Reviewed, UniProtKB/Swiss-Prot O14832 (PAHX_HUMAN)

Names and origin

Protein names

Recommended name:
    Phytanoyl-CoA dioxygenase, peroxisomal
    EC=1.14.11.18
Alternative name(s):
    Phytanoyl-CoA alpha-hydroxylase
      Short name=PhyH
    Phytanic acid oxidase

Gene names

Name:	PHYH
Synonyms:	PAHX

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	338 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA.
Catalytic activity	Phytanoyl-CoA + 2-oxoglutarate + O(2) = 2-hydroxyphytanoyl-CoA + succinate + CO(2).
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	Defects in PHYH are a cause of Refsum disease (RD) [MIM:266500]. RD is an autosomal recessive disorder characterized clinically by a tetrad of abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF). Patients exhibit accumulation of the branched-chain fatty acid, phytanic acid, in blood and tissues. Less constant features are nerve deafness, anosmia, skeletal abnormalities, ichthyosis, cataracts and cardiac impairment. Manifestations of the disease appear in the second or third decade of life. Ref.1 Ref.2 Ref.4 Ref.10
Sequence similarities	Belongs to the PhyH family.

Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Peroxisome
Coding sequence diversity	Polymorphism
Disease	Cataract Deafness Disease mutation Ichthyosis Peroxisome biogenesis disorder Retinitis pigmentosa
Domain	Transit peptide
Ligand	Iron Metal-binding Vitamin C
Molecular function	Dioxygenase Oxidoreductase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	lipid metabolic process Traceable author statement. Source: ProtInc nervous system development Ref.2 Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW sensory perception of sound Inferred from electronic annotation. Source: UniProtKB-KW visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	peroxisome Traceable author statement. Source: ProtInc
Molecular function	L-ascorbic acid binding Inferred from electronic annotation. Source: UniProtKB-KW electron carrier activity Traceable author statement. Source: UniProtKB iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW phytanoyl-CoA dioxygenase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
COPS3	Q9UNS2	1	EBI-721853,EBI-350590
WDR8	Q9P2S5	1	EBI-721853,EBI-1054904

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 30

30

Peroxisome By similarity

Chain

31 – 338

308

Phytanoyl-CoA dioxygenase, peroxisomal

PRO_0000024053

Regions

Region

175 – 177

3

Alpha-ketoglutarate binding

Sites

Metal binding

175

1

Iron

Metal binding

177

1

Iron

Metal binding

264

1

Iron

Binding site

120

1

Alpha-ketoglutarate

Binding site

157

1

Alpha-ketoglutarate

Binding site

193

1

Alpha-ketoglutarate

Binding site

266

1

Alpha-ketoglutarate

Binding site

275

1

Alpha-ketoglutarate

Natural variations

Natural variant

29

1

P → S in RD; could be a rare polymorphism. Ref.4

VAR_017482

Natural variant

83

1

N → Y in RD.

VAR_018619

Natural variant

173

1

P → S in RD. Ref.4

VAR_017483

Natural variant

175

1

H → R in RD.

VAR_018631

Natural variant

176

1

Q → K in RD. Ref.4

VAR_017484

Natural variant

177

1

D → G in RD; total loss of activity. Ref.4

VAR_017485

Natural variant

192

1

A → AA in RD. Ref.4

VAR_012980

Natural variant

193

1

W → R in RD. Ref.4

VAR_017486

Natural variant

197

1

E → Q in RD. Ref.4

VAR_017487

Natural variant

199

1

I → F in RD. Ref.4

VAR_017488

Natural variant

204

1

G → S in RD; total loss of activity. Ref.4 Ref.10

VAR_017489

Natural variant

215

1

G → S: dbSNP rs7901902.

VAR_050528

Natural variant

220

1

H → Y in RD. Ref.4

VAR_017490

Natural variant

245

1

R → Q in RD; partial loss of activity. Ref.4

VAR_017491

Natural variant

257

1

F → S in RD. Ref.4

VAR_017492

Natural variant

269

1

N → H in RD. Ref.2 Ref.4

VAR_005525

Natural variant

275

1

R → Q in RD; total loss of activity. Ref.1 Ref.4

VAR_017493

Natural variant

275

1

R → W in RD; total loss of activity. Ref.1 Ref.4

VAR_005526

Secondary structure

1

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338

Helix Strand Turn

Details...

Helix

57 – 64

8

Beta strand

65 – 69

5

Helix

75 – 89

15

Beta strand

99 – 101

3

Beta strand

104 – 107

4

Beta strand

115 – 117

3

Beta strand

120 – 122

3

Helix

128 – 135

8

Helix

137 – 147

11

Beta strand

149 – 161

13

Helix

177 – 180

4

Helix

186 – 188

3

Beta strand

189 – 197

9

Beta strand

206 – 208

3

Helix

212 – 214

3

Beta strand

246 – 248

3

Beta strand

255 – 258

4

Beta strand

264 – 266

3

Beta strand

271 – 273

3

Beta strand

275 – 284

10

Helix

296 – 301

6

Helix

320 – 327

8

Beta strand

329 – 333

5

Sequences

	Sequence		Length	Mass (Da)
	O14832-1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: FBF9639E7C79A6B0	FASTA	338	38,538
	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

References

	« Hide 'large scale' referencesShow '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: 9326939] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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: 9326940] [Abstract] Cited for: NUCLEOTIDE SEQUENCE, 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: 10051602] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. 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: 10767344] [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. , 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: 15164054] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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: 10686344] [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: 16186124] [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: 14974078] [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: 10709665] [Abstract] Cited for: VARIANT RD SER-204.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF023462 mRNA. Translation: AAB81834.1. AF112977 mRNA. Translation: AAD20602.1. AF242386 , AF242379, AF242380,