SCNN1B Membrane Protein Introduction

Introduction of SCNN1B

SCNN1B is located on chromosome 16p12.2 and it encodes β-subunit of the epithelial sodium channel (ENaC). The amiloride-sensitive ENaC complex is composed of three homologous subunits, α (gene symbol SCNN1A), β (gene symbol SCNN1B), and γ (gene symbol SCNN1C). These three subunits share similar structures characterized by two transmembrane domains, a large extracellular loop, and short cytoplasmic amino and carboxyl termini. ENaC is functional only when all three subunits are coexpressed on the epithelial membrane.

Basic Information of SCNN1B
Protein Name	Amiloride-sensitive sodium channel subunit beta
Gene Name	SCNN1B
Aliases	Beta-NaCH, Epithelial Na(+) channel subunit beta(Beta-ENaC, ENaCB), Nonvoltage-gated sodium channel 1 subunit beta, SCNEB
Organism	Homo sapiens (Human)
UniProt ID	P51168
Transmembrane Times	2
Length (aa)	640
Sequence	MHVKKYLLKGLHRLQKGPGYTYKELLVWYCDNTNTHGPKRIICEGPKKKAMWFLLTLLFAALVCWQWGIFIRTYLSWEVSVSLSVGFKTMDFPAVTICNASPFKYSKIKHLLKDLDELMEAVLERILAPELSHANATRNLNFSIWNHTPLVLIDERNPHHPMVLDLFGDNHNGLTSSSASEKICNAHGCKMAMRLCSLNRTQCTFRNFTSATQALTEWYILQATNIFAQVPQQELVEMSYPGEQMILACLFGAEPCNYRNFTSIFYPHYGNCYIFNWGMTEKALPSANPGTEFGLKLILDIGQEDYVPFLASTAGVRLMLHEQRSYPFIRDEGIYAMSGTETSIGVLVDKLQRMGEPYSPCTVNGSEVPVQNFYSDYNTTYSIQACLRSCFQDHMIRNCNCGHYLYPLPRGEKYCNNRDFPDWAHCYSDLQMSVAQRETCIGMCKESCNDTQYKMTISMADWPSEASEDWIFHVLSQERDQSTNITLSRKGIVKLNIYFQEFNYRTIEESAANNIVWLLSNLGGQFGFWMGGSVLCLIEFGEIIIDFVWITIIKLVALAKSLRQRRAQASYAGPPPTVAELVEAHTNFGFQPDTAPRSPNTGPYPSEQALPIPGTPPPNYDSLRLQPLDVIESDSEGDAI

Function of SCNN1B Membrane Protein

SCNN1B is a part of the amiloride-sensitive ENaC complex consisting of three subunits (α, β, and γ) that acts as the rate-limiting step in Na⁺ transport in the distal nephron and plays an important role in Na⁺ homeostasis and blood pressure regulation. SCNN1B is classified as a membrane channel, but accumulating evidence also indicates that ENaC subunits, including SCNN1B, participate in cellular differentiation. Mutations in the COOH terminus of ENaC β or γ subunit can increase Na⁺ absorption in the distal nephron of the kidney and thus lead to Liddle’s syndrome. SCNN1B mutations also result in severe hyperkalemia due to pseudohypoaldosteronism type 1.

Fig.1 Schematic representation of sodium handling by the kidney, syndromes causing hypotension and hypertension, genetic factors influencing sodium reabsorption, and potential targeted therapeutic options. (Spence, 2018)

Application of SCNN1B Membrane Protein in Literature

Zhong Q., et al. Association of SCNN1B promoter methylation with essential hypertension. Molecular Medicine Reports. 2016, 14(6):5422-5428. PubMed ID: 27840946

This article finds a drug-, age-, and gender-dependent association between SCNN1B promoter methylation and EH.
Nobel Y.R., et al. Pseudohypoaldosteronism type 1 due to novel variants of SCNN1B gene. Endocrinol Diabetes Metab Case Rep. 2016, 2016:150104. PubMed ID: 26807262

This article reports a patient with novel variants of the SCNN1B gene causing PHA1 with persistent, symptomatic hyperkalemia.
Wang L.P., et al. Genetic diagnosis of Liddle's syndrome by mutation analysis of SCNN1B and SCNN1G in a Chinese family. Chinese medical journal. 2012, 125(8):1401-4. PubMed ID: 22613642

This article suggests that Pro616Ser in SCNN1B is a critical amino acid that has a key role in the inhibition of sodium channel activity.
Ramos M.D., et al. Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosis-like phenotypes. Clinical Genetics. 2014, 86(1):91-5. PubMed ID: 23837941

This article reveals that CF-like disease probably results from complex genotypes in several genes in an oligogenic form, with rare variants interacting with environmental factors.
Qian Y., et al. Sodium channel subunit SCNN1B suppresses gastric cancer growth and metastasis via GRP78 degradation. Cancer Research. 2017, 77(8):1968-1982. PubMed ID: 28202509

This article suggests that SCNN1B as a tumor-suppressive function that triggers unfolded protein response (UPR) in gastric cancer cells, with implications for its potential clinical applications as a survival biomarker in gastric cancer patients.

SCNN1B Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SCNN1B antibody development services.

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

Spence J D and Rayner B L. (2018). Hypertension in blacks: Individualized therapy based on renin/aldosterone phenotyping. Hypertension. 72(2), 263-269.

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