Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

ATP-binding cassette sub-family G member 5

Gene

Abcg5

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 dietary plant sterols and 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:19846887, PubMed:25378657). Required for normal sterol homeostasis (PubMed:12444248, PubMed:14657202). The heterodimer with ABCG8 has ATPase activity (PubMed:16352607, PubMed:16867993).8 Publications

Cofactori

Mg2+2 Publications

Enzyme regulationi

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

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi87 – 94ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

  • cholesterol efflux Source: BHF-UCL
  • cholesterol homeostasis Source: MGI
  • drug transmembrane transport Source: GO_Central
  • 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
  • response to ionizing radiation Source: Ensembl
  • response to nutrient Source: Ensembl

Keywordsi

Biological processLipid transport, Transport
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-1369062. ABC transporters in lipid homeostasis.
R-MMU-8963749. Sterol transport.

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-binding cassette sub-family G member 5
Alternative name(s):
Sterolin-12 Publications
Gene namesi
Name:Abcg5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1351659. Abcg5.

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 – 384CytoplasmicBy similarityAdd BLAST384
Transmembranei385 – 405Helical; Name=1By similarityAdd BLAST21
Topological domaini406 – 422ExtracellularBy similarityAdd BLAST17
Transmembranei423 – 443Helical; Name=2By similarityAdd BLAST21
Topological domaini444 – 468CytoplasmicBy similarityAdd BLAST25
Transmembranei469 – 490Helical; Name=3By similarityAdd BLAST22
Topological domaini491 – 501ExtracellularBy similarityAdd BLAST11
Transmembranei502 – 522Helical; Name=4By similarityAdd BLAST21
Topological domaini523 – 529CytoplasmicBy similarity7
Transmembranei530 – 550Helical; Name=5By similarityAdd BLAST21
Topological domaini551 – 624ExtracellularBy similarityAdd BLAST74
Transmembranei625 – 645Helical; Name=6By similarityAdd BLAST21
Topological domaini646 – 652CytoplasmicBy similarity7

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

A spontaneous mutation gives raise to thrombocytopenia and cardiomyopathy (trac), with recessive inheritance and fully penetrant phenotype. Mice are small, infertile, and have shortened lifespan.1 Publication

Disruption phenotypei

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).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi61C → A: Abolishes palmitoylation. No effect on function and subcellular location. 1 Publication1
Mutagenesisi93K → M: Disrupts sterol transport activity. Decreases expression of both ABCG5 and ABCG8. 2 Publications1
Mutagenesisi93K → R: Strongly reduces cholesterol transport activity, but has little effect on biliary secretion of campesterol and sitosterol. No effect on ATP-binding and on expression of ABCG5 and ABCG8. 1 Publication1
Mutagenesisi194I → V: No effect on cholesterol and sitosterol transport activity; when associated with G-196. 1 Publication1
Mutagenesisi196S → G: No effect on cholesterol and sitosterol transport activity; when associated with V-194. 1 Publication1
Mutagenesisi197G → D: No effect on cholesterol and sitosterol transport activity. Mildly reduced expression of ABCG5 and ABCG8. 1 Publication1
Mutagenesisi219E → D: Decreases expression of both ABCG5 and ABCG8. Disrupts sterol transport activity. 1 Publication1
Mutagenesisi219E → Q: Strongly decreases expression of both ABCG5 and ABCG8. Disrupts sterol transport activity. 1 Publication1
Mutagenesisi585N → Q: Loss of one N-glycosylation site. Abolishes N-glycosylation; when associated with Q-592. 1 Publication1
Mutagenesisi592N → Q: Loss of one N-glycosylation site. Abolishes N-glycosylation; when associated with Q-585. 1 Publication1

Keywords - Diseasei

Disease mutation

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000933941 – 652ATP-binding cassette sub-family G member 5Add BLAST652

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi61S-palmitoyl cysteine1 Publication1
Glycosylationi410N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi585N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi592N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

N-glycosylated (PubMed:12208867, PubMed:12444248, PubMed:16867993, PubMed:15040800, PubMed:15054092, PubMed:18402465, PubMed:25378657). N-glycosylation is important for efficient export out of the endoplasmic reticulum (PubMed:15054092).7 Publications

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

MaxQBiQ99PE8.
PaxDbiQ99PE8.
PRIDEiQ99PE8.

PTM databases

iPTMnetiQ99PE8.
PhosphoSitePlusiQ99PE8.

Expressioni

Tissue specificityi

Detected in liver and jejunum (PubMed:12444248, PubMed:15040800, PubMed:18402465, PubMed:25378657). Detected on enterocyte villi (at protein level) (PubMed:15040800). Expressed in jejunum, ileum and, at lower level, in the liver (PubMed:11138003, PubMed:11907139, PubMed:11099417, PubMed:12444248, PubMed:25378657).7 Publications

Inductioni

Up-regulated in liver and small intestine by cholesterol feeding (PubMed:11099417). Up-regulated via the oxysterols receptor LXR/retinoic X receptor (LXR/RXR) pathway (PubMed:14657202). Endotoxin (LPS) significantly decreased mRNA levels in the liver but not in the small intestine (PubMed:12777468).3 Publications

Gene expression databases

BgeeiENSMUSG00000040505.
ExpressionAtlasiQ99PE8. baseline and differential.
GenevisibleiQ99PE8. MM.

Interactioni

Subunit structurei

Heterodimer with ABCG8.6 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB

Protein-protein interaction databases

CORUMiQ99PE8.
STRINGi10090.ENSMUSP00000069495.

Structurei

3D structure databases

ProteinModelPortaliQ99PE8.
SMRiQ99PE8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini39 – 294ABC transporterPROSITE-ProRule annotationAdd BLAST256
Domaini389 – 646ABC transmembrane type-2Add BLAST258

Domaini

The Walker motif (consensus sequence G-X-X-G-X-G-K-[ST]-T) is expected to bind ATP. Within this motif, the conserved Lys is essential for transport activity mediated by the heterodimer with ABCG8.1 Publication

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0061. Eukaryota.
COG1131. LUCA.
GeneTreeiENSGT00870000136471.
HOGENOMiHOG000033763.
HOVERGENiHBG050443.
InParanoidiQ99PE8.
KOiK05683.
OMAiNAVNLFP.
OrthoDBiEOG091G0FOJ.
PhylomeDBiQ99PE8.
TreeFamiTF105212.

Family and domain databases

InterProiView protein in InterPro
IPR003593. AAA+_ATPase.
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.
SMARTiView protein in SMART
SM00382. AAA. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiView protein in PROSITE
PS00211. ABC_TRANSPORTER_1. 1 hit.
PS50893. ABC_TRANSPORTER_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Q99PE8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGELPFLSPE GARGPHINRG SLSSLEQGSV TGTEARHSLG VLHVSYSVSN
60 70 80 90 100
RVGPWWNIKS CQQKWDRQIL KDVSLYIESG QIMCILGSSG SGKTTLLDAI
110 120 130 140 150
SGRLRRTGTL EGEVFVNGCE LRRDQFQDCF SYVLQSDVFL SSLTVRETLR
160 170 180 190 200
YTAMLALCRS SADFYNKKVE AVMTELSLSH VADQMIGSYN FGGISSGERR
210 220 230 240 250
RVSIAAQLLQ DPKVMMLDEP TTGLDCMTAN QIVLLLAELA RRDRIVIVTI
260 270 280 290 300
HQPRSELFQH FDKIAILTYG ELVFCGTPEE MLGFFNNCGY PCPEHSNPFD
310 320 330 340 350
FYMDLTSVDT QSREREIETY KRVQMLECAF KESDIYHKIL ENIERARYLK
360 370 380 390 400
TLPTVPFKTK DPPGMFGKLG VLLRRVTRNL MRNKQAVIMR LVQNLIMGLF
410 420 430 440 450
LIFYLLRVQN NTLKGAVQDR VGLLYQLVGA TPYTGMLNAV NLFPMLRAVS
460 470 480 490 500
DQESQDGLYH KWQMLLAYVL HVLPFSVIAT VIFSSVCYWT LGLYPEVARF
510 520 530 540 550
GYFSAALLAP HLIGEFLTLV LLGIVQNPNI VNSIVALLSI SGLLIGSGFI
560 570 580 590 600
RNIQEMPIPL KILGYFTFQK YCCEILVVNE FYGLNFTCGG SNTSMLNHPM
610 620 630 640 650
CAITQGVQFI EKTCPGATSR FTANFLILYG FIPALVILGI VIFKVRDYLI

SR
Length:652
Mass (Da):73,244
Last modified:June 1, 2001 - v1
Checksum:i80CE37ADCC19771E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti462 – 652Missing in trac; strongly increased levels of sitosterol, brassicasterol and campesterol in blood plasma. 1 PublicationAdd BLAST191

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF312713 mRNA. Translation: AAG53097.1.
AH011511
, AF351786, AF351787, AF351789, AF351790, AF351791, AF351792, AF351793, AF351794, AF351795, AF351796, AF351797 Genomic DNA. Translation: AAL82586.1.
AY195873 mRNA. Translation: AAO45094.1.
AK149569 mRNA. Translation: BAE28965.1.
CH466537 Genomic DNA. Translation: EDL38580.1.
BC106766 mRNA. Translation: AAI06767.1.
CCDSiCCDS29001.1.
RefSeqiNP_114090.1. NM_031884.2.
UniGeneiMm.289590.

Genome annotation databases

EnsembliENSMUST00000066175; ENSMUSP00000069495; ENSMUSG00000040505.
GeneIDi27409.
KEGGimmu:27409.
UCSCiuc008dsz.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiABCG5_MOUSE
AccessioniPrimary (citable) accession number: Q99PE8
Secondary accession number(s): Q540E8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: June 1, 2001
Last modified: December 20, 2017
This is version 142 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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