OTOP3 Membrane Protein Introduction

Introduction of OTOP3

OTOP3 is a transmembrane protein belonging to the proton channel otopetrin family and is encoded by the gene OTOP3. OTOP3 biased expression is only observed in the duodenum (RPKM 38.1) and small intestine (RPKM 6.4). A preliminary secondary structure prediction of OTOP3 based on the human, mouse, rat, zebrafish, and fugu protein sequences suggested a topology of 12 transmembrane domains (TM) with cytosolic amino and carboxy termini. OTOP3 has proton channel activity, which enables the diffusion of hydrogen ions through the channel. Additionally, it also has a nucleic acid binding activity. At present, no alternative transcript variant of OTOP3 has been reported.

Basic Information of OTOP3
Protein Name	Proton channel OTOP3
Gene Name	OTOP3
Aliases	Otopetrin-3
Organism	Homo sapiens (Human)
UniProt ID	Q7RTS5
Transmembrane Times	12
Length (aa)	596
Sequence	MGRGARAAAAQSRWGRASRASVSPGRTIRSAPAVGEAQETEAAPEKENRVDVGAEERAAATRPRQKSWLVRHFSLLLRRDRQAQKAGQLFSGLLALNVVFLGGAFICSMIFNKVAVTLGDVWILLATLKVLSLLWLLYYVASTTRRPHAVLYQDPHAGPLWVRGSLVLFGSCTFCLNIFRVGYDVSHIRCKSQLDLVFSVIEMVFIGVQTWVLWKHCKDCVRVQTNFTRCGLMLTLATNLLLWVLAVTNDSMHREIEAELGILMEKSTGNETNTCLCLNATACEAFRRGFLMLYPFSTEYCLICCAVLFVMWKNVGRHVAPHMGAHPATAPFHLHGAIFGPLLGLLVLLAGVCVFVLFQIEASGPAIACQYFTLYYAFYVAVLPTMSLACLAGTAIHGLEERELDTVKNPTRSLDVVLLMGAALGQMGIAYFSIVAIVAKRPHELLNRLILAYSLLLILQHIAQNLFIIEGLHRRPLWETVPEGLAGKQEAEPPRRGSLLELGQGLQRASLAYIHSYSHLNWKRRALKEISLFLILCNITLWMMPAFGIHPEFENGLEKDFYGYQIWFAIVNFGLPLGVFYRMHSVGGLVEVYLGA

Function of OTOP3 Membrane Protein

Similar to OTOP2, OTOP3 is also identified for the first time because of its essential role in the vestibular system. OTOP3 functions remain unknown clearly. But as a proton-selective channel, OTOP3 can specifically control the transportation of protons into cells, which is generally indispensable in cell types that make use of changes in intracellular pH or to regulate biochemical or developmental processes. As a type of otopetrins, OTOP3 is essential for normal formation of otoliths/otoconia in the inner ear. Otoconia are complex calcium carbonate biominerals in the utricle and saccule of the vertebrate inner ear, which are essential for the normal sensation of linear acceleration and gravity. Degeneration or displacement of otoconia can lead to vertigo and loss of balance. Notably, the Otop2-Otop3 gene tandem is physically clustered (head-to-tail) with the Usher syndrome (USH) subtype 1G gene (USH1G), which may reflect lineage-specific genomic features and gene associations worthy of exploration.

Fig.1 Part of the vestibular system.

Application of OTOP3 Membrane Protein in Literature

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 studying the probable interaction(s) of Otop and Ush1g in developmental pathways and clarifies the evolutionary history of the vertebrate Ush1g and Otop families.
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.
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.
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.

OTOP3 Preparation Options

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