Q9H222 (ABCG5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
ATP-binding cassette sub-family G member 5

Alternative name(s):
Sterolin-1

Gene names

Name:

ABCG5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	651 AA.
Sequence status	Complete.
Protein existence	Evidence 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.4 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 process	Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ATP 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 lipid metabolic process Traceable author statement. Source: Reactome 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: Compara response to ionizing radiation Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	apical plasma membrane Inferred from mutant phenotype PubMed 14504269. Source: BHF-UCL integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATPase activity Inferred from electronic annotation. Source: InterPro cholesterol transporter activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	2	EBI-1761423,EBI-389883

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 651	651	ATP-binding cassette sub-family G member 5		PRO_0000093393
Regions
	Topological domain	1 – 383	383	Cytoplasmic Potential
	Transmembrane	384 – 404	21	Helical; Name=1; Potential
	Topological domain	405 – 421	17	Extracellular Potential
	Transmembrane	422 – 442	21	Helical; Name=2; Potential
	Topological domain	443 – 462	20	Cytoplasmic Potential
	Transmembrane	463 – 483	21	Helical; Name=3; Potential
	Topological domain	484 – 503	20	Extracellular Potential
	Transmembrane	504 – 524	21	Helical; Name=4; Potential
	Topological domain	525 – 528	4	Cytoplasmic Potential
	Transmembrane	529 – 549	21	Helical; Name=5; Potential
	Topological domain	550 – 623	74	Extracellular Potential
	Transmembrane	624 – 644	21	Helical; Name=6; Potential
	Topological domain	645 – 651	7	Cytoplasmic Potential
	Domain	52 – 293	242	ABC transporter
	Domain	388 – 645	258	ABC transmembrane type-2
	Nucleotide binding	86 – 93	8	ATP Potential
Amino acid modifications
	Modified residue	21	1	Phosphoserine By similarity
	Glycosylation	584	1	N-linked (GlcNAc...) Potential
	Glycosylation	591	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	50	1	R → C. Corresponds to variant rs6756629 [ dbSNP | Ensembl ].		VAR_048142
	Natural variant	146	1	E → Q in STSL. Ref.4		VAR_012244
	Natural variant	389	1	R → H in STSL. Ref.2 Ref.4		VAR_012245
	Natural variant	419	1	R → H in STSL. Ref.2 Ref.4		VAR_012246
	Natural variant	419	1	R → P in STSL. Ref.2 Ref.4		VAR_012247
	Natural variant	437	1	N → K in STSL. Ref.5		VAR_020781
	Natural variant	517	1	T → S. Corresponds to variant rs17031672 [ dbSNP | Ensembl ].		VAR_033457
	Natural variant	523	1	I → V. Ref.5		VAR_020782
	Natural variant	550	1	R → S in STSL. Ref.4		VAR_012248
	Natural variant	600	1	C → Y. Ref.5		VAR_020783
	Natural variant	604	1	Q → E. Ref.1 Ref.2 Ref.4 Ref.5 Corresponds to variant rs6720173 [ dbSNP | Ensembl ].		VAR_012249
	Natural variant	622	1	M → V. Ref.5		VAR_020784

Sequences

	Sequence		Length	Mass (Da)
	Q9H222 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 950BABFCBB6A1536	FASTA	651	72,504
	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

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]	"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.
[4]	"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: VARIANTS STSL GLN-146; HIS-389; PRO-419; HIS-419 AND SER-550, VARIANT GLU-604.
[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.
IPI	IPI00007839.
RefSeq	NP_071881.1. NM_022436.2.
UniGene	Hs.132992.
3D structure databases
ProteinModelPortal	Q9H222.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H222. 2 interactions.
MINT	MINT-2840498.
STRING	9606.ENSP00000260645.
Protein family/group databases
TCDB	3.A.1.204.5. ATP-binding cassette (ABC) superfamily.
PTM databases
PhosphoSite	Q9H222.
Polymorphism databases
DMDM	17432917.
Proteomic databases
PaxDb	Q9H222.
PRIDE	Q9H222.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000260645; ENSP00000260645; ENSG00000138075.
GeneID	64240.
KEGG	hsa:64240.
UCSC	uc002rtn.3. human.
Organism-specific databases
CTD	64240.
GeneCards	GC02M044039.
HGNC	HGNC:13886. ABCG5.
HPA	HPA016514.
MIM	210250. phenotype. 605459. gene.
neXtProt	NX_Q9H222.
Orphanet	406. Familial hypercholesterolemia. 2882. Sitosterolemia.
PharmGKB	PA24411.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1131.
HOGENOM	HOG000033763.
HOVERGEN	HBG050443.
InParanoid	Q9H222.
KO	K05683.
OMA	RNIQEMP.
OrthoDB	EOG4X97GZ.
PhylomeDB	Q9H222.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q9H222.
Bgee	Q9H222.
CleanEx	HS_ABCG5.
Genevestigator	Q9H222.
GermOnline	ENSG00000138075. Homo sapiens.
Family and domain databases
InterPro	IPR003593. AAA+_ATPase. IPR013525. ABC_2_trans. IPR003439. ABC_transporter-like. [Graphical view]
Pfam	PF01061. ABC2_membrane. 1 hit. PF00005. ABC_tran. 1 hit. [Graphical view]
SMART	SM00382. AAA. 1 hit. [Graphical view]
PROSITE	PS51012. ABC_TM2. False negative. PS00211. ABC_TRANSPORTER_1. False negative. PS50893. ABC_TRANSPORTER_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	64240.
NextBio	66188.
SOURCE	Search...

Entry information

Entry name

ABCG5_HUMAN

Accession

Primary (citable) accession number: Q9H222

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.