ABCG4_MOUSE
ID ABCG4_MOUSE Reviewed; 646 AA.
AC Q91WA9; Q8K4E1; Q8VBS9;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=ATP-binding cassette subfamily G member 4;
DE EC=7.6.2.- {ECO:0000269|PubMed:15210959, ECO:0000269|PubMed:17916878, ECO:0000269|PubMed:18039927};
DE AltName: Full=ATP-binding cassette transporter White2 {ECO:0000303|Ref.2};
GN Name=Abcg4 {ECO:0000312|MGI:MGI:1890594};
GN Synonyms=White2 {ECO:0000303|Ref.2};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11856881; DOI=10.1159/000048816;
RA Annilo T., Tammur J., Hutchinson A., Rzhetsky A., Dean M., Allikmets R.;
RT "Human and mouse orthologs of a new ATP-binding cassette gene, ABCG4.";
RL Cytogenet. Cell Genet. 94:196-201(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE, AND NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RA Kameya S., Naggert J.K., Nishina P.M.;
RT "Cloning and expression analysis of a novel ABC transporter, White2, that
RT is expressed in the mouse retina.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Retina;
RX PubMed=12183068; DOI=10.1016/s0167-4889(02)00269-0;
RA Oldfield S., Lowry C., Ruddick J., Lightman S.;
RT "ABCG4: a novel human white family ABC-transporter expressed in the brain
RT and eye.";
RL Biochim. Biophys. Acta 1591:175-179(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=12137944; DOI=10.1016/s0378-1119(02)00719-9;
RA Yoshikawa M., Yabuuchi H., Kuroiwa A., Ikegami Y., Sai Y., Tamai I.,
RA Tsuji A., Matsuda Y., Yoshida H., Ishikawa T.;
RT "Molecular and cytogenetic characterization of the mouse ATP-binding
RT cassette transporter Abcg4.";
RL Gene 293:67-75(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC STRAIN=129;
RA Lu K., Patel S.B.;
RT "Genomic organization, expression and charectarization of murine ABCG4
RT gene.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15210959; DOI=10.1073/pnas.0403506101;
RA Wang N., Lan D., Chen W., Matsuura F., Tall A.R.;
RT "ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol
RT efflux to high-density lipoproteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:9774-9779(2004).
RN [9]
RP DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=18039927; DOI=10.1096/fj.07-9944com;
RA Wang N., Yvan-Charvet L., Luetjohann D., Mulder M., Vanmierlo T., Kim T.W.,
RA Tall A.R.;
RT "ATP-binding cassette transporters G1 and G4 mediate cholesterol and
RT desmosterol efflux to HDL and regulate sterol accumulation in the brain.";
RL FASEB J. 22:1073-1082(2008).
RN [10]
RP MISCELLANEOUS, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, CATALYTIC
RP ACTIVITY, AND FUNCTION.
RX PubMed=17916878; DOI=10.1194/jlr.m700364-jlr200;
RA Tarr P.T., Edwards P.A.;
RT "ABCG1 and ABCG4 are coexpressed in neurons and astrocytes of the CNS and
RT regulate cholesterol homeostasis through SREBP-2.";
RL J. Lipid Res. 49:169-182(2008).
RN [11]
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=19633360; DOI=10.1194/jlr.m900250-jlr200;
RA Bojanic D.D., Tarr P.T., Gale G.D., Smith D.J., Bok D., Chen B.,
RA Nusinowitz S., Loevgren-Sandblom A., Bjoerkhem I., Edwards P.A.;
RT "Differential expression and function of ABCG1 and ABCG4 during development
RT and aging.";
RL J. Lipid Res. 51:169-181(2010).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=29042617; DOI=10.1038/s41598-017-13750-0;
RA Dodacki A., Wortman M., Saubamea B., Chasseigneaux S., Nicolic S.,
RA Prince N., Lochus M., Raveu A.L., Decleves X., Scherrmann J.M., Patel S.B.,
RA Bourasset F.;
RT "Expression and function of Abcg4 in the mouse blood-brain barrier: role in
RT restricting the brain entry of amyloid-beta peptide.";
RL Sci. Rep. 7:13393-13393(2017).
CC -!- FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC)
CC family that may be involved in the cellular efflux of sterols, in
CC particular cholesterol and desmosterol (a cholesterol precursor), to
CC high-density lipoprotein (HDL) (PubMed:15210959, PubMed:18039927,
CC PubMed:17916878). May play an important role in the removal of amyloid-
CC beta peptides from brain, in a process that can be antagonized by
CC desmosterol. However it is unclear whether ABCG4 can directly transport
CC amyloid-beta peptides or whether peptide export may be facilitated due
CC to changes in the membrane lipid environment (PubMed:29042617). Induces
CC apoptosis in various cells (By similarity).
CC {ECO:0000250|UniProtKB:Q9H172, ECO:0000269|PubMed:15210959,
CC ECO:0000269|PubMed:17916878, ECO:0000269|PubMed:18039927,
CC ECO:0000269|PubMed:29042617}.
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:0000269|PubMed:15210959, ECO:0000269|PubMed:17916878,
CC ECO:0000269|PubMed:18039927};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39052;
CC Evidence={ECO:0000305|PubMed:15210959, ECO:0000305|PubMed:18039927};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + desmosterol(in) + H2O = ADP + desmosterol(out) + H(+) +
CC phosphate; Xref=Rhea:RHEA:67932, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17737, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:18039927};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67933;
CC Evidence={ECO:0000305|PubMed:18039927};
CC -!- SUBUNIT: Half-transporter that forms a functional transporter via
CC homo- or heterodimerization. Homodimer. Heterodimers with ABCG1.
CC {ECO:0000250|UniProtKB:Q9H172}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9H172};
CC Multi-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:17916878}; Multi-pass membrane protein
CC {ECO:0000255}. Endosome membrane {ECO:0000269|PubMed:17916878}; Multi-
CC pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain, in particular in
CC neurons, microglia and astrocytes (PubMed:11856881, PubMed:12183068,
CC PubMed:18039927, PubMed:17916878). Expressed on blood brain barrier
CC endothelial cells (PubMed:29042617). Expressed in the spleen
CC (PubMed:11856881). {ECO:0000269|PubMed:11856881,
CC ECO:0000269|PubMed:12183068, ECO:0000269|PubMed:17916878,
CC ECO:0000269|PubMed:18039927, ECO:0000269|PubMed:29042617}.
CC -!- DEVELOPMENTAL STAGE: Highly but transiently expressed in enterocytes
CC and hemopoietic cells populating the liver during development, but is
CC absent when animals are fully developed. Highly expressed in the eyes
CC of the developing embryos as early as 12.5 dpc and developing CNS.
CC {ECO:0000269|PubMed:19633360}.
CC -!- DISRUPTION PHENOTYPE: Abcg4 deficiency does not significantly affect
CC the levels of sterols in the brain except for brain lathosterol levels,
CC which are slightly elevated (PubMed:18039927). Abcg1/Abcg4 double
CC knockout mice display significant accumulation of 24(S)-
CC hydroxycholesterol (24S-HC) and 27-hydroxy-cholesterol (27-HC) in
CC addition to the cholesterol synthesis intermediates, desmosterol,
CC lanosterol and lathosterol (PubMed:19633360, PubMed:18039927).
CC {ECO:0000269|PubMed:18039927, ECO:0000269|PubMed:19633360}.
CC -!- MISCELLANEOUS: Whether ABCG4 is an LXR target gene, is still under
CC debate. Studies performed in monocytes, and in one astrocyte cell line
CC indicated that ABCG4 expression could be up-regulated by oxysterols and
CC other LXR ligands (By similarity). However, subsequent observations in
CC a number of different cell types (primary mouse cells, oligodendrocytes
CC and neuron-like cell lines) have not confirmed this observation
CC (PubMed:17916878) (By similarity). {ECO:0000250|UniProtKB:D3ZCM3,
CC ECO:0000250|UniProtKB:Q9H172, ECO:0000269|PubMed:17916878}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCG family.
CC Eye pigment precursor importer (TC 3.A.1.204) subfamily. {ECO:0000305}.
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DR EMBL; AY040865; AAK91781.1; -; mRNA.
DR EMBL; AF411084; AAL57369.1; -; mRNA.
DR EMBL; AF378330; AAO13805.1; -; mRNA.
DR EMBL; AJ426047; CAD19779.2; -; mRNA.
DR EMBL; AF425077; AAN03012.1; -; mRNA.
DR EMBL; AH011944; AAN31516.1; -; Genomic_DNA.
DR EMBL; AF425078; AAN31516.1; JOINED; Genomic_DNA.
DR EMBL; AC124577; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016200; AAH16200.2; -; mRNA.
DR CCDS; CCDS23101.1; -.
DR RefSeq; NP_620405.3; NM_138955.3.
DR RefSeq; XP_011240723.1; XM_011242421.2.
DR AlphaFoldDB; Q91WA9; -.
DR SMR; Q91WA9; -.
DR STRING; 10090.ENSMUSP00000124647; -.
DR PhosphoSitePlus; Q91WA9; -.
DR MaxQB; Q91WA9; -.
DR PaxDb; Q91WA9; -.
DR PRIDE; Q91WA9; -.
DR ProteomicsDB; 335265; -.
DR Antibodypedia; 32624; 202 antibodies from 31 providers.
DR DNASU; 192663; -.
DR Ensembl; ENSMUST00000034648; ENSMUSP00000034648; ENSMUSG00000032131.
DR Ensembl; ENSMUST00000161354; ENSMUSP00000124647; ENSMUSG00000032131.
DR GeneID; 192663; -.
DR KEGG; mmu:192663; -.
DR UCSC; uc009pcp.1; mouse.
DR CTD; 64137; -.
DR MGI; MGI:1890594; Abcg4.
DR VEuPathDB; HostDB:ENSMUSG00000032131; -.
DR eggNOG; KOG0061; Eukaryota.
DR GeneTree; ENSGT00940000157853; -.
DR HOGENOM; CLU_000604_57_6_1; -.
DR InParanoid; Q91WA9; -.
DR OMA; VTDVDHI; -.
DR OrthoDB; 324553at2759; -.
DR PhylomeDB; Q91WA9; -.
DR TreeFam; TF105210; -.
DR Reactome; R-MMU-1369062; ABC transporters in lipid homeostasis.
DR BioGRID-ORCS; 192663; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Abcg4; mouse.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q91WA9; protein.
DR Bgee; ENSMUSG00000032131; Expressed in retinal neural layer and 149 other tissues.
DR ExpressionAtlas; Q91WA9; baseline and differential.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:BHF-UCL.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0034041; F:ABC-type sterol transporter activity; IMP:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:MGI.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0071403; P:cellular response to high density lipoprotein particle stimulus; IDA:BHF-UCL.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0033344; P:cholesterol efflux; IMP:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IDA:BHF-UCL.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:BHF-UCL.
DR GO; GO:0015918; P:sterol transport; IMP:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
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 SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Cytoplasmic vesicle; Endosome; Membrane;
KW Nucleotide-binding; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..646
FT /note="ATP-binding cassette subfamily G member 4"
FT /id="PRO_0000453165"
FT TOPO_DOM 1..393
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 394..414
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 415..425
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 426..446
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 447..472
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 473..493
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 494..503
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 504..524
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 525..532
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 533..553
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 554..617
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 618..638
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 639..646
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 61..301
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 102..109
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CONFLICT 601..603
FT /note="DPQ -> GPT (in Ref. 5; AAN03012/AAN31516)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 646 AA; 72098 MW; ED83A4C4301ED6FB CRC64;
MAEKALEAVG CGLGPGAVAM AVTLEDGAEP PVLTTHLKKV ENHITEAQRF SHLPKRSAVD
IEFVELSYSV REGPCWRKRG YKTLLKCLSG KFCRRELIGI MGPSGAGKST FMNILAGYRE
SGMKGQILVN GRPRELRTFR KMSCYIMQDD MLLPHLTVLE AMMVSANLKL SEKQEVKKEL
VTEILTALGL MSCSHTRTAL LSGGQRKRLA IALELVNNPP VMFFDEPTSG LDSASCFQVV
SLMKSLAHGG RTVICTIHQP SAKLFEMFDK LYILSQGQCI FKGVVTNLIP YLKGLGLHCP
TYHNPADFII EVASGEYGDL NPMLFRAVQN GLCTMAEKKS SPGKNELPAH CPTCPPELDP
IESHTFATST LTQFCILFRR TFLSILRDTV LTHLRFMSHV LIGVLIGLLY LHIGDDASKV
FNNTGFLFFS MLFLMFAALM PTVLTFPLEM AVFMREHLNY WYTLKAYYLA KTMADVPFQV
VCPVVYCSIV YWMTGQPAET SRFLLFSALA IATALVAQSL GLLIGAASTS LQVATFVGPV
TAIPVLLFSG FFVSFKTIPT YLQWSSYLSY VRYGFEGLIL TIYGMERGHL TCLDEQCPFR
DPQIILRELD VEEAKLYMDF LVLGIFFLAL RLLAYLVLRY RVKSER
