Identification of the Otopetrin Domain, a conserved domain in vertebrate otopetrins and invertebrate otopetrin-like family members

Nisc Comparative Sequencing Program ,Eric D Green,Inna Hughes,Belen Hurle,David M Ornitz,Arend Sidow,Jonathan Binkley

doi:10.1186/1471-2148-8-41

Abstract

BackgroundOtopetrin 1 (Otop1) encodes a multi-transmembrane domain protein with no homology to known transporters, channels, exchangers, or receptors. Otop1 is necessary for the formation of otoconia and otoliths, calcium carbonate biominerals within the inner ear of mammals and teleost fish that are required for the detection of linear acceleration and gravity. Vertebrate Otop1 and its paralogues Otop2 and Otop3 define a new gene family with homology to the invertebrate Domain of Unknown Function 270 genes (DUF270; pfam03189).ResultsMulti-species comparison of the predicted primary sequences and predicted secondary structures of 62 vertebrate otopetrin, and arthropod and nematode DUF270 proteins, has established that the genes encoding these proteins constitute a single family that we renamed the Otopetrin Domain Protein (ODP) gene family. Signature features of ODP proteins are three "Otopetrin Domains" that are highly conserved between vertebrates, arthropods and nematodes, and a highly constrained predicted loop structure.ConclusionOur studies suggest a refined topologic model for ODP insertion into the lipid bilayer of 12 transmembrane domains, and highlight conserved amino-acid residues that will aid in the biochemical examination of ODP family function. The high degree of sequence and structural similarity of the ODP proteins may suggest a conserved role in the intracellular trafficking of calcium and the formation of biominerals.

Highlights

Otopetrin 1 (Otop1) encodes a multi-transmembrane domain protein with no homology to known transporters, channels, exchangers, or receptors
The phylogenetic relationships of vertebrate otopetrin and arthropod and nematode Domain of Unknown Function 270 genes (DUF270) genes were deduced from a total of 62 complete or nearly complete open reading frames in 25 species
Phylogenetic relationships and revised nomenclature of vertebrate otopetrins and arthropod and nematode DUF270 genes A maximum-likelihood phylogenetic tree was created from the multi-sequence alignment of each encoded protein (Figure 1)

Summary

Introduction

Otopetrin 1 (Otop1) encodes a multi-transmembrane domain protein with no homology to known transporters, channels, exchangers, or receptors. Otop is necessary for the formation of otoconia and otoliths, calcium carbonate biominerals within the inner ear of mammals and teleost fish that are required for the detection of linear acceleration and gravity. Three mutant mice and one zebrafish model with mutations in Otop have been described: tilted (tlt) [6]; mergulhador (mlh) [7]; inner ear defect (ied) [8]; and backstroke (bks) [9], respectively. All of these mutants lack otoconia or otoliths, but have normal inner ear development. The morpholino knockdown of Otop phenocopies the tlt mutation, showing otolith agenesis with no disruption of the patterning of the developing inner ear [9,10]

Methods

Results

Conclusion