ABCD2_RAT
ID ABCD2_RAT Reviewed; 741 AA.
AC Q9QY44; G3V7Z6;
DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 2.
DT 03-AUG-2022, entry version 118.
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:11342107}, Aldrp;
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], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11342107; DOI=10.1016/s0167-4781(00)00291-8;
RA Albet S., Bentejac M., Savary S., Gondcaille C., Netik A., Berger J.,
RA Szpirer C., Troffer-Charlier N., Bugaut M.;
RT "Rat adrenoleukodystrophy-related (ALDR) gene: full-length cDNA sequence
RT and new insight in expression.";
RL Biochim. Biophys. Acta 1517:257-269(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [5]
RP FUNCTION, SUBSTRATE SPECIFICITY, INTERACTION WITH ABCD1, AND MUTAGENESIS OF
RP ASP-207.
RX PubMed=21209459; DOI=10.1074/jbc.m110.211912;
RA Genin E.C., Geillon F., Gondcaille C., Athias A., Gambert P., Trompier D.,
RA Savary S.;
RT "Substrate specificity overlap and interaction between adrenoleukodystrophy
RT protein (ALDP/ABCD1) and adrenoleukodystrophy-related protein
RT (ALDRP/ABCD2).";
RL J. Biol. Chem. 286:8075-8084(2011).
RN [6]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=28258215; DOI=10.1074/jbc.m116.772806;
RA Geillon F., Gondcaille C., Raas Q., Dias A.M.M., Pecqueur D., Truntzer C.,
RA Lucchi G., Ducoroy P., Falson P., Savary S., Trompier D.;
RT "Peroxisomal ATP-binding cassette transporters form mainly tetramers.";
RL J. Biol. Chem. 292:6965-6977(2017).
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) (PubMed:21209459). Thus, plays a role in regulation of VLCFAs
CC and energy metabolism namely, in the degradation and biosynthesis of
CC fatty acids by beta-oxidation (PubMed:21209459). However,the actual
CC function of ABCD2 in vivo is still unclear (By similarity).
CC {ECO:0000250|UniProtKB:P33897, ECO:0000250|UniProtKB:Q9UBJ2,
CC ECO:0000269|PubMed:21209459}.
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 (PubMed:28258215). Homotetramers (PubMed:28258215).
CC The minimal functional unit is a homodimer but the major oligomeric
CC form in peroxisomal membrane is a homotetramer. Forms heterotetramers
CC with ABCD1 (PubMed:28258215). Forms heterodimers with ABCD1
CC (PubMed:21209459). Forms heterodimers with ABCD3 (By similarity). In
CC addition to tetramers, some larger molecular assemblies are also found
CC but represented only a minor fraction (PubMed:28258215). Interacts with
CC PEX19; facilitates ABCD2 insertion into the peroxisome membrane (By
CC similarity). {ECO:0000250|UniProtKB:Q9UBJ2,
CC ECO:0000269|PubMed:21209459, ECO:0000269|PubMed:28258215}.
CC -!- SUBCELLULAR LOCATION: Peroxisome membrane
CC {ECO:0000269|PubMed:28258215}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in brain and testis.
CC {ECO:0000269|PubMed:11342107}.
CC -!- DEVELOPMENTAL STAGE: Expression is high in the liver before weaning and
CC very low in adult rats; the reverse developmental regulation is
CC observed in the brain. {ECO:0000269|PubMed:11342107}.
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; AF131294; AAF22142.1; -; mRNA.
DR EMBL; AC120768; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474027; EDL76598.1; -; Genomic_DNA.
DR RefSeq; NP_203503.1; NM_033352.1.
DR AlphaFoldDB; Q9QY44; -.
DR SMR; Q9QY44; -.
DR BioGRID; 249916; 1.
DR STRING; 10116.ENSRNOP00000021064; -.
DR GlyGen; Q9QY44; 2 sites.
DR iPTMnet; Q9QY44; -.
DR PhosphoSitePlus; Q9QY44; -.
DR PaxDb; Q9QY44; -.
DR PRIDE; Q9QY44; -.
DR Ensembl; ENSRNOT00000021064; ENSRNOP00000021064; ENSRNOG00000015538.
DR GeneID; 84356; -.
DR KEGG; rno:84356; -.
DR CTD; 225; -.
DR RGD; 69244; Abcd2.
DR eggNOG; KOG0064; Eukaryota.
DR GeneTree; ENSGT00950000182955; -.
DR HOGENOM; CLU_007587_1_1_1; -.
DR InParanoid; Q9QY44; -.
DR OMA; IPEMQNR; -.
DR OrthoDB; 309052at2759; -.
DR PhylomeDB; Q9QY44; -.
DR TreeFam; TF105205; -.
DR Reactome; R-RNO-1369062; ABC transporters in lipid homeostasis.
DR Reactome; R-RNO-9603798; Class I peroxisomal membrane protein import.
DR PRO; PR:Q9QY44; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Proteomes; UP000234681; Chromosome 7.
DR Bgee; ENSRNOG00000015538; Expressed in quadriceps femoris and 18 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005778; C:peroxisomal membrane; IDA:HGNC-UCL.
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:RGD.
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; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; ISO:RGD.
DR GO; GO:0015910; P:long-chain fatty acid import into peroxisome; IBA:GO_Central.
DR GO; GO:0043217; P:myelin maintenance; ISS:UniProtKB.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; ISS:UniProtKB.
DR GO; GO:1990535; P:neuron projection maintenance; ISS:UniProtKB.
DR GO; GO:0007031; P:peroxisome organization; IBA:GO_Central.
DR GO; GO:0032000; P:positive regulation of fatty acid beta-oxidation; ISS:UniProtKB.
DR GO; GO:2001280; P:positive regulation of unsaturated fatty acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
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; IMP: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; Membrane; Nucleotide-binding;
KW Peroxisome; Reference proteome; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..741
FT /note="ATP-binding cassette sub-family D member 2"
FT /id="PRO_0000093308"
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 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 MUTAGEN 207
FT /note="D->H: Does not affect ABCD1 interaction."
FT /evidence="ECO:0000269|PubMed:21209459"
FT CONFLICT 455
FT /note="R -> G (in Ref. 1; AAF22142)"
SQ SEQUENCE 741 AA; 83468 MW; D84E24386A5E024A CRC64;
MIHMLNAAAY RVKWTRSGAA KRAACLVAAA YALKTLYPIL GRRLKQPGHR KAKAEDYPPA
ENRERLHCTE IICKKPAPGL NADFFKQLLE LRKILFPKLV TTETGWLCLH SVALISRTFL
SIYVAGLDGK IVKSIVEKKP RTFIIKLVKW LMIAVPATFV NSAIRYLECK LALAFRTRLV
DHAYETYFAN QTYYKVINMD GRLANPDQSL TEDIMMFSQS VAHLYSNLTK PILDVILTSY
TLIRTATSRG ASPIGPTLLA GLVVYATAKV LKACSPKFGT LVAEEAHRKG YLRYVHSRII
ANVEEIAFYR GHKVEMKQLQ KCYKALAYQM NLILSKRLWY IMIEQFLMKY VWSGCGLIMV
AIPIITATGF ADGDLEDGPK QAMVSDRTEA FTTARNLLAS GADAIERIMS SYKEITELAG
YTARVYNMFW VFDEVKRGIY KRTVTQEPEN NSKSRGGLEL PLSDTLAIKG TVIDVDHGIL
CENVPIITPA GEVVASSLNF KVEEGMHLLI TGPNGCGKSS LFRILSGLWP VYEGVLYKPP
PQHMFYIPQR PYMSLGSLRD QVIYPDSVDD MHEKGYTDRD LEHILHSVHL YHIVQREGGW
DAVMDWKDVL SGGEKQRMGM ARMFYHKPKY ALLDECTSAV SIDVEGKIFQ AAIGAGISLL
SITHRPSLWK YHTHLLQFDG EGGWRFEQLD TAIRLTLSEE KQKLESQLAG IPKMQQRLNE
LCKILGEDSV LKTIQTAEDT S
