SLC46A2 Membrane Protein Introduction

Introduction of SLC46A2

SLC46A2, also known as TSCOT, is a member of the SLC46A family, and another member, SLC46A1, has been characterized as a proton-coupled folate transporter. This protein is encoded by SLC46A2 gene and has 475 acid amino acid residues. Topological analyses predict TSCOT protein possesses 12 transmembrane helices and a central inner loop without ATP binding domain. SLC46A2 is expressed in spleen, lymph nodes, thymus, PBL, bone marrow, and fetal liver.

Basic Information of SLC46A2
Protein Name	Thymic stromal cotransporter homolog
Gene Name	SLC46A2
Aliases	Ly110, TSCOT
Organism	Homo sapiens (Human)
UniProt ID	Q9BY10
Transmembrane Times	12
Length (aa)	475
Sequence	MSPEVTCPRRGHLPRFHPRTWVEPVVASSQVAASLYDAGLLLVVKASYGTGGSSNHSASPSPRGALEDQQQRAISNFYIIYNLVVGLSPLLSAYGLGWLSDRYHRKISICMSLLGFLLSRLGLLLKVLLDWPVEVLYGAAALNGLFGGFSAFWSGVMALGSLGSSEGRRSVRLILIDLMLGLAGFCGSMASGHLFKQMAGHSGQGLILTACSVSCASFALLYSLLVLKVPESVAKPSQELPAVDTVSGTVGTYRTLDPDQLDQQYAVGHPPSPGKAKPHKTTIALLFVGAIIYDLAVVGTVDVIPLFVLREPLGWNQVQVGYGMAAGYTIFITSFLGVLVFSRCFRDTTMIMIGMVSFGSGALLLAFVKETYMFYIARAVMLFALIPVTTIRSAMSKLIKGSSYGKVFVILQLSLALTGVVTSTLYNKIYQLTMDMFVGSCFALSSFLSFLAIIPISIVAYKQVPLSPYGDIIEK

Function of SLC46A2 Membrane Protein

Although the biological and biochemical functions of SLC46A2 are still unclear, the structural features indicate it may act as a transporter to move small hydrophobic molecules. SLC46A2/TSCOT is a specific membrane protein of cortical thymic epithelial cells. It may involve the survival of thymic epithelial cells. Besides, it is also a necessary component to maintain normal lung epithelium. The loss of SLC46A2 function in lung epithelium may result in carcinogenesis progresses. Some studies have revealed that SLC46A2 may be a novel member of tumor suppressors. The inhibition of SLC46A2 has been detected in three types of lung cancers including large lung cell carcinoma, squamous lung carcinoma, and lung adenocarcinoma. Moreover, TSCOT also functions in the same way for the genetic type of cervical cancer susceptibility. TSCOT SNPs are associated with the susceptibility of cervical cancer. In addition, mammalian SLC46A2 also involves the stimulation of tracheal cytotoxin-triggered NOD1 activation in human epithelial cell lines, which suggests SLC46As contribute to cytosolic immune recognition.

Fig.1 Tissue and cell type specific TSCOT expression profiling. (Kim, 2015)

Application of SLC46A2 Membrane Protein in Literature

Paik D., et al. SLC46 family transporters facilitate cytosolic innate immune recognition of monomeric peptidoglycans. Journal of Immunology. 2017, 199(1):263-270. PubMed ID: 28539433

In this study, the authors find that mammalian SLC46A2s are involved in the stimulation of tracheal cytotoxin-triggered NOD1 activation in human epithelial cell lines.
Kim K.Y., et al. Expression analyses revealed thymic stromal co-transporter/Slc46A2 is in stem cell populations and is a putative tumor suppressor. Molecules & Cells. 2015, 38(6):548-561. PubMed ID: 26013383

The article demonstrates that Slc46A2 may be associated with the inhibition of lung tumor development.
Ahn S., et al. TSCOT⁺ thymic epithelial cell-mediated sensitive cd4 tolerance by direct presentation. Plos Biology. 2008, 6(8):e191. PubMed ID: 18684012

The study reports that the introduction of a neoantigen into TSCOT-expressing cells can efficiently establish complete tolerance and suggests a possible application for the deletion of antigen-specific T cells by antigen introduction into TSCOT⁺ cells.
Engelmark M.T., et al. Polymorphisms in 9q32 and TSCOT are linked to cervical cancer in affected sib-pairs with high mean age at diagnosis. Human Genetics. 2008, 123(5):437-443. PubMed ID: 18392855

Authors identify that the human TSCOT locus (9q32) is mapped to the susceptibility of cervical cancer through the SNP study.

SLC46A2 Preparation Options

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Reference

Kim K Y, et al. (2015). Expression analyses revealed thymic stromal co-transporter/Slc46A2 is in stem cell populations and is a putative tumor suppressor. Molecules & Cells. 38(6): 548-561.

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