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SLC6A8 Membrane Protein Introduction

Introduction of SLC6A8

SLC6A8 (solute carrier family 6 member 8), encoded by the SLC6A8 gene, is also known as sodium- and chloride-dependent creatine transporter 1 (CT1). SLC6A8 gene, containing 13 exons, is mapped to the long arm of the sex chromosome Xq28, and there are multiple transcript variants encoding different isoforms. The transporter SLC6A8 is a multi-pass membrane protein required for the uptake of creatinine in the skeletal and cardiac muscle. SLC6A8 is predominantly expressed in skeletal muscle and kidney, as well as other diverse tissues, including brain, heart, kidney, small intestine, colon, testis, prostate, etc. Regulated by AMP activated kinase, cyclosporine A, mTOR, serum and glucocorticoid inducible kinase isoforms and so on, SLC6A8 expression is largely increased by growth hormone.

Basic Information of SLC6A8
Protein Name Sodium- and chloride-dependent creatine transporter 1
Gene Name SLC6A8
Aliases CT1
Organism Homo sapiens (Human)
UniProt ID P48029
Transmembrane Times 12
Length (aa) 635
Sequence MAKKSAENGIYSVSGDEKKGPLIAPGPDGAPAKGDGPVGLGTPGGRLAVPPRETWTRQMDFIMSCVGFAVGLGNVWRFPYLCYKNGGGVFLIPYVLIALVGGIPIFFLEISLGQFMKAGSINVWNICPLFKGLGYASMVIVFYCNTYYIMVLAWGFYYLVKSFTTTLPWATCGHTWNTPDCVEIFRHEDCANASLANLTCDQLADRRSPVIEFWENKVLRLSGGLEVPGALNWEVTLCLLACWVLVYFCVWKGVKSTGKIVYFTATFPYVVLVVLLVRGVLLPGALDGIIYYLKPDWSKLGSPQVWIDAGTQIFFSYAIGLGALTALGSYNRFNNNCYKDAIILALINSGTSFFAGFVVFSILGFMAAEQGVHISKVAESGPGLAFIAYPRAVTLMPVAPLWAALFFFMLLLLGLDSQFVGVEGFITGLLDLLPASYYFRFQREISVALCCALCFVIDLSMVTDGGMYVFQLFDYYSASGTTLLWQAFWECVVVAWVYGADRFMDDIACMIGYRPCPWMKWCWSFFTPLVCMGIFIFNVVYYEPLVYNNTYVYPWWGEAMGWAFALSSMLCVPLHLLGCLLRAKGTMAERWQHLTQPIWGLHHLEYRAQDADVRGLTTLTPVSESSKVVVVESVM

Function of SLC6A8 Membrane Protein

As a member of the superfamily of Na+, Cl- coupled transporters for neurotransmitters (e.g. dopamine, GABA, serotonin and norepinephrine), amino acids (e.g. glycine) as well as the organic osmolytes betaine and taurine, SLC6A8 mediates the transportation of creatine into and out of cells. Creatine is synthesized primarily in the liver, kidneys, and pancreas and then transported to other tissues to participate in different physiological processes. It is documented that creatine in brain can be recognized as a neuromodulator and plays an important role in the energy homeostasis of the nervous system. The abundance of SLC6A8 in skeletal muscle is closely associated with muscle physiology, and inhibition of creatine transport in experimental animals causes muscle weakness. In brain, SLC6A8 is predominantly expressed in the cortical and subcortical regions, involved in motor and sensory processing, learning, memory, and regulation of emotion-related behavior. Mutations of SLC6A8 result in X-linked cerebral creatine transporter deficiency (CTD) syndrome, characterized by reduced intra-cerebral creatine, delays in speech and language development, intellectual disabilities, behavioral disturbance, and in some cases, seizures.

Locations of missense and 3 bp deletions in SLC6A8 protein. Missense mutations with a residual activity are marked by an asterisk. Fig.1 Locations of missense and 3 bp deletions in SLC6A8 protein. Missense mutations with a residual activity are marked by an asterisk (*). (van de Kamp,2013)

Application of SLC6A8 Membrane Protein in Literature

  1. Cervera-Acedo C., et al. A novel SLC6A8 mutation associated with motor dysfunction in a child exhibiting creatine transporter deficiency. Human genome variation. 2015, 2: 15037. PubMed ID: 27081545

    In this article, the authors identified a new mutation of SLC6A8 in a child with X-linked cerebral creatine deficiency, characterized by increased urinary creatine/creatinine ratio, abnormal brain proton magnetic resonance spectroscopy and reduced creatine transport, and the mutation is hemizygous in the child and not detected in his mother.

  2. Fezai M., et al. Negative regulation of the creatine transporter SLC6A8 by SPAK and OSR1. Kidney and Blood Pressure Research. 2014, 39(6): 546-554. PubMed ID: 25531585

    The authors injected cRNA encoding SLC6A8 into Xenopus laevis oocytes with or without wild-type or mutant SPAK/ OSR1, and they revealed that coexpression of wild-type SPAK and of T233ESPAK, wild-type OSR1, T185EOSR1 and T185AOSR1 significantly negatively regulated SLC6A8 activity. So SPAK and OSR1 can be recognized as negative regulators of the creatine transporter SLC6A8.

  3. Almilaji A., et al. Upregulation of the creatine transporter Slc6A8 by Klotho. Kidney and Blood Pressure Research. 2014, 39(6): 516-525. PubMed ID: 25531216

    The authors used two-electrode voltage-clamp technology to test creatine-induced current and they found that coexpression of Klotho protein can significantly increase creatine-induced current in Slc6A8 expressing Xenopus oocytes.

  4. Fezai M., et al. Regulation of the Na+, Cl-coupled creatine transporter CreaT (SLC6A8) by the janus kinase JAK3. Neurosignals. 2015, 23(1): 11-19. PubMed ID: 26666525

    This article used the Xenopus oocyte expression assay to demonstrate that the creatine-induced current is significantly increased by JAK3 inhibitor WHI-P154 (22 µM) in CreaT and JAK3 coexpressing oocytes. So JAK3 is a powerful negative regulator of SLC6A8.

  5. van de Kamp J.M., et al. Phenotype and genotype in 101 males with X-linked creatine transporter deficiency. Journal of medical genetics. 2013, 50(7):463-72. PubMed ID: 23644449

    This article performed a retrospective study of creatine transporter gene (SLC6A8) in 101 males with X-linked creatine transporter deficiency from 85 families with a pathogenic mutation and presented different phenotype and genotype.

SLC6A8 Preparation Options

To obtain the soluble and functional target protein, Creative Biolabs exploits the versatile Magic™ membrane protein production platform to provide many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SLC6A8 antibody development services.


Over years, Creative Biolabs has successfully generated massive functional membrane proteins for our customers. We are glad to tailor one-stop, custom-oriented service packages regarding a variety of membrane protein targets. Please feel free to contact us for more information.

Reference

  1. van de Kamp J M, et al. (2013). Phenotype and genotype in 101 males with X-linked creatine transporter deficiency. Journal of medical genetics. 50(7), 463-72.

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