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O14832 (PAHX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phytanoyl-CoA dioxygenase, peroxisomal

EC=1.14.11.18
Alternative name(s):
Phytanic acid oxidase
Phytanoyl-CoA alpha-hydroxylase
Short name=PhyH
Gene names
Name:PHYH
Synonyms:PAHX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length338 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA.

Catalytic activity

Phytanoyl-CoA + 2-oxoglutarate + O2 = 2-hydroxyphytanoyl-CoA + succinate + CO2.

Cofactor

Iron. Ref.8

Ascorbate. Ref.8

Pathway

Lipid metabolism; fatty acid metabolism.

Subunit structure

Interacts specifically with the immunophilin FKBP52 and PHYHIP. Ref.7

Subcellular location

Peroxisome.

Tissue specificity

Expressed in liver, kidney, and T-cells, but not in spleen, brain, heart, lung and skeletal muscle.

Involvement in disease

Refsum disease (RD) [MIM:266500]: A rare autosomal recessive peroxisomal disorder characterized by the accumulation of the branched-chain fatty acid, phytanic acid, in blood and tissues. Cardinal clinical features are retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF). Half of all patients exhibit generalized, mild to moderate ichthyosis resembling ichthyosis vulgaris. Less constant features are nerve deafness, anosmia, skeletal abnormalities, cataracts and cardiac impairment.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.2 Ref.4 Ref.10

Sequence similarities

Belongs to the PhyH family.

Ontologies

Keywords
   Cellular componentPeroxisome
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCataract
Deafness
Disease mutation
Ichthyosis
Peroxisome biogenesis disorder
Retinitis pigmentosa
   DomainTransit peptide
   LigandIron
Metal-binding
Vitamin C
   Molecular functionDioxygenase
Oxidoreductase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular lipid metabolic process

Traceable author statement. Source: Reactome

fatty acid alpha-oxidation

Inferred from direct assay Ref.1. Source: UniProtKB

isoprenoid metabolic process

Inferred from direct assay PubMed 11555634. Source: UniProtKB

methyl-branched fatty acid metabolic process

Inferred from direct assay PubMed 10744784. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentmitochondrion

Inferred from electronic annotation. Source: Ensembl

peroxisomal matrix

Traceable author statement. Source: Reactome

peroxisome

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionL-ascorbic acid binding

Inferred from electronic annotation. Source: UniProtKB-KW

cofactor binding

Inferred from direct assay PubMed 10744784PubMed 11555634Ref.1. Source: UniProtKB

electron carrier activity

Traceable author statement PubMed 8954107. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

phytanoyl-CoA dioxygenase activity

Inferred from direct assay PubMed 10744784PubMed 11555634Ref.1. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.3Ref.1. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14832-1)

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: O14832-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: Missing.
Note: No experimental confirmation available. Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3030Peroxisome By similarity
Chain31 – 338308Phytanoyl-CoA dioxygenase, peroxisomal
PRO_0000024053

Regions

Region175 – 1773Alpha-ketoglutarate binding

Sites

Metal binding1751Iron
Metal binding1771Iron
Metal binding2641Iron
Binding site1201Alpha-ketoglutarate
Binding site1571Alpha-ketoglutarate
Binding site1931Alpha-ketoglutarate
Binding site2661Alpha-ketoglutarate
Binding site2751Alpha-ketoglutarate

Amino acid modifications

Modified residue591N6-succinyllysine By similarity
Modified residue1081N6-succinyllysine By similarity
Modified residue2311N6-succinyllysine By similarity
Modified residue2521N6-succinyllysine By similarity

Natural variations

Alternative sequence1 – 100100Missing in isoform 2.
VSP_046289
Natural variant291P → S in RD; unknown pathological significance. Ref.4
Corresponds to variant rs28938169 [ dbSNP | Ensembl ].
VAR_017482
Natural variant831N → Y in RD.
VAR_018619
Natural variant1731P → S in RD. Ref.4
VAR_017483
Natural variant1751H → R in RD.
VAR_018631
Natural variant1761Q → K in RD. Ref.4
Corresponds to variant rs28939672 [ dbSNP | Ensembl ].
VAR_017484
Natural variant1771D → G in RD; total loss of activity. Ref.4
VAR_017485
Natural variant1921A → AA in RD. Ref.4
VAR_012980
Natural variant1931W → R in RD. Ref.4
VAR_017486
Natural variant1971E → Q in RD. Ref.4
VAR_017487
Natural variant1991I → F in RD. Ref.4
VAR_017488
Natural variant2041G → S in RD; total loss of activity. Ref.4 Ref.10
Corresponds to variant rs28939673 [ dbSNP | Ensembl ].
VAR_017489
Natural variant2151G → S.
Corresponds to variant rs7901902 [ dbSNP | Ensembl ].
VAR_050528
Natural variant2201H → Y in RD. Ref.4
VAR_017490
Natural variant2451R → Q in RD; partial loss of activity. Ref.4
Corresponds to variant rs62619919 [ dbSNP | Ensembl ].
VAR_017491
Natural variant2571F → S in RD. Ref.4
VAR_017492
Natural variant2691N → H in RD. Ref.2 Ref.4
VAR_005525
Natural variant2751R → Q in RD; total loss of activity. Ref.4
Corresponds to variant rs28939674 [ dbSNP | Ensembl ].
VAR_017493
Natural variant2751R → W in RD; total loss of activity. Ref.1 Ref.4
Corresponds to variant rs28939671 [ dbSNP | Ensembl ].
VAR_005526

Secondary structure

............................................. 338
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: FBF9639E7C79A6B0

FASTA33838,538
        10         20         30         40         50         60 
MEQLRAAARL QIVLGHLGRP SAGAVVAHPT SGTISSASFH PQQFQYTLDN NVLTLEQRKF 

        70         80         90        100        110        120 
YEENGFLVIK NLVPDADIQR FRNEFEKICR KEVKPLGLTV MRDVTISKSE YAPSEKMITK 

       130        140        150        160        170        180 
VQDFQEDKEL FRYCTLPEIL KYVECFTGPN IMAMHTMLIN KPPDSGKKTS RHPLHQDLHY 

       190        200        210        220        230        240 
FPFRPSDLIV CAWTAMEHIS RNNGCLVVLP GTHKGSLKPH DYPKWEGGVN KMFHGIQDYE 

       250        260        270        280        290        300 
ENKARVHLVM EKGDTVFFHP LLIHGSGQNK TQGFRKAISC HFASADCHYI DVKGTSQENI 

       310        320        330 
EKEVVGIAHK FFGAENSVNL KDIWMFRARL VKGERTNL 

« Hide

Isoform 2 [UniParc].

Checksum: BB9006A60F16E0C6
Show »

FASTA23827,291

References

« Hide 'large scale' references
[1]"Identification of PAHX, a Refsum disease gene."
Mihalik S.J., Morrell J.C., Kim D., Sachsteder K.A., Watkins P.A., Gould S.J.
Nat. Genet. 17:185-189(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT RD TRP-275.
[2]"Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase gene."
Jansen G.A., Ofman R., Ferdinandusse S., Ijlst L., Muijsers A.O., Skjeldal O.H., Stokke O., Jakobs C., Besley G.T.N., Wraith J.E., Wanders R.J.A.
Nat. Genet. 17:190-193(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT RD HIS-269.
[3]"Immunophilins, Refsum disease, and lupus nephritis: the peroxisomal enzyme phytanoyl-CoA alpha-hydroxylase is a new FKBP-associated protein."
Chambraud B., Radanyi C., Camonis J.H., Rajkowski K., Schumacher M., Baulieu E.-E.
Proc. Natl. Acad. Sci. U.S.A. 96:2104-2109(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Leukemia.
[4]"Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease."
Jansen G.A., Hogenhout E.M., Ferdinandusse S., Waterham H.R., Ofman R., Jakobs C., Skjeldal O.H., Wanders R.J.A.
Hum. Mol. Genet. 9:1195-1200(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS RD SER-29; SER-173; LYS-176; GLY-177; ALA-192 INS; ARG-193; GLN-197; PHE-199; SER-204; TYR-220; GLN-245; SER-257; HIS-269; GLN-275 AND TRP-275.
[5]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[7]"Identification of a brain specific protein that associates with a Refsum disease gene product, phytanoyl-CoA alpha-hydroxylase."
Lee Z.H., Kim H.-H., Ahn K.Y., Seo K.H., Kim J.K., Bae C.S., Kim K.K.
Brain Res. Mol. Brain Res. 75:237-247(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PHYHIP.
[8]"Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease."
McDonough M.A., Kavanagh K.L., Butler D., Searls T., Oppermann U., Schofield C.J.
J. Biol. Chem. 280:41101-41110(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 31-338 IN COMPLEX WITH IRON AND ALPHA-KETOGLUTARATE, COFACTOR.
[9]"Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7)."
Jansen G.A., Waterham H.R., Wanders R.J.A.
Hum. Mutat. 23:209-218(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS RD.
[10]"Phytanoyl-CoA hydroxylase deficiency. Enzymological and molecular basis of classical Refsum disease."
Jansen G.A., Ferdinandusse S., Hogenhout E.M., Verhoeven N.M., Jakobs C., Wanders R.J.A.
Adv. Exp. Med. Biol. 466:371-376(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT RD SER-204.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF023462 mRNA. Translation: AAB81834.1.
AF112977 mRNA. Translation: AAD20602.1.
AF242386 expand/collapse EMBL AC list , AF242379, AF242380, AF242381, AF242382, AF242383, AF242384, AF242385 Genomic DNA. Translation: AAF74123.1.
AL138764 Genomic DNA. Translation: CAI12911.2.
BC029512 mRNA. Translation: AAH29512.1.
CCDSCCDS41489.1. [O14832-2]
CCDS7097.1. [O14832-1]
RefSeqNP_001032626.1. NM_001037537.1. [O14832-2]
NP_006205.1. NM_006214.3. [O14832-1]
UniGeneHs.498732.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2A1XX-ray2.50A31-338[»]
DisProtDP00327.
ProteinModelPortalO14832.
SMRO14832. Positions 44-338.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111282. 10 interactions.
IntActO14832. 2 interactions.
MINTMINT-1411634.
STRING9606.ENSP00000263038.

Chemistry

DrugBankDB00025. Antihemophilic Factor.
DB00126. Vitamin C.

PTM databases

PhosphoSiteO14832.

Proteomic databases

MaxQBO14832.
PaxDbO14832.
PRIDEO14832.

Protocols and materials databases

DNASU5264.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263038; ENSP00000263038; ENSG00000107537. [O14832-1]
ENST00000396913; ENSP00000380121; ENSG00000107537. [O14832-2]
GeneID5264.
KEGGhsa:5264.
UCSCuc001ime.3. human. [O14832-1]

Organism-specific databases

CTD5264.
GeneCardsGC10M013319.
GeneReviewsPHYH.
HGNCHGNC:8940. PHYH.
HPAHPA007598.
HPA011796.
MIM266500. phenotype.
602026. gene.
neXtProtNX_O14832.
Orphanet773. Refsum disease.
PharmGKBPA33280.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5285.
HOGENOMHOG000007341.
HOVERGENHBG000392.
KOK00477.
OMARKSISCH.
OrthoDBEOG7NGQC7.
PhylomeDBO14832.
TreeFamTF313667.

Enzyme and pathway databases

BioCycMetaCyc:HS03003-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00199.

Gene expression databases

ArrayExpressO14832.
BgeeO14832.
CleanExHS_PHYH.
GenevestigatorO14832.

Family and domain databases

InterProIPR008775. Phytyl_CoA_dOase.
[Graphical view]
PfamPF05721. PhyH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO14832.
GenomeRNAi5264.
NextBio20330.
PROO14832.
SOURCESearch...

Entry information

Entry namePAHX_HUMAN
AccessionPrimary (citable) accession number: O14832
Secondary accession number(s): A8MTS8, B1ALH5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM