Q9H221 (ABCG8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	673 AA.
Sequence status	Complete.
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	Gallbladder disease 4 (GBD4) [MIM:611465]: One of the major digestive diseases. Gallstones composed of cholesterol (cholelithiasis) are the common manifestations in western countries. Most people with gallstones, however, remain asymptomatic through their lifetimes. Note: Disease susceptibility may be associated with variations affecting the gene represented in this entry. Ref.7 Sitosterolemia (STSL) [MIM:210250]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. 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 Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ATP catabolic process Inferred from direct assay PubMed 16893193. Source: GOC cholesterol efflux Inferred from genetic interaction PubMed 14504269. Source: BHF-UCL cholesterol homeostasis Inferred from mutant phenotype Ref.1. Source: BHF-UCL excretion Inferred from genetic interaction PubMed 14504269. Source: BHF-UCL intestinal cholesterol absorption Inferred by curator PubMed 12208868. Source: BHF-UCL lipid metabolic process Traceable author statement. Source: Reactome negative regulation of intestinal cholesterol absorption Inferred from mutant phenotype Ref.1. Source: BHF-UCL negative regulation of intestinal phytosterol absorption Inferred from mutant phenotype Ref.1. Source: BHF-UCL phospholipid transport Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	apical plasma membrane Inferred from mutant phenotype PubMed 14504269. Source: BHF-UCL integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: InterPro ATPase activity Inferred from electronic annotation. Source: InterPro sterol transporter activity Inferred from electronic annotation. Source: Compara
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	Helical; Name=1; Potential
	Topological domain	438 – 447	10	Extracellular Potential
	Transmembrane	448 – 468	21	Helical; Name=2; Potential
	Topological domain	469 – 492	24	Cytoplasmic Potential
	Transmembrane	493 – 513	21	Helical; Name=3; Potential
	Topological domain	514 – 531	18	Extracellular Potential
	Transmembrane	532 – 552	21	Helical; Name=4; Potential
	Topological domain	553 – 569	17	Cytoplasmic Potential
	Transmembrane	570 – 590	21	Helical; Name=5; Potential
	Topological domain	591 – 639	49	Extracellular Potential
	Transmembrane	640 – 660	21	Helical; Name=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. Ref.2 Ref.5 Ref.7 Corresponds to variant rs11887534 [ dbSNP | Ensembl ].		VAR_012250
	Natural variant	54	1	Y → C. Ref.1 Ref.2 Ref.5 Ref.6 Corresponds to variant rs4148211 [ dbSNP | Ensembl ].		VAR_012251
	Natural variant	184	1	R → H in STSL. Ref.2		VAR_012252
	Natural variant	210	1	V → M. Corresponds to variant rs9282574 [ dbSNP | Ensembl ].		VAR_022074
	Natural variant	231	1	P → T in STSL. Ref.1 Ref.2		VAR_012253
	Natural variant	238	1	E → K. Ref.2 Corresponds to variant rs34754243 [ dbSNP | Ensembl ].		VAR_012254
	Natural variant	259	1	A → V. Ref.2 Corresponds to variant rs35518570 [ dbSNP | Ensembl ].		VAR_012255
	Natural variant	263	1	R → Q in STSL. Ref.1 Ref.2		VAR_012256
	Natural variant	400	1	T → K. Ref.2 Ref.5 Ref.6 Corresponds to variant rs4148217 [ dbSNP | Ensembl ].		VAR_012257
	Natural variant	405	1	R → H in STSL. Ref.2		VAR_012258
	Natural variant	501	1	L → P in STSL. Ref.2		VAR_012259
	Natural variant	543	1	R → S in STSL. Ref.2		VAR_012260
	Natural variant	570	1	Missing in STSL. Ref.2		VAR_012261
	Natural variant	572	1	L → P in STSL. Ref.2		VAR_012262
	Natural variant	574	1	G → E in STSL. Ref.2		VAR_012263
	Natural variant	574	1	G → R in STSL. Ref.1 Ref.2		VAR_012264
	Natural variant	575	1	G → R. Ref.2 Corresponds to variant rs36209700 [ dbSNP | Ensembl ].		VAR_012265
	Natural variant	596	1	L → R in STSL. Ref.1 Ref.2		VAR_012266
	Natural variant	632	1	V → A. Ref.2 Ref.5 Corresponds to variant rs6544718 [ dbSNP | Ensembl ].		VAR_012267
	Natural variant	641	1	Y → F. Ref.5		VAR_020785
	Natural variant	655	1	M → V. Corresponds to variant rs9282573 [ dbSNP | Ensembl ].		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 [UniParc]. 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS STSL 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), VARIANTS STSL 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: VARIANT HIS-19, ASSOCIATION WITH GBD4.
+	Additional computationally mapped references.

Web resources

GeneReviews

ABCMdb

Database for mutations in ABC proteins

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. NM_022437.2.
UniGene	Hs.413931.
3D structure databases
ProteinModelPortal	Q9H221.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H221. 7 interactions.
MINT	MINT-2840535.
STRING	9606.ENSP00000272286.
Protein family/group databases
TCDB	3.A.1.204.5. ATP-binding cassette (ABC) superfamily.
PTM databases
PhosphoSite	Q9H221.
Polymorphism databases
DMDM	17432916.
Proteomic databases
PaxDb	Q9H221.
PRIDE	Q9H221.
Protocols and materials databases
DNASU	64241.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000272286; ENSP00000272286; ENSG00000143921.
GeneID	64241.
KEGG	hsa:64241.
UCSC	uc002rtq.3. human. uc010yoa.2. human.
Organism-specific databases
CTD	64241.
GeneCards	GC02P043977.
HGNC	HGNC:13887. ABCG8.
HPA	HPA019556.
MIM	210250. phenotype. 605460. gene. 611465. phenotype.
neXtProt	NX_Q9H221.
Orphanet	406. Familial hypercholesterolemia. 2882. Sitosterolemia.
PharmGKB	PA24412.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1131.
HOGENOM	HOG000033764.
HOVERGEN	HBG050444.
InParanoid	Q9H221.
KO	K05684.
OMA	YGMPTYW.
OrthoDB	EOG4J3WGN.
PhylomeDB	Q9H221.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_15518. Transmembrane transport of small molecules.
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. IPR027417. P-loop_NTPase. [Graphical view]
Pfam	PF01061. ABC2_membrane. 1 hit. PF00005. ABC_tran. 1 hit. [Graphical view]
SUPFAM	SSF52540. SSF52540. 1 hit.
PROSITE	PS51012. ABC_TM2. False negative. PS00211. ABC_TRANSPORTER_1. 1 hit. PS50893. ABC_TRANSPORTER_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	64241.
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:	May 29, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.