SMO Membrane Protein Introduction

Introduction of SMO

Smoothened is a protein that in humans is encoded by the SMO gene. It is one of the Class Frizzled (Class F) G protein-coupled receptors. It participates in the hedgehog signaling pathway and can be easily conserved from flies to humans. It is the target of the natural teratogen cyclopamine and Vismodegib, which is the first hedgehog pathway inhibitor approved by the U.S. Food and Drug Administration (FDA).

Basic Information of SMO
Protein Name	Smoothened homolog
Gene Name	SMO
Aliases	Protein Gx
Organism	Homo sapiens (Human)
UniProt ID	Q99835
Transmembrane Times	7
Length (aa)	787
Sequence	MAAARPARGPELPLLGLLLLLLLGDPGRGAASSGNATGPGPRSAGGSARRSAAVTGPPPPLSHCGRAAPCEPLRYNVCLGSVLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFPEGCTNEVQNIKFNSSGQCEVPLVRTDNPKSWYEDVEGCGIQCQNPLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADGTMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWRRTWCRLTGQSDDEPKRIKKSKMIAKAFSKRHELLQNPGQELSFSMHTVSHDGPVAGLAFDLNEPSADVSSAWAQHVTKMVARRGAILPQDISVTPVATPVPPEEQANLWLVEAEISPELQKRLGRKKKRRKRKKEVCPLAPPPELHPPAPAPSTIPRLPQLPRQKCLVAAGAWGAGDSCRQGAWTLVSNPFCPEPSPPQDPFLPSAPAPVAWAHGRRQGLGPIHSRTNLMDTELMDADSDF

Function of SMO Membrane Protein

Cellular localization effectively regulates the function of SMO. Stimulation of this transmembrane receptor may bring about translocation of SMO to the primary cilium in vertebrates in the exit of patched from the primary cilium. Vertebrate SMO mutation often cannot contribute to hedgehog pathway activation. However, SMO can positively regulate pathway signaling after a tryptophan to leucine mutation in the aforementioned domain. It has been shown that SMO moves from the plasma membrane near the primary cilium to the ciliary membrane itself via a lateral transport pathway, which is opposed to via directed transport by vesicles. The cAMP-PKA pathway is proven to promote the lateral movement of SMO and hedgehog signal transduction in general. After cellular localization, SMO will then be activated by a distinct mechanism to stimulate hedgehog signal transduction, but the mechanism is still unclear. It seems that the existence of an unidentified endogenous ligand can bind SMO and activate it. It is believed that mutations of SMO can copy the ligand-induced conformation of SMO and in further activate constitutive signal transduction.

SMO Membrane Protein Introduction Fig.1 Structure of Smoothened homolog.

Application of SMO Membrane Protein in Literature

Yauch R.L., et al. Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science. 2009, 326(5952):572-4. PubMed ID: 19726788

This article shows that smoothened mutations can serve as a mechanism of drug resistance in human cancer.
Moraes R.C., et al. Constitutive activation of smoothened (SMO) in mammary glands of transgenic mice leads to increased proliferation, altered differentiation and ductal dysplasia. Development. 2007, 134(6):1231-42. PubMed ID: 17287253

The results of this study suggest that change of hedgehog signaling may contribute to breast cancer development by promoting proliferation and increasing the pool of division-competent cells.
Zhang X., et al. Cyclopamine inhibition of human breast cancer cell growth independent of Smoothened (Smo). Breast Cancer Res Treat. 2009, 115(3):505-21. PubMed ID: 18563554

This article suggests that cyclopamine and CUR0199691 have unique secondary molecular targets at the dosages required for growth inhibition that are unrelated to smoothened.
Pricl S., et al. Smoothened (SMO) receptor mutations dictate resistance to vismodegib in basal cell carcinoma. Mol Oncol. 2015, 9(2):389-97. PubMed ID: 25306392

The article suggests that two mutations of SMO may be under different mechanisms directing primary and secondary resistance to vismodegib, respectively.
Sinha S. and Chen J.K. Purmorphamine activates the Hedgehog pathway by targeting Smoothened. Nat Chem Biol. 2006, 2(1):29-30. PubMed ID: 16408088

The authors find a purine derivative to activate the Hh pathway and can affect osteoblast differentiation. They demonstrate that smoothened is the direct target of purmorphamine.

SMO Preparation Options

We keep in a leading position of membrane protein studies over the past few years. Based on our versatile Magic™ membrane protein production platform, we can provide a series of advanced membrane protein preparation services in reconstitution forms as well as multiple active formats for worldwide customers. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SMO antibody development services.

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. It’s our duty to promote the development of our clients’ programs with our experienced service. For more details, please feel free to contact us.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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