ABCG8_RAT
ID ABCG8_RAT Reviewed; 694 AA.
AC P58428; Q8CIQ5; Q923R7;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=ATP-binding cassette sub-family G member 8 {ECO:0000305};
DE EC=7.6.2.- {ECO:0000250|UniProtKB:Q9DBM0};
DE AltName: Full=Sterolin-2 {ECO:0000303|PubMed:11452359};
GN Name=Abcg8 {ECO:0000312|RGD:620300};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=Sprague-Dawley;
RX PubMed=11452359; DOI=10.1086/321294;
RA Lu K., Lee M.-H., Hazard S., Brooks-Wilson A., Hidaka H., Kojima H.,
RA Ose L., Stalenhoef A.F.H., Mietinnen T., Bjorkhem I., Bruckert E.,
RA Pandya A., Brewer H.B. Jr., Salen G., Dean M., Srivastava A.K., Patel S.B.;
RT "Two genes that map to the STSL locus cause sitosterolemia: genomic
RT structure and spectrum of mutations involving sterolin-1 and sterolin-2,
RT encoded by ABCG5 and ABCG8, respectively.";
RL Am. J. Hum. Genet. 69:278-290(2001).
RN [2]
RP SEQUENCE REVISION TO 3-4.
RA Lu K., Yu H., Lee M.-H., Patel S.B.;
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3), AND TISSUE
RP SPECIFICITY.
RC STRAIN=GH, SHR, SHRSP, Sprague-Dawley, Wistar, Wistar Kyoto, and WKA;
RC TISSUE=Intestine, and Liver;
RX PubMed=12783625; DOI=10.1186/1471-2261-3-4;
RA Yu H., Pandit B., Klett E., Lee M.-H., Lu K., Helou K., Ikeda I.,
RA Egashira N., Sato M., Klein R., Batta A., Salen G., Patel S.B.;
RT "The rat STSL locus: characterization, chromosomal assignment, and genetic
RT variations in sitosterolemic hypertensive rats.";
RL BMC Cardiovasc. Disord. 3:4-4(2003).
CC -!- FUNCTION: ABCG5 and ABCG8 form an obligate heterodimer that mediates
CC Mg(2+)- and ATP-dependent sterol transport across the cell membrane.
CC Plays an essential role in the selective transport of the dietary
CC cholesterol in and out of the enterocytes and in the selective sterol
CC excretion by the liver into bile. Required for normal sterol
CC homeostasis. The heterodimer with ABCG5 has ATPase activity.
CC {ECO:0000250|UniProtKB:Q9H221}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + cholesterol(in) + H2O = ADP + cholesterol(out) + H(+) +
CC phosphate; Xref=Rhea:RHEA:39051, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16113, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9DBM0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + sitosterol(in) = ADP + H(+) + phosphate +
CC sitosterol(out); Xref=Rhea:RHEA:39103, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:27693, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9DBM0};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9DBM0};
CC -!- SUBUNIT: Heterodimer with ABCG8. {ECO:0000250|UniProtKB:Q9H221}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9H221};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9H221}. Apical cell
CC membrane {ECO:0000250|UniProtKB:Q9H221}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9H221}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3;
CC IsoId=P58428-3; Sequence=Displayed;
CC Name=1;
CC IsoId=P58428-1; Sequence=VSP_008767;
CC Name=2;
CC IsoId=P58428-2; Sequence=VSP_008767, VSP_000054;
CC -!- TISSUE SPECIFICITY: Highest expression in liver, with lower levels in
CC small intestine and colon. {ECO:0000269|PubMed:12783625}.
CC -!- DOMAIN: A functional Walker motif (consensus sequence G-X-X-G-X-G-K-
CC [ST]-T) is expected to bind ATP. The essential Lys in this region is
CC not conserved in ABCG8 (G-S-S-G-C-R-A-S) and is not required for
CC transport activity mediated by the heterodimer with ABCG5.
CC {ECO:0000250|UniProtKB:Q9DBM0}.
CC -!- PTM: N-glycosylated. N-glycosylation is important for efficient export
CC out of the endoplasmic reticulum. {ECO:0000250|UniProtKB:Q9DBM0}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCG family.
CC Eye pigment precursor importer (TC 3.A.1.204) subfamily. {ECO:0000305}.
CC -!- CAUTION: Seems to have a defective ATP-binding region. {ECO:0000305}.
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DR EMBL; AF351785; AAK84831.2; -; mRNA.
DR EMBL; AY145899; AAN64276.1; -; Genomic_DNA.
DR EMBL; AF404109; AAK85393.1; -; Genomic_DNA.
DR RefSeq; NP_569098.2; NM_130414.2. [P58428-1]
DR AlphaFoldDB; P58428; -.
DR SMR; P58428; -.
DR STRING; 10116.ENSRNOP00000058587; -.
DR GlyGen; P58428; 1 site.
DR PaxDb; P58428; -.
DR PRIDE; P58428; -.
DR Ensembl; ENSRNOT00000007638; ENSRNOP00000007638; ENSRNOG00000005420. [P58428-1]
DR Ensembl; ENSRNOT00000061871; ENSRNOP00000058587; ENSRNOG00000005420. [P58428-3]
DR GeneID; 155192; -.
DR KEGG; rno:155192; -.
DR UCSC; RGD:620300; rat. [P58428-3]
DR CTD; 64241; -.
DR RGD; 620300; Abcg8.
DR eggNOG; KOG0061; Eukaryota.
DR GeneTree; ENSGT00940000159739; -.
DR HOGENOM; CLU_000604_57_9_1; -.
DR InParanoid; P58428; -.
DR OMA; RDTDDHM; -.
DR OrthoDB; 1022017at2759; -.
DR PhylomeDB; P58428; -.
DR Reactome; R-RNO-1369062; ABC transporters in lipid homeostasis.
DR PRO; PR:P58428; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000005420; Expressed in jejunum and 4 other tissues.
DR Genevisible; P58428; RN.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0043190; C:ATP-binding cassette (ABC) transporter complex; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:Ensembl.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:Ensembl.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0120020; F:cholesterol transfer activity; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0038183; P:bile acid signaling pathway; IEP:RGD.
DR GO; GO:0033344; P:cholesterol efflux; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; IEP:RGD.
DR GO; GO:0045796; P:negative regulation of intestinal cholesterol absorption; ISO:RGD.
DR GO; GO:0010949; P:negative regulation of intestinal phytosterol absorption; ISO:RGD.
DR GO; GO:0015914; P:phospholipid transport; ISO:RGD.
DR GO; GO:0014850; P:response to muscle activity; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0055092; P:sterol homeostasis; ISO:RGD.
DR GO; GO:0015918; P:sterol transport; ISS:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0070328; P:triglyceride homeostasis; IEP:RGD.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR013525; ABC_2_trans.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR043926; ABCG_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF01061; ABC2_membrane; 1.
DR Pfam; PF19055; ABC2_membrane_7; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Glycoprotein; Lipid transport;
KW Magnesium; Membrane; Metal-binding; Reference proteome; Translocase;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..694
FT /note="ATP-binding cassette sub-family G member 8"
FT /id="PRO_0000093398"
FT TOPO_DOM 1..437
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TRANSMEM 438..458
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TOPO_DOM 459..468
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TRANSMEM 469..489
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TOPO_DOM 490..518
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TRANSMEM 519..539
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TOPO_DOM 540..548
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TRANSMEM 549..569
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TOPO_DOM 570..576
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TRANSMEM 577..597
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TOPO_DOM 598..660
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TRANSMEM 661..681
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT TOPO_DOM 682..694
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9H221"
FT DOMAIN 91..335
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 436..684
FT /note="ABC transmembrane type-2"
FT CARBOHYD 640
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 56..77
FT /note="Missing (in isoform 1 and isoform 2)"
FT /evidence="ECO:0000303|PubMed:11452359"
FT /id="VSP_008767"
FT VAR_SEQ 398
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11452359"
FT /id="VSP_000054"
FT CONFLICT 3..4
FT /note="EK -> QT (in Ref. 3; AAK85393)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 694 AA; 78236 MW; 67F67C195F417587 CRC64;
MAEKTKEETQ LWNGTVLQDA SSLQDSVFSS ESDNSLYFTY SGQSNTLEVR DLTYQGGTCL
RSWGQEDPHM SLGLSESVDM ASQVPWFEQL AQFKLPWRSR GSQDSWDLGI RNLSFKVRSG
QMLAIIGSAG CGRATLLDVI TGRDHGGKMK SGQIWINGQP STPQLIQKCV AHVRQQDQLL
PNLTVRETLT FIAQMRLPKT FSQAQRDKRV EDVIAELRLR QCANTRVGNT YVRGVSGGER
RRVSIGVQLL WNPGILILDE PTSGLDSFTA HNLVRTLSRL AKGNRLVLIS LHQPRSDIFR
LFDLVLLMTS GTPIYLGVAQ HMVQYFTSIG YPCPRYSNPA DFYVDLTSID RRSKEQEVAT
MEKARLLAAL FLEKVQGFDD FLWKAEAKSL DTGTYAVSQT LTQDTNCGTA AELPGMIQQF
TTLIRRQISN DFRDLPTLFI HGAEACLMSL IIGFLYYGHA DKPLSFMDMA ALLFMIGALI
PFNVILDVVS KCHSERSLLY YELEDGLYTA GPYFFAKVLG ELPEHCAYVI IYGMPIYWLT
NLRPGPELFL LHFMLLWLVV FCCRTMALAA SAMLPTFHMS SFCCNALYNS FYLTAGFMIN
LNNLWIVPAW ISKMSFLRWC FSGLMQIQFN GHIYTTQIGN LTFSVPGDAM VTAMDLNSHP
LYAIYLIVIG ISCGFLSLYY LSLKFIKQKS IQDW
