ABCD2_MOUSE
ID ABCD2_MOUSE Reviewed; 741 AA.
AC Q61285; A0A0R4J0U5; Q8BQ63; Q8C4B6;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=ATP-binding cassette sub-family D member 2;
DE EC=3.1.2.- {ECO:0000250|UniProtKB:Q9UBJ2};
DE EC=7.6.2.- {ECO:0000250|UniProtKB:Q9UBJ2};
DE AltName: Full=Adrenoleukodystrophy-related protein;
GN Name=Abcd2; Synonyms=Aldr {ECO:0000303|PubMed:8577752};
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], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC STRAIN=DBA/2J;
RX PubMed=8577752; DOI=10.1073/pnas.93.3.1265;
RA Lombard-Platet G., Savary S., Sarde C.-O., Mandel J.-L., Chimini G.;
RT "A close relative of the adrenoleukodystrophy (ALD) gene codes for a
RT peroxisomal protein with a specific expression pattern.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:1265-1269(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, and Spinal ganglion;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17208939; DOI=10.1074/mcp.m600218-mcp200;
RA Lee J., Xu Y., Chen Y., Sprung R., Kim S.C., Xie S., Zhao Y.;
RT "Mitochondrial phosphoproteome revealed by an improved IMAC method and
RT MS/MS/MS.";
RL Mol. Cell. Proteomics 6:669-676(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, and Liver;
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).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=16223892; DOI=10.1093/hmg/ddi384;
RA Ferrer I., Kapfhammer J.P., Hindelang C., Kemp S., Troffer-Charlier N.,
RA Broccoli V., Callyzot N., Mooyer P., Selhorst J., Vreken P., Wanders R.J.,
RA Mandel J.L., Pujol A.;
RT "Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to
RT late-onset ataxia involving mitochondria, Golgi and endoplasmic reticulum
RT damage.";
RL Hum. Mol. Genet. 14:3565-3577(2005).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=18854420; DOI=10.1152/ajpendo.90736.2008;
RA Fourcade S., Ruiz M., Camps C., Schlueter A., Houten S.M., Mooyer P.A.,
RA Pampols T., Dacremont G., Wanders R.J., Giros M., Pujol A.;
RT "A key role for the peroxisomal ABCD2 transporter in fatty acid
RT homeostasis.";
RL Am. J. Physiol. 296:E211-E221(2009).
CC -!- FUNCTION: ATP-dependent transporter of the ATP-binding cassette (ABC)
CC family involved in the transport of very long chain fatty acid (VLCFA)-
CC CoA from the cytosol to the peroxisome lumen (By similarity). Like
CC ABCD1 seems to have fatty acyl-CoA thioesterase (ACOT) and ATPase
CC activities, according to this model, VLCFA-CoA as free VLCFA is
CC transpoted in an ATP-dependent manner into peroxisomes after the
CC hydrolysis of VLCFA-CoA mediated by the ACOT activity of ABCD2 (By
CC similarity). Shows overlapping substrate specificities with ABCD1
CC toward saturated fatty acids (FA) and monounsaturated FA (MUFA) but has
CC a distinct substrate preference for shorter VLCFA (C22:0) and
CC polyunsaturated fatty acid (PUFA) such as C22:6-CoA and C24:6-CoA (in
CC vitro) (By similarity). Thus, may play a role in regulation of VLCFAs
CC and energy metabolism namely, in the degradation and biosynthesis of
CC fatty acids by beta-oxidation (PubMed:18854420, PubMed:16223892).
CC {ECO:0000250|UniProtKB:P33897, ECO:0000250|UniProtKB:Q9UBJ2,
CC ECO:0000269|PubMed:16223892, ECO:0000269|PubMed:18854420}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a very long-chain fatty acyl-CoA + H2O = a very long-chain
CC fatty acid + CoA + H(+); Xref=Rhea:RHEA:67072, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:58950,
CC ChEBI:CHEBI:138261; Evidence={ECO:0000250|UniProtKB:Q9UBJ2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67073;
CC Evidence={ECO:0000250|UniProtKB:Q9UBJ2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a very long-chain fatty acid(in) + ATP + H2O = a very long-
CC chain fatty acid(out) + ADP + H(+) + phosphate; Xref=Rhea:RHEA:67080,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58950, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9UBJ2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67081;
CC Evidence={ECO:0000250|UniProtKB:Q9UBJ2};
CC -!- SUBUNIT: Homodimers. Homotetramers. The minimal functional unit is a
CC homodimer but the major oligomeric form in peroxisomal membrane is a
CC homotetramer. Forms heterotramers with ABCD1. Forms heterodimers with
CC ABCD3. In addition to tetramers, some larger molecular assemblies are
CC also found but represented only a minor fraction. Interacts with PEX19.
CC {ECO:0000250|UniProtKB:Q9UBJ2}.
CC -!- SUBCELLULAR LOCATION: Peroxisome membrane {ECO:0000269|PubMed:8577752};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in brain and adrenals, and
CC weakly expressed in liver. {ECO:0000269|PubMed:8577752}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice exhibit a late-onset cerebellar
CC and sensory ataxia, loss of Purkinje cells, dorsal root ganglia cell
CC degeneration, axonal degeneration in the spinal cord, and an
CC accumulation of very long chain fatty acids (C26:0 and C24:0) in dorsal
CC root ganglia cells, and reduced levels of C22:6omega3 in primary
CC neurons. {ECO:0000269|PubMed:16223892, ECO:0000269|PubMed:18854420}.
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}.
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DR EMBL; Z48670; CAA88589.1; -; mRNA.
DR EMBL; AK051445; BAC34641.1; -; mRNA.
DR EMBL; AK082588; BAC38542.1; -; mRNA.
DR EMBL; AC113102; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC019187; AAH19187.1; -; mRNA.
DR CCDS; CCDS27760.1; -.
DR RefSeq; NP_036124.2; NM_011994.2.
DR AlphaFoldDB; Q61285; -.
DR SMR; Q61285; -.
DR BioGRID; 205032; 3.
DR IntAct; Q61285; 4.
DR STRING; 10090.ENSMUSP00000068940; -.
DR GlyGen; Q61285; 2 sites.
DR iPTMnet; Q61285; -.
DR PhosphoSitePlus; Q61285; -.
DR SwissPalm; Q61285; -.
DR MaxQB; Q61285; -.
DR PaxDb; Q61285; -.
DR PRIDE; Q61285; -.
DR ProteomicsDB; 297498; -.
DR ProteomicsDB; 338909; -.
DR Antibodypedia; 42512; 272 antibodies from 31 providers.
DR DNASU; 26874; -.
DR Ensembl; ENSMUST00000069511; ENSMUSP00000068940; ENSMUSG00000055782.
DR GeneID; 26874; -.
DR KEGG; mmu:26874; -.
DR UCSC; uc007xhx.1; mouse.
DR CTD; 225; -.
DR MGI; MGI:1349467; Abcd2.
DR VEuPathDB; HostDB:ENSMUSG00000055782; -.
DR eggNOG; KOG0064; Eukaryota.
DR GeneTree; ENSGT00950000182955; -.
DR InParanoid; Q61285; -.
DR OMA; IPEMQNR; -.
DR OrthoDB; 309052at2759; -.
DR PhylomeDB; Q61285; -.
DR TreeFam; TF105205; -.
DR BRENDA; 7.6.2.4; 3474.
DR Reactome; R-MMU-1369062; ABC transporters in lipid homeostasis.
DR Reactome; R-MMU-9603798; Class I peroxisomal membrane protein import.
DR BioGRID-ORCS; 26874; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Abcd2; mouse.
DR PRO; PR:Q61285; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q61285; protein.
DR Bgee; ENSMUSG00000055782; Expressed in white adipose tissue and 193 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005778; C:peroxisomal membrane; ISO:MGI.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0047617; F:acyl-CoA hydrolase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:MGI.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005324; F:long-chain fatty acid transporter activity; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IMP:UniProtKB.
DR GO; GO:0015910; P:long-chain fatty acid import into peroxisome; IBA:GO_Central.
DR GO; GO:0043217; P:myelin maintenance; IMP:UniProtKB.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; IMP:UniProtKB.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IMP:UniProtKB.
DR GO; GO:1990535; P:neuron projection maintenance; IMP:UniProtKB.
DR GO; GO:0007031; P:peroxisome organization; IBA:GO_Central.
DR GO; GO:0032000; P:positive regulation of fatty acid beta-oxidation; IMP:UniProtKB.
DR GO; GO:2001280; P:positive regulation of unsaturated fatty acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
DR GO; GO:0042760; P:very long-chain fatty acid catabolic process; IMP:UniProtKB.
DR GO; GO:0000038; P:very long-chain fatty acid metabolic process; ISS:UniProtKB.
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; IPR031239; ABCD2.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11384:SF24; PTHR11384:SF24; 1.
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; Glycoprotein; Hydrolase; Lipid metabolism; Membrane;
KW Nucleotide-binding; Peroxisome; Phosphoprotein; Reference proteome;
KW Translocase; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..741
FT /note="ATP-binding cassette sub-family D member 2"
FT /id="PRO_0000093307"
FT TRANSMEM 107..127
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 251..271
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT TRANSMEM 351..371
FT /note="Helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 107..399
FT /note="ABC transmembrane type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 479..705
FT /note="ABC transporter"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 1..218
FT /note="Interaction with PEX19"
FT /evidence="ECO:0000250|UniProtKB:Q9UBJ2"
FT BINDING 512..519
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17208939"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 296
FT /note="H -> R (in Ref. 2; BAC38542)"
FT /evidence="ECO:0000305"
FT CONFLICT 737
FT /note="A -> P (in Ref. 1; CAA88589 and 4; AAH19187)"
SQ SEQUENCE 741 AA; 83457 MW; 24B9952F61AB49D9 CRC64;
MIHMLNAAAY RVKWTRSGAA KRAACLVAAA YALKTLYPII GKRLKQPGHR KAKAEAYSPA
ENREILHCTE IICKKPAPGL NAAFFKQLLE LRKILFPKLV TTETGWLCLH SVALISRTFL
SIYVAGLDGK IVKSIVEKKP RTFIIKLIKW LMIAIPATFV NSAIRYLECK LALAFRTRLV
DHAYETYFAN QTYYKVINMD GRLANPDQSL TEDIMMFSQS VAHLYSNLTK PILDVILTSY
TLIRTATSRG ASPIGPTLLA GLVVYATAKV LKACSPKFGS LVAEEAHRKG YLRYVHSRII
ANVEEIAFYR GHKVEMKQLQ KCYKALAYQM NLILSKRLWY IMIEQFLMKY VWSSCGLIMV
AIPIITATGF ADGDLEDGPK QAMVSDRTEA FTTARNLLAS GADAIERIMS SYKEITELAG
YTARVYNMFW VFDEVKRGIY KRTVTQEPEN HSKRGGNLEL PLSDTLAIKG TVIDVDHGII
CENVPIITPA GEVVASRLNF KVEEGMHLLI TGPNGCGKSS LFRILSGLWP VYEGVLYKPP
PQHMFYIPQR PYMSLGSLRD QVIYPDSADD MREKGYTDQD LERILHSVHL YHIVQREGGW
DAVMDWKDVL SGGEKQRMGM ARMFYHKPKY ALLDECTSAV SIDVEGKIFQ AAIGAGISLL
SITHRPSLWK YHTHLLQFDG EGGWRFEQLD TAIRLTLSEE KQKLESQLAG IPKMQQRLNE
LCKILGEDSV LKTIQTAEKT S
