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Q9H221 (ABCG8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ATP-binding cassette sub-family G member 8
Alternative name(s):
Sterolin-2
Gene names
Name:ABCG8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length673 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processTransport
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP 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

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: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to nutrient

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

sterol transport

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentapical plasma membrane

Inferred from mutant phenotype PubMed 14504269. Source: BHF-UCL

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: InterPro

ATPase activity

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 16870176. Source: IntAct

protein heterodimerization activity

Inferred from physical interaction PubMed 16870176. Source: BHF-UCL

sterol transporter activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ABCG5Q9H2222EBI-3908684,EBI-1761423

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 673673ATP-binding cassette sub-family G member 8
PRO_0000093396

Regions

Topological domain1 – 416416Cytoplasmic Potential
Transmembrane417 – 43721Helical; Name=1; Potential
Topological domain438 – 44710Extracellular Potential
Transmembrane448 – 46821Helical; Name=2; Potential
Topological domain469 – 49224Cytoplasmic Potential
Transmembrane493 – 51321Helical; Name=3; Potential
Topological domain514 – 53118Extracellular Potential
Transmembrane532 – 55221Helical; Name=4; Potential
Topological domain553 – 56917Cytoplasmic Potential
Transmembrane570 – 59021Helical; Name=5; Potential
Topological domain591 – 63949Extracellular Potential
Transmembrane640 – 66021Helical; Name=6; Potential
Topological domain661 – 67313Cytoplasmic Potential
Domain47 – 313267ABC transporter
Domain411 – 665255ABC transmembrane type-2

Amino acid modifications

Glycosylation6191N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence3761Missing in isoform 2.
VSP_000052
Natural variant191D → H Associated significantly with GBD4. Ref.2 Ref.5 Ref.7
Corresponds to variant rs11887534 [ dbSNP | Ensembl ].
VAR_012250
Natural variant541Y → C. Ref.1 Ref.2 Ref.5 Ref.6
Corresponds to variant rs4148211 [ dbSNP | Ensembl ].
VAR_012251
Natural variant1841R → H in STSL. Ref.2
VAR_012252
Natural variant2101V → M.
Corresponds to variant rs9282574 [ dbSNP | Ensembl ].
VAR_022074
Natural variant2311P → T in STSL. Ref.1 Ref.2
VAR_012253
Natural variant2381E → K. Ref.2
Corresponds to variant rs34754243 [ dbSNP | Ensembl ].
VAR_012254
Natural variant2591A → V. Ref.2
Corresponds to variant rs35518570 [ dbSNP | Ensembl ].
VAR_012255
Natural variant2631R → Q in STSL. Ref.1 Ref.2
Corresponds to variant rs137852990 [ dbSNP | Ensembl ].
VAR_012256
Natural variant4001T → K. Ref.2 Ref.5 Ref.6
Corresponds to variant rs4148217 [ dbSNP | Ensembl ].
VAR_012257
Natural variant4051R → H in STSL. Ref.2
VAR_012258
Natural variant5011L → P in STSL. Ref.2
VAR_012259
Natural variant5431R → S in STSL. Ref.2
Corresponds to variant rs201690654 [ dbSNP | Ensembl ].
VAR_012260
Natural variant5701Missing in STSL. Ref.2
VAR_012261
Natural variant5721L → P in STSL. Ref.2
VAR_012262
Natural variant5741G → E in STSL. Ref.2
VAR_012263
Natural variant5741G → R in STSL. Ref.1 Ref.2
VAR_012264
Natural variant5751G → R. Ref.2
Corresponds to variant rs36209700 [ dbSNP | Ensembl ].
VAR_012265
Natural variant5961L → R in STSL. Ref.1 Ref.2
VAR_012266
Natural variant6321V → A. Ref.2 Ref.5
Corresponds to variant rs6544718 [ dbSNP | Ensembl ].
VAR_012267
Natural variant6411Y → F. Ref.5
VAR_020785
Natural variant6551M → V.
Corresponds to variant rs9282573 [ dbSNP | Ensembl ].
VAR_022075

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 594AFD1D6C1BB50F

FASTA67375,679
        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 

« Hide

Isoform 2 [UniParc].

Checksum: A7F428ED11B104DE
Show »

FASTA67275,592

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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

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 expand/collapse EMBL AC list , AF351812, AF351813, AF351814, AF351815, AF351816, AF351817, AF351818, AF351819, AF351820, AF351821, AF351822, AF351823 Genomic DNA. Translation: AAK84663.1.
AC108476 Genomic DNA. Translation: AAY24011.1.
CCDSCCDS1815.1. [Q9H221-1]
RefSeqNP_071882.1. NM_022437.2. [Q9H221-1]
XP_005264540.1. XM_005264483.1. [Q9H221-2]
UniGeneHs.413931.

3D structure databases

ProteinModelPortalQ9H221.
SMRQ9H221. Positions 44-322.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122125. 8 interactions.
IntActQ9H221. 8 interactions.
MINTMINT-2840535.
STRING9606.ENSP00000272286.

Protein family/group databases

TCDB3.A.1.204.5. the atp-binding cassette (abc) superfamily.

PTM databases

PhosphoSiteQ9H221.

Polymorphism databases

DMDM17432916.

Proteomic databases

PaxDbQ9H221.
PRIDEQ9H221.

Protocols and materials databases

DNASU64241.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000272286; ENSP00000272286; ENSG00000143921. [Q9H221-1]
GeneID64241.
KEGGhsa:64241.
UCSCuc002rtq.3. human. [Q9H221-1]
uc010yoa.2. human. [Q9H221-2]

Organism-specific databases

CTD64241.
GeneCardsGC02P043977.
GeneReviewsABCG8.
HGNCHGNC:13887. ABCG8.
HPAHPA019556.
MIM210250. phenotype.
605460. gene.
611465. phenotype.
neXtProtNX_Q9H221.
Orphanet2882. Sitosterolemia.
PharmGKBPA24412.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1131.
HOGENOMHOG000033764.
HOVERGENHBG050444.
InParanoidQ9H221.
KOK05684.
OMACFEGLMK.
OrthoDBEOG70W3CV.
PhylomeDBQ9H221.
TreeFamTF105212.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ9H221.
BgeeQ9H221.
CleanExHS_ABCG8.
GenevestigatorQ9H221.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR013525. ABC_2_trans.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF01061. ABC2_membrane. 1 hit.
PF00005. ABC_tran. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
PROSITEPS00211. ABC_TRANSPORTER_1. 1 hit.
PS50893. ABC_TRANSPORTER_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiABCG8.
GenomeRNAi64241.
NextBio66192.
PROQ9H221.
SOURCESearch...

Entry information

Entry nameABCG8_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM