TY - JOUR
T1 - Identification of the Otopetrin Domain, a conserved domain in vertebrate otopetrins and invertebrate otopetrin-like family members
AU - Hughes, Inna
AU - Binkley, Jonathan
AU - Hurle, Belen
AU - Green, Eric D.
AU - Blakesley, Robert
AU - Bouffard, Gerry
AU - McDowell, Jennifer
AU - Maskeri, Baishali
AU - Hansen, Nancy
AU - Park, Morgan
AU - Thomas, Pamela
AU - Young, Alice
AU - Sidow, Arend
AU - Ornitz, David M.
N1 - Funding Information:
This research was supported by National Institute on Deafness and Other Communication Disorders Grants DC02236 (DMO), DC06974 (IH), and in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. We thank Linda Lobos for assembling loop length data. We thank numerous people associated with the NISC Comparative Sequencing Program, in particular Robert Blakesley, Gerry Bouffard, Jennifer McDowell, Baishali Maskeri, Nancy Hansen, Morgan Park, Pamela Thomas, Alice Young and the many dedicated mapping, sequencing and finishing technicians.
PY - 2008
Y1 - 2008
N2 - Background. Otopetrin 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). Results. Multi-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. Conclusion. Our 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.
AB - Background. Otopetrin 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). Results. Multi-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. Conclusion. Our 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.
UR - http://www.scopus.com/inward/record.url?scp=40949164745&partnerID=8YFLogxK
U2 - 10.1186/1471-2148-8-41
DO - 10.1186/1471-2148-8-41
M3 - Article
C2 - 18254951
AN - SCOPUS:40949164745
SN - 1471-2148
VL - 8
JO - BMC Evolutionary Biology
JF - BMC Evolutionary Biology
IS - 1
M1 - 41
ER -