Reviewed, UniProtKB/Swiss-Prot Q15067 (ACOX1_HUMAN)

Names and origin

Protein names

Recommended name:
    Peroxisomal acyl-coenzyme A oxidase 1
      Short name=AOX
    EC=1.3.3.6
Alternative name(s):
    Palmitoyl-CoA oxidase
    Straight-chain acyl-CoA oxidase
      Short name=SCOX

Gene names

Name:	ACOX1
Synonyms:	ACOX

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	660 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the desaturation of very long chain acyl-CoAs to 2-trans-enoyl-CoAs.
Catalytic activity	Acyl-CoA + O2 = trans-2,3-dehydroacyl-CoA + H2O2.
Cofactor	FAD.
Pathway	Lipid metabolism; peroxisomal fatty acid beta-oxidation.
Subcellular location	Peroxisome.
Involvement in disease	Defects in ACOX1 are the cause of adrenoleukodystrophy pseudoneonatal (Pseudo-NALD) [MIM:264470]; also known as peroxisomal acyl-CoA oxidase deficiency. Pseudo-NALD is a peroxisomal single-enzyme disorder. Clinical features include mental retardation, leukodystrophy, seizures, mild hepatomegaly, hearing deficit. Pseudo-NALD is characterized by increased plasma levels of very-long chain fatty cids, due to decreased or absent peroxisome acyl-CoA oxidase activity. Peroxisomes are intact and functioning.
Sequence similarities	Belongs to the acyl-CoA oxidase family.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Peroxisome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Gene Ontology (GO)
Biological process	fatty acid beta-oxidation Inferred from electronic annotation. Source: InterPro generation of precursor metabolites and energy Ref.2 Inferred from mutant phenotype. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW prostaglandin metabolic process Ref.2 Inferred from mutant phenotype. Source: UniProtKB
Molecular function	FAD binding Inferred from electronic annotation. Source: InterPro acyl-CoA dehydrogenase activity Inferred from electronic annotation. Source: InterPro acyl-CoA oxidase activity Ref.2 Ref.4 Inferred from direct assay. Source: UniProtKB electron carrier activity Inferred from electronic annotation. Source: InterPro protein N-terminus binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q15067-1)

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.

Isoform 2 (identifier: Q15067-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 660	660	Peroxisomal acyl-coenzyme A oxidase 1		PRO_0000204677
Regions
	Motif	658 – 660	3	Microbody targeting signal
Sites
	Active site	421	1	Proton acceptor By similarity
	Binding site	139	1	FAD By similarity
	Binding site	178	1	FAD; via amide nitrogen By similarity
Amino acid modifications
	Modified residue	26	1	Phosphoserine Ref.6 Ref.7
	Modified residue	267	1	N6-acetyllysine By similarity
	Modified residue	310	1	Phosphoserine By similarity
	Modified residue	643	1	N6-acetyllysine By similarity
	Modified residue	649	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	90 – 131	42	KLHLV…SKGLQ → NFVHRGRPEPLDLHLGMFLP TLLHQATAEQQERFFMPAWN LE in isoform 2.		VSP_000146
	Natural variant	101	1	G → S: dbSNP rs3744032.		VAR_048182
	Natural variant	153	1	T → I: dbSNP rs17855420. Ref.5		VAR_030619
	Natural variant	178	1	G → C in pseudo-NALD. Ref.9		VAR_025789
	Natural variant	278	1	M → V in pseudo-NALD. Ref.9		VAR_025790
	Natural variant	312	1	I → M: dbSNP rs1135640. Ref.5 Ref.3 Ref.4		VAR_021529
Experimental info
	Sequence conflict	27	1	P → L in CAA50574. Ref.3
	Sequence conflict	80	1	A → R in CAA50574. Ref.3
	Sequence conflict	119	1	Q → E in AAB30019. Ref.4
	Sequence conflict	200	1	Y → H in AAA18595. Ref.2
	Sequence conflict	212 – 213	2	IG → NR in AAA19113. Ref.1
	Sequence conflict	212 – 213	2	IG → NR in AAA18595. Ref.2
	Sequence conflict	264	1	T → P in AAA19113. Ref.1
	Sequence conflict	264	1	T → P in AAA18595. Ref.2
	Sequence conflict	332	1	F → L in AAA18595. Ref.2
	Sequence conflict	449	1	C → R in AAA18595. Ref.2
	Sequence conflict	531	1	C → L in AAA19113. Ref.1
	Sequence conflict	531	1	C → L in AAA18595. Ref.2
	Sequence conflict	534 – 535	2	VV → GL in AAA19113. Ref.1
	Sequence conflict	534 – 535	2	VV → GL in AAA18595. Ref.2
	Sequence conflict	615	1	V → A in CAA50574. Ref.3
	Sequence conflict	650	1	Y → YH in AAB30019. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 20, 2007. Version 3. Checksum: D713768A47374EA1	FASTA	660	74,424
	10 20 30 40 50 60 MNPDLRRERD SASFNPELLT HILDGSPEKT RRRREIENMI LNDPDFQHED LNFLTRSQRY 70 80 90 100 110 120 EVAVRKSAIM VKKMREFGIA DPDEIMWFKK LHLVNFVEPV GLNYSMFIPT LLNQGTTAQK 130 140 150 160 170 180 EKWLLSSKGL QIIGTYAQTE MGHGTHLRGL ETTATYDPET QEFILNSPTV TSIKWWPGGL 190 200 210 220 230 240 GKTSNHAIVL AQLITKGKCY GLHAFIVPIR EIGTHKPLPG ITVGDIGPKF GYDEIDNGYL 250 260 270 280 290 300 KMDNHRIPRE NMLMKYAQVK PDGTYVKPLS NKLTYGTMVF VRSFLVGEAA RALSKACTIA 310 320 330 340 350 360 IRYSAVRHQS EIKPGEPEPQ ILDFQTQQYK LFPLLATAYA FQFVGAYMKE TYHRINEGIG 370 380 390 400 410 420 QGDLSELPEL HALTAGLKAF TSWTANTGIE ACRMACGGHG YSHCSGLPNI YVNFTPSCTF 430 440 450 460 470 480 EGENTVMMLQ TARFLMKSYD QVHSGKLVCG MVSYLNDLPS QRIQPQQVAV WPTMVDINSP 490 500 510 520 530 540 ESLTEAYKLR AARLVEIAAK NLQKEVIHRK SKEVAWNLTS VDLVRASEAH CHYVVVKLFS 550 560 570 580 590 600 EKLLKIQDKA IQAVLRSLCL LYSLYGISQN AGDFLQGSIM TEPQITQVNQ RVKELLTLIR 610 620 630 640 650 660 SDAVALVDAF DFQDVTLGSV LGRYDGNVYE NLFEWAKNSP LNKAEVHESY KHLKSLQSKL
	Isoform 2. Checksum: 761C97B5043F9068	FASTA	660	74,668
	10 20 30 40 50 60 MNPDLRRERD SASFNPELLT HILDGSPEKT RRRREIENMI LNDPDFQHED LNFLTRSQRY 70 80 90 100 110 120 EVAVRKSAIM VKKMREFGIA DPDEIMWFKN FVHRGRPEPL DLHLGMFLPT LLHQATAEQQ 130 140 150 160 170 180 ERFFMPAWNL EIIGTYAQTE MGHGTHLRGL ETTATYDPET QEFILNSPTV TSIKWWPGGL 190 200 210 220 230 240 GKTSNHAIVL AQLITKGKCY GLHAFIVPIR EIGTHKPLPG ITVGDIGPKF GYDEIDNGYL 250 260 270 280 290 300 KMDNHRIPRE NMLMKYAQVK PDGTYVKPLS NKLTYGTMVF VRSFLVGEAA RALSKACTIA 310 320 330 340 350 360 IRYSAVRHQS EIKPGEPEPQ ILDFQTQQYK LFPLLATAYA FQFVGAYMKE TYHRINEGIG 370 380 390 400 410 420 QGDLSELPEL HALTAGLKAF TSWTANTGIE ACRMACGGHG YSHCSGLPNI YVNFTPSCTF 430 440 450 460 470 480 EGENTVMMLQ TARFLMKSYD QVHSGKLVCG MVSYLNDLPS QRIQPQQVAV WPTMVDINSP 490 500 510 520 530 540 ESLTEAYKLR AARLVEIAAK NLQKEVIHRK SKEVAWNLTS VDLVRASEAH CHYVVVKLFS 550 560 570 580 590 600 EKLLKIQDKA IQAVLRSLCL LYSLYGISQN AGDFLQGSIM TEPQITQVNQ RVKELLTLIR 610 620 630 640 650 660 SDAVALVDAF DFQDVTLGSV LGRYDGNVYE NLFEWAKNSP LNKAEVHESY KHLKSLQSKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of the human peroxisomal acyl-CoA oxidase gene: organization, promoter analysis, and chromosomal localization." Varanasi U., Chu R., Chu S., Espinosa R., Lebeau M.M., Reddy J.K. Proc. Natl. Acad. Sci. U.S.A. 91:3107-3111(1994) [PubMed: 8159712] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2). Tissue: Foreskin.
[2]	"Overexpression and characterization of the human peroxisomal acyl-CoA oxidase in insect cells." Chu R., Varanasi U., Chu S., Lin Y., Usuda N., Rao M.S., Reddy J.K. J. Biol. Chem. 270:4908-4915(1995) [PubMed: 7876265] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[3]	"Large deletion of the peroxisomal acyl-CoA oxidase gene in pseudoneonatal adrenoleukodystrophy." Fourner B., Saudubray J.-M., Benichou B., Lyonnet S., Munnich A., Clevers H., Poll-The B.T. J. Clin. Invest. 94:526-531(1994) [PubMed: 8040306] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT MET-312, INVOLVEMENT IN PSEUDONEONATAL ADRENOLEUKODYSTROPHY. Tissue: Liver.
[4]	"Molecular cloning and functional expression of a human peroxisomal acyl-coenzyme A oxidase." Aoyama T., Tsushima K., Souri M., Kamijo T., Suzuki Y., Shimozawa N., Orii T., Hashimoto T. Biochem. Biophys. Res. Commun. 198:1113-1118(1994) [PubMed: 8117268] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-312. Tissue: Liver.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS ILE-153 AND MET-312. Tissue: Colon and Eye.
[6]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, MASS SPECTROMETRY.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"Peroxisomal acyl-CoA oxidase deficiency." Suzuki Y., Iai M., Kamei A., Tanabe Y., Chida S., Yamaguchi S., Zhang Z., Takemoto Y., Shimozawa N., Kondo N. J. Pediatr. 140:128-130(2002) [PubMed: 11815777] [Abstract] Cited for: VARIANTS PEROXISOMAL ACYL-COA OXIDASE DEFICIENCY CYS-178 AND VAL-278.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	U03268 , U03254, U03255, U03256, U03258, U03259, U03260, U03261, U03263, U03264, U03265, U03266, U03267 Unassigned DNA. Translation: AAA19113.1. U03268 , U03254, U03255, U03257, U03258, U03259, U03260, U03261, U03263, U03264, U03265, U03266, U03267 Unassigned DNA. Translation: AAA19114.1. U07866 mRNA. Translation: AAA18595.1. X71440 mRNA. Translation: CAA50574.1. S69189 mRNA. Translation: AAB30019.2. BC008767 mRNA. Translation: AAH08767.1. BC010425 mRNA. Translation: AAH10425.1.
IPI	IPI00296907. IPI00477729.
PIR	A54942. B54942. I38095.
RefSeq	NP_004026.2. NP_009223.2.
UniGene	Hs.464137
3D structure databases
HSSP	HSSP built from PDB template 1IS2 based on UniProtKB P07872.
SMR	Q15067. Positions 1-654.
ModBase	Search...
PTM databases
PhosphoSite	Q15067.
Proteomic databases
PeptideAtlas	Q15067.
PRIDE	Q15067.
Genome annotation databases
Ensembl	ENSG00000161533. Homo sapiens. [Contig view]
GeneID	51.
KEGG	hsa:51.
NMPDR	fig|9606.3.peg.14420.
Organism-specific databases
GeneCards	GC17M071453.
H-InvDB	HIX0021139.
HGNC	HGNC:119. ACOX1.
MIM	264470. phenotype. 609751. gene.
Orphanet	2971. Pseudoadrenoleukodystrophy.
PharmGKB	PA21.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q15067.
HOVERGEN	Q15067.
OMA	Q15067. QGSIMTE.
Enzyme and pathway databases
BRENDA	1.3.3.6. 247.
Gene expression databases
ArrayExpress	Q15067.
Bgee	Q15067.
CleanEx	HS_ACOX1.
GermOnline	ENSG00000161533. Homo sapiens.
Family and domain databases
InterPro	IPR006091. Acyl-CoA_Oxase/DH_M. IPR012258. Acyl-CoA_oxidase. IPR002655. Acyl-CoA_oxidase_C. IPR013786. AcylCoA_DH/ox_N. IPR013764. AcylCoA_oxidase/DH_1/2_C. [Graphical view]
Gene3D	G3DSA:2.40.110.10. Acyl_CoA_DH/ox_M. 1 hit. G3DSA:1.10.540.10. AcylCoA_DH/ox_N. 1 hit. G3DSA:1.20.140.10. AcylCoA_DH_1/2_C. 2 hits.
PANTHER	PTHR10909:SF11. Acyl-CoA_oxidase. 1 hit.
Pfam	PF01756. ACOX. 1 hit. PF02770. Acyl-CoA_dh_M. 1 hit. [Graphical view]
PIRSF	PIRSF000168. Acyl-CoA_oxidase. 1 hit.
ProtoNet	Search...
Other Resources
NextBio	199.
SOURCE	Search...

Entry information

Entry name

ACOX1_HUMAN

Accession

Primary (citable) accession number: Q15067
Secondary accession number(s): Q12863 , Q15068, Q15101, Q16131, Q9UD31

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 20, 2007
Last modified:	June 16, 2009
This is version 99 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)