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Protein

ATP-binding cassette sub-family G member 8

Gene

Abcg8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 (PubMed:16352607, PubMed:16867993, PubMed:18402465). 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:12444248, PubMed:14504269, PubMed:14657202, PubMed:25378657). Plays an important role in preventing the accumulation of dietary plant sterols in the body (PubMed:12444248, PubMed:14657202). Required for normal sterol homeostasis (PubMed:12444248, PubMed:14657202). The heterodimer with ABCG5 has ATPase activity (PubMed:16352607, PubMed:16867993).7 Publications

Cofactori

Mg2+1 Publication

Enzyme regulationi

Cholesterol transport is inhibited by vanadate and by beryllium fluoride.1 Publication

GO - Molecular functioni

GO - Biological processi

  • cholesterol efflux Source: BHF-UCL
  • cholesterol homeostasis Source: MGI
  • excretion Source: BHF-UCL
  • intestinal cholesterol absorption Source: BHF-UCL
  • negative regulation of intestinal cholesterol absorption Source: MGI
  • negative regulation of intestinal phytosterol absorption Source: MGI
  • phospholipid transport Source: MGI
  • response to drug Source: Ensembl
  • response to nutrient Source: Ensembl
  • sterol homeostasis Source: MGI
  • sterol transport Source: MGI

Keywordsi

Biological processLipid transport, Transport
LigandMagnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-1369062. ABC transporters in lipid homeostasis.

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-binding cassette sub-family G member 8
Alternative name(s):
Sterolin-22 Publications
Gene namesi
Name:Abcg8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1914720. Abcg8.

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 – 416CytoplasmicBy similarityAdd BLAST416
Transmembranei417 – 437Helical; Name=1By similarityAdd BLAST21
Topological domaini438 – 447ExtracellularBy similarity10
Transmembranei448 – 468Helical; Name=2By similarityAdd BLAST21
Topological domaini469 – 497CytoplasmicBy similarityAdd BLAST29
Transmembranei498 – 518Helical; Name=3By similarityAdd BLAST21
Topological domaini519 – 527ExtracellularBy similarity9
Transmembranei528 – 548Helical; Name=4By similarityAdd BLAST21
Topological domaini549 – 555CytoplasmicBy similarity7
Transmembranei556 – 576Helical; Name=5By similarityAdd BLAST21
Topological domaini577 – 639ExtracellularBy similarityAdd BLAST63
Transmembranei640 – 660Helical; Name=6By similarityAdd BLAST21
Topological domaini661 – 673CytoplasmicBy similarityAdd BLAST13

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice are born at the expected Mendelian rate. They display decreased cholesterol levels, but strongly increased levels of the food-derived plant sterols campesterol and beta-sitosterol in blood plasma, liver and spleen (PubMed:25378657). Besides, mutant mice may have slightly increased total plasma triglyceride levels. Expression of Abcg5 is not affected. Mutant mice display decreased biliary sterol secretion (PubMed:15040800). Mice deficient for both Abcg5 and Abcg8 appear healthy and are fertile, but display strongly increased levels of the food-derived plant sterols sitosterol and campesterol in liver and blood plasma (PubMed:12444248, PubMed:14657202, PubMed:25378657). When mice are fed chow containing 0.02% cholesterol, cholesterol levels in blood plasma and in liver are considerably lower than in wild-type (PubMed:12444248, PubMed:14657202). In spite of the increased plasma and liver levels of plant sterols, and the decreased cholesterol levels, the total sterol levels in plasma and liver are closely similar in wild-type and mutant mice (PubMed:14657202). When mice are fed chow containing 2% cholesterol, plasma cholesterol levels remain stable in wild-type, but increase 2.4-fold in mutant mice. In the liver of mice kept on chow containing 2% cholesterol, cholesterol levels increase 3-fold for wild-type mice and 18-fold for mutant mice, resulting in much higher cholesterol levels than in wild-type livers (PubMed:12444248). Dietary cholesterol absorption appears normal in mutant mice, but the absorption of dietary cholestanol, campesterol and sitosterol is increased (PubMed:12444248). At the same time, mutant mice have very low cholesterol levels in bile, suggesting that the increased hepatic cholesterol levels are due to impaired cholesterol secretion into bile (PubMed:12444248). Likewise, the levels of the food-derived plant sterols stigmasterol, sitosterol, campesterol and brassicasterol are strongly decreased in bile from mutant mice (PubMed:14657202). In contrast, biliary phospholipid and bile acid levels appear unchanged relative to wild-type (PubMed:12444248). The blood plasma of mice with liver-specific or intestine-specific disruption of Abcg5 and Abcg8 has nearly normal levels of cholesterol, and mildly increased levels of sitosterol and campesterol (PubMed:25378657). Mice with intestine-specific disruption of Abcg5 and Abcg8 have strongly increased levels of sitosterol and campesterol in enterocytes, similar to that observed for mice with complete gene disruption (PubMed:25378657). In addition, they display strongly increased levels of sitosterol and campesterol in bile (PubMed:25378657). Mice with liver-specific disruption of Abcg5 and Abcg8 have slightly increased levels of campesterol and sitosterol in the liver, and normal, low levels of sitosterol and campesterol in bile (PubMed:25378657). Enterocytes and liver from mice with liver-specific or intestine-specific disruption of Abcg5 and Abcg8 have normal cholesterol levels (PubMed:25378657).4 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi112R → K or M: No effect on ATP-binding and on expression of both ABCG5 and ABCG8. No effect on sterol transport. 1 Publication1
Mutagenesisi214V → I: No effect on sterol transport; when associated with S-216. 1 Publication1
Mutagenesisi216G → S: No effect on sterol transport; when associated with I-214. 1 Publication1
Mutagenesisi217G → D: Abolishes cholesterol transport activity, and nearly abolishes plant sterol transport. 2 Publications1
Mutagenesisi239E → D: No effect on sterol transport. 1 Publication1
Mutagenesisi239E → Q: Mildly decreases cholesterol transport. No effect on plant sterol transport. 1 Publication1
Mutagenesisi619N → A or Q: Abolishes N-glycosylation. 1 Publication1
Mutagenesisi664 – 673Missing : Abolishes expression at the apical cell membrane. Strongly decreases cholesterol secretion into bile. 1 Publication10

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000933971 – 673ATP-binding cassette sub-family G member 8Add BLAST673

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi619N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

N-glycosylated (PubMed:12208867, PubMed:12444248, PubMed:16867993, PubMed:15054092, PubMed:18402465). N-glycosylation is important for efficient export out of the endoplasmic reticulum (PubMed:15054092).5 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9DBM0.
PRIDEiQ9DBM0.

PTM databases

iPTMnetiQ9DBM0.
PhosphoSitePlusiQ9DBM0.

Expressioni

Tissue specificityi

Detected in liver and jejunum (at protein level) (PubMed:12444248, PubMed:18402465, PubMed:25378657). Expressed in jejunum and ileum and, at lower level, in the liver (PubMed:11907139, PubMed:11099417, PubMed:12444248, PubMed:15040800, PubMed:25378657).6 Publications

Inductioni

Up-regulated in liver and small intestine by cholesterol feeding (PubMed:11099417). Possibly mediated by the liver X receptor/retinoic X receptor (LXR/RXR) pathway. Endotoxin (LPS) significantly decreased mRNA levels in the liver but not in the small intestine (PubMed:12777468).2 Publications

Gene expression databases

BgeeiENSMUSG00000024254.
ExpressionAtlasiQ9DBM0. baseline and differential.
GenevisibleiQ9DBM0. MM.

Interactioni

Subunit structurei

Heterodimer with ABCG5.6 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB

Protein-protein interaction databases

CORUMiQ9DBM0.
STRINGi10090.ENSMUSP00000035246.

Structurei

3D structure databases

ProteinModelPortaliQ9DBM0.
SMRiQ9DBM0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini48 – 314ABC 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 ABCG5.1 Publication

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0061. Eukaryota.
COG1131. LUCA.
GeneTreeiENSGT00870000136471.
HOGENOMiHOG000033764.
HOVERGENiHBG050444.
InParanoidiQ9DBM0.
KOiK05684.
OMAiRRQISND.
OrthoDBiEOG091G0E38.
PhylomeDBiQ9DBM0.
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: Q9DBM0-1) [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
MAEKTKEETQ LWNGTVLQDA SQGLQDSLFS SESDNSLYFT YSGQSNTLEV
60 70 80 90 100
RDLTYQVDIA SQVPWFEQLA QFKIPWRSHS SQDSCELGIR NLSFKVRSGQ
110 120 130 140 150
MLAIIGSSGC GRASLLDVIT GRGHGGKMKS GQIWINGQPS TPQLVRKCVA
160 170 180 190 200
HVRQHDQLLP NLTVRETLAF IAQMRLPRTF SQAQRDKRVE DVIAELRLRQ
210 220 230 240 250
CANTRVGNTY VRGVSGGERR RVSIGVQLLW NPGILILDEP TSGLDSFTAH
260 270 280 290 300
NLVTTLSRLA KGNRLVLISL HQPRSDIFRL FDLVLLMTSG TPIYLGAAQQ
310 320 330 340 350
MVQYFTSIGH PCPRYSNPAD FYVDLTSIDR RSKEREVATV EKAQSLAALF
360 370 380 390 400
LEKVQGFDDF LWKAEAKELN TSTHTVSLTL TQDTDCGTAV ELPGMIEQFS
410 420 430 440 450
TLIRRQISND FRDLPTLLIH GSEACLMSLI IGFLYYGHGA KQLSFMDTAA
460 470 480 490 500
LLFMIGALIP FNVILDVVSK CHSERSMLYY ELEDGLYTAG PYFFAKILGE
510 520 530 540 550
LPEHCAYVII YAMPIYWLTN LRPVPELFLL HFLLVWLVVF CCRTMALAAS
560 570 580 590 600
AMLPTFHMSS FFCNALYNSF YLTAGFMINL DNLWIVPAWI SKLSFLRWCF
610 620 630 640 650
SGLMQIQFNG HLYTTQIGNF TFSILGDTMI SAMDLNSHPL YAIYLIVIGI
660 670
SYGFLFLYYL SLKLIKQKSI QDW
Length:673
Mass (Da):75,996
Last modified:June 1, 2001 - v1
Checksum:i78012611A5DF2589
GO
Isoform 2 (identifier: Q9DBM0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     377-377: Missing.

Note: No experimental confirmation available.
Show »
Length:672
Mass (Da):75,909
Checksum:iFC57D60AB2D79D1F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti544T → N in AAL82898 (PubMed:11907139).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000053377Missing in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AH011518
, AF351799, AF351800, AF351801, AF351802, AF351803, AF351804, AF351807, AF351808, AF351809, AF351810 Genomic DNA. Translation: AAL82898.1.
AF324495 mRNA. Translation: AAK84079.1.
AK004871 mRNA. Translation: BAB23630.1.
CCDSiCCDS29002.1. [Q9DBM0-1]
RefSeqiNP_001272934.1. NM_001286005.1.
NP_001334347.1. NM_001347418.1.
NP_080456.1. NM_026180.3. [Q9DBM0-1]
UniGeneiMm.26581.

Genome annotation databases

EnsembliENSMUST00000045714; ENSMUSP00000035246; ENSMUSG00000024254. [Q9DBM0-1]
GeneIDi67470.
KEGGimmu:67470.
UCSCiuc008dta.2. mouse. [Q9DBM0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiABCG8_MOUSE
AccessioniPrimary (citable) accession number: Q9DBM0
Secondary accession number(s): Q8R543
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: June 1, 2001
Last modified: January 31, 2018
This is version 140 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Seems to have a defective ATP-binding region.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families