745:
shuttles cholesterol from the inner leaflet of the canalicular membrane through a chamber formed by the two half-transporters. Following ATP binding and hydrolysis, the complex undergoes a conformational change, flipping a cholesterol molecule into the outer membrane leaflet in a configuration that favors its release into the canalicular space.
788:
Lu K, Lee M-H, Hazard S,Brooks-Wilson A, Hidaka H, Kojima H, Ose L, Stalenhoef A F H,Mietinnen T,Bjorkhem I,Bruckert E, Pandya A, Brewer H B Jr., Salen G,Dean M,Srivastava A, Patel S B. Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving
780:
Lee M H, Gordon D, Ott J, Lu K, Ose L, Miettinen T, Gylling H, Stalenhoef A F, Pandya A, Hidaka H, B Jr. Brewer, Kojima H, Sakuma N, Pegoraro R, Salen G, Patel S B. Fine mapping of a gene responsible for regulating dietary cholesterol absorption: founder effects underlie cases of phytosterolaemia
723:
Typical ABC transporter consists of two transmembrane domains and two nucleotide-binding domains. However, the ABCG or White subfamily with its five fully characterized human members consists of half-size ABC proteins which probably dimerize to form active membrane transporters. In our case, it is
744:
and in selective sterol excretion by the liver into bile, as evidenced by the consequences when it is deficient or over expressed. The exact mechanism(s) whereby ABCG5/ABCG8 exert their effects on sterol metabolism has not yet been clarified. But it is suggested that the ABCG5/ABCG8 heterodimer
776:
Patel S B, Salen G, Hidaka H, Kwiterovich P O, Stalenhoef A F, Miettinen T A, Grundy S M, Lee M H, Rubenstein J S, Polymeropoulos M H, Brownstein M J. Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21. J. Clin. Invest.,
763:
Mutations in both alleles of either ABCG5 or ABCG8 in the human results in sitosterolemia. Sitosterolemia (also known as phytosterolemia) is a rare autosomal recessively inherited lipid metabolic disorder characterized by the presence of tendon xanthomas, premature coronary artery disease and
732:
Under normal circumstances, a western diet contains almost equal amounts of cholesterol and noncholesterol sterols (such as plant sterols sitosterol, campesterol, and brassicasterol). However, only about 55% of total dietary cholesterol is absorbed and retained while almost none of the
692:
inherited lipid metabolic disorder characterized by hyperabsorption and decreased biliary excretion of dietary sterols, studies have focused on the molecular basis of sitosterolemia to shed light on important principles concerning intestinal sterol absorption as well as
784:
Lee M-H, Lu K, Hazard S, Yu H, Shulenin S, Hidaka H, Kojima H, Allikmets R, Sakuma N, Pegoraro R, Srivastava AK, Salen G, Dean M, Patel SB Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat Genet,
724:
suggested that ABCG5 and ABCG8 form a heterodimer . Among the half-size molecules, ABCG proteins have a peculiar domain organization characterized by a nucleotide-binding domain at the N-terminus followed by six transmembrane-spanning domains.
715:
family, named sterolin-1 and sterolin-2, respectively, Sterolin-2, discovered after sterolin-1, is located <400 base pair (bp) upstream of sterolin-1 in the opposite orientation.
1007:
708:(2p21) after studying 10 well-characterized families with this disorder. Subsequently, the STSL locus has been further localized to a less than 2 centimorgans (cM) region.
764:
atherosclerotic disease, hemolytic episodes, arthralgias and arthritis. The hallmark of sitosterolemia is diagnostically elevated levels of plant sterols in the plasma.
921:
539:
398:
1187:
826:
982:
795:
Wittenburg H, Carey M C.Biliary cholesterol secretion by the twinned sterol half-transporters ABCG5 and ABCG8. J Clin Invest., 2002; 110(5): 605–609.
752:. 5 These genes respond to environmental dietary sterols, although whether they are also increased by high phytosterols has yet to be determined.
804:
792:
Stefkoa J, Poledne R, Hubacek J A.ATP-Binding
Cassette (ABC) Transporters in Human Metabolism and Diseases. Physiol. Res., 2004;53: 235–243.
1182:
733:
noncholesterol sterols are retained since the small amount of dietary non-cholesterols that do enter the body are rapidly excreted by the
688:
The molecular mechanisms regulating the absorption of dietary sterols in the body are poorly understood, and as sitosterolemia is a rare
850:
563:
422:
1157:
551:
410:
664:
genes encode for two proteins sterolin-1 and -2, respectively. Sterolin-1 and –2 are two ‘half’ adenosine triphosphate binding (
544:
403:
819:
668:) cassette (ABC) transporters which found to be indispensable for the regulation of sterol absorption and excretion.
843:
798:
Klett E L, Patel S.Genetic defenses against noncholesterol sterols. Curr Opin
Lipidol.,2003 ; 14(4): 341–345.
812:
755:
It is worth to mention that other gene products play a role in dietary-cholesterol transport (such as ABCA1).
801:
Salen G, Shefer S, Nguyen L, Ness G C,Tint G S,Shore V . Sitosterolemia . J Lipid Res., 1992;33(7):945–955.
689:
665:
556:
415:
1012:
711:
In 2001, The STSL locus was found to be comprises two genes, ABCG5 and ABCG8, encoding 2 members of the
789:
sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively. Am J Hum Genet,. 2001;69:278–290.
773:
Lee M, Lu K, Patel S B. Genetic basis of sitosterolemia. Curr. Opin. Lipidol., 2001; 12(2): 141–149.
1177:
609:
468:
748:
Based on the clinical defects in sitosterolemia, ABCG5/ABCG8 are expressed in the liver and/or the
740:
Sterolins are likely involved both in the selective transport of dietary cholesterol in and out of
58:
37:
835:
604:
463:
846:
839:
712:
633:
492:
613:
472:
916:
677:
55:
1171:
705:
580:
439:
741:
694:
643:
502:
704:
In 1998, sitosterolemia (STSL) locus has been mapped to the short arm of human
587:
446:
749:
669:
74:
51:
592:
451:
348:
359:
178:
137:
1036:
1031:
1026:
961:
900:
895:
575:
434:
326:
96:
62:
196:
192:
1143:
1139:
1130:
1125:
1120:
1104:
1099:
1083:
1067:
1062:
1057:
1052:
1020:
1016:
1002:
997:
992:
987:
977:
956:
951:
946:
941:
936:
890:
885:
880:
875:
870:
865:
734:
660:
656:
532:
517:
391:
376:
518:
ATP-binding cassette, sub-family G (WHITE), member 8 (sterolin 2)
377:
ATP-binding cassette, sub-family G (WHITE), member 5 (sterolin 1)
930:
925:
698:
673:
568:
427:
808:
781:
in multiple communities. Eur. J. Hum. Genet. 2001;9: 375–384.
1113:
1092:
1076:
1045:
970:
909:
858:
639:
629:
624:
603:
598:
586:
574:
562:
550:
538:
528:
523:
516:
498:
488:
483:
462:
457:
445:
433:
421:
409:
397:
387:
382:
375:
293:
274:
250:
231:
820:
8:
827:
813:
805:
621:
480:
70:
759:Disorders involving ABCG5 and ABCG8 genes
513:
372:
18:
7:
290:
271:
247:
228:
206:
183:
159:
142:
118:
101:
14:
1188:ATP-binding cassette transporters
719:Structure of the encoded proteins
1:
737:into bile, almost unchanged.
676:result in a lipid disorder,
1183:Genes on human chromosome 2
844:membrane transport proteins
16:Family of protein complexes
1204:
1158:ABC transporter disorders
1153:
620:
479:
363:
358:
354:
347:
325:
310:
297:
278:
267:
254:
235:
224:
213:
209:
190:
186:
177:
166:
162:
149:
145:
136:
125:
121:
108:
104:
95:
80:
73:
69:
49:
46:
42:
35:
30:
26:
21:
690:autosomal recessively
777:1998;102: 1041–1044.
684:Locus of the genes
1165:
1164:
836:Membrane proteins
653:
652:
649:
648:
512:
511:
508:
507:
371:
370:
367:
366:
343:
342:
306:
305:
287:
286:
263:
262:
244:
243:
220:
219:
203:
202:
173:
172:
156:
155:
132:
131:
115:
114:
1195:
840:carrier proteins
829:
822:
815:
806:
622:
514:
481:
373:
356:
355:
339:
334:
321:
316:
301:
291:
282:
272:
268:RefSeq (protein)
258:
248:
239:
229:
207:
184:
160:
143:
119:
102:
71:
65:
40:
19:
1203:
1202:
1198:
1197:
1196:
1194:
1193:
1192:
1168:
1167:
1166:
1161:
1149:
1109:
1088:
1072:
1041:
966:
905:
854:
847:ABC transporter
833:
770:
761:
730:
721:
713:ABC-transporter
697:secretion into
686:
360:View/Edit Human
337:
332:
319:
314:
311:Location (UCSC)
299:
280:
256:
237:
195:
50:
36:
17:
12:
11:
5:
1201:
1199:
1191:
1190:
1185:
1180:
1170:
1169:
1163:
1162:
1154:
1151:
1150:
1148:
1147:
1133:
1128:
1123:
1117:
1115:
1111:
1110:
1108:
1107:
1102:
1096:
1094:
1090:
1089:
1087:
1086:
1080:
1078:
1074:
1073:
1071:
1070:
1065:
1060:
1055:
1049:
1047:
1043:
1042:
1040:
1039:
1034:
1029:
1024:
1010:
1005:
1000:
995:
990:
985:
980:
974:
972:
968:
967:
965:
964:
959:
954:
949:
944:
939:
934:
928:
919:
913:
911:
907:
906:
904:
903:
898:
893:
888:
883:
878:
873:
868:
862:
860:
856:
855:
834:
832:
831:
824:
817:
809:
803:
802:
799:
796:
793:
790:
786:
785:2001;27:79–83.
782:
778:
774:
769:
766:
760:
757:
729:
726:
720:
717:
685:
682:
678:sitosterolemia
651:
650:
647:
646:
641:
637:
636:
631:
627:
626:
618:
617:
607:
601:
600:
596:
595:
590:
584:
583:
578:
572:
571:
566:
560:
559:
554:
548:
547:
542:
536:
535:
530:
526:
525:
521:
520:
510:
509:
506:
505:
500:
496:
495:
490:
486:
485:
477:
476:
466:
460:
459:
455:
454:
449:
443:
442:
437:
431:
430:
425:
419:
418:
413:
407:
406:
401:
395:
394:
389:
385:
384:
380:
379:
369:
368:
365:
364:
362:
352:
351:
345:
344:
341:
340:
335:
330:
323:
322:
317:
312:
308:
307:
304:
303:
295:
294:
288:
285:
284:
276:
275:
269:
265:
264:
261:
260:
252:
251:
245:
242:
241:
233:
232:
226:
222:
221:
218:
217:
211:
210:
204:
201:
200:
188:
187:
181:
175:
174:
171:
170:
164:
163:
157:
154:
153:
147:
146:
140:
134:
133:
130:
129:
123:
122:
116:
113:
112:
106:
105:
99:
93:
92:
87:
82:
78:
77:
67:
66:
48:
44:
43:
41:
33:
32:
28:
27:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
1200:
1189:
1186:
1184:
1181:
1179:
1176:
1175:
1173:
1160:
1159:
1152:
1145:
1141:
1137:
1134:
1132:
1129:
1127:
1124:
1122:
1119:
1118:
1116:
1112:
1106:
1103:
1101:
1098:
1097:
1095:
1091:
1085:
1082:
1081:
1079:
1075:
1069:
1066:
1064:
1061:
1059:
1056:
1054:
1051:
1050:
1048:
1044:
1038:
1035:
1033:
1030:
1028:
1025:
1022:
1018:
1014:
1011:
1009:
1006:
1004:
1001:
999:
996:
994:
991:
989:
986:
984:
981:
979:
976:
975:
973:
969:
963:
960:
958:
955:
953:
950:
948:
945:
943:
940:
938:
935:
932:
929:
927:
923:
920:
918:
915:
914:
912:
908:
902:
899:
897:
894:
892:
889:
887:
884:
882:
879:
877:
874:
872:
869:
867:
864:
863:
861:
857:
852:
848:
845:
841:
837:
830:
825:
823:
818:
816:
811:
810:
807:
800:
797:
794:
791:
787:
783:
779:
775:
772:
771:
767:
765:
758:
756:
753:
751:
746:
743:
738:
736:
727:
725:
718:
716:
714:
709:
707:
702:
700:
696:
691:
683:
681:
679:
675:
671:
667:
663:
662:
658:
645:
642:
638:
635:
632:
628:
623:
619:
616:
615:
611:
608:
606:
602:
597:
594:
591:
589:
585:
582:
579:
577:
573:
570:
567:
565:
561:
558:
555:
553:
549:
546:
543:
541:
537:
534:
531:
527:
522:
519:
515:
504:
501:
497:
494:
491:
487:
482:
478:
475:
474:
470:
467:
465:
461:
456:
453:
450:
448:
444:
441:
438:
436:
432:
429:
426:
424:
420:
417:
414:
412:
408:
405:
402:
400:
396:
393:
390:
386:
381:
378:
374:
361:
357:
353:
350:
346:
336:
331:
328:
324:
318:
313:
309:
302:
296:
292:
289:
283:
277:
273:
270:
266:
259:
253:
249:
246:
240:
234:
230:
227:
225:RefSeq (mRNA)
223:
216:
212:
208:
205:
199:
198:
194:
189:
185:
182:
180:
176:
169:
165:
161:
158:
152:
148:
144:
141:
139:
135:
128:
124:
120:
117:
111:
107:
103:
100:
98:
94:
91:
88:
86:
83:
79:
76:
72:
68:
64:
60:
56:
53:
45:
39:
34:
29:
25:
20:
1155:
1135:
762:
754:
747:
739:
731:
722:
710:
706:chromosome 2
703:
687:
655:
654:
612:
471:
298:
279:
255:
236:
214:
191:
167:
150:
126:
109:
89:
84:
47:External IDs
1178:Human genes
742:enterocytes
695:cholesterol
634:Swiss-model
524:Identifiers
493:Swiss-model
383:Identifiers
63:- orthologs
31:Identifiers
1172:Categories
768:References
672:in either
630:Structures
625:Search for
599:Other data
489:Structures
484:Search for
458:Other data
1156:see also
750:intestine
670:Mutations
581:NM_022437
540:NCBI gene
440:NM_022436
399:NCBI gene
75:Orthologs
52:GeneCards
1136:Sterolin
728:Function
644:InterPro
503:InterPro
349:Wikidata
22:Sterolin
640:Domains
588:UniProt
499:Domains
447:UniProt
179:UniProt
138:Ensembl
81:Species
38:Aliases
851:TC 3A1
610:Chr. 2
593:Q9H221
576:RefSeq
569:605460
529:Symbol
469:Chr. 2
452:Q9H222
435:RefSeq
428:605459
388:Symbol
329:search
327:PubMed
97:Entrez
735:liver
674:genes
661:ABCG8
657:ABCG5
605:Locus
557:13887
545:64241
533:ABCG8
464:Locus
416:13886
404:64240
392:ABCG5
90:Mouse
85:Human
1013:C8-9
922:B2-3
699:bile
659:and
564:OMIM
552:HGNC
423:OMIM
411:HGNC
1037:C13
1032:C11
1027:C10
962:B11
901:A13
896:A12
666:ATP
614:p21
473:p21
338:n/a
333:n/a
320:n/a
315:n/a
300:n/a
281:n/a
257:n/a
238:n/a
215:n/a
168:n/a
151:n/a
127:n/a
110:n/a
59:OMA
1174::
1144:G8
1142:,
1140:G5
1131:G4
1126:G2
1121:G1
1105:F2
1100:F1
1084:E1
1068:D4
1063:D3
1058:D2
1053:D1
1021:C9
1019:,
1017:C8
1008:C7
1003:C6
998:C5
993:C4
988:C3
983:C2
978:C1
957:B9
952:B7
947:B6
942:B5
937:B4
931:B3
926:B2
917:B1
891:A8
886:A7
881:A4
876:A3
871:A2
866:A1
842::
838:,
701:.
680:.
57:;
54::
1146:)
1138:(
1114:G
1093:F
1077:E
1046:D
1023:)
1015:(
971:C
933:)
924:(
910:B
859:A
853:)
849:(
828:e
821:t
814:v
197:a
193:n
61::
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.