OTOP2 Membrane Protein Introduction

Introduction of OTOP2

OTOP2, encoded by the gene OTOP2, is a transmembrane protein belonging to the proton channel OTOP family. OTOP2 gene is mapped to chromosome 17q25.3 in human and is conserved in Rhesus monkey, chicken, chimpanzee, dog, mouse, cow, rat, fruit fly, zebrafish, and frog. Only biased expression of OTOP2 is observed in colon and testis. Specifically transporting protons into cells, OTOP2 is necessary for the cells that use changes in intracellular pH for cell signaling or to regulate biochemical or developmental processes. No alternative transcript variant has been reported so far.

Basic Information of OTOP2
Protein Name	Proton channel OTOP2
Gene Name	OTOP2
Aliases	Otopetrin-2
Organism	Homo sapiens (Human)
UniProt ID	Q7RTS6
Transmembrane Times	12
Length (aa)	562
Sequence	MSEELAQGPKESPPAPRAGPREVWKKGGRLLSVLLAVNVLLLACTLISGGAFNKVAVYDTDVFALLTAMMLLATLWILFYLLRTVRCPCAVPYRDAHAGPIWLRGGLVLFGICTLIMDVFKTGYYSSFFECQSAIKILHPLIQAVFVIIQTYFLWVSAKDCVHVHLDLTWCGLMFTLTTNLAIWMAAVVDESVHQSHSYSSSHSNASHARLISDQHADNPVGGDSCLCSTAVCQIFQQGYFYLYPFNIEYSLFASTMLYVMWKNVGRFLASTPGHSHTPTPVSLFRETFFAGPVLGLLLFVVGLAVFIIYEVQVSGDGSRTRQALVIYYSFNIVCLGLTTLVSLSGSIIYRFDRRAMDHHKNPTRTLDVALLMGAALGQYAISYYSIVAVVAGTPQDLLAGLNLTHALLMIAQHTFQNMFIIESLHRGPPGAEPHSTHPKEPCQDLTFTNLDALHTLSACPPNPGLVSPSPSDQREAVAIVSTPRSQWRRQCLKDISLFLLLCNVILWIMPAFGARPHFSNTVEVDFYGYSLWAVIVNICLPFGIFYRMHAVSSLLEVYVLS

Function of OTOP2 Membrane Protein

OTOP2 is first identified for its essential role in the vestibular system. Fig.1 shows the structure of the vestibular system. As a type of proton-selective channel, OTOP2 is responsible for specific transportation of protons into cells, which leads to changes in intracellular pH to modulate physiological processes. There are two important paralogs of OTOP2 gene: OTOP1 and OTOP3. As a type of otopetrins, OTOP2 is essential for normal formation of otoliths/otoconia in the inner ear. And otoconia are essential for normal processing of information regarding acceleration, the perception of gravity and spatial orientation. Different from canonical 7-transmembrane receptors, OTOP2 has 12 transmembrane regions composing of the ion channel, which almost occupies 80 percents of the whole sequence. Diseases associated with OTOP2 include vestibular disease and Usher syndrome.

Fig.1 Schematic representation of the vestibular system.

Application of OTOP2 Membrane Protein in Literature

Tu Y.H., et al. An evolutionarily conserved gene family encodes proton-selective ion channels. Science. 2018, 359(6379): 1047-1050. PubMed ID: 29371428

This report demonstrates that otopetrin family is of evolutionary conservation and it may have widespread tissue distribution, suggesting a broad role of proton channels in pathophysiology and physiology.
Hurle B., et al. Lineage-specific evolution of the vertebrate Otopetrin gene family revealed by comparative genomic analyses. BMC Evol Biol. 2011, 11: 23. PubMed ID: 21261979

This article sets up a framework for researching the probable interaction(s) of Otop and Ush1g in developmental pathways and clarifies the evolutionary history of the vertebrate Ush1g and Otop families.
Hughes I., et al. Identification of the Otopetrin Domain, a conserved domain in vertebrate otopetrins and invertebrate otopetrin-like family members. BMC Evol Biol. 2008, 8: 41. PubMed ID: 18254951

This article confirms that the distinct identity of ODP proteins is three "Otopetrin Domains" that are highly conserved between arthropods, vertebrates, and nematodes.
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, 12(7): 777-89. PubMed ID: 12651873

This article defines a novel gene family (Otop3 and Otop2, Otop1 and Otop1-like paralogues) with homology to the D. melanogaster and C. elegans DUF270 genes.

OTOP2 Preparation Options

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