ID ACOX1_DROME Reviewed; 669 AA.
AC Q7KML2; Q95ST5;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 1.
DT 24-JAN-2024, entry version 126.
DE RecName: Full=Probable peroxisomal acyl-coenzyme A oxidase 1 {ECO:0000305};
DE EC=1.3.3.6 {ECO:0000269|PubMed:32169171};
GN ORFNames=CG5009;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=10731138; DOI=10.1126/science.287.5461.2222;
RA Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M.,
RA Harvey D.A.;
RT "A Drosophila complementary DNA resource.";
RL Science 287:2222-2224(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-544 AND SER-551, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17372656; DOI=10.1039/b617545g;
RA Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A.,
RA Eng J.K., Aebersold R., Tao W.A.;
RT "An integrated chemical, mass spectrometric and computational strategy for
RT (quantitative) phosphoproteomics: application to Drosophila melanogaster
RT Kc167 cells.";
RL Mol. Biosyst. 3:275-286(2007).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF ASN-250, AND CATALYTIC ACTIVITY.
RX PubMed=32169171; DOI=10.1016/j.neuron.2020.02.021;
RG Members of Undiagnosed Diseases Network;
RA Chung H.L., Wangler M.F., Marcogliese P.C., Jo J., Ravenscroft T.A.,
RA Zuo Z., Duraine L., Sadeghzadeh S., Li-Kroeger D., Schmidt R.E.,
RA Pestronk A., Rosenfeld J.A., Burrage L., Herndon M.J., Chen S.,
RA Shillington A., Vawter-Lee M., Hopkin R., Rodriguez-Smith J.,
RA Henrickson M., Lee B., Moser A.B., Jones R.O., Watkins P., Yoo T., Mar S.,
RA Choi M., Bucelli R.C., Yamamoto S., Lee H.K., Prada C.E., Chae J.H.,
RA Vogel T.P., Bellen H.J.;
RT "Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via
RT Different Mechanisms.";
RL Neuron 106:589.e6-606.e6(2020).
CC -!- FUNCTION: Catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-
CC CoAs. First enzyme of the fatty acid beta-oxidation pathway.
CC {ECO:0000269|PubMed:32169171}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2,3-saturated acyl-CoA + O2 = a (2E)-enoyl-CoA + H2O2;
CC Xref=Rhea:RHEA:38959, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:58856, ChEBI:CHEBI:65111; EC=1.3.3.6;
CC Evidence={ECO:0000269|PubMed:32169171};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38960;
CC Evidence={ECO:0000269|PubMed:32169171};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P07872};
CC -!- PATHWAY: Lipid metabolism; peroxisomal fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:32169171}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:32169171}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000250}. Nucleus
CC {ECO:0000269|PubMed:32169171}.
CC -!- TISSUE SPECIFICITY: Expressed in glia. {ECO:0000269|PubMed:32169171}.
CC -!- DEVELOPMENTAL STAGE: Expressed in glia. {ECO:0000269|PubMed:32169171}.
CC -!- DISRUPTION PHENOTYPE: Most mutants die as pupae. They have increased
CC VLCFA, loss of vision and have glial loss and reduced neuronal
CC survival. {ECO:0000269|PubMed:32169171}.
CC -!- SIMILARITY: Belongs to the acyl-CoA oxidase family. {ECO:0000305}.
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DR EMBL; AE013599; AAF57794.1; -; Genomic_DNA.
DR EMBL; AF145642; AAD38617.1; -; mRNA.
DR EMBL; AY060596; AAL28144.1; -; mRNA.
DR RefSeq; NP_611264.2; NM_137420.3.
DR AlphaFoldDB; Q7KML2; -.
DR SMR; Q7KML2; -.
DR BioGRID; 62713; 56.
DR DIP; DIP-18503N; -.
DR IntAct; Q7KML2; 25.
DR STRING; 7227.FBpp0088517; -.
DR iPTMnet; Q7KML2; -.
DR PaxDb; 7227-FBpp0088517; -.
DR DNASU; 37028; -.
DR EnsemblMetazoa; FBtr0089548; FBpp0088517; FBgn0027572.
DR GeneID; 37028; -.
DR KEGG; dme:Dmel_CG5009; -.
DR UCSC; CG5009-RA; d. melanogaster.
DR AGR; FB:FBgn0027572; -.
DR CTD; 51; -.
DR FlyBase; FBgn0027572; CG5009.
DR VEuPathDB; VectorBase:FBgn0027572; -.
DR eggNOG; KOG0136; Eukaryota.
DR GeneTree; ENSGT00940000166003; -.
DR HOGENOM; CLU_014629_3_1_1; -.
DR InParanoid; Q7KML2; -.
DR OMA; WNMYNVL; -.
DR OrthoDB; 5777at2759; -.
DR PhylomeDB; Q7KML2; -.
DR Reactome; R-DME-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-DME-2046106; alpha-linolenic acid (ALA) metabolism.
DR Reactome; R-DME-389887; Beta-oxidation of pristanoyl-CoA.
DR Reactome; R-DME-390247; Beta-oxidation of very long chain fatty acids.
DR Reactome; R-DME-9033241; Peroxisomal protein import.
DR UniPathway; UPA00661; -.
DR BioGRID-ORCS; 37028; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 37028; -.
DR PRO; PR:Q7KML2; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0027572; Expressed in capitellum (Drosophila) and 30 other cell types or tissues.
DR ExpressionAtlas; Q7KML2; baseline and differential.
DR Genevisible; Q7KML2; DM.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0003997; F:acyl-CoA oxidase activity; ISS:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0005504; F:fatty acid binding; IBA:GO_Central.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; ISS:FlyBase.
DR GO; GO:0033540; P:fatty acid beta-oxidation using acyl-CoA oxidase; IMP:FlyBase.
DR GO; GO:0009062; P:fatty acid catabolic process; IMP:FlyBase.
DR GO; GO:0019395; P:fatty acid oxidation; ISS:UniProtKB.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; ISS:UniProtKB.
DR GO; GO:0050665; P:hydrogen peroxide biosynthetic process; IMP:FlyBase.
DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0006693; P:prostaglandin metabolic process; ISS:UniProtKB.
DR GO; GO:0140493; P:very long-chain fatty acid beta-oxidation; IMP:FlyBase.
DR CDD; cd01150; AXO; 1.
DR Gene3D; 1.10.540.10; Acyl-CoA dehydrogenase/oxidase, N-terminal domain; 1.
DR Gene3D; 2.40.110.10; Butyryl-CoA Dehydrogenase, subunit A, domain 2; 1.
DR Gene3D; 1.20.140.10; Butyryl-CoA Dehydrogenase, subunit A, domain 3; 2.
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_sf.
DR PANTHER; PTHR10909; ELECTRON TRANSPORT OXIDOREDUCTASE; 1.
DR PANTHER; PTHR10909:SF250; PEROXISOMAL ACYL-COENZYME A OXIDASE 1; 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; Acyl-CoA dehydrogenase C-terminal domain-like; 2.
DR SUPFAM; SSF56645; Acyl-CoA dehydrogenase NM domain-like; 1.
PE 1: Evidence at protein level;
KW FAD; Fatty acid metabolism; Flavoprotein; Lipid metabolism; Nucleus;
KW Oxidoreductase; Peroxisome; Phosphoprotein; Reference proteome.
FT CHAIN 1..669
FT /note="Probable peroxisomal acyl-coenzyme A oxidase 1"
FT /id="PRO_0000348222"
FT MOTIF 667..669
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 434
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P07872"
FT BINDING 152
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P07872"
FT BINDING 191
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P07872"
FT MOD_RES 544
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:17372656"
FT MOD_RES 551
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17372656"
FT MUTAGEN 250
FT /note="N->S: No effect on VLCA levels. Increases
FT dimerization. Induces a high level of ROS and severe axonal
FT loss. Lethal."
FT /evidence="ECO:0000269|PubMed:32169171"
FT CONFLICT 191
FT /note="G -> C (in Ref. 4; AAL28144)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 669 AA; 74287 MW; 10DEE761437E92FE CRC64;
MPAKPVNPDL QKERSTATFN PREFSVLWAG GEERFKEKKA LEKLFLEDPA LQDDLPISYL
SHKELYEHSL RKACIIGEKI RKLRADGEDG VDTYNALLGG SLGSAILKEG NPLALHYVMF
VPTIMGQGTM DQQVEWLSKA WDCEIIGTYA QTELGHGTFL RGLETRADYD ASTQEFVINT
PSLSAYKWWP GGLGHTANHA VVVAQLYTKG EFRGLAPFIV QLRDSDTHRP MPGIDIGDIG
TKLGMKGVNN GYLGLKNVRV PLNNMLMKNQ QVLPDGTYVA PKNSVLTYGT MMFVRCALIR
DTAQSLAKAS TIATRYSAVR RQSPIDPNQP EPQIMDHTTQ QLKLFPQIAK AIVFKTTGDG
IWNMYNVISG EIEQGNLDRL PEMHALSCCL KAICSADAAA GVETCRLSCG GHGYMDCSNF
PTIYGMTTAV CTYEGENTVM LLQTARYLVK VYGQALNGEK LVPTVSYISD AINQTKFVNF
DGSLRSIVKA FQFVAANKTR IAYEQIELRR KQGYGTEVAA NLCGTFLTAA ADLHGRAFLA
QTAYTELLAL SREVSPELAE VLKVVLELYL VDACLNRIGD FLRFIDLTDQ DVTKLEVRLE
NCLKRFRPNA VSLVDSFDLH DRVLDSALGA YDGNVYEHIF ESTKKNPLNK EPVNGAFHKY
LKPFMKAHL
//
