ACX12_CAEEL
ID ACX12_CAEEL Reviewed; 661 AA.
AC O62137;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Acyl-coenzyme A oxidase acox-1.2 {ECO:0000305};
DE EC=1.3.3.- {ECO:0000269|PubMed:25775534, ECO:0000269|PubMed:27551084};
GN Name=acox-1.2 {ECO:0000312|WormBase:F08A8.2};
GN Synonyms=acox-2 {ECO:0000312|WormBase:F08A8.2};
GN ORFNames=F08A8.2 {ECO:0000312|WormBase:F08A8.2};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY,
RP SUBUNIT, INTERACTION WITH ACOX-1.1, INDUCTION, AND MUTAGENESIS OF
RP 496-TRP--LEU-661.
RX PubMed=25775534; DOI=10.1073/pnas.1423951112;
RA Zhang X., Feng L., Chinta S., Singh P., Wang Y., Nunnery J.K.,
RA Butcher R.A.;
RT "Acyl-CoA oxidase complexes control the chemical message produced by
RT Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:3955-3960(2015).
RN [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=29863473; DOI=10.7554/elife.33286;
RA Zhou Y., Wang Y., Zhang X., Bhar S., Jones Lipinski R.A., Han J., Feng L.,
RA Butcher R.A.;
RT "Biosynthetic tailoring of existing ascaroside pheromones alters their
RT biological function in C. elegans.";
RL Elife 7:0-0(2018).
RN [4] {ECO:0007744|PDB:5K3J}
RP X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS) OF MUTANT ALA-432 IN COMPLEX WITH
RP ATP; FAD AND ASCAROSIDE-OMEGA-C5-COA, FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, ACTIVITY REGULATION, PATHWAY, SUBUNIT, AND MUTAGENESIS OF
RP GLU-432.
RX PubMed=27551084; DOI=10.1073/pnas.1608262113;
RA Zhang X., Li K., Jones R.A., Bruner S.D., Butcher R.A.;
RT "Structural characterization of acyl-CoA oxidases reveals a direct link
RT between pheromone biosynthesis and metabolic state in Caenorhabditis
RT elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:10055-10060(2016).
CC -!- FUNCTION: Involved in the first step of peroxisomal beta-oxidation by
CC catalyzing the desaturation of fatty acid-derived side chains of
CC ascaroside pheromones, which regulates development and behavior
CC (PubMed:25775534, PubMed:27551084). Specifically, shortens ascarosides
CC with 5-carbon omega side chain (asc-omega-C5) (PubMed:25775534,
CC PubMed:27551084). Does not shorten indol-3-carbonyl(IC)-ascaroside with
CC 7-carbon or 9-carbon side chains (PubMed:29863473). Does not catalyze
CC the desaturation of fatty acids or hydroxylated fatty acids
CC (PubMed:25775534, PubMed:27551084). {ECO:0000269|PubMed:25775534,
CC ECO:0000269|PubMed:27551084, ECO:0000269|PubMed:29863473}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=asc-omegaC5-CoA + O2 = asc-omegaDeltaC5-CoA + H2O2;
CC Xref=Rhea:RHEA:66212, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:140060, ChEBI:CHEBI:166969;
CC Evidence={ECO:0000269|PubMed:25775534, ECO:0000269|PubMed:27551084};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:27551084};
CC -!- ACTIVITY REGULATION: Activated by ATP (PubMed:27551084). ATP binding
CC leads to a conformational change that promotes FAD cofactor binding and
CC enzyme activity (PubMed:27551084). ATP binding likely occurs during
CC acox-1.2 folding and/or dimer formation (PubMed:27551084). The
CC preference for processing substrates with shorter fatty acid chains is
CC likely due to the closed conformation of the active site
CC (PubMed:27551084). {ECO:0000269|PubMed:27551084}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=175 uM for asc-omega-C5-CoA (at 30 degrees Celsius and pH 7.4)
CC {ECO:0000269|PubMed:25775534};
CC KM=152 uM for asc-omega-C5-CoA (at 30 degrees Celsius, pH 7.4 and in
CC complex with acox-1.1) {ECO:0000269|PubMed:25775534};
CC Note=kcat is 364 sec(-1) with asc-omega-C5-CoA (at 30 degrees Celsius
CC and pH 7.4) (PubMed:25775534). kcat is 478 sec(-1) with asc-omega-C5-
CC CoA (at 30 degrees Celsius, pH 7.4 and in complex with acox-1.1)
CC (PubMed:25775534). {ECO:0000269|PubMed:25775534};
CC -!- PATHWAY: Lipid metabolism; peroxisomal fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:25775534, ECO:0000269|PubMed:27551084}.
CC -!- SUBUNIT: Homodimer (Probable) (PubMed:27551084). Forms a heterodimer
CC with acox-1.1 (PubMed:25775534). {ECO:0000269|PubMed:25775534,
CC ECO:0000269|PubMed:27551084, ECO:0000305|PubMed:25775534}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000250|UniProtKB:O62140}.
CC -!- INDUCTION: Induced by high temperatures (25 degrees Celsius)
CC (PubMed:25775534). Down-regulated in dauer conditions
CC (PubMed:25775534). {ECO:0000269|PubMed:25775534}.
CC -!- SIMILARITY: Belongs to the acyl-CoA oxidase family.
CC {ECO:0000255|PIRNR:PIRNR000168}.
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DR EMBL; BX284601; CAB16864.2; -; Genomic_DNA.
DR RefSeq; NP_493262.2; NM_060861.3.
DR PDB; 5K3J; X-ray; 2.68 A; A/B=1-661.
DR PDBsum; 5K3J; -.
DR AlphaFoldDB; O62137; -.
DR SMR; O62137; -.
DR STRING; 6239.F08A8.2; -.
DR EPD; O62137; -.
DR PaxDb; O62137; -.
DR PeptideAtlas; O62137; -.
DR EnsemblMetazoa; F08A8.2.1; F08A8.2.1; WBGene00008565.
DR GeneID; 173163; -.
DR KEGG; cel:CELE_F08A8.2; -.
DR UCSC; F08A8.2; c. elegans.
DR CTD; 173163; -.
DR WormBase; F08A8.2; CE43421; WBGene00008565; acox-1.2.
DR eggNOG; KOG0136; Eukaryota.
DR GeneTree; ENSGT00940000168827; -.
DR HOGENOM; CLU_014629_3_1_1; -.
DR InParanoid; O62137; -.
DR OMA; GRRFFTM; -.
DR OrthoDB; 416859at2759; -.
DR PhylomeDB; O62137; -.
DR BRENDA; 1.3.3.6; 1045.
DR Reactome; R-CEL-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-CEL-389887; Beta-oxidation of pristanoyl-CoA.
DR Reactome; R-CEL-9033241; Peroxisomal protein import.
DR UniPathway; UPA00661; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00008565; Expressed in larva and 2 other tissues.
DR GO; GO:0005777; C:peroxisome; IBA:GO_Central.
DR GO; GO:0003997; F:acyl-CoA oxidase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA: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:1904070; P:ascaroside biosynthetic process; IDA:UniProtKB.
DR GO; GO:0033540; P:fatty acid beta-oxidation using acyl-CoA oxidase; IDA:UniProtKB.
DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central.
DR Gene3D; 1.10.540.10; -; 1.
DR Gene3D; 2.40.110.10; -; 1.
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 3D-structure; ATP-binding; FAD; Fatty acid metabolism; Flavoprotein;
KW Lipid metabolism; Nucleotide-binding; Oxidoreductase; Peroxisome;
KW Reference proteome.
FT CHAIN 1..661
FT /note="Acyl-coenzyme A oxidase acox-1.2"
FT /id="PRO_0000452303"
FT MOTIF 659..661
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 432
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PIRSR:PIRSR000168-1"
FT BINDING 147..150
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT BINDING 155..156
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT BINDING 189
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|PIRSR:PIRSR000168-2,
FT ECO:0000269|PubMed:27551084, ECO:0007744|PDB:5K3J"
FT BINDING 283..286
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT BINDING 293
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT BINDING 318
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT BINDING 338..341
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT BINDING 340
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT BINDING 390
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:O62140"
FT BINDING 394
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:O62140"
FT BINDING 402
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT BINDING 409
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT BINDING 431..432
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT BINDING 434
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT BINDING 525..528
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT BINDING 573
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0007744|PDB:5K3J"
FT SITE 299
FT /note="Important for asc-omega-C5-CoA binding and thus
FT substrate specificity"
FT /evidence="ECO:0000269|PubMed:27551084,
FT ECO:0000312|PDB:5K3J"
FT MUTAGEN 432
FT /note="E->A: Increases ATP and FAD binding."
FT /evidence="ECO:0000269|PubMed:27551084"
FT MUTAGEN 496..661
FT /note="Missing: In gk386052; increases production of asc-
FT omega-C5 and reduces the production of asc-omega-C3."
FT /evidence="ECO:0000269|PubMed:25775534"
FT HELIX 12..18
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 25..32
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 36..49
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 66..82
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 84..87
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 93..103
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 112..116
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 118..125
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 128..133
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 135..139
FT /evidence="ECO:0007829|PDB:5K3J"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:5K3J"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:5K3J"
FT TURN 169..172
FT /evidence="ECO:0007829|PDB:5K3J"
FT STRAND 173..177
FT /evidence="ECO:0007829|PDB:5K3J"
FT STRAND 184..189
FT /evidence="ECO:0007829|PDB:5K3J"
FT TURN 190..194
FT /evidence="ECO:0007829|PDB:5K3J"
FT STRAND 196..208
FT /evidence="ECO:0007829|PDB:5K3J"
FT STRAND 210..219
FT /evidence="ECO:0007829|PDB:5K3J"
FT TURN 223..225
FT /evidence="ECO:0007829|PDB:5K3J"
FT STRAND 232..236
FT /evidence="ECO:0007829|PDB:5K3J"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:5K3J"
FT STRAND 248..259
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 284..286
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 287..315
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 332..334
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 336..340
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 343..363
FT /evidence="ECO:0007829|PDB:5K3J"
FT TURN 364..370
FT /evidence="ECO:0007829|PDB:5K3J"
FT STRAND 371..373
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 379..405
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 406..412
FT /evidence="ECO:0007829|PDB:5K3J"
FT TURN 414..416
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 418..426
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 427..429
FT /evidence="ECO:0007829|PDB:5K3J"
FT TURN 430..432
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 435..450
FT /evidence="ECO:0007829|PDB:5K3J"
FT TURN 451..456
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 458..460
FT /evidence="ECO:0007829|PDB:5K3J"
FT TURN 463..465
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 466..468
FT /evidence="ECO:0007829|PDB:5K3J"
FT STRAND 478..480
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 481..507
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 512..518
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 520..543
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 549..569
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 571..574
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 581..597
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 598..600
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 601..606
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 612..615
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 626..636
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 638..641
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 646..650
FT /evidence="ECO:0007829|PDB:5K3J"
FT HELIX 652..661
FT /evidence="ECO:0007829|PDB:5K3J"
SQ SEQUENCE 661 AA; 75091 MW; EF005188A6A87472 CRC64;
MANRSIRDGD NPELLEERRM ATFDTDKMAA VIYGSEEFAR RRREITDAVS KIPELADIKP
YPFLTREEKV TEGTRKISIL TKYLNQLIDR DNEEESLHLH REVIGYEGHP FALHDALFIP
TLQSQASDEQ QEKWLERARR REIIGCYAQT ELGHGSNLRN LETTAVYDIA SQEFVLHTPT
TTALKWWPGA LGKSCNYALV VAELIIKRNN YGPHFFMVQL RDEKTHIPLK GVTVGDIGPK
MNFNAADNGY LGLNNLRVPR TNLLMRHCKV EADGTYVKPP HAKIGYSGMV KIRSQMAMEQ
GLFLAHALTI AARYSAVRRQ GHLDDKQVEV KVLDYQTQQH RLFPSLARAY AFIFTGFETI
HLYSQLLKDV DMGNTSGMAD LHALTSGLKS VVAHETGEGI EQARMACGGH GYSMASYISV
VYGIAIGGCT YEGENMVMLL QLARYLVKSV ELIKAGKAKK LGPVASYLAD KSDETDLTSL
NGYVKMFENM ARRQAWKATE KFLKLMESGE SREVAWNKSA VELTRASRLH TRLFIIEAFM
RRVSRIEDIP VKEVLTDLLH LHVNYELLDV ATYALEFMSF TQLDYVRDQL YLYLEKIRPN
AVSLVDSFQI SDMQLRSVLG RRDGHVYENL FKWAKSSPLN NADVLPSVEK YLKPMMEKAK
L
