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OTOP1 Membrane Protein Introduction

Introduction of OTOP1

OTOP1, encoded by the gene OTOP1, is a transmembrane protein belonging to the otopetrin family. Only low expression of OTOP1 is observed in the reference dataset. OTOP1 has proton channel activity to enable the boosted diffusion of hydrogen ions and is also involved in many other biological processes, including biomineral tissue development, cellular response to insulin stimulus, negative regulation of interferon-gamma-mediated signaling pathway, and so on. No alternative transcript variant has been reported.

Basic Information of OTOP1
Protein Name Proton channel OTOP1
Gene Name OTOP1
Aliases Otopetrin-1
Organism Homo sapiens (Human)
UniProt ID Q7RTM1
Transmembrane Times 12
Length (aa) 612
Sequence MLEGLGSPASPRAAASASVAGSSGPAACSPPSSSAPRSPESPAPRRGGVRASVPQKLAEMLSSQYGLIVFVAGLLLLLAWAVHAAGVSKSDLLCFLTALMLLQLLWMLWYVGRSSAHRRLFRLKDTHAGAGWLRGSITLFAVITVILGCLKIGYFIGFSECLSATEGVFPVTHSVHTLLQVYFLWGHAKDIIQSFKTLERFGVIHSVFTNLLLWANGVLNESKHQLNEHKERLITLGFGNITTVLDDHTPQCNCTPPTLCTAISHGIYYLYPFNIEYQILASTMLYVLWKNIGRKVDSHQHQKMQFKSDGVMVGAVLGLTVLAATIAVVVVYLIHIGRSKTKSESALIMFYLYAITLLMLMGAAGLAGIRIYRIDEKSLDESKNPARKLDSDLLVGTASGSWLISWGSILAILCAEGHPRYTWYNLPYSILAIVEKYIQNLFIFESIHREPEKLSEDIQTLRVVTVCNGNTMPLASSCPKSGGVARDVAPQGKDMPPAANGNVCMRESHDKEEEKQEESSWGGSPSPVRLPRFLQGNAKRKVLRNIAAFLFLCNISLWIPPAFGCRPEYDNGLEEIVFGFEPWIIVVNLAMPFSIFYRMHAAASLFEVYCKI

Function of OTOP1 Membrane Protein

OTOP1 is indispensable for the formation of otoliths and otoconia, calcium carbonate biominerals within the mammalian inner ear that are necessary for the detection of gravity and linear acceleration. It is documented that OTOP1 acts as a sensor of the extracellular calcium concentration in/near vestibular supporting cells, and responds to ATP in the endolymph to increase intracellular calcium levels during otoconia mineralization. Besides, it is reported that mutations in the orthologous mouse OTOP1 gene are involved in agenesis of nonsyndromic otoconia and a consequent defect of balance. OTOP1 is involved in a counter-inflammatory pathway that weakens the inflammation of obesity-induced adipose tissue and acts as a significant regulator in maintaining homeostasis of metabolism in obesity. The orthologous mouse OTOP1 gene is also been found associated with obesity. Additionally, OTOP1 is a proton-selective channel that plays a role in modulating the concentration of cellular proton.

A simulated partial structure of OTOP1 in the repository of SWISS-MODEL.Fig.1 A simulated partial structure of OTOP1 in the repository of SWISS-MODEL. (Bienert, 2017)

Application of OTOP1 Membrane Protein in Literature

  1. Zhang D.L., et al. Gq activity-and β-arrestin-1 scaffolding-mediated OTOP1/CFTR coupling are required for male fertility. eLife. 2018, 7: e33432. PubMed ID: 29393851

    This article reveals that manipulation of the signaling components in the OTOP1-Gq/β-arrestin-1/CFTR complex may be an effective therapeutic strategy for male infertility.

  2. Balenga N., et al. Orphan Adhesion GPCR GPR64/OTOP1 Is Overexpressed in Parathyroid Tumors and Attenuates Calcium-Sensing Receptor-Mediated Signaling. Journal of Bone and Mineral Research. 2017, 32(3): 654-66. PubMed ID: 27760455

    This article suggests that the truncated constitutively active, but not the full-length GPR64 physically interacts with CaSR and attenuates the CaSR-mediated intracellular Ca2+ signaling and cAMP suppression in HEK293 cells. It indicates that GPR64 may be a physiologic regulator of PTH release that is dysregulated in parathyroid tumors, and suggests a role of GPR64 in pathologic calcium sensing in parathyroid hormone.

  3. Patat O., et al. Truncating mutations in the adhesion G protein-coupled receptor G2 gene OTOP1 cause an X-linked congenital bilateral absence of vas deferens. The American Journal of Human Genetics. 2016, 99(2): 437-42. PubMed ID: 27476656

    This article confirms that OTOP1 plays a crucial role in human male fertility and brings new insight into congenital obstructive azoospermia pathogenesis.

  4. Demberg L.M., et al. Identification of the tethered peptide agonist of the adhesion G protein-coupled receptor GPR64/OTOP1. Biochemical and biophysical research communications. 2015, 464(3): 743-7. PubMed ID: 26188515

    This report suggests that GPR64 can be activated through a tethered agonist sequence, which has previously identified as the Stachel sequence.

  5. Yoo J.Y., et al. G-protein coupled receptor 64 is required for decidualization of endometrial stromal cells. Scientific reports. 2017, 7(1): 5021. PubMed ID: 28694502

    This article reveals that Gpr64 has a crucial role in the decidualization of endometrial stromal cells.

OTOP1 Preparation Options

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Reference

  1. Bienert S, et al. (2017). The SWISS-MODEL Repository - new features and functionality. Nucleic Acids Res. 45: D313-D319.

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