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Protein

Peroxisomal acyl-coenzyme A oxidase 1

Gene

ACOX1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

    HGNCiHGNC:119. ACOX1.

    Subcellular locationi

    • Peroxisome By similarity

    GO - Cellular componenti

    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

    GO - Molecular functioni

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

    Protein-protein interaction databases

    BioGridi106567. 44 interactors.
    IntActiQ15067. 9 interactors.
    MINTiMINT-4717708.
    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.
    Gene3Di1.10.540.10. 1 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.
    IPR009075. AcylCo_DH/oxidase_C.
    IPR013786. AcylCoA_DH/ox_N.
    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: August 30, 2017
    This is version 179 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

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. SIMILARITY comments
      Index of protein domains and families