| TCID | Name | Domain | Kingdom/Phylum | Protein(s) |
|---|---|---|---|---|
|
2.A.90.1.1 | The STRA6 vitamin A transporter/RBP receptor mediates cellular uptake of Vitamin A (Sun, 2011). It has 668 aas and probably 9 TMSs (Kawaguchi et al. 2015). Transport is reversible, and is probably mediated by a carrier or group translocation mechanism (Kelly and von Lintig 2015). Mechanistic features have been discussed (Kawaguchi et al. 2015), and it was concluded that energy-independent facilitated diffusion, from external retinol binding protein (RBP) to internal CRBP-1 or the corresponding CRABP (for retinoic acid) after release of the substrate into the iipid environment of the membrane or an enzyme that forms retinol esters (LRAT) provides the most probable mechanism. These vitamin A transporters play roles in visual functions. They serve as membrane receptors for dietary vitamin A uptake, storage, and transport to the eye (Martin Ask et al. 2021). | Eukaryota |
Metazoa, Chordata | STRA6 of Bos taurus (ABG81428) |
|
2.A.90.1.2 | Stimulated by retinoic acid gene 6, STRA6 (670 aas; 8-10 TMSs predicted with N- and C-termini outside) (Kawaguchi et al., 2008). Mechanistic features have been discussed (Kawaguchi et al. 2015), and it was concluded that energy-independent facilitated diffusion, from external holo-retinol binding protein (RBP) to internal CRBP-1 or the corresponding CRABP (for retinoic acid) after release of the substrate into the iipid environment of the membrane or an enzyme that forms retinol esters (LRAT) provides the most probable mechanism. | Eukaryota |
Metazoa, Chordata | STRA6 of Mus musculus (O70491) |
|
2.A.90.1.3 | STRA6 of 667 aas and 9 - 12 putative TMSs (Zhong et al. 2013). Mechanistic features have been discussed (Kawaguchi et al. 2015), and it was concluded that energy-independent facilitated diffusion, from external holo-retinol binding protein (RBP) to internal CRBP-1 or the corresponding CRABP (for retinoic acid) after release of the substrate into the iipid environment of the membrane or an enzyme that forms retinol esters (LRAT) provides the most probable mechanism of transport. STRA6 binds RBP with a 1:1 stoichiometry (Breen et al. 2015). Zhong et al. 2020 purified and identified STRA6-associated proteins and found that the major STRA6-associated protein is calmodulin, consistent with the cryo-EM study of zebrafish STRA6 associated with calmodulin. They showed that increased calcium/calmodulin promotes cellular vitamin A efflux and suppresses vitamin A influx through STRA6. Also, calmodulin enhances the binding of apo-RBP to STRA6, and this enhancement is much more pronounced for apo-RBP than holo-RBP. Thus, calmodulin seems to regulate STRA6's vitamin A influx vs efflux activities by modulating its preferential interaction with apo-RBP or holo-RBP (Zhong et al. 2020). | Eukaryota |
Metazoa, Chordata | STRA6 of Homo sapiens |
|
2.A.90.1.4 | STRA6 of 670 aas, mediates cellular uptake of vitamin A by recognizing RBP-retinol to trigger release and internalization of retinol. Chen et al. 2016 presented the structure of zebrafish STRA6, determined to 3.9-angstrom resolution by single-particle cryo-electron microscopy. STRA6 has one intramembrane and nine transmembrane helices in an intricate dimeric assembly. Calmodulin is bound tightly to STRA6 in a noncanonical arrangement. Residues involved with RBP binding map to an arch-like structure that covers a deep lipophilic cleft. This cleft is open to the membrane, suggesting a possible mode for internalization of retinol through direct diffusion into the lipid bilayer. | Eukaryota |
Metazoa, Chordata | STRA6 of Danio rerio (Zebrafish) (Brachydanio rerio) |
|
2.A.90.2.1 | Sea urchin protein of unknown function | Eukaryota |
Metazoa, Echinodermata | Uncharacterized protein of Strongylocentrotus purpuratus |
|
2.A.90.2.2 | Eukaryota |
Metazoa, Rotifera | Stra6 homologue of Adineta (Callidina) vaga | |
|
2.A.90.2.3 | Stra6 homologue of 716 aas | Eukaryota |
Stra6 homologue of Capsaspora owczarzaki | |
|
2.A.90.2.4 | Stra6 homologue of 1327 aas | Eukaryota |
Stra6 homologue of Monosiga brevicollis | |
|
2.A.90.2.5 | Stimulated by retinoic acid gene 6 protein-like, Str61, RBPR2, of 621 aas and 11 or 12 TMSs. It acts as a high-affinity cell-surface receptor for retinol-binding protein RBP4 and mediates RBP4-dependent retinol uptake in the liver (Alapatt et al. 2013). The extracellular RBP4 ligand binding domain on the RBPR2 receptor for Vitamin A transporthas been mapped (Radhakrishnan et al. 2023). | Eukaryota |
Metazoa, Chordata | RBPR2 of Mus musculus (Mouse) |
|
2.A.90.3.1 | Harmful bloom algal protein of unknown function, of 962 aas and 16 putative TMSs. TMSs 1-5 or 6 correspond to synaptic glycoprotein SC2, possibly a sterol reductase (TC@2.A.90.3.2 and3.3), while the last 5 TMSs are homologous to TMSs 7 - 11 in the 11 TMS STRA6 protein (2.A.90.1.1). Thus, this protein may be a fusion protein. | Eukaryota |
Uncharacterized protein of Aureococcus anophagefferens | |
|
2.A.90.3.2 | Synaptic glycoprotein SC2 of 299 aas and 6 TMSs. | Eukaryota |
Metazoa, Arthropoda | SC2 of Culex quinquefasciatus (Southern house mosquito) (Culex pungens) |
|
2.A.90.3.3 | Putative steroid reductase required for elongation of the very long chain fatty acids, of 285 aas and 6 TMSs. | Eukaryota |
Metazoa, Mollusca | Reductase of Ixodes ricinus (Common tick) |
|
2.A.90.3.4 | Steroid 5-alpha reductase, putative, of 252 aas and 6 TMSs. | Eukaryota |
Evosea | Reductase of Entamoeba histolytica |
|
2.A.90.3.5 | Uncharacterized protein of 287 aas and 5 or 6 TMSs. | Eukaryota |
Evosea | UP of Entamoeba histolytica |
|
2.A.90.3.6 | The human steroid 5alpha-reductase 2 of 254 aas and 7 TMSs. The x-ray structure has been determined to 2.8 Å with the anti-androgen drug finasteride bound (Xiao et al. 2020). It catalyzes the reduction of testosterone to dihydrotestosterone, and mutations in the SRD5A2 gene have been linked to 5alpha-reductase deficiency and prostate cancer. Finasteride and dutasteride, as SRD5A2 inhibitors, are widely used antiandrogen drugs for benign prostate hyperplasia. Xiao et al. 2020 showed a unique 7-TMS topology and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride in a largely enclosed binding cavity inside the transmembrane domain. Structural analysis together with computational and mutagenesis studies reveal the molecular mechanisms of the catalyzed reaction and of finasteride inhibition involving residues E57 and Y91. Molecular dynamics simulation results indicated conformational dynamics of the cytosolic region that regulate NADPH/NADP(+) exchange (Xiao et al. 2020). | Eukaryota |
Metazoa, Chordata | SRD5A2 of Homo sapiens |