ACOX2_MOUSE
ID ACOX2_MOUSE Reviewed; 681 AA.
AC Q9QXD1; Q8VCB0;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Peroxisomal acyl-coenzyme A oxidase 2 {ECO:0000250|UniProtKB:Q99424};
DE EC=1.17.99.3 {ECO:0000250|UniProtKB:P97562};
DE AltName: Full=3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanoyl-CoA 24-hydroxylase;
DE AltName: Full=3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanoyl-CoA oxidase {ECO:0000250|UniProtKB:O02767};
DE AltName: Full=Trihydroxycoprostanoyl-CoA oxidase {ECO:0000250|UniProtKB:P97562, ECO:0000312|EMBL:CAB65251.1};
DE Short=THCA-CoA oxidase {ECO:0000250|UniProtKB:O02767};
DE Short=THCCox;
GN Name=Acox2 {ECO:0000312|MGI:MGI:1934852};
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].
RA Amery L., Van Veldhoven P.P.;
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, 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 [4]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-66; LYS-137; LYS-303; LYS-453;
RP LYS-561 AND LYS-667, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Oxidizes the CoA esters of the bile acid intermediates
CC di- and tri-hydroxycoprostanic acids (By similarity). Capable of
CC oxidizing short as well as long chain 2-methyl branched fatty acids (By
CC similarity). {ECO:0000250|UniProtKB:P97562}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oyl-
CC CoA + A + H2O = (24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy-
CC 5beta-cholestan-26-oyl-CoA + AH2; Xref=Rhea:RHEA:15733,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:58677, ChEBI:CHEBI:59807; EC=1.17.99.3;
CC Evidence={ECO:0000250|UniProtKB:P97562};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15734;
CC Evidence={ECO:0000250|UniProtKB:P97562};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25S)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oyl-
CC CoA + O2 = (24E)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-
CC en-26-oyl-CoA + H2O2; Xref=Rhea:RHEA:46728, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:59879, ChEBI:CHEBI:77251;
CC Evidence={ECO:0000250|UniProtKB:O02767};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46729;
CC Evidence={ECO:0000250|UniProtKB:O02767};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P07872};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P07872}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000250|UniProtKB:Q99424}.
CC -!- PTM: Acetylation of Lys-667 is observed in liver mitochondria from
CC fasted mice but not from fed mice.
CC -!- SIMILARITY: Belongs to the acyl-CoA oxidase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ238492; CAB65251.1; -; mRNA.
DR EMBL; BC021339; AAH21339.1; -; mRNA.
DR CCDS; CCDS36801.1; -.
DR RefSeq; NP_001155139.1; NM_001161667.1.
DR RefSeq; NP_444345.2; NM_053115.2.
DR RefSeq; XP_006518171.1; XM_006518108.3.
DR AlphaFoldDB; Q9QXD1; -.
DR SMR; Q9QXD1; -.
DR STRING; 10090.ENSMUSP00000126464; -.
DR CarbonylDB; Q9QXD1; -.
DR iPTMnet; Q9QXD1; -.
DR PhosphoSitePlus; Q9QXD1; -.
DR SwissPalm; Q9QXD1; -.
DR jPOST; Q9QXD1; -.
DR MaxQB; Q9QXD1; -.
DR PaxDb; Q9QXD1; -.
DR PeptideAtlas; Q9QXD1; -.
DR PRIDE; Q9QXD1; -.
DR ProteomicsDB; 285844; -.
DR Antibodypedia; 31666; 323 antibodies from 33 providers.
DR DNASU; 93732; -.
DR Ensembl; ENSMUST00000022271; ENSMUSP00000022271; ENSMUSG00000021751.
DR Ensembl; ENSMUST00000164598; ENSMUSP00000126464; ENSMUSG00000021751.
DR GeneID; 93732; -.
DR KEGG; mmu:93732; -.
DR UCSC; uc007sey.2; mouse.
DR CTD; 8309; -.
DR MGI; MGI:1934852; Acox2.
DR VEuPathDB; HostDB:ENSMUSG00000021751; -.
DR eggNOG; KOG0136; Eukaryota.
DR GeneTree; ENSGT00940000160985; -.
DR HOGENOM; CLU_014629_3_1_1; -.
DR InParanoid; Q9QXD1; -.
DR OMA; PMMRGKL; -.
DR OrthoDB; 416859at2759; -.
DR PhylomeDB; Q9QXD1; -.
DR TreeFam; TF300672; -.
DR Reactome; R-MMU-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-MMU-389887; Beta-oxidation of pristanoyl-CoA.
DR Reactome; R-MMU-9033241; Peroxisomal protein import.
DR BioGRID-ORCS; 93732; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Acox2; mouse.
DR PRO; PR:Q9QXD1; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q9QXD1; protein.
DR Bgee; ENSMUSG00000021751; Expressed in left lobe of liver and 63 other tissues.
DR ExpressionAtlas; Q9QXD1; baseline and differential.
DR Genevisible; Q9QXD1; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0033791; F:3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoyl-CoA 24-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0003997; F:acyl-CoA oxidase activity; IBA:GO_Central.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0005504; F:fatty acid binding; ISO:MGI.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:UniProtKB.
DR GO; GO:0016401; F:palmitoyl-CoA oxidase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; ISO:MGI.
DR GO; GO:0033540; P:fatty acid beta-oxidation using acyl-CoA oxidase; ISO:MGI.
DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central.
DR GO; GO:0010942; P:positive regulation of cell death; ISS:UniProtKB.
DR GO; GO:1902884; P:positive regulation of response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0000038; P:very long-chain fatty acid metabolic process; IBA:GO_Central.
DR CDD; cd01150; AXO; 1.
DR Gene3D; 1.10.540.10; -; 1.
DR Gene3D; 2.40.110.10; -; 1.
DR InterPro; IPR034171; ACO.
DR InterPro; IPR029320; Acyl-CoA_ox_N.
DR InterPro; IPR006091; Acyl-CoA_Oxase/DH_mid-dom.
DR InterPro; IPR046373; Acyl-CoA_Oxase/DH_mid-dom_sf.
DR InterPro; IPR012258; Acyl-CoA_oxidase.
DR InterPro; IPR002655; Acyl-CoA_oxidase_C.
DR InterPro; IPR036250; AcylCo_DH-like_C.
DR InterPro; IPR037069; AcylCoA_DH/ox_N_sf.
DR InterPro; IPR009100; AcylCoA_DH/oxidase_NM_dom.
DR PANTHER; PTHR10909; PTHR10909; 1.
DR Pfam; PF01756; ACOX; 1.
DR Pfam; PF02770; Acyl-CoA_dh_M; 1.
DR Pfam; PF14749; Acyl-CoA_ox_N; 1.
DR PIRSF; PIRSF000168; Acyl-CoA_oxidase; 1.
DR SUPFAM; SSF47203; SSF47203; 2.
DR SUPFAM; SSF56645; SSF56645; 1.
PE 1: Evidence at protein level;
KW Acetylation; FAD; Fatty acid metabolism; Flavoprotein; Lipid metabolism;
KW Oxidoreductase; Peroxisome; Phosphoprotein; Reference proteome.
FT CHAIN 1..681
FT /note="Peroxisomal acyl-coenzyme A oxidase 2"
FT /id="PRO_0000204682"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 679..681
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 12..28
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99424"
FT MOD_RES 13
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99424"
FT MOD_RES 66
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 137
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 303
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 453
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 561
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 667
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 26
FT /note="R -> W (in Ref. 1; CAB65251)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 681 AA; 76863 MW; 32C65231326BA0FB CRC64;
MGNPGDRVSL GETWSREVHP DIDSERHSPS FSVERLTNIL DGGIPNTELR RRVESLIQRD
PVFNLKHLYF MTRDELYEDA VQKRFHLEKL AWSLGWSEDG PERIYADRVL AGYNNLNLHG
IAMNAIRSLG SDEQIAKWGQ LGKNFQIITT YAQTELGHGT YLQGLETEAT YDATTQEFVI
HSPTMTSIKW WPGDLGRTVT HAVVLAHLIC LGARHGMHAF IVPIRSLEDH TPLPGITVGD
IGPKMGFENI DNGFLRLNHV RVPRENMLSR FAEVLPDGTY QRLGTPQSNY LGMLVTRVQL
LYKGFLPTLQ KACTIAVRYA VIRHQSRLRP SDPEAKILEY QTQQQKLLPQ LAVSYALHFM
TTSLLQFFHS SYSDILKRDF SLLPELHALS TGMKAMSSDF CAQGTEICRR ACGGHGYSKL
SGLPTLVTQA IASCTYEGEN TVLYLQVARF LMKSYLQAQV SPGSIPQKPL PQSVMYLATP
RPARCPAQTA ADFRCPEVYT TAWAYVSARL IRDATQHTQT LMRSGVDQYD AWNQTSVIHL
QAAKAHCYFL TVRNFKEAVE KLDNEPEIQR VLQNLCDLYA LNGILTNSGD FLHDGFLSGA
QVDMARTAFL DLLPLIRKDA ILLTDAFDFS DHCLNSALGC YDGHVYQRLF EWAQKSPANT
QENPAYKKYI RPLMQSWKPK L
