8.A.121.  The Transmembrane Protein 237 (TMEM237) Family 

The apically localized riboflavin (RF) transporter-3 (RFVT-3) is involved in the intestinal absorption of vitamin B2. Transmembrane protein 237 (TMEM237)  interacts with the human (h)RFVT-3. TMEM237 is highly expressed in human native intestine and in human intestinal epithelial cell lines, and it co-localizes with hRFVT-3. Expressing TMEM237 caused induction in RF uptake, while its knockdown (with the use of gene-specific siRNA) led to a significant reduction in uptake. Transfecting TMEM237 into HuTu-80 cells also led to a marked enhancement in hRFVT-3 protein stability (reflected by an increase in the protein half-life). Moreover, the level of expression of TMEM237 was reduced following treatment with TNF-alpha (a pro- inflammatory cytokine that inhibits intestinal RF uptake), while its expression was significantly upregulated following treatment with butyrate (an inducer of intestinal RF uptake). Thus, TMEM237 is an interactor with of intestinal hRFVT-3, enhancing its stability and activity (Sabui et al. 2019).


 

References:

Sabui, S., V.S. Subramanian, Q. Pham, and H.M. Said. (2019). Identification of transmembrane protein 237 as a novel interactor with the intestinal riboflavin transporter-3 (RFVT-3): role in functionality and cell biology. Am. J. Physiol. Cell Physiol. [Epub: Ahead of Print]

Examples:

TC#NameOrganismal TypeExample
8.A.121.1.1

TMEM237 (ALS2CR4) has 408 aas with 4 C-terminal TMSs.  It interacts with the human riboflavin transporter, (h)RFVT-3 (TC#2.A.125.1.2). TMEM237 co-localizes with hRFVT-3 and expressing it caused induces RF uptake, while its knockdown leads to a reduction in uptake. Transfecting TMEM237 into HuTu-80 cells also led to a marked enhancement in hRFVT-3 protein stability, and the level of expression of TMEM237 was reduced following treatment with TNF-alpha (a pro- inflammatory cytokine that inhibits intestinal RF uptake), while its expression was significantly upregulated following treatment with butyrate (an inducer of intestinal RF uptake). Thus, TMEM237 is an interactor with intestinal hRFVT-3, and this interaction affects its stability and activity (Sabui et al. 2019).

TMEM237 of Homo sapiens

 
8.A.121.1.2

TMEM237 of 341 aas and 4 C-terminal TMSs.

TMEM237 of Bemisia tabaci (Sweetpotato whitefly) (Aleurodes tabaci)

 
8.A.121.1.3

TMEM237 homologue of 523 aas ad 4 C-terminal TMSs.

TMEM237 of Spodoptera litura

 
8.A.121.1.4

Rhotekin-2of 747 aas and 5 TMSs, 1 N-terminal and 4 C-terminal as well as several potential TMSs in the middle of the protein.

Rhotekin-2 of Trichinella spiralis

 
8.A.121.1.5

TMEM237 of 399 aas and 4 C-terminal TMSs.

TMEM237 of Caenorhabditis elegans