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   27-MAR-2024, entry version 162.
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; 10090-ENSMUSP00000021666; -.
DR   PeptideAtlas; O89016; -.
DR   ProteomicsDB; 285956; -.
DR   Pumba; O89016; -.
DR   Antibodypedia; 184; 271 antibodies from 30 providers.
DR   DNASU; 19300; -.
DR   Ensembl; ENSMUST00000021666.6; ENSMUSP00000021666.5; ENSMUSG00000021240.7.
DR   GeneID; 19300; -.
DR   KEGG; mmu:19300; -.
DR   UCSC; uc007ofo.2; mouse.
DR   AGR; MGI:1349217; -.
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; KQFHDME; -.
DR   OrthoDB; 7698at2759; -.
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 78 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 217 other cell types or tissues.
DR   ExpressionAtlas; O89016; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
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:0016887; F:ATP hydrolysis activity; IEA:InterPro.
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   CDD; cd03223; ABCD_peroxisomal_ALDP; 1.
DR   Gene3D; 1.20.1560.10; ABC transporter type 1, transmembrane domain; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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   PANTHER; PTHR11384; ATP-BINDING CASSETTE, SUB-FAMILY D MEMBER; 1.
DR   PANTHER; PTHR11384:SF71; LYSOSOMAL COBALAMIN TRANSPORTER ABCD4; 1.
DR   Pfam; PF06472; ABC_membrane_2; 1.
DR   Pfam; PF00005; ABC_tran; 1.
DR   SMART; SM00382; AAA; 1.
DR   SUPFAM; SSF90123; ABC transporter transmembrane region; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   PROSITE; PS50929; ABC_TM1F; 1.
DR   PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR   PROSITE; PS50893; ABC_TRANSPORTER_2; 1.
DR   Genevisible; O89016; MM.
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
//