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Protein

ATP-binding cassette sub-family G member 8

Gene

ABCG8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg2+- and ATP-dependent sterol transport across the cell membrane. Plays an essential 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 (PubMed:11099417, PubMed:11452359, PubMed:27144356, PubMed:15054092). Required for normal sterol homeostasis (PubMed:11099417, PubMed:11452359, PubMed:15054092). The heterodimer with ABCG5 has ATPase activity (PubMed:16893193, PubMed:20210363, PubMed:27144356).5 Publications

Caution

Seems to have a defective ATP-binding region.Curated

Cofactori

Mg2+By similarity

Enzyme regulationi

The ATPase activity of the heterodimer is stimulated by cholate. Taurocholate, glycocholate, taurochenodeoxycholate, glycochenodeoxycholate and taurodeoxycholate also stimulate ATPase activity, but to a lower degree. Glycodeoxycholate has no significant effect on ATPase activity. ATPase activity is inhibited by vanadate and by berillium fluoride.2 Publications

GO - Molecular functioni

  • ATPase activity, coupled to transmembrane movement of substances Source: UniProtKB
  • ATP binding Source: InterPro
  • metal ion binding Source: UniProtKB-KW
  • protein heterodimerization activity Source: BHF-UCL

GO - Biological processi

  • cholesterol efflux Source: UniProtKB
  • cholesterol homeostasis Source: UniProtKB
  • excretion Source: BHF-UCL
  • intestinal cholesterol absorption Source: BHF-UCL
  • negative regulation of intestinal cholesterol absorption Source: BHF-UCL
  • negative regulation of intestinal phytosterol absorption Source: BHF-UCL

Keywordsi

Biological processLipid transport, Transport
LigandMagnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-1369062 ABC transporters in lipid homeostasis
R-HSA-5679090 Defective ABCG8 causes gallbladder disease 4 and sitosterolemia
R-HSA-5679096 Defective ABCG5 causes sitosterolemia
SIGNORiQ9H221

Protein family/group databases

TCDBi3.A.1.204.5 the atp-binding cassette (abc) superfamily

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-binding cassette sub-family G member 8
Alternative name(s):
Sterolin-21 Publication
Gene namesi
Name:ABCG8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000143921.6
HGNCiHGNC:13887 ABCG8
MIMi605460 gene
neXtProtiNX_Q9H221

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 416Cytoplasmic1 PublicationAdd BLAST416
Transmembranei417 – 437Helical; Name=11 PublicationAdd BLAST21
Topological domaini438 – 447Extracellular1 Publication10
Transmembranei448 – 468Helical; Name=21 PublicationAdd BLAST21
Topological domaini469 – 497Cytoplasmic1 PublicationAdd BLAST29
Transmembranei498 – 518Helical; Name=31 PublicationAdd BLAST21
Topological domaini519 – 527Extracellular1 Publication9
Transmembranei528 – 548Helical; Name=41 PublicationAdd BLAST21
Topological domaini549 – 555Cytoplasmic1 Publication7
Transmembranei556 – 576Helical; Name=51 PublicationAdd BLAST21
Topological domaini577 – 639Extracellular1 PublicationAdd BLAST63
Transmembranei640 – 660Helical; Name=61 PublicationAdd BLAST21
Topological domaini661 – 673Cytoplasmic1 PublicationAdd BLAST13

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Gallbladder disease 4 (GBD4)1 Publication
Disease susceptibility may be associated with variations affecting the gene represented in this entry.
Disease descriptionOne 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.
See also OMIM:611465
Sitosterolemia (STSL)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare 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.
See also OMIM:210250
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012252184R → H in STSL; strongly decreased maturation of glycan chains. 2 PublicationsCorresponds to variant dbSNP:rs766212636EnsemblClinVar.1
Natural variantiVAR_012253231P → T in STSL; strongly decreased maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs137852993EnsemblClinVar.1
Natural variantiVAR_012254238E → K in STSL; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs34754243EnsemblClinVar.1
Natural variantiVAR_012256263R → Q in STSL; strongly decreased maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs137852990EnsemblClinVar.1
Natural variantiVAR_012258405R → H in STSL. 1 Publication1
Natural variantiVAR_012259501L → P in STSL; strongly decreased maturation of glycan chains. 2 Publications1
Natural variantiVAR_012260543R → S in STSL; decreased maturation of glycan chains. 2 PublicationsCorresponds to variant dbSNP:rs201690654EnsemblClinVar.1
Natural variantiVAR_012261570Missing in STSL. 1 Publication1
Natural variantiVAR_012262572L → P in STSL. 1 PublicationCorresponds to variant dbSNP:rs769576789Ensembl.1
Natural variantiVAR_012263574G → E in STSL; strongly decreased maturation of glycan chains. 2 Publications1
Natural variantiVAR_012264574G → R in STSL; decreased maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs137852988EnsemblClinVar.1
Natural variantiVAR_012266596L → R in STSL; strongly decreased maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs137852992EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi216G → D: Loss of ATPase activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi64241
GeneReviewsiABCG8
MalaCardsiABCG8
MIMi210250 phenotype
611465 phenotype
OpenTargetsiENSG00000143921
Orphaneti2882 Sitosterolemia
PharmGKBiPA24412

Chemistry databases

DrugBankiDB00973 Ezetimibe

Polymorphism and mutation databases

BioMutaiABCG8
DMDMi17432916

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000933961 – 673ATP-binding cassette sub-family G member 8Add BLAST673

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi619N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.2 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9H221
PeptideAtlasiQ9H221
PRIDEiQ9H221
ProteomicsDBi80473
80474 [Q9H221-2]

PTM databases

iPTMnetiQ9H221
PhosphoSitePlusiQ9H221

Expressioni

Tissue specificityi

Predominantly expressed in the liver (PubMed:11099417, PubMed:11452359). Low expression levels in the small intestine and colon (PubMed:11099417). Very low levels in other tissues, including brain, heart and spleen (PubMed:11452359).2 Publications

Gene expression databases

BgeeiENSG00000143921
CleanExiHS_ABCG8
GenevisibleiQ9H221 HS

Organism-specific databases

HPAiHPA019556

Interactioni

Subunit structurei

Heterodimer with ABCG8.3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein heterodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi122125, 13 interactors
DIPiDIP-42631N
IntActiQ9H221, 8 interactors
MINTiQ9H221
STRINGi9606.ENSP00000272286

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DO7X-ray3.93B/D2-673[»]
ProteinModelPortaliQ9H221
SMRiQ9H221
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini47 – 313ABC transporterPROSITE-ProRule annotationAdd BLAST267
Domaini411 – 665ABC transmembrane type-2Add BLAST255

Domaini

A functional Walker motif (consensus sequence G-X-X-G-X-G-K-[ST]-T) is expected to bind ATP. The essential Lys in this region is not conserved in ABCG8 (G-S-S-G-C-R-A-S) and is not required for transport activity mediated by the heterodimer with ABCG5.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0061 Eukaryota
COG1131 LUCA
GeneTreeiENSGT00920000149166
HOGENOMiHOG000033764
HOVERGENiHBG050444
InParanoidiQ9H221
KOiK05684
OMAiLLPTFHM
OrthoDBiEOG091G0E38
PhylomeDBiQ9H221
TreeFamiTF105212

Family and domain databases

InterProiView protein in InterPro
IPR013525 ABC_2_trans
IPR003439 ABC_transporter-like
IPR017871 ABC_transporter_CS
IPR027417 P-loop_NTPase
PfamiView protein in Pfam
PF01061 ABC2_membrane, 1 hit
PF00005 ABC_tran, 1 hit
SUPFAMiSSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00211 ABC_TRANSPORTER_1, 1 hit
PS50893 ABC_TRANSPORTER_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H221-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAGKAAEERG LPKGATPQDT SGLQDRLFSS ESDNSLYFTY SGQPNTLEVR
60 70 80 90 100
DLNYQVDLAS QVPWFEQLAQ FKMPWTSPSC QNSCELGIQN LSFKVRSGQM
110 120 130 140 150
LAIIGSSGCG RASLLDVITG RGHGGKIKSG QIWINGQPSS PQLVRKCVAH
160 170 180 190 200
VRQHNQLLPN LTVRETLAFI AQMRLPRTFS QAQRDKRVED VIAELRLRQC
210 220 230 240 250
ADTRVGNMYV RGLSGGERRR VSIGVQLLWN PGILILDEPT SGLDSFTAHN
260 270 280 290 300
LVKTLSRLAK GNRLVLISLH QPRSDIFRLF DLVLLMTSGT PIYLGAAQHM
310 320 330 340 350
VQYFTAIGYP CPRYSNPADF YVDLTSIDRR SREQELATRE KAQSLAALFL
360 370 380 390 400
EKVRDLDDFL WKAETKDLDE DTCVESSVTP LDTNCLPSPT KMPGAVQQFT
410 420 430 440 450
TLIRRQISND FRDLPTLLIH GAEACLMSMT IGFLYFGHGS IQLSFMDTAA
460 470 480 490 500
LLFMIGALIP FNVILDVISK CYSERAMLYY ELEDGLYTTG PYFFAKILGE
510 520 530 540 550
LPEHCAYIII YGMPTYWLAN LRPGLQPFLL HFLLVWLVVF CCRIMALAAA
560 570 580 590 600
ALLPTFHMAS FFSNALYNSF YLAGGFMINL SSLWTVPAWI SKVSFLRWCF
610 620 630 640 650
EGLMKIQFSR RTYKMPLGNL TIAVSGDKIL SVMELDSYPL YAIYLIVIGL
660 670
SGGFMVLYYV SLRFIKQKPS QDW
Length:673
Mass (Da):75,679
Last modified:March 1, 2001 - v1
Checksum:i594AFD1D6C1BB50F
GO
Isoform 2 (identifier: Q9H221-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:672
Mass (Da):75,592
Checksum:iA7F428ED11B104DE
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01225019D → H Associated significantly with GBD4. 3 PublicationsCorresponds to variant dbSNP:rs11887534EnsemblClinVar.1
Natural variantiVAR_01225154Y → C4 PublicationsCorresponds to variant dbSNP:rs4148211EnsemblClinVar.1
Natural variantiVAR_012252184R → H in STSL; strongly decreased maturation of glycan chains. 2 PublicationsCorresponds to variant dbSNP:rs766212636EnsemblClinVar.1
Natural variantiVAR_022074210V → M. Corresponds to variant dbSNP:rs9282574EnsemblClinVar.1
Natural variantiVAR_012253231P → T in STSL; strongly decreased maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs137852993EnsemblClinVar.1
Natural variantiVAR_012254238E → K in STSL; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs34754243EnsemblClinVar.1
Natural variantiVAR_012255259A → V1 PublicationCorresponds to variant dbSNP:rs35518570Ensembl.1
Natural variantiVAR_012256263R → Q in STSL; strongly decreased maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs137852990EnsemblClinVar.1
Natural variantiVAR_012257400T → K3 PublicationsCorresponds to variant dbSNP:rs4148217EnsemblClinVar.1
Natural variantiVAR_012258405R → H in STSL. 1 Publication1
Natural variantiVAR_012259501L → P in STSL; strongly decreased maturation of glycan chains. 2 Publications1
Natural variantiVAR_012260543R → S in STSL; decreased maturation of glycan chains. 2 PublicationsCorresponds to variant dbSNP:rs201690654EnsemblClinVar.1
Natural variantiVAR_012261570Missing in STSL. 1 Publication1
Natural variantiVAR_012262572L → P in STSL. 1 PublicationCorresponds to variant dbSNP:rs769576789Ensembl.1
Natural variantiVAR_012263574G → E in STSL; strongly decreased maturation of glycan chains. 2 Publications1
Natural variantiVAR_012264574G → R in STSL; decreased maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs137852988EnsemblClinVar.1
Natural variantiVAR_012265575G → R1 Publication1
Natural variantiVAR_012266596L → R in STSL; strongly decreased maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs137852992EnsemblClinVar.1
Natural variantiVAR_012267632V → A2 PublicationsCorresponds to variant dbSNP:rs6544718EnsemblClinVar.1
Natural variantiVAR_020785641Y → F1 PublicationCorresponds to variant dbSNP:rs145125968Ensembl.1
Natural variantiVAR_022075655M → V. Corresponds to variant dbSNP:rs9282573Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000052376Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS1815.1 [Q9H221-1]
RefSeqiNP_071882.1, NM_022437.2 [Q9H221-1]
XP_005264540.1, XM_005264483.3
UniGeneiHs.413931

Genome annotation databases

EnsembliENST00000272286; ENSP00000272286; ENSG00000143921 [Q9H221-1]
ENST00000645013; ENSP00000496450; ENSG00000143921 [Q9H221-1]
GeneIDi64241
KEGGihsa:64241
UCSCiuc002rtq.3 human [Q9H221-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiABCG8_HUMAN
AccessioniPrimary (citable) accession number: Q9H221
Secondary accession number(s): Q53QN8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: March 1, 2001
Last modified: June 20, 2018
This is version 169 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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