269). Might also participate in alkaline sensation (PubMed:37798269). Plays a role in the regulation of Ca(2+) flux in response to purigenic (ATP, ADP and UDP) stimuli, leading to increase in cytosolic Ca(2+) due to influx of extracellular calcium (PubMed:17606897, PubMed:20554841). May play this role by inhibiting P2Y purinoceptor-mediated Ca(2+) release in a Ca(2+)-dependent manner and promote an influx of Ca(2+) in response to ATP (PubMed:20554841). Through this mechanism and possibly others, plays a role in the formation and function of calcium carbonate-based structures in the vestibular system of the inner ear, called otoconia, that sense gravity and linear acceleration (PubMed:12651873, PubMed:20554841). In obesity, may attenuate adipose tissue inflammation, through the negative regulation of IFNG signaling, hence may play an adaptive role in the maintainance of metabolic homeostasis (PubMed:24379350). Following alkali activation, may also be permeable Na(+), K(+), Cs(+) and Li(+) (PubMed:37798269)

Subcellular Location

Cell membrane (Multi-pass membrane protein); Cell projection, microvillus

Tissue Specificity

Expressed in thymus, heart, kidney, skin, vestibular system of the inner ear, sour taste cells, heart, uterus, dorsal root ganglion, adrenal gland, lactating mammary gland and stimulated mast cells (PubMed:12651873, PubMed:29371428). In the inner ear, expressed in the supporting cells in extrastriolar regions of the saccule and in the utricle, but not in the cochlea (PubMed:20554841). Expressed in brown adipose tissue. Expressed in epididymal white adipose tissue (eWAT), as well as in inguinal fat, in obese animals, but hardly detectable in eWAT from lean mice (PubMed:24379350). Expressed in acid-sensing taste receptor cells (PKD2L1-positive cells), but not in other types of taste cells (at protein level) (PubMed:29371428, PubMed:31543264, PubMed:31543453, PubMed:36596786)

Subunit

Homodimer (By similarity). Interacts with STAT1, independently of STAT1 phosphorylation status (PubMed:24379350)

• Hurle B. et al. Non-syndromic vestibular disorder with otoconial agenesis in tilted/mergulhador mice caused by mutations in otopetrin 1. — Hum. Mol. Genet. (2003)
• Carninci P. et al. The transcriptional landscape of the mammalian genome. — Science (2005)
• Church D.M. et al. Lineage-specific biology revealed by a finished genome assembly of the mouse. — PLoS Biol. (2009)
• Hughes I. et al. Otopetrin 1 activation by purinergic nucleotides regulates intracellular calcium. — Proc. Natl. Acad. Sci. U.S.A. (2007)
• Kim E. et al. Regulation of cellular calcium in vestibular supporting cells by otopetrin 1. — J. Neurophysiol. (2010)
• Kim E. et al. Missense mutations in Otopetrin 1 affect subcellular localization and inhibition of purinergic signaling in vestibular supporting cells. — Mol. Cell. Neurosci. (2011)
• Wang G.X. et al. Otopetrin 1 protects mice from obesity-associated metabolic dysfunction through attenuating adipose tissue inflammation. — Diabetes (2014)
• Tu Y.H. et al. An evolutionarily conserved gene family encodes proton-selective ion channels. — Science (2018)