ABCD4_MOUSE
ID ABCD4_MOUSE Reviewed; 606 AA.
AC O89016; E9QKU3;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Lysosomal cobalamin transporter ABCD4 {ECO:0000250|UniProtKB:O14678};
DE EC=7.6.2.8 {ECO:0000250|UniProtKB:O14678};
DE AltName: Full=ATP-binding cassette sub-family D member 4;
DE AltName: Full=PMP70-related protein;
DE Short=P70R;
DE AltName: Full=Peroxisomal membrane protein 1-like;
DE Short=PXMP1-L;
DE AltName: Full=Peroxisomal membrane protein 69;
DE Short=PMP69;
GN Name=Abcd4 {ECO:0000312|MGI:MGI:1349217}; Synonyms=Pxmp1l;
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].
RX PubMed=9738957; DOI=10.1016/s0014-5793(98)00873-4;
RA Holzinger A., Muntau A., Mayerhofer P., Kammerer S., Albet S., Bugaut M.,
RA Roscher A.A.;
RT "The mouse gene encoding the peroxisomal membrane protein 1-like protein
RT (PXMP1-L): cDNA cloning, genomic organization and comparative expression
RT studies.";
RL FEBS Lett. 433:179-183(1998).
RN [2]
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Lysosomal membrane protein that transports cobalamin (Vitamin
CC B12) from the lysosomal lumen to the cytosol in an ATP-dependent
CC manner. Targeted by LMBRD1 lysosomal chaperone from the endoplasmic
CC reticulum to the lysosomal membrane. Then forms a complex with
CC lysosomal chaperone LMBRD1 and cytosolic MMACHC to transport cobalamin
CC across the lysosomal membrane. {ECO:0000250|UniProtKB:O14678}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an R-cob(III)alamin(out) + ATP + H2O = ADP + an R-
CC cob(III)alamin(in) + H(+) + phosphate; Xref=Rhea:RHEA:17873,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:140785, ChEBI:CHEBI:456216;
CC EC=7.6.2.8; Evidence={ECO:0000250|UniProtKB:O14678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17874;
CC Evidence={ECO:0000250|UniProtKB:O14678};
CC -!- SUBUNIT: Homodimer or heterodimer. Interacts with LMBRD1; this
CC interaction induces the translocation of ABCD4 from the ER to the
CC lysosome membrane. Interacts with LMBRD1 and MMACHC; this interaction
CC ensures the transport of cobalamin from the lysosome to the cytosol.
CC {ECO:0000250|UniProtKB:O14678}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O14678}; Multi-pass membrane protein
CC {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:O14678}; Multi-
CC pass membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCD family.
CC Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: Originally proposed to be a peroxisomal protein (By
CC similarity). Recent studies have suggested its localization to the
CC endoplasmic reticulum and within the lysosome (By similarity).
CC {ECO:0000250|UniProtKB:O14678}.
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DR EMBL; AJ001166; CAA04570.1; -; mRNA.
DR EMBL; AC110564; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS26047.1; -.
DR RefSeq; NP_033018.2; NM_008992.2.
DR AlphaFoldDB; O89016; -.
DR SMR; O89016; -.
DR STRING; 10090.ENSMUSP00000021666; -.
DR iPTMnet; O89016; -.
DR PhosphoSitePlus; O89016; -.
DR EPD; O89016; -.
DR MaxQB; O89016; -.
DR PaxDb; O89016; -.
DR PeptideAtlas; O89016; -.
DR PRIDE; O89016; -.
DR ProteomicsDB; 285956; -.
DR Antibodypedia; 184; 243 antibodies from 30 providers.
DR DNASU; 19300; -.
DR Ensembl; ENSMUST00000021666; ENSMUSP00000021666; ENSMUSG00000021240.
DR GeneID; 19300; -.
DR KEGG; mmu:19300; -.
DR UCSC; uc007ofo.2; mouse.
DR CTD; 5826; -.
DR MGI; MGI:1349217; Abcd4.
DR VEuPathDB; HostDB:ENSMUSG00000021240; -.
DR eggNOG; KOG0060; Eukaryota.
DR GeneTree; ENSGT00950000182955; -.
DR HOGENOM; CLU_007587_7_0_1; -.
DR InParanoid; O89016; -.
DR OMA; RFWISAR; -.
DR OrthoDB; 309052at2759; -.
DR PhylomeDB; O89016; -.
DR TreeFam; TF105205; -.
DR Reactome; R-MMU-9758881; Uptake of dietary cobalamins into enterocytes.
DR Reactome; R-MMU-9758890; Transport of RCbl within the body.
DR BioGRID-ORCS; 19300; 5 hits in 73 CRISPR screens.
DR ChiTaRS; Abcd4; mouse.
DR PRO; PR:O89016; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; O89016; protein.
DR Bgee; ENSMUSG00000021240; Expressed in metanephric proximal tubule and 213 other tissues.
DR ExpressionAtlas; O89016; baseline and differential.
DR Genevisible; O89016; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005778; C:peroxisomal membrane; IBA:GO_Central.
DR GO; GO:0015420; F:ABC-type vitamin B12 transporter activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
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:0005324; F:long-chain fatty acid transporter activity; IBA:GO_Central.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0009235; P:cobalamin metabolic process; ISS:UniProtKB.
DR GO; GO:0015889; P:cobalamin transport; ISS:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IBA:GO_Central.
DR GO; GO:0015910; P:long-chain fatty acid import into peroxisome; IBA:GO_Central.
DR GO; GO:0007031; P:peroxisome organization; IBA:GO_Central.
DR GO; GO:0042760; P:very long-chain fatty acid catabolic process; IBA:GO_Central.
DR Gene3D; 1.20.1560.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF06472; ABC_membrane_2; 1.
DR Pfam; PF00005; ABC_tran; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF90123; SSF90123; 1.
DR PROSITE; PS50929; ABC_TM1F; 1.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Endoplasmic reticulum; Lysosome; Membrane; Nucleotide-binding;
KW Reference proteome; Translocase; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..606
FT /note="Lysosomal cobalamin transporter ABCD4"
FT /id="PRO_0000093313"
FT TRANSMEM 43..63
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 76..96
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 190..210
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 279..299
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 314..334
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 39..332
FT /note="ABC transmembrane type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 389..603
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 421..428
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CONFLICT 43
FT /note="F -> L (in Ref. 1; CAA04570)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 606 AA; 68583 MW; F93CF046ADA776A0 CRC64;
MAVPGPTARA GARPRLDLQL VQRFVRIQKV FFPSWSSQNV LMFMTLLCVT LLEQLVIYQV
GLIPSQYYGV LGNKDLDGFK ALTLLAVTLI VLNSTLKSFD QFTCNLLYVS WRKDLTEHLH
HLYFRARVYY TLNVLRDDID NPDQRISQDV ERFCRQLSSV TSKLIISPFT LTYYTYQCFQ
STGWLGPVSI FGYFIVGTMV NKTLMGPIVT KLVQQEKLEG DFRFKHMQIR VNAEPAAFYR
AGLVEHMRTD RRLQRLLQTQ RELMSRELWL YIGINTFDYL GSILSYVVIA IPIFSGVYGD
LSPTELSTLV SKNAFVCIYL ISCFTQLIDL STTLSDVAGY THRIGELQEA LLDMSRKSQD
CEALGESEWD LDKTPGCPTT EPSDTAFLLD RVSILAPSSD KPLIKDLSLK ICEGQSLLIT
GNTGTGKTSL LRVLGGLWEG MKGSVQMLAD FGPHGVLFLP QKPFFTDGTL REQVIYPLKE
IYPDSGSADD ERIVRFLELA GLSSLVARTG GLDQQVDWNW YDVLSPGEMQ RLSFARLFYL
QPKYAVLDEA TSALTEEAES ELYRIGQQLG MTFISVGHRP SLEKFHSWVL RLHGGGSWEL
TRIKLE
