ACOX1_PHACI
ID ACOX1_PHACI Reviewed; 661 AA.
AC Q8HYL8; Q8HYL7;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 2.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Peroxisomal acyl-coenzyme A oxidase 1 {ECO:0000250|UniProtKB:Q15067};
DE Short=AOX {ECO:0000303|PubMed:12758125};
DE EC=1.3.3.6 {ECO:0000269|PubMed:12758125};
DE AltName: Full=Palmitoyl-CoA oxidase {ECO:0000250|UniProtKB:Q15067};
DE AltName: Full=Peroxisomal fatty acyl-CoA oxidase;
DE AltName: Full=Straight-chain acyl-CoA oxidase;
GN Name=ACOX1;
OS Phascolarctos cinereus (Koala).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Metatheria; Diprotodontia; Phascolarctidae; Phascolarctos.
OX NCBI_TaxID=38626;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, CATALYTIC ACTIVITY
RP (ISOFORMS 1 AND 2), BIOPHYSICOCHEMICAL PROPERTIES (ISOFORMS 1 AND 2),
RP PATHWAY, COFACTOR, AND SUBCELLULAR LOCATION.
RC TISSUE=Liver;
RX PubMed=12758125; DOI=10.1016/s0378-1119(03)00491-8;
RA Ngo S.N.T., McKinnon R.A., Stupans I.;
RT "Identification and cloning of two forms of liver peroxisomal fatty Acyl
RT CoA oxidase from the koala (Phascolarctos cinereus).";
RL Gene 309:91-99(2003).
CC -!- FUNCTION: Involved in the initial and rate-limiting step of peroxisomal
CC beta-oxidation of straight-chain saturated and unsaturated very-long-
CC chain fatty acids (PubMed:12758125). Catalyzes the desaturation of
CC fatty acyl-CoAs such as palmitoyl-CoA (hexadecanoyl-CoA) to 2-trans-
CC enoyl-CoAs ((2E)-enoyl-CoAs) such as (2E)-hexadecenoyl-CoA, and donates
CC electrons directly to molecular oxygen (O(2)), thereby producing
CC hydrogen peroxide (H(2)O(2)) (PubMed:12758125). Isoform 2 shows higher
CC activity with hexadecanoyl-CoA as substrate than isoform 1
CC (PubMed:12758125). {ECO:0000269|PubMed:12758125}.
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
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:12758125};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38960;
CC Evidence={ECO:0000305|PubMed:12758125};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
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:12758125};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38960;
CC Evidence={ECO:0000305|PubMed:12758125};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=hexadecanoyl-CoA + O2 = (2E)-hexadecenoyl-CoA + H2O2;
CC Xref=Rhea:RHEA:40167, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57379, ChEBI:CHEBI:61526;
CC Evidence={ECO:0000269|PubMed:12758125};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40168;
CC Evidence={ECO:0000305|PubMed:12758125};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=hexadecanoyl-CoA + O2 = (2E)-hexadecenoyl-CoA + H2O2;
CC Xref=Rhea:RHEA:40167, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57379, ChEBI:CHEBI:61526;
CC Evidence={ECO:0000269|PubMed:12758125};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40168;
CC Evidence={ECO:0000305|PubMed:12758125};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + O2 = (2E)-dodecenoyl-CoA + H2O2;
CC Xref=Rhea:RHEA:40171, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57330, ChEBI:CHEBI:57375;
CC Evidence={ECO:0000250|UniProtKB:Q15067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40172;
CC Evidence={ECO:0000250|UniProtKB:Q15067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + octanoyl-CoA = (2E)-octenoyl-CoA + H2O2;
CC Xref=Rhea:RHEA:40175, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57386, ChEBI:CHEBI:62242;
CC Evidence={ECO:0000250|UniProtKB:Q15067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40176;
CC Evidence={ECO:0000250|UniProtKB:Q15067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=decanoyl-CoA + O2 = (2E)-decenoyl-CoA + H2O2;
CC Xref=Rhea:RHEA:40179, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:61406, ChEBI:CHEBI:61430;
CC Evidence={ECO:0000250|UniProtKB:Q15067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40180;
CC Evidence={ECO:0000250|UniProtKB:Q15067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + tetradecanoyl-CoA = (2E)-tetradecenoyl-CoA + H2O2;
CC Xref=Rhea:RHEA:40183, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57385, ChEBI:CHEBI:61405;
CC Evidence={ECO:0000250|UniProtKB:Q15067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40184;
CC Evidence={ECO:0000250|UniProtKB:Q15067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanedioyl-CoA + O2 = (2E)-hexadecenedioyl-CoA + H2O2;
CC Xref=Rhea:RHEA:40275, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:77075, ChEBI:CHEBI:77085;
CC Evidence={ECO:0000250|UniProtKB:Q15067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40276;
CC Evidence={ECO:0000250|UniProtKB:Q15067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + tetracosanoyl-CoA = (2E)-tetracosenoyl-CoA + H2O2;
CC Xref=Rhea:RHEA:40319, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:65052, ChEBI:CHEBI:74693;
CC Evidence={ECO:0000250|UniProtKB:P07872};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40320;
CC Evidence={ECO:0000250|UniProtKB:P07872};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glutaryl-CoA + O2 = (2E)-glutaconyl-CoA + H2O2;
CC Xref=Rhea:RHEA:40315, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57353, ChEBI:CHEBI:57378;
CC Evidence={ECO:0000250|UniProtKB:P07872};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40316;
CC Evidence={ECO:0000250|UniProtKB:P07872};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexanoyl-CoA + O2 = (2E)-hexenoyl-CoA + H2O2;
CC Xref=Rhea:RHEA:40311, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:62077, ChEBI:CHEBI:62620;
CC Evidence={ECO:0000250|UniProtKB:P07872};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40312;
CC Evidence={ECO:0000250|UniProtKB:P07872};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + octadecanoyl-CoA = (2E)-octadecenoyl-CoA + H2O2;
CC Xref=Rhea:RHEA:38971, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:57394, ChEBI:CHEBI:71412;
CC Evidence={ECO:0000250|UniProtKB:P07872};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38972;
CC Evidence={ECO:0000250|UniProtKB:P07872};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + O2 =
CC (2E,5Z,8Z,11Z,14Z,17Z)-icosahexaenoyl-CoA + H2O2;
CC Xref=Rhea:RHEA:69643, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:73862, ChEBI:CHEBI:187901;
CC Evidence={ECO:0000250|UniProtKB:Q15067};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69644;
CC Evidence={ECO:0000250|UniProtKB:Q15067};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA + O2 =
CC (2E,6Z,9Z,12Z,15Z,18Z,21Z)-tetracosaheptaenoyl-CoA + H2O2;
CC Xref=Rhea:RHEA:39119, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:74086, ChEBI:CHEBI:76360;
CC Evidence={ECO:0000250|UniProtKB:Q9R0H0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39120;
CC Evidence={ECO:0000250|UniProtKB:Q9R0H0};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:12758125};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 1]:
CC Kinetic parameters:
CC KM=38 uM for hexadecanoyl-CoA (palmitoyl-CoA)
CC {ECO:0000269|PubMed:12758125};
CC Vmax=677 nmol/min/g enzyme using hexadecanoyl-CoA (palmitoyl-CoA) as
CC substrate {ECO:0000269|PubMed:12758125};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 2]:
CC Kinetic parameters:
CC KM=28 uM for hexadecanoyl-CoA (palmitoyl-CoA)
CC {ECO:0000269|PubMed:12758125};
CC Vmax=1499 nmol/min/g enzyme using hexadecanoyl-CoA (palmitoyl-CoA) as
CC substrate {ECO:0000269|PubMed:12758125};
CC -!- PATHWAY: Lipid metabolism; peroxisomal fatty acid beta-oxidation.
CC {ECO:0000305|PubMed:12758125}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with LONP2 (By
CC similarity). {ECO:0000250|UniProtKB:P07872,
CC ECO:0000250|UniProtKB:Q15067}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:12758125}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=AOX2;
CC IsoId=Q8HYL8-2; Sequence=Displayed;
CC Name=2; Synonyms=AOX1;
CC IsoId=Q8HYL8-1; Sequence=VSP_042478;
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; AF463453; AAO15576.1; -; mRNA.
DR EMBL; AF463454; AAO15577.1; -; mRNA.
DR AlphaFoldDB; Q8HYL8; -.
DR SMR; Q8HYL8; -.
DR BRENDA; 1.3.3.6; 4730.
DR UniPathway; UPA00661; -.
DR Proteomes; UP000515140; Unplaced.
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; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0009062; P:fatty acid catabolic process; ISS:UniProtKB.
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; ISS:UniProtKB.
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; ISS:UniProtKB.
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; Alternative splicing; FAD; Fatty acid metabolism;
KW Flavoprotein; Lipid metabolism; Oxidoreductase; Peroxisome; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..661
FT /note="Peroxisomal acyl-coenzyme A oxidase 1"
FT /id="PRO_0000204679"
FT MOTIF 659..661
FT /note="Microbody targeting signal"
FT ACT_SITE 421
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P07872"
FT BINDING 139
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P07872"
FT BINDING 178
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P07872"
FT MOD_RES 89
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 90
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 159
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 216
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 241
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 255
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15067"
FT MOD_RES 267
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15067"
FT MOD_RES 272
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 349
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 437
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q15067"
FT MOD_RES 437
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 446
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 446
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 512
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 512
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 637
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 637
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 643
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 652
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT MOD_RES 655
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0H0"
FT VAR_SEQ 90..131
FT /note="KPQLINFVEPVGLTYSMFIPTLLDQGTTAQQQKWLPPTQGLQ -> NFVHRG
FT RPEPLDLHLGMFLPTLLHQATQEQQERFFIPAWNLE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12758125"
FT /id="VSP_042478"
FT CONFLICT 313
FT /note="R -> Q (in Ref. 1; AAO15576)"
FT /evidence="ECO:0000305"
FT CONFLICT 360
FT /note="N -> S (in Ref. 1; AAO15576)"
FT /evidence="ECO:0000305"
FT CONFLICT 374
FT /note="T -> A (in Ref. 1; AAO15577)"
FT /evidence="ECO:0000305"
FT CONFLICT 528
FT /note="E -> G (in Ref. 1; AAO15577)"
FT /evidence="ECO:0000305"
FT CONFLICT 564
FT /note="L -> P (in Ref. 1; AAO15577)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 661 AA; 74732 MW; 2211E4594980A37A CRC64;
MNPDLRRERD AASFDAEKLT YILDGGSERT RRRREIENLI LNDPDFKHED LNFLTRSERY
EIAVRKSATM VKKMRDFGIA DPEEIMWFKK PQLINFVEPV GLTYSMFIPT LLDQGTTAQQ
QKWLPPTQGL QIIGTYAQTE MGHGTHLRGL ETTATYDPKT QEFILNSPTV TSIKWWPGGL
GKTSNHAIVL AQLYTKGECY GLHAFIVPIR EMGTHKPFPG IIVGDIGPKF GYDEMDNGYL
KMDNYRIPRE NMLMKYAQVK PDGTYVKPLS NKLTYGTMVF VRSFLVGEAA RSLSKACTIA
IRYSLIRHQS EIRPGDPEPQ ILDFQTQQYK LFPLLATAYA FQFVGAYMKE TYHRINVDIN
QGNLNELPEL HALTAGLKAF TSWTTNSGIE ACRMACGGHG YSHCSGLPNI YVTFTPTCTF
EGENTVMMLQ TARFLMKSYD QVHSGKLVGG MVSYLNDLPS QRIQPQQVAA WPAMVDINNP
DSLTEAYKHR AARLVEAAAR NLQAEMKHRK SKEIAWNFTS VDLVRASEAH CHYVVVKLFS
GNLSKIDDKP IQAVLTNLCL LYALYGISQN SGDFLQGGIL TESQLTQVNQ RVKELLTLIR
PESAALVDAF DFQDVSLGSV LGRYDGNIYE NMFEWAKKSP LNKSEVHESY HKHLKPLQSK
L
