ASBT | ASBT is a 348-amino acid glycoprotein found on cell surface membranes of proximal renal convoluted tubule cells, large cholangiocytes, gall bladder epithelial cells, apical cells of the duodenum (in small amounts), and most abundantly, the apical surface of brush border enterocytes of the terminal ileum, with its carboxyl terminus within the cell cytoplasm and its glycosylated amino terminus located extracellularly. ASBT is responsible for the luminal uptake of bile acids from the intestine whereas other transporters carry out the subsequent intracellular translocation and export of the bile acid at the basolateral side of the cell back to the portal circulation. | | Dawson, 2011; Bienert et al., 2017 |
FR | FR present in the human small intestine constitutes of the RFC and the proton-coupled folic acid (FA) transporter among others. The RFC is made up of 591 amino acids and can be found on the apical brush border membrane of gastrointestinal cells, the basolateral membrane of the proximal renal tubule, and the apical membranes of the choroid plexus and retinal pigment epithelium, as well as on most tissues and cell lines. The PCFT consists of 459 amino acids. Unlike the RFC, which prefers neutral pH environments and has a relatively low affinity for FA, the PCFT operates optimally at lower pH levels and has a much higher affinity for FA. High levels of PCFT are expressed in the human duodenum and jejunum. Lower levels of PCFT expression are found in the large intestine, although the level of folate transport activity across the proximal and distal human colonic apical brush border membranes (pH 5.5) can be high. Both RFC and PCFT have their amino and carboxyl termini located in the cytoplasm. These proteins play a crucial role in facilitating the uptake of folate, required for RNA and DNA synthesis, across the apical brush border membrane of enterocytes and express specificity to the monoglutamate form of their folate substrates. | | Ashokkumar et al., 2007; Desmoulin et al., 2012; Hou and Matherly, 2014; Visentin et al., 2014; Bienert et al., 2017 |
HSPG | HSPG refers to a group of glycoproteins, characterized by one or more covalently attached heparan sulfate chains. HSPG can be classified into three main classes according to their location of expression—membrane, extracellular matrix, and secretory vesicles; their structures and functions vary with the location of expression. HSPG found on secretory vesicles is expressed on mast cells and hematopoietic cells, whereas HSPG located in the extracellular matrix is usually found on the basement membrane of cells. The membrane-bound HSPG can be found on epithelial cells and/or fibroblasts and has 1–3 heparan sulfate–bound chains. These HSPG have multiple physiologic functions such as protease inhibitor receptors, growth factor coreceptors, and endocytic receptors for clearance of bound ligands in lipoprotein metabolism of liver. | | Sarrazin et al., 2011; Christianson and Belting, 2014; UniProt Consortium, 2021 |
FcRn | FcRn is a 365-residue-long transmembrane protein, essential from birth and expressed throughout life. It aids in the transport of human IgG across the placenta during gestation, conferring passive immunity from mother to fetus. FcRn is expressed throughout the intestine across a large surface area. Found on the apical region, FcRn binds to the CH2–CH3 portion of IgG’s Fc domain and is responsible for its transcytosis, inclusive of protection of IgG through its intracellular journey, to the basolateral side of enterocytes. | | Brambell, 1963; Brambell et al., 1964; Leach et al., 1996; Simister et al., 1996; Pridgen et al., 2013; Rath et al., 2015; Lawrence et al., 2021; UniProt Consortium, 2021 |
TfR | TfR presents in the human body in two forms: TfR1 and TfR2, of which TfR2 has two isoforms, TfR2-α and TfR2-β. TfR1 and TfR2-α have molecular masses ranging from 90 to 105 kDa. They are type 2 membrane proteins that can form homodimers, which function to mediate transepithelial iron transport. Tf stabilizes iron through binding to it. Thereafter, Tf-bound iron is taken up into cells by TfR1 (and TfR2-α at a fraction of TfR1’s binding affinity) via clathrin-mediated endocytosis. TfR1 and TfR2-α receptors can be found on most cells, especially primitive erythrocytes, hepatocytes, and cells with a high turnover rate. They are also present in sizeable amounts at the epithelium of the small intestine. | | Bienert et al., 2017; Liu et al., 2018; Kawabata, 2019; UniProt Consortium, 2021 |
IF-VB12 | Cubilin, the IF-VB12 receptor, is a 460 kDa peripheral membrane protein. Human cubilin consists of 27 complement C1r/C1s, Uegf, BMP1 (CUB) domains; of the 27 CUB domains, four domains, CUB5–8, bind to the IF-VB12 complex. Cubilin is mainly expressed in the kidney, where VB12 reabsorption occurs, and the ileum, where the IF-VB12 complex is absorbed. | | Chalasani et al., 2007b; Andersen et al., 2010; Kozyraki and Cases, 2013; Ke et al., 2015; UniProt Consortium, 2021 |
PAT1 | PAT1 is a 476-residue-long transmembrane protein. It is found on the cell membrane and is largely expressed on the small intestine, where it partners with protons to facilitate transepithelial amino acid uptake. It transports amino acids such as glycine, alanine, and proline and can bind to a variety of substrates, such as α-(methylamino)isobutyric acid, α-aminoisobutyrate, γ-aminobutyrate, D-serine, and D-cysteine. | | Chen et al., 2003; Bienert et al., 2017 |
NPC1L1 | Human NPC1L1 is a 1359-amino acid transmembrane protein, well known clinically as the target of the cholesterol-lowering drug ezetimibe. It plays a key role in the intestinal cholesterol absorption. There is some disagreement over NPC1L1 expression; some papers claimed ubiquitous expression, whereas others claimed limited expression in the liver and the apical surface of the duodenum and proximal jejunum. Ample intestinal expression of NPC1L1 has been identified. | | Davies et al., 2000; Altmann et al., 2004; Yamanashi et al., 2007; UniProt Consortium, 2021 |