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Q9H222 (ABCG5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. 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·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 5
Alternative name(s):
Sterolin-1
Gene names
Name:ABCG5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length651 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 ABCG8 or be tightly coupled to ABCG8 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.

Involvement in disease

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.2 Ref.3 Ref.5

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.

Ontologies

Keywords
   Biological processTransport
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   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

response to drug

Inferred from electronic annotation. Source: Ensembl

response to ionizing radiation

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: UniProtKB-KW

ATPase activity

Inferred from electronic annotation. Source: InterPro

cholesterol transporter activity

Inferred from electronic annotation. Source: Ensembl

protein heterodimerization activity

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

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 651651ATP-binding cassette sub-family G member 5
PRO_0000093393

Regions

Topological domain1 – 383383Cytoplasmic Potential
Transmembrane384 – 40421Helical; Name=1; Potential
Topological domain405 – 42117Extracellular Potential
Transmembrane422 – 44221Helical; Name=2; Potential
Topological domain443 – 46220Cytoplasmic Potential
Transmembrane463 – 48321Helical; Name=3; Potential
Topological domain484 – 50320Extracellular Potential
Transmembrane504 – 52421Helical; Name=4; Potential
Topological domain525 – 5284Cytoplasmic Potential
Transmembrane529 – 54921Helical; Name=5; Potential
Topological domain550 – 62374Extracellular Potential
Transmembrane624 – 64421Helical; Name=6; Potential
Topological domain645 – 6517Cytoplasmic Potential
Domain52 – 293242ABC transporter
Domain388 – 645258ABC transmembrane type-2
Nucleotide binding86 – 938ATP Potential

Amino acid modifications

Glycosylation5841N-linked (GlcNAc...) Potential
Glycosylation5911N-linked (GlcNAc...) Potential

Natural variations

Natural variant501R → C.
Corresponds to variant rs6756629 [ dbSNP | Ensembl ].
VAR_048142
Natural variant1461E → Q in STSL. Ref.3
VAR_012244
Natural variant3891R → H in STSL. Ref.2 Ref.3
VAR_012245
Natural variant4191R → H in STSL. Ref.2 Ref.3
VAR_012246
Natural variant4191R → P in STSL. Ref.2 Ref.3
VAR_012247
Natural variant4371N → K in STSL. Ref.5
VAR_020781
Natural variant5171T → S.
Corresponds to variant rs17031672 [ dbSNP | Ensembl ].
VAR_033457
Natural variant5231I → V. Ref.5
VAR_020782
Natural variant5501R → S in STSL. Ref.3
VAR_012248
Natural variant6001C → Y. Ref.5
VAR_020783
Natural variant6041Q → E. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs6720173 [ dbSNP | Ensembl ].
VAR_012249
Natural variant6221M → V. Ref.5
Corresponds to variant rs140374206 [ dbSNP | Ensembl ].
VAR_020784

Sequences

Sequence LengthMass (Da)Tools
Q9H222 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 950BABFCBB6A1536

FASTA65172,504
        10         20         30         40         50         60 
MGDLSSLTPG GSMGLQVNRG SQSSLEGAPA TAPEPHSLGI LHASYSVSHR VRPWWDITSC 

        70         80         90        100        110        120 
RQQWTRQILK DVSLYVESGQ IMCILGSSGS GKTTLLDAMS GRLGRAGTFL GEVYVNGRAL 

       130        140        150        160        170        180 
RREQFQDCFS YVLQSDTLLS SLTVRETLHY TALLAIRRGN PGSFQKKVEA VMAELSLSHV 

       190        200        210        220        230        240 
ADRLIGNYSL GGISTGERRR VSIAAQLLQD PKVMLFDEPT TGLDCMTANQ IVVLLVELAR 

       250        260        270        280        290        300 
RNRIVVLTIH QPRSELFQLF DKIAILSFGE LIFCGTPAEM LDFFNDCGYP CPEHSNPFDF 

       310        320        330        340        350        360 
YMDLTSVDTQ SKEREIETSK RVQMIESAYK KSAICHKTLK NIERMKHLKT LPMVPFKTKD 

       370        380        390        400        410        420 
SPGVFSKLGV LLRRVTRNLV RNKLAVITRL LQNLIMGLFL LFFVLRVRSN VLKGAIQDRV 

       430        440        450        460        470        480 
GLLYQFVGAT PYTGMLNAVN LFPVLRAVSD QESQDGLYQK WQMMLAYALH VLPFSVVATM 

       490        500        510        520        530        540 
IFSSVCYWTL GLHPEVARFG YFSAALLAPH LIGEFLTLVL LGIVQNPNIV NSVVALLSIA 

       550        560        570        580        590        600 
GVLVGSGFLR NIQEMPIPFK IISYFTFQKY CSEILVVNEF YGLNFTCGSS NVSVTTNPMC 

       610        620        630        640        650 
AFTQGIQFIE KTCPGATSRF TMNFLILYSF IPALVILGIV VFKIRDHLIS R 

« Hide

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], VARIANT GLU-604.
Tissue: Liver.
[2]"Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption."
Lee M.-H., Lu K., Hazard S., Yu H., Shulenin S., Hidaka H., Kojima H., Allikmets R., Sakuma N., Pegoraro R., Srivastava A.K., Salen G., Dean M., Patel S.B.
Nat. Genet. 27:79-83(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS STSL HIS-389; HIS-419 AND PRO-419, VARIANT GLU-604.
Tissue: Liver.
[3]"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 [MRNA] OF 1-88, VARIANTS STSL GLN-146; HIS-389; PRO-419; HIS-419 AND SER-550, VARIANT GLU-604.
[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: VARIANT STSL LYS-437, VARIANTS VAL-523; TYR-600; GLU-604 AND VAL-622.
+Additional computationally mapped references.

Web resources

GeneReviews
ABCMdb

Database for mutations in ABC proteins

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF320293 mRNA. Translation: AAG40003.1.
AF312715 mRNA. Translation: AAG53099.1.
AF404106 Genomic DNA. Translation: AAK85387.1.
AF404107 Genomic DNA. Translation: AAK85388.1.
RefSeqNP_071881.1. NM_022436.2.
UniGeneHs.132992.

3D structure databases

ProteinModelPortalQ9H222.
SMRQ9H222. Positions 37-324.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122124. 2 interactions.
IntActQ9H222. 4 interactions.
MINTMINT-2840498.
STRING9606.ENSP00000260645.

Protein family/group databases

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

PTM databases

PhosphoSiteQ9H222.

Polymorphism databases

DMDM17432917.

Proteomic databases

PaxDbQ9H222.
PRIDEQ9H222.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260645; ENSP00000260645; ENSG00000138075.
GeneID64240.
KEGGhsa:64240.
UCSCuc002rtn.3. human.

Organism-specific databases

CTD64240.
GeneCardsGC02M044039.
HGNCHGNC:13886. ABCG5.
HPAHPA016514.
MIM210250. phenotype.
605459. gene.
neXtProtNX_Q9H222.
Orphanet406. Familial hypercholesterolemia.
2882. Sitosterolemia.
PharmGKBPA24411.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1131.
HOGENOMHOG000033763.
HOVERGENHBG050443.
InParanoidQ9H222.
KOK05683.
OMAMCAFTQG.
OrthoDBEOG7QNVKG.
PhylomeDBQ9H222.
TreeFamTF105212.

Enzyme and pathway databases

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

Gene expression databases

ArrayExpressQ9H222.
BgeeQ9H222.
CleanExHS_ABCG5.
GenevestigatorQ9H222.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR003593. AAA+_ATPase.
IPR013525. ABC_2_trans.
IPR003439. ABC_transporter-like.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF01061. ABC2_membrane. 1 hit.
PF00005. ABC_tran. 1 hit.
[Graphical view]
SMARTSM00382. AAA. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
PROSITEPS50893. ABC_TRANSPORTER_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiABCG5.
GenomeRNAi64240.
NextBio66188.
PROQ9H222.
SOURCESearch...

Entry information

Entry nameABCG5_HUMAN
AccessionPrimary (citable) accession number: Q9H222
Secondary accession number(s): Q96QZ2, Q96QZ3
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 123 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