Reviewed, UniProtKB/Swiss-Prot Q9H221 (ABCG8_HUMAN)

Names and origin

Protein names

Recommended name:
    ATP-binding cassette sub-family G member 8
Alternative name(s):
    Sterolin-2

Gene names

Name:

ABCG8

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	673 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Transporter that appears to play an indispensable role in the selective transport of the dietary cholesterol in and out of the enterocytes and in the selective sterol excretion by the liver into bile.
Subunit structure	May form heterodimers with ABCG5 or be tightly coupled to ABCG5 along a pathway regulating diatery-sterol absorption and excretion.
Subcellular location	Membrane; Multi-pass membrane protein Probable.
Tissue specificity	Strongly expressed in the liver, lower levels in the small intestine and colon. Detectable in a wide variety of human tissues.
Involvement in disease	Genetic variations in ABCG8 can be associated with susceptibility to gallbladder disease type 4 (GBD4) [MIM:611465]. With an overall prevalence of 10-20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries. Ref.7 Defects in ABCG8 are a cause of sitosterolemia [MIM:210250]; also known as phytosterolemia or shellfish sterolemia. It is a rare autosomal recessive disorder characterized by increased intestinal absorption of all sterols including cholesterol, plant and shellfish sterols, and decreased biliary excretion of dietary sterols into bile. Sitosterolemia patients have hypercholesterolemia, very high levels of plant sterols in the plasma, and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. Ref.1 Ref.2
Sequence similarities	Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily. [View classification] Contains 1 ABC transmembrane type-2 domain. Contains 1 ABC transporter domain.
Caution	Seems to have a defective ATP-binding region.

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transmembrane
PTM	Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cholesterol efflux Inferred from genetic interaction. Source: UniProtKB cholesterol homeostasis Ref.1 Inferred from mutant phenotype. Source: UniProtKB excretion Inferred from genetic interaction. Source: UniProtKB intestinal cholesterol absorption Inferred by curator. Source: UniProtKB negative regulation of intestinal cholesterol absorption Ref.1 Inferred from mutant phenotype. Source: UniProtKB negative regulation of intestinal phytosterol absorption Ref.1 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	apical plasma membrane Inferred from mutant phenotype. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro ATPase activity Inferred from electronic annotation. Source: InterPro protein heterodimerization activity Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9H221-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9H221-2)

The sequence of this isoform differs from the canonical sequence as follows:
     376-376: Missing.

Note: Minor form detected in approximately 10% of the cDNA clones.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 673	673	ATP-binding cassette sub-family G member 8		PRO_0000093396
Regions
	Topological domain	1 – 416	416	Cytoplasmic Potential
	Transmembrane	417 – 437	21	1 Potential
	Topological domain	438 – 447	10	Extracellular Potential
	Transmembrane	448 – 468	21	2 Potential
	Topological domain	469 – 492	24	Cytoplasmic Potential
	Transmembrane	493 – 513	21	3 Potential
	Topological domain	514 – 531	18	Extracellular Potential
	Transmembrane	532 – 552	21	4 Potential
	Topological domain	553 – 569	17	Cytoplasmic Potential
	Transmembrane	570 – 590	21	5 Potential
	Topological domain	591 – 639	49	Extracellular Potential
	Transmembrane	640 – 660	21	6 Potential
	Topological domain	661 – 673	13	Cytoplasmic Potential
	Domain	47 – 313	267	ABC transporter
	Domain	411 – 665	255	ABC transmembrane type-2
Amino acid modifications
	Glycosylation	619	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	376	1	Missing in isoform 2.		VSP_000052
	Natural variant	19	1	D → H Associated significantly with GBD4. dbSNP rs11887534. Ref.7 Ref.2 Ref.5		VAR_012250
	Natural variant	54	1	Y → C: dbSNP rs4148211. Ref.1 Ref.2 Ref.5 Ref.6		VAR_012251
	Natural variant	184	1	R → H in sitosterolemia. Ref.2		VAR_012252
	Natural variant	210	1	V → M: dbSNP rs9282574.		VAR_022074
	Natural variant	231	1	P → T in sitosterolemia. Ref.1 Ref.2		VAR_012253
	Natural variant	238	1	E → K: dbSNP rs34754243. Ref.2		VAR_012254
	Natural variant	259	1	A → V: dbSNP rs35518570. Ref.2		VAR_012255
	Natural variant	263	1	R → Q in sitosterolemia. Ref.1 Ref.2		VAR_012256
	Natural variant	400	1	T → K: dbSNP rs4148217. Ref.2 Ref.5 Ref.6		VAR_012257
	Natural variant	405	1	R → H in sitosterolemia. Ref.2		VAR_012258
	Natural variant	501	1	L → P in sitosterolemia. Ref.2		VAR_012259
	Natural variant	543	1	R → S in sitosterolemia. Ref.2		VAR_012260
	Natural variant	570	1	Missing in sitosterolemia.		VAR_012261
	Natural variant	572	1	L → P in sitosterolemia. Ref.2		VAR_012262
	Natural variant	574	1	G → E in sitosterolemia. Ref.2		VAR_012263
	Natural variant	574	1	G → R in sitosterolemia. Ref.1 Ref.2		VAR_012264
	Natural variant	575	1	G → R: dbSNP rs36209700.		VAR_012265
	Natural variant	596	1	L → R in sitosterolemia. Ref.1 Ref.2		VAR_012266
	Natural variant	632	1	V → A: dbSNP rs6544718. Ref.2 Ref.5		VAR_012267
	Natural variant	641	1	Y → F		VAR_020785
	Natural variant	655	1	M → V: dbSNP rs9282573.		VAR_022075

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 594AFD1D6C1BB50F	FASTA	673	75,679
	10 20 30 40 50 60 MAGKAAEERG LPKGATPQDT SGLQDRLFSS ESDNSLYFTY SGQPNTLEVR DLNYQVDLAS 70 80 90 100 110 120 QVPWFEQLAQ FKMPWTSPSC QNSCELGIQN LSFKVRSGQM LAIIGSSGCG RASLLDVITG 130 140 150 160 170 180 RGHGGKIKSG QIWINGQPSS PQLVRKCVAH VRQHNQLLPN LTVRETLAFI AQMRLPRTFS 190 200 210 220 230 240 QAQRDKRVED VIAELRLRQC ADTRVGNMYV RGLSGGERRR VSIGVQLLWN PGILILDEPT 250 260 270 280 290 300 SGLDSFTAHN LVKTLSRLAK GNRLVLISLH QPRSDIFRLF DLVLLMTSGT PIYLGAAQHM 310 320 330 340 350 360 VQYFTAIGYP CPRYSNPADF YVDLTSIDRR SREQELATRE KAQSLAALFL EKVRDLDDFL 370 380 390 400 410 420 WKAETKDLDE DTCVESSVTP LDTNCLPSPT KMPGAVQQFT TLIRRQISND FRDLPTLLIH 430 440 450 460 470 480 GAEACLMSMT IGFLYFGHGS IQLSFMDTAA LLFMIGALIP FNVILDVISK CYSERAMLYY 490 500 510 520 530 540 ELEDGLYTTG PYFFAKILGE LPEHCAYIII YGMPTYWLAN LRPGLQPFLL HFLLVWLVVF 550 560 570 580 590 600 CCRIMALAAA ALLPTFHMAS FFSNALYNSF YLAGGFMINL SSLWTVPAWI SKVSFLRWCF 610 620 630 640 650 660 EGLMKIQFSR RTYKMPLGNL TIAVSGDKIL SVMELDSYPL YAIYLIVIGL SGGFMVLYYV 670 SLRFIKQKPS QDW
	Isoform 2. Checksum: A7F428ED11B104DE	FASTA	672	75,592
	10 20 30 40 50 60 MAGKAAEERG LPKGATPQDT SGLQDRLFSS ESDNSLYFTY SGQPNTLEVR DLNYQVDLAS 70 80 90 100 110 120 QVPWFEQLAQ FKMPWTSPSC QNSCELGIQN LSFKVRSGQM LAIIGSSGCG RASLLDVITG 130 140 150 160 170 180 RGHGGKIKSG QIWINGQPSS PQLVRKCVAH VRQHNQLLPN LTVRETLAFI AQMRLPRTFS 190 200 210 220 230 240 QAQRDKRVED VIAELRLRQC ADTRVGNMYV RGLSGGERRR VSIGVQLLWN PGILILDEPT 250 260 270 280 290 300 SGLDSFTAHN LVKTLSRLAK GNRLVLISLH QPRSDIFRLF DLVLLMTSGT PIYLGAAQHM 310 320 330 340 350 360 VQYFTAIGYP CPRYSNPADF YVDLTSIDRR SREQELATRE KAQSLAALFL EKVRDLDDFL 370 380 390 400 410 420 WKAETKDLDE DTCVESVTPL DTNCLPSPTK MPGAVQQFTT LIRRQISNDF RDLPTLLIHG 430 440 450 460 470 480 AEACLMSMTI GFLYFGHGSI QLSFMDTAAL LFMIGALIPF NVILDVISKC YSERAMLYYE 490 500 510 520 530 540 LEDGLYTTGP YFFAKILGEL PEHCAYIIIY GMPTYWLANL RPGLQPFLLH FLLVWLVVFC 550 560 570 580 590 600 CRIMALAAAA LLPTFHMASF FSNALYNSFY LAGGFMINLS SLWTVPAWIS KVSFLRWCFE 610 620 630 640 650 660 GLMKIQFSRR TYKMPLGNLT IAVSGDKILS VMELDSYPLY AIYLIVIGLS GGFMVLYYVS 670 LRFIKQKPSQ DW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters." Berge K.E., Tian H., Graf G.A., Yu L., Grishin N.V., Schultz J., Kwiterovich P., Shan B., Barnes R., Hobbs H.H. Science 290:1771-1775(2000) [PubMed: 11099417] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS SITOSTEROLEMIA THR-231; GLN-263; ARG-574 AND ARG-596, VARIANT CYS-54.
[2]	"Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively." 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.K., Patel S.B. Am. J. Hum. Genet. 69:278-290(2001) [PubMed: 11452359] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), VARIANTS SITOSTEROLEMIA HIS-184; THR-231; GLN-263; HIS-405; PRO-501; SER-543; PHE-570 DEL; PRO-572; ARG-574; GLU-574 AND ARG-596, VARIANTS HIS-19; CYS-54; LYS-238; VAL-259; LYS-400; ARG-575 AND ALA-632. Tissue: Liver.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Role of ABCG1 and other ABCG family members in lipid metabolism." Schmitz G., Langmann T., Heimerl S. J. Lipid Res. 42:1513-1520(2001) [PubMed: 11590207] [Abstract] Cited for: REVIEW.
[5]	"Mutations in ATP-cassette binding proteins G5 (ABCG5) and G8 (ABCG8) causing sitosterolemia." Hubacek J.A., Berge K.E., Cohen J.C., Hobbs H.H. Hum. Mutat. 18:359-360(2001) [PubMed: 11668628] [Abstract] Cited for: VARIANTS HIS-19; CYS-54; LYS-400; ALA-632 AND PHE-641.
[6]	"Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8." Iida A., Saito S., Sekine A., Mishima C., Kitamura Y., Kondo K., Harigae S., Osawa S., Nakamura Y. J. Hum. Genet. 47:285-310(2002) [PubMed: 12111378] [Abstract] Cited for: VARIANTS CYS-54 AND LYS-400.
[7]	"A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease." Buch S., Schafmayer C., Voelzke H., Becker C., Franke A., von Eller-Eberstein H., Kluck C., Baessmann I., Brosch M., Lammert F., Miquel J.F., Nervi F., Wittig M., Rosskopf D., Timm B., Hoell C., Seeger M., ElSharawy A. , Lu T., Egberts J., Faendrich F., Foelsch U.R., Krawczak M., Schreiber S., Nuernberg P., Tepel J., Hampe J. Nat. Genet. 39:995-999(2007) [PubMed: 17632509] [Abstract] Cited for: VARIANT HIS-19, ASSOCIATION WITH GBD4.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF320294 mRNA. Translation: AAG40004.1. AF324494 mRNA. Translation: AAK84078.1. AF351824 , AF351812, AF351813, AF351814, AF351815, AF351816, AF351817, AF351818, AF351819, AF351820, AF351821, AF351822, AF351823 Genomic DNA. Translation: AAK84663.1. AC108476 Genomic DNA. Translation: AAY24011.1.
IPI	IPI00007840. IPI00218892.
RefSeq	NP_071882.1.
UniGene	Hs.413931
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q9H221.
Protein family/group databases
TCDB	3.A.1.204.5. ATP-binding cassette (ABC) superfamily.
Proteomic databases
PRIDE	Q9H221.
Genome annotation databases
Ensembl	ENST00000272286; ENSP00000272286; ENSG00000143921; Homo sapiens. [Genome view]
GeneID	64241.
KEGG	hsa:64241.
UCSC	uc002rtq.1. human.
Organism-specific databases
CTD	64241.
GeneCards	GC02P043977.
H-InvDB	HIX0029841.
HGNC	HGNC:13887. ABCG8.
HPA	HPA019556.
MIM	210250. phenotype. 605460. gene. 611465. phenotype.
Orphanet	406. Hypercholesterolemia, familial. 2882. Phytosterolemia.
PharmGKB	PA24412.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9H221.
HOVERGEN	Q9H221.
OMA	IKSGQIW
OrthoDB	EOG9T7BNX
Enzyme and pathway databases
Reactome	REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	Q9H221.
Bgee	Q9H221.
CleanEx	HS_ABCG8.
Genevestigator	Q9H221.
GermOnline	ENSG00000143921. Homo sapiens.
Family and domain databases
InterPro	IPR013525. ABC_2_trans. IPR003439. ABC_transporter-like. IPR017871. ABC_transporter_CS. [Graphical view]
Pfam	PF01061. ABC2_membrane. 1 hit. PF00005. ABC_tran. 1 hit. [Graphical view]
PROSITE	PS51012. ABC_TM2. False negative. PS00211. ABC_TRANSPORTER_1. 1 hit. PS50893. ABC_TRANSPORTER_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	66192.
SOURCE	Search...

Entry information

Entry name

ABCG8_HUMAN

Accession

Primary (citable) accession number: Q9H221
Secondary accession number(s): Q53QN8

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	March 1, 2001
Last modified:	November 24, 2009
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.