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Protein

ATP-binding cassette sub-family G member 5

Gene

ABCG5

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 (PubMed:27144356). 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:11099417, PubMed:11138003, PubMed:27144356, PubMed:15054092). Required for normal sterol homeostasis (PubMed:11099417, PubMed:11138003, PubMed:15054092). The heterodimer with ABCG8 has ATPase activity (PubMed:16893193, PubMed:20210363, PubMed:27144356).1 Publication1 Publication5 Publications

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

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi86 – 93ATPPROSITE-ProRule annotation8

GO - Molecular functioni

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

GO - Biological processi

  • cholesterol efflux Source: UniProtKB
  • cholesterol homeostasis Source: UniProtKB
  • drug transmembrane transport Source: GO_Central
  • 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
  • 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-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
SIGNORiQ9H222

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 5
Alternative name(s):
Sterolin-1
Gene namesi
Name:ABCG5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000138075.11
HGNCiHGNC:13886 ABCG5
MIMi605459 gene
neXtProtiNX_Q9H222

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 – 383Cytoplasmic1 PublicationAdd BLAST383
Transmembranei384 – 404Helical; Name=11 PublicationAdd BLAST21
Topological domaini405 – 421Extracellular1 PublicationAdd BLAST17
Transmembranei422 – 442Helical; Name=21 PublicationAdd BLAST21
Topological domaini443 – 467Cytoplasmic1 PublicationAdd BLAST25
Transmembranei468 – 489Helical; Name=31 PublicationAdd BLAST22
Topological domaini490 – 500Extracellular1 PublicationAdd BLAST11
Transmembranei501 – 521Helical; Name=41 PublicationAdd BLAST21
Topological domaini522 – 528Cytoplasmic1 Publication7
Transmembranei529 – 549Helical; Name=51 PublicationAdd BLAST21
Topological domaini550 – 623Extracellular1 PublicationAdd BLAST74
Transmembranei624 – 644Helical; Name=61 PublicationAdd BLAST21
Topological domaini645 – 651Cytoplasmic1 Publication7

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Sitosterolemia (STSL)4 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_012244146E → Q in STSL; decreased maturation of glycan chains. 2 PublicationsCorresponds to variant dbSNP:rs758551848Ensembl.1
Natural variantiVAR_012245389R → H in STSL; loss of normal maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs119480069EnsemblClinVar.1
Natural variantiVAR_012246419R → H in STSL; loss of normal maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs119479067EnsemblClinVar.1
Natural variantiVAR_012247419R → P in STSL; strongly decreased maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs119479067EnsemblClinVar.1
Natural variantiVAR_020781437N → K in STSL; loss of normal maturation of glycan chains. 2 PublicationsCorresponds to variant dbSNP:rs575266356Ensembl.1
Natural variantiVAR_012248550R → S in STSL. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi92 – 93KT → RA: Abolishes increase of the very low basal ATPase activity by cholate. 1 Publication2
Mutagenesisi432Y → A: Strongly decreases cholesterol secretion into bile. 1 Publication1
Mutagenesisi540A → F: Strongly decreases cholesterol secretion into bile. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi64240
GeneReviewsiABCG5
MalaCardsiABCG5
MIMi210250 phenotype
OpenTargetsiENSG00000138075
Orphaneti2882 Sitosterolemia
PharmGKBiPA24411

Chemistry databases

DrugBankiDB00973 Ezetimibe

Polymorphism and mutation databases

BioMutaiABCG5
DMDMi17432917

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000933931 – 651ATP-binding cassette sub-family G member 5Add BLAST651

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi584N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi591N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.2 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9H222
PeptideAtlasiQ9H222
PRIDEiQ9H222
ProteomicsDBi80475

PTM databases

iPTMnetiQ9H222
PhosphoSitePlusiQ9H222

Expressioni

Tissue specificityi

Strongly expressed in the liver, lower levels in the small intestine and colon.2 Publications

Gene expression databases

BgeeiENSG00000138075
CleanExiHS_ABCG5
ExpressionAtlasiQ9H222 baseline and differential
GenevisibleiQ9H222 HS

Organism-specific databases

HPAiHPA016514

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

BioGridi122124, 1 interactor
DIPiDIP-42630N
IntActiQ9H222, 5 interactors
MINTiQ9H222
STRINGi9606.ENSP00000260645

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DO7X-ray3.93A/C1-651[»]
ProteinModelPortaliQ9H222
SMRiQ9H222
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini52 – 293ABC transporterPROSITE-ProRule annotationAdd BLAST242
Domaini388 – 645ABC 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.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0061 Eukaryota
COG1131 LUCA
GeneTreeiENSGT00740000114855
HOGENOMiHOG000033763
HOVERGENiHBG050443
InParanoidiQ9H222
KOiK05683
OMAiNAVNLFP
OrthoDBiEOG091G0FOJ
PhylomeDBiQ9H222
TreeFamiTF105212

Family and domain databases

InterProiView protein in InterPro
IPR003593 AAA+_ATPase
IPR013525 ABC_2_trans
IPR003439 ABC_transporter-like
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
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: Q9H222-1) [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
MGDLSSLTPG GSMGLQVNRG SQSSLEGAPA TAPEPHSLGI LHASYSVSHR
60 70 80 90 100
VRPWWDITSC RQQWTRQILK DVSLYVESGQ IMCILGSSGS GKTTLLDAMS
110 120 130 140 150
GRLGRAGTFL GEVYVNGRAL RREQFQDCFS YVLQSDTLLS SLTVRETLHY
160 170 180 190 200
TALLAIRRGN PGSFQKKVEA VMAELSLSHV ADRLIGNYSL GGISTGERRR
210 220 230 240 250
VSIAAQLLQD PKVMLFDEPT TGLDCMTANQ IVVLLVELAR RNRIVVLTIH
260 270 280 290 300
QPRSELFQLF DKIAILSFGE LIFCGTPAEM LDFFNDCGYP CPEHSNPFDF
310 320 330 340 350
YMDLTSVDTQ SKEREIETSK RVQMIESAYK KSAICHKTLK NIERMKHLKT
360 370 380 390 400
LPMVPFKTKD SPGVFSKLGV LLRRVTRNLV RNKLAVITRL LQNLIMGLFL
410 420 430 440 450
LFFVLRVRSN VLKGAIQDRV GLLYQFVGAT PYTGMLNAVN LFPVLRAVSD
460 470 480 490 500
QESQDGLYQK WQMMLAYALH VLPFSVVATM IFSSVCYWTL GLHPEVARFG
510 520 530 540 550
YFSAALLAPH LIGEFLTLVL LGIVQNPNIV NSVVALLSIA GVLVGSGFLR
560 570 580 590 600
NIQEMPIPFK IISYFTFQKY CSEILVVNEF YGLNFTCGSS NVSVTTNPMC
610 620 630 640 650
AFTQGIQFIE KTCPGATSRF TMNFLILYSF IPALVILGIV VFKIRDHLIS

R
Length:651
Mass (Da):72,504
Last modified:March 1, 2001 - v1
Checksum:i950BABFCBB6A1536
GO
Isoform 2 (identifier: Q9H222-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-395: Missing.

Note: No experimental confirmation available.
Show »
Length:256
Mass (Da):28,480
Checksum:iE8AB9B5738CDA01C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04814250R → C. Corresponds to variant dbSNP:rs6756629EnsemblClinVar.1
Natural variantiVAR_012244146E → Q in STSL; decreased maturation of glycan chains. 2 PublicationsCorresponds to variant dbSNP:rs758551848Ensembl.1
Natural variantiVAR_012245389R → H in STSL; loss of normal maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs119480069EnsemblClinVar.1
Natural variantiVAR_012246419R → H in STSL; loss of normal maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs119479067EnsemblClinVar.1
Natural variantiVAR_012247419R → P in STSL; strongly decreased maturation of glycan chains. 3 PublicationsCorresponds to variant dbSNP:rs119479067EnsemblClinVar.1
Natural variantiVAR_020781437N → K in STSL; loss of normal maturation of glycan chains. 2 PublicationsCorresponds to variant dbSNP:rs575266356Ensembl.1
Natural variantiVAR_033457517T → S. Corresponds to variant dbSNP:rs17031672Ensembl.1
Natural variantiVAR_020782523I → V1 PublicationCorresponds to variant dbSNP:rs140899003EnsemblClinVar.1
Natural variantiVAR_012248550R → S in STSL. 1 Publication1
Natural variantiVAR_020783600C → Y1 PublicationCorresponds to variant dbSNP:rs779109455Ensembl.1
Natural variantiVAR_012249604Q → E4 PublicationsCorresponds to variant dbSNP:rs6720173EnsemblClinVar.1
Natural variantiVAR_020784622M → V1 PublicationCorresponds to variant dbSNP:rs140374206EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0557701 – 395Missing in isoform 2. 1 PublicationAdd BLAST395

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF320293 mRNA Translation: AAG40003.1
AF312715 mRNA Translation: AAG53099.1
AC011242 Genomic DNA No translation available.
AC108476 Genomic DNA No translation available.
CH471053 Genomic DNA Translation: EAX00286.1
BC111541 mRNA Translation: AAI11542.1
AF404106 Genomic DNA Translation: AAK85387.1
AF404107 Genomic DNA Translation: AAK85388.1
CCDSiCCDS1814.1 [Q9H222-1]
RefSeqiNP_071881.1, NM_022436.2 [Q9H222-1]
UniGeneiHs.132992

Genome annotation databases

EnsembliENST00000260645; ENSP00000260645; ENSG00000138075 [Q9H222-1]
ENST00000405322; ENSP00000384513; ENSG00000138075 [Q9H222-1]
GeneIDi64240
KEGGihsa:64240
UCSCiuc002rtn.3 human [Q9H222-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiABCG5_HUMAN
AccessioniPrimary (citable) accession number: Q9H222
Secondary accession number(s): Q2T9G2, Q96QZ2, Q96QZ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: March 1, 2001
Last modified: June 20, 2018
This is version 164 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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