Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Peroxisomal acyl-coenzyme A oxidase 1

Gene

ACOX1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs. Isoform 1 shows highest activity against medium-chain fatty acyl-CoAs and activity decreases with increasing chain length. Isoform 2 is active against a much broader range of substrates and shows activity towards very long-chain acyl-CoAs. Isoform 2 is twice as active as isoform 1 against 16-hydroxy-palmitoyl-CoA and is 25% more active against 1,16-hexadecanodioyl-CoA.2 Publications

Miscellaneous

Isoform 1 and isoform 2 can reverse the Acox1 null phenotype in mouse which is characterized by severe microvesicular hepatic steatosis, sustained activation of Ppara, spontaneous massive peroxisome proliferation and eventual development of hepatocellular carcinomas. Isoform 2 is more effective in reversal of the phenotype than isoform 1 (PubMed:20195242).1 Publication

Caution

Catalytic activityi

Acyl-CoA + O2 = trans-2,3-dehydroacyl-CoA + H2O2.By similarity

Cofactori

FAD1 Publication

Kineticsi

  1. KM=73 µM for palmitoyl-CoA (isoform 1)1 Publication
  2. KM=90 µM for palmitoyl-CoA (isoform 2)1 Publication

    pH dependencei

    Optimum pH is 8.5 for isoform 1 and 7.5-8.5 for isoform 2.1 Publication

    Temperature dependencei

    Optimum temperature for isoform 1 at pH 7.5 is 40 degrees Celsius with no activity at 50 degrees Celsius. Optimum temperature for isoform 2 at pH 7.5 is 47.5 degrees Celsius with 57% activity retained at 50 degrees Celsius.1 Publication

    Pathwayi: peroxisomal fatty acid beta-oxidation

    This protein is involved in the pathway peroxisomal fatty acid beta-oxidation, which is part of Lipid metabolism.
    View all proteins of this organism that are known to be involved in the pathway peroxisomal fatty acid beta-oxidation and in Lipid metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei139FADBy similarity1
    Binding sitei178FAD; via amide nitrogenBy similarity1
    Active sitei421Proton acceptorBy similarity1

    GO - Molecular functioni

    • acyl-CoA dehydrogenase activity Source: GO_Central
    • acyl-CoA oxidase activity Source: UniProtKB
    • FAD binding Source: UniProtKB
    • flavin adenine dinucleotide binding Source: GO_Central
    • palmitoyl-CoA oxidase activity Source: UniProtKB
    • PDZ domain binding Source: MGI
    • protein N-terminus binding Source: UniProtKB
    • receptor binding Source: UniProtKB

    GO - Biological processi

    • alpha-linolenic acid metabolic process Source: Reactome
    • fatty acid beta-oxidation using acyl-CoA dehydrogenase Source: GO_Central
    • fatty acid beta-oxidation using acyl-CoA oxidase Source: BHF-UCL
    • fatty acid oxidation Source: UniProtKB
    • generation of precursor metabolites and energy Source: UniProtKB
    • lipid homeostasis Source: UniProtKB
    • lipid metabolic process Source: UniProtKB
    • peroxisome fission Source: UniProtKB
    • positive regulation of cholesterol homeostasis Source: UniProtKB
    • prostaglandin metabolic process Source: UniProtKB
    • regulation of lipid metabolic process Source: Reactome
    • spermatogenesis Source: Ensembl
    • very long-chain fatty acid metabolic process Source: BHF-UCL

    Keywordsi

    Molecular functionOxidoreductase
    Biological processFatty acid metabolism, Lipid metabolism
    LigandFAD, Flavoprotein

    Enzyme and pathway databases

    BioCyciMetaCyc:HS08589-MONOMER
    BRENDAi1.3.3.6 2681
    ReactomeiR-HSA-1989781 PPARA activates gene expression
    R-HSA-2046106 alpha-linolenic acid (ALA) metabolism
    R-HSA-390247 Beta-oxidation of very long chain fatty acids
    SABIO-RKiQ15067
    UniPathwayiUPA00661

    Chemistry databases

    SwissLipidsiSLP:000000536 [Q15067-1]
    SLP:000000537 [Q15067-2]

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Peroxisomal acyl-coenzyme A oxidase 11 Publication (EC:1.3.3.6By similarity)
    Short name:
    AOX1 Publication
    Alternative name(s):
    Palmitoyl-CoA oxidase1 Publication
    Straight-chain acyl-CoA oxidase
    Short name:
    SCOX
    Gene namesi
    Name:ACOX1Imported
    Synonyms:ACOX
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 17

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000161533.11
    HGNCiHGNC:119 ACOX1
    MIMi609751 gene
    neXtProtiNX_Q15067

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Peroxisome

    Pathology & Biotechi

    Involvement in diseasei

    Adrenoleukodystrophy, pseudoneonatal (Pseudo-NALD)3 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA peroxisomal single-enzyme disorder of fatty acid beta-oxidation, resulting in clinical manifestations that remind neonatal adrenoleukodystrophy. Clinical features include mental retardation, leukodystrophy, seizures, mild hepatomegaly, hearing deficit. Pseudo-NALD is characterized by increased plasma levels of very-long chain fatty acids, due to decreased or absent peroxisome acyl-CoA oxidase activity. Peroxisomes are intact and functioning.
    See also OMIM:264470

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi51
    MalaCardsiACOX1
    MIMi264470 phenotype
    OpenTargetsiENSG00000161533
    Orphaneti2971 Peroxisomal acyl-CoA oxidase deficiency
    PharmGKBiPA21

    Chemistry databases

    DrugBankiDB07930 (3R)-3-HYDROXYDODECANOIC ACID
    DB03147 Flavin adenine dinucleotide

    Polymorphism and mutation databases

    BioMutaiACOX1
    DMDMi126302511

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002046771 – 660Peroxisomal acyl-coenzyme A oxidase 1Add BLAST660

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei26PhosphoserineCombined sources1
    Modified residuei89N6-succinyllysineBy similarity1
    Modified residuei90N6-succinyllysineBy similarity1
    Modified residuei216N6-acetyllysineBy similarity1
    Modified residuei241N6-succinyllysineBy similarity1
    Modified residuei255N6-acetyllysineCombined sources1
    Modified residuei267N6-acetyllysineCombined sources1
    Modified residuei272N6-acetyllysineBy similarity1
    Modified residuei349N6-succinyllysineBy similarity1
    Modified residuei437N6-acetyllysine; alternateCombined sources1
    Modified residuei437N6-succinyllysine; alternateBy similarity1
    Modified residuei446N6-acetyllysine; alternateBy similarity1
    Modified residuei446N6-succinyllysine; alternateBy similarity1
    Modified residuei500N6-acetyllysineCombined sources1
    Modified residuei504N6-acetyllysineCombined sources1
    Modified residuei512N6-acetyllysine; alternateBy similarity1
    Modified residuei512N6-succinyllysine; alternateBy similarity1
    Modified residuei542N6-succinyllysineBy similarity1
    Modified residuei637N6-acetyllysine; alternateBy similarity1
    Modified residuei637N6-succinyllysine; alternateBy similarity1
    Modified residuei643N6-succinyllysineBy similarity1
    Modified residuei649PhosphoserineBy similarity1
    Modified residuei651N6-acetyllysineBy similarity1
    Modified residuei654N6-succinyllysineBy similarity1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiQ15067
    MaxQBiQ15067
    PaxDbiQ15067
    PeptideAtlasiQ15067
    PRIDEiQ15067
    TopDownProteomicsiQ15067-1 [Q15067-1]

    PTM databases

    iPTMnetiQ15067
    PhosphoSitePlusiQ15067
    SwissPalmiQ15067

    Expressioni

    Tissue specificityi

    Widely expressed with highest levels of isoform 1 and isoform 2 detected in testis. Isoform 1 is expressed at higher levels than isoform 2 in liver and kidney while isoform 2 levels are higher in brain, lung, muscle, white adipose tissue and testis. Levels are almost equal in heart.2 Publications

    Gene expression databases

    BgeeiENSG00000161533
    CleanExiHS_ACOX1
    ExpressionAtlasiQ15067 baseline and differential
    GenevisibleiQ15067 HS

    Organism-specific databases

    HPAiCAB021094
    HPA021192
    HPA021195
    HPA028759

    Interactioni

    Subunit structurei

    Homodimer (By similarity). Interacts with LONP2 (PubMed:18281296).By similarity1 Publication

    GO - Molecular functioni

    • PDZ domain binding Source: MGI
    • protein N-terminus binding Source: UniProtKB
    • receptor binding Source: UniProtKB

    Protein-protein interaction databases

    BioGridi10656744 interactors.
    IntActiQ15067 9 interactors.
    STRINGi9606.ENSP00000293217

    Structurei

    3D structure databases

    ProteinModelPortaliQ15067
    SMRiQ15067
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi658 – 660Microbody targeting signal3

    Sequence similaritiesi

    Belongs to the acyl-CoA oxidase family.Curated

    Phylogenomic databases

    eggNOGiKOG0136 Eukaryota
    COG1960 LUCA
    GeneTreeiENSGT00530000062919
    HOVERGENiHBG050451
    InParanoidiQ15067
    KOiK00232
    OMAiGRRFFTM
    OrthoDBiEOG091G0A1P
    PhylomeDBiQ15067
    TreeFamiTF300672

    Family and domain databases

    CDDicd01150 AXO, 1 hit
    Gene3Di1.10.540.101 hit
    InterProiView protein in InterPro
    IPR034171 ACO
    IPR029320 Acyl-CoA_ox_N
    IPR006091 Acyl-CoA_Oxase/DH_cen-dom
    IPR012258 Acyl-CoA_oxidase
    IPR002655 Acyl-CoA_oxidase_C
    IPR036250 AcylCo_DH-like_C
    IPR037069 AcylCoA_DH/ox_N_sf
    IPR009100 AcylCoA_DH/oxidase_NM_dom
    PfamiView protein in Pfam
    PF01756 ACOX, 1 hit
    PF02770 Acyl-CoA_dh_M, 1 hit
    PF14749 Acyl-CoA_ox_N, 1 hit
    PIRSFiPIRSF000168 Acyl-CoA_oxidase, 1 hit
    SUPFAMiSSF47203 SSF47203, 2 hits
    SSF56645 SSF56645, 1 hit

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q15067-1) [UniParc]FASTAAdd to basket
    Also known as: ACOX1a, SCOX-exon 3I

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MNPDLRRERD SASFNPELLT HILDGSPEKT RRRREIENMI LNDPDFQHED
    60 70 80 90 100
    LNFLTRSQRY EVAVRKSAIM VKKMREFGIA DPDEIMWFKK LHLVNFVEPV
    110 120 130 140 150
    GLNYSMFIPT LLNQGTTAQK EKWLLSSKGL QIIGTYAQTE MGHGTHLRGL
    160 170 180 190 200
    ETTATYDPET QEFILNSPTV TSIKWWPGGL GKTSNHAIVL AQLITKGKCY
    210 220 230 240 250
    GLHAFIVPIR EIGTHKPLPG ITVGDIGPKF GYDEIDNGYL KMDNHRIPRE
    260 270 280 290 300
    NMLMKYAQVK PDGTYVKPLS NKLTYGTMVF VRSFLVGEAA RALSKACTIA
    310 320 330 340 350
    IRYSAVRHQS EIKPGEPEPQ ILDFQTQQYK LFPLLATAYA FQFVGAYMKE
    360 370 380 390 400
    TYHRINEGIG QGDLSELPEL HALTAGLKAF TSWTANTGIE ACRMACGGHG
    410 420 430 440 450
    YSHCSGLPNI YVNFTPSCTF EGENTVMMLQ TARFLMKSYD QVHSGKLVCG
    460 470 480 490 500
    MVSYLNDLPS QRIQPQQVAV WPTMVDINSP ESLTEAYKLR AARLVEIAAK
    510 520 530 540 550
    NLQKEVIHRK SKEVAWNLTS VDLVRASEAH CHYVVVKLFS EKLLKIQDKA
    560 570 580 590 600
    IQAVLRSLCL LYSLYGISQN AGDFLQGSIM TEPQITQVNQ RVKELLTLIR
    610 620 630 640 650
    SDAVALVDAF DFQDVTLGSV LGRYDGNVYE NLFEWAKNSP LNKAEVHESY
    660
    KHLKSLQSKL
    Length:660
    Mass (Da):74,424
    Last modified:February 20, 2007 - v3
    Checksum:iD713768A47374EA1
    GO
    Isoform 2 (identifier: Q15067-2) [UniParc]FASTAAdd to basket
    Also known as: ACOX1b, SCOX-exon 3II

    The sequence of this isoform differs from the canonical sequence as follows:
         90-131: KLHLVNFVEP...KWLLSSKGLQ → NFVHRGRPEP...RFFMPAWNLE

    Show »
    Length:660
    Mass (Da):74,668
    Checksum:i761C97B5043F9068
    GO
    Isoform 3 (identifier: Q15067-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-38: Missing.
         90-131: KLHLVNFVEP...KWLLSSKGLQ → NFVHRGRPEP...RFFMPAWNLE

    Note: No experimental confirmation available.
    Show »
    Length:622
    Mass (Da):70,136
    Checksum:iFE52A881C050EB78
    GO

    Sequence cautioni

    The sequence CAD97622 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti27P → L in CAA50574 (PubMed:8040306).Curated1
    Sequence conflicti80A → R in CAA50574 (PubMed:8040306).Curated1
    Sequence conflicti84E → D in CAD97622 (PubMed:17974005).Curated1
    Sequence conflicti119Q → E in AAB30019 (PubMed:8117268).Curated1
    Sequence conflicti200Y → H in AAA18595 (PubMed:7876265).Curated1
    Sequence conflicti212 – 213IG → NR in AAA19113 (PubMed:8159712).Curated2
    Sequence conflicti212 – 213IG → NR in AAA19114 (PubMed:8159712).Curated2
    Sequence conflicti212 – 213IG → NR in AAA18595 (PubMed:7876265).Curated2
    Sequence conflicti264T → P in AAA19113 (PubMed:8159712).Curated1
    Sequence conflicti264T → P in AAA19114 (PubMed:8159712).Curated1
    Sequence conflicti264T → P in AAA18595 (PubMed:7876265).Curated1
    Sequence conflicti332F → L in AAA18595 (PubMed:7876265).Curated1
    Sequence conflicti449C → R in AAA18595 (PubMed:7876265).Curated1
    Sequence conflicti490R → L in BAF85654 (PubMed:14702039).Curated1
    Sequence conflicti531C → L in AAA19113 (PubMed:8159712).Curated1
    Sequence conflicti531C → L in AAA19114 (PubMed:8159712).Curated1
    Sequence conflicti531C → L in AAA18595 (PubMed:7876265).Curated1
    Sequence conflicti534 – 535VV → GL in AAA19113 (PubMed:8159712).Curated2
    Sequence conflicti534 – 535VV → GL in AAA19114 (PubMed:8159712).Curated2
    Sequence conflicti534 – 535VV → GL in AAA18595 (PubMed:7876265).Curated2
    Sequence conflicti615V → A in CAA50574 (PubMed:8040306).Curated1
    Sequence conflicti650Y → YH in AAB30019 (PubMed:8117268).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_06704064Missing in pseudo-NALD. 1 Publication1
    Natural variantiVAR_048182101G → S. Corresponds to variant dbSNP:rs3744032Ensembl.1
    Natural variantiVAR_030619153T → I1 PublicationCorresponds to variant dbSNP:rs17855420Ensembl.1
    Natural variantiVAR_025789178G → C in pseudo-NALD. 2 PublicationsCorresponds to variant dbSNP:rs118204091Ensembl.1
    Natural variantiVAR_067041184S → L in pseudo-NALD. 1 PublicationCorresponds to variant dbSNP:rs780887410Ensembl.1
    Natural variantiVAR_067042231G → V in pseudo-NALD. 1 Publication1
    Natural variantiVAR_025790278M → V in pseudo-NALD. 2 PublicationsCorresponds to variant dbSNP:rs118204090Ensembl.1
    Natural variantiVAR_067043309Q → R in pseudo-NALD. 1 PublicationCorresponds to variant dbSNP:rs118204092Ensembl.1
    Natural variantiVAR_067044310S → P in pseudo-NALD. 1 PublicationCorresponds to variant dbSNP:rs758962364Ensembl.1
    Natural variantiVAR_021529312I → M5 PublicationsCorresponds to variant dbSNP:rs1135640Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0461291 – 38Missing in isoform 3. 1 PublicationAdd BLAST38
    Alternative sequenceiVSP_00014690 – 131KLHLV…SKGLQ → NFVHRGRPEPLDLHLGMFLP TLLHQATAEQQERFFMPAWN LE in isoform 2 and isoform 3. 4 PublicationsAdd BLAST42

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U03268
    , U03254, U03255, U03256, U03258, U03259, U03260, U03261, U03263, U03264, U03265, U03266, U03267 Genomic DNA Translation: AAA19113.1
    U03268
    , U03254, U03255, U03257, U03258, U03259, U03260, U03261, U03263, U03264, U03265, U03266, U03267 Genomic DNA Translation: AAA19114.1
    U07866 mRNA Translation: AAA18595.1
    X71440 mRNA Translation: CAA50574.1
    S69189 mRNA Translation: AAB30019.2
    AK291793 mRNA Translation: BAF84482.1
    AK292965 mRNA Translation: BAF85654.1
    AK296409 mRNA Translation: BAG59073.1
    BX537380 mRNA Translation: CAD97622.1 Different initiation.
    AC040980 Genomic DNA No translation available.
    AC087289 Genomic DNA No translation available.
    CH471099 Genomic DNA Translation: EAW89351.1
    BC008767 mRNA Translation: AAH08767.1
    BC010425 mRNA Translation: AAH10425.1
    CCDSiCCDS11734.1 [Q15067-2]
    CCDS11735.1 [Q15067-1]
    PIRiA54942
    B54942
    I38095
    RefSeqiNP_001171968.1, NM_001185039.1 [Q15067-3]
    NP_004026.2, NM_004035.6 [Q15067-2]
    NP_009223.2, NM_007292.5 [Q15067-1]
    UniGeneiHs.464137

    Genome annotation databases

    EnsembliENST00000293217; ENSP00000293217; ENSG00000161533 [Q15067-2]
    ENST00000301608; ENSP00000301608; ENSG00000161533 [Q15067-1]
    GeneIDi51
    KEGGihsa:51
    UCSCiuc002jqe.5 human [Q15067-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiACOX1_HUMAN
    AccessioniPrimary (citable) accession number: Q15067
    Secondary accession number(s): A8K6X8
    , A8KAA0, B4DK61, F5GYQ8, Q12863, Q15068, Q15101, Q16131, Q7Z3W5, Q9UD31
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: February 20, 2007
    Last modified: February 28, 2018
    This is version 184 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome