Recombinant Human Ileal sodium/bile acid cotransporter (SLC10A2), partial

1. A cysteine-less form of hASBT was made by creating point mutations at all 13 endogenous cysteines. Cysless hASBT had significantly reduced function correlated with lowered surface expression.Chemical cross-linking of wild-type and Cysless species revealed that hASBT has a dominant negative effect and exists as an active dimer and/or higher order oligomer with apparently no requirement for endogenous cysteine residues. PMID: 29198943
2. Two single-nucleotide polymorphisms at novel loci, rs112404845 (P = 3.8 x 10-8), upstream of COBL, and rs16961023 (P = 4.6 x 10-8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability of late-onset Alzheimer's disease in African Americans. PMID: 27770636
3. Data (including data from studies in knockout/transgenic mice) suggest that SLC10A2 is a functional receptor for hepatitis D virus in hepatocytes. PMID: 25902143
4. Results unravel novel roles for N-glycosylation of ASBT and suggest that high levels of glucose alter the composition of the glycan and may contribute to the increase in ASBT function in diabetes mellitus. PMID: 25855079
5. The p.Ser267Phe NTCP variant is significantly associated with resistance to chronic hepatitis B and a lower incidence of acute-on-chronic liver failure. Our results support that NTCP is a cellular receptor for HBV in human infection PMID: 25418280
6. Data indicate that the lipid flippase (ATP8B1)-transmembrane protein 30A (CDC50A) heterodimer is essential for the apical localization of sodium-dependent bile acid transporter (SLC10A2/ASBT) in Caco-2 cells. PMID: 25239307
7. It was conclude that regulation of ASBT expression by resveratrol (RSV) may have clinical relevance with regard to the observed cholesterol-lowering effects of RSV. PMID: 24498857
8. Transmembrane domain II of the human bile acid transporter SLC10A2 coordinates sodium translocation. PMID: 24045943
9. ASBT evolved from the earliest vertebrates by gaining affinity for modern bile salts while retaining affinity for older bile salts PMID: 22669917
10. This study provided novel evidence for the alterations in the activity of ASBT by enteropathogenic Escherichia coli infection. PMID: 22403793
11. There was no significant association of rs9514089 with gallstone risk, serum lipid parameters and BMI in the Sorbs and in the meta-analysis of all three cohorts. [meta-analysis] PMID: 22093174
12. Presence of multiple functionally relevant variants in SLC10A2 that may influence bile acid homeostasis and physiology. PMID: 21649730
13. The human ASBT promoter was activated transcriptionally by CDX1 and CDX2. PMID: 22016432
14. The beneficial effect of rifampicin in cholestasis is associated with an increase in DME expression involved in toxic, bile acid and cholesterol metabolism, as well as a reduction in the bile acid importing system in hepatocytes. PMID: 21526375
15. data demonstrate that TM1 plays a pivotal role in ASBT function and stability, thereby providing further insight in its dynamic transport mechanism PMID: 21646357
16. the essential role of ASBT in the uptake of bile acids, by which the enterohepatic recirculation of bile acids is maintained PMID: 21341987
17. Results show that bile acid conjugates are potential prolonged release prodrugs with binding affinity for ASBT. PMID: 20600720
18. These data confirm that bile acids and upregulation of ASBT play a crucial role in NEC pathogenesis and suggest that inhibition of ASBT could be utilized as a therapeutic modality against this disease. PMID: 20616306
19. Data demonstrate a novel role of lipid rafts in the modulation of ASBT function by the dietary component EGCG, which may underlie the hypocholesterolemic effects of green tea. PMID: 20056894
20. SLC10A2 is a novel susceptibility gene for cholelithiasis in humans PMID: 19823678
21. There was no apparent correlation between the SLC10A2 polymorphisms and bile acid production or turnover in familial hypertriglyceridemia patients. PMID: 11742882
22. reglation of the ASBT gene by PPARalpha PMID: 12055195
23. role in transport of bile acids in multidrug-resistance-protein 3-overexpressing cells PMID: 12220224
24. Positively regulated by retinoic acid. Bile acids induce negative feedback regulation of human ASBT via farnesoid X-receptor-mediated, short heterodimer partner-dependent effect upon retinoic acid receptor/retinoid X receptor activation of ASBT. PMID: 15239098
25. SLC10A2 expression is regulated by the ubiquitin-proteasome pathway PMID: 15304498
26. On the basis of seven transmembrane topology, a three-dimensional model of ASBT is built. The model agrees with available data for pathological mutation P290S because the mutant model after in silico mutagenesis loses the ability to bind bile acids. PMID: 15350125
27. BIle acid-methanethiosulfonyl can serve as novel and powerful tools to probe the role of endogenous as well as engineered Cys residues in the bile acid binding region(s) of hASBT. PMID: 15952798
28. current data provide the first evidence that I-BABP is functionally associated with FXR and IBAT in the nucleus and on the membrane, respectively, stimulating FXR transcriptional activity and the conjugated bile acid uptake mediated by IBAT in the ileum PMID: 16230354
29. ASBT and ILBP protein were 48% and 67% lower in normal weight gallstone carriers than in controls (P < 0.05); similar differences were found for mRNA expression levels. PMID: 16237211
30. this study determines a 7TM topology for hASBT and refutes the previously proposed 9TM model PMID: 16411770
31. hASBT-mediated prodrug targeting is discussed, including QSAR, in vitro models for hASBT assay, and the current progress in utilizing hASBT as a drug delivery target. PMID: 16749855
32. Although the presence of a single negative charge was not essential for interaction with hASBT, monoanionic conjugates are favored for hASBT-mediated transport compared to cationic and zwitterionic conjugates. PMID: 16749860
33. These data suggest that transmembrane segment 7 (TM7) plays a dominant role in the hASBT translocation process. PMID: 16899538
34. One or more constituents of human serum stimulate ASBT gene expression largely via the down-stream AP-1 response element. PMID: 17942302
35. Extracellular loop 3 amino acids are essential for human ASBT activity as primary substrate interaction points using long-range electrostatic attractive forces. PMID: 18028035
36. cholesterol content of lipid rafts is essential for the optimal activity of ASBT PMID: 18063707
37. involvement of transmembrane domain 4 (TM4) of hASBT in forming the putative translocation pathway. TM4 has distinct helical face that contains residues critical for transport & conformational stability. PMID: 18311924
38. analysis of how conserved aspartic acid residues lining the extracellular loop 1 of sodium-coupled bile acid transporter ASBT interact with Na+ and 7alpha-OH moieties on the ligand cholestane skeleton PMID: 18508772
39. Common variants of the SLC10A2 gene are not associated with sporadic or familial colorectal cancer PMID: 18644122
40. dysfunction, and impaired adaptive responses of several of the bile acid transporters, e.g. BSEP and ASBT, results in liver and intestinal disease PMID: 18668439
41. Cyclic AMP-mediated phosphoinositide-3-kinase{ISBT)-independent activation of Rab4 facilitates Ntcp translocation in a hepatoma cell line. PMID: 18688880
42. haplotype carriers with the minor allele exhibited significant reduced ileal SLC10A2 expression on mRNA levels (2.6-fold, P = 0.0009) and protein levels (2.4-fold, P = 0.0157) PMID: 19184108
43. Integration of results for transmembrane (TM)3 and TM7 cysteine mutants suggests a putative scenario to describe substrate entry and exit into the ASBT permeation pathway during translocation mechanisms. PMID: 19653651

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HGNC: 10906

OMIM: 601295

KEGG: hsa:6555

STRING: 9606.ENSP00000245312

UniGene: Hs.194783