PAHX_HUMAN
ID PAHX_HUMAN Reviewed; 338 AA.
AC O14832; A8MTS8; B1ALH5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Phytanoyl-CoA dioxygenase, peroxisomal;
DE EC=1.14.11.18 {ECO:0000269|PubMed:10767344, ECO:0000269|PubMed:12031666, ECO:0000269|PubMed:9326939};
DE AltName: Full=Phytanic acid oxidase;
DE AltName: Full=Phytanoyl-CoA alpha-hydroxylase;
DE Short=PhyH;
DE Flags: Precursor;
GN Name=PHYH; Synonyms=PAHX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT RD TRP-275,
RP CHARACTERIZATION OF VARIANT RD TRP-275, FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, AND COFACTOR.
RX PubMed=9326939; DOI=10.1038/ng1097-185;
RA Mihalik S.J., Morrell J.C., Kim D., Sachsteder K.A., Watkins P.A.,
RA Gould S.J.;
RT "Identification of PAHX, a Refsum disease gene.";
RL Nat. Genet. 17:185-189(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT RD HIS-269.
RX PubMed=9326940; DOI=10.1038/ng1097-190;
RA Jansen G.A., Ofman R., Ferdinandusse S., Ijlst L., Muijsers A.O.,
RA Skjeldal O.H., Stokke O., Jakobs C., Besley G.T.N., Wraith J.E.,
RA Wanders R.J.A.;
RT "Refsum disease is caused by mutations in the phytanoyl-CoA hydroxylase
RT gene.";
RL Nat. Genet. 17:190-193(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH FKBP52.
RC TISSUE=Leukemia;
RX PubMed=10051602; DOI=10.1073/pnas.96.5.2104;
RA Chambraud B., Radanyi C., Camonis J.H., Rajkowski K., Schumacher M.,
RA Baulieu E.-E.;
RT "Immunophilins, Refsum disease, and lupus nephritis: the peroxisomal enzyme
RT phytanoyl-CoA alpha-hydroxylase is a new FKBP-associated protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:2104-2109(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS RD SER-173; LYS-176; GLY-177;
RP ALA-192 INS; ARG-193; GLN-197; PHE-199; SER-204; TYR-220; SER-257; HIS-269;
RP GLN-275 AND TRP-275, VARIANTS SER-29 AND GLN-245, CHARACTERIZATION OF
RP VARIANTS RD GLY-177; SER-204; GLN-275 AND TRP-275, AND CATALYTIC ACTIVITY.
RX PubMed=10767344; DOI=10.1093/hmg/9.8.1195;
RA Jansen G.A., Hogenhout E.M., Ferdinandusse S., Waterham H.R., Ofman R.,
RA Jakobs C., Skjeldal O.H., Wanders R.J.A.;
RT "Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the
RT molecular basis of Refsum's disease.";
RL Hum. Mol. Genet. 9:1195-1200(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INTERACTION WITH PHYHIP.
RX PubMed=10686344; DOI=10.1016/s0169-328x(99)00304-6;
RA Lee Z.H., Kim H.-H., Ahn K.Y., Seo K.H., Kim J.K., Bae C.S., Kim K.K.;
RT "Identification of a brain specific protein that associates with a Refsum
RT disease gene product, phytanoyl-CoA alpha-hydroxylase.";
RL Brain Res. Mol. Brain Res. 75:237-247(2000).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=10744784;
RA Croes K., Foulon V., Casteels M., Van Veldhoven P.P., Mannaerts G.P.;
RT "Phytanoyl-CoA hydroxylase: recognition of 3-methyl-branched acyl-coAs and
RT requirement for GTP or ATP and Mg(2+) in addition to its known
RT hydroxylation cofactors.";
RL J. Lipid Res. 41:629-636(2000).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12031666; DOI=10.1016/s1074-5521(02)00139-4;
RA Mukherji M., Kershaw N.J., Schofield C.J., Wierzbicki A.S., Lloyd M.D.;
RT "Utilization of sterol carrier protein-2 by phytanoyl-CoA 2-hydroxylase in
RT the peroxisomal alpha oxidation of phytanic acid.";
RL Chem. Biol. 9:597-605(2002).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12923223; DOI=10.1194/jlr.m300230-jlr200;
RA Foulon V., Asselberghs S., Geens W., Mannaerts G.P., Casteels M.,
RA Van Veldhoven P.P.;
RT "Further studies on the substrate spectrum of phytanoyl-CoA hydroxylase:
RT implications for Refsum disease?";
RL J. Lipid Res. 44:2349-2355(2003).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-317, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 31-338 IN COMPLEX WITH IRON AND
RP ALPHA-KETOGLUTARATE, COFACTOR, SUBSTRATE-BINDING SITES, AND METAL-BINDING
RP SITES.
RX PubMed=16186124; DOI=10.1074/jbc.m507528200;
RA McDonough M.A., Kavanagh K.L., Butler D., Searls T., Oppermann U.,
RA Schofield C.J.;
RT "Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular
RT mechanisms of Refsum disease.";
RL J. Biol. Chem. 280:41101-41110(2005).
RN [14]
RP REVIEW ON VARIANTS RD.
RX PubMed=14974078; DOI=10.1002/humu.10315;
RA Jansen G.A., Waterham H.R., Wanders R.J.A.;
RT "Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA
RT hydroxylase (PHYH) and the PTS2 receptor (PEX7).";
RL Hum. Mutat. 23:209-218(2004).
RN [15]
RP VARIANT RD SER-204.
RX PubMed=10709665;
RA Jansen G.A., Ferdinandusse S., Hogenhout E.M., Verhoeven N.M., Jakobs C.,
RA Wanders R.J.A.;
RT "Phytanoyl-CoA hydroxylase deficiency. Enzymological and molecular basis of
RT classical Refsum disease.";
RL Adv. Exp. Med. Biol. 466:371-376(1999).
RN [16]
RP VARIANT GLN-245.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
CC -!- FUNCTION: Catalyzes the 2-hydroxylation of not only racemic phytanoyl-
CC CoA and the isomers of 3-methylhexadecanoyl-CoA, but also a variety of
CC other mono-branched 3-methylacyl-CoA esters (with a chain length of at
CC least seven carbon atoms) and straight-chain acyl-CoA esters (with a
CC chain length longer than four carbon atoms) (PubMed:9326939,
CC PubMed:10744784, PubMed:12031666, PubMed:12923223). Does not
CC hydroxylate long and very long straight chain acyl-CoAs or 2-
CC methyl- and 4-methyl-branched acyl-CoAs (PubMed:10744784,
CC PubMed:12923223). {ECO:0000269|PubMed:10744784,
CC ECO:0000269|PubMed:12031666, ECO:0000269|PubMed:12923223,
CC ECO:0000269|PubMed:9326939}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + O2 + phytanoyl-CoA = 2-hydroxyphytanoyl-CoA +
CC CO2 + succinate; Xref=Rhea:RHEA:16065, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:57334, ChEBI:CHEBI:57391; EC=1.14.11.18;
CC Evidence={ECO:0000269|PubMed:10767344, ECO:0000269|PubMed:12031666,
CC ECO:0000269|PubMed:9326939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16066;
CC Evidence={ECO:0000305|PubMed:12031666, ECO:0000305|PubMed:9326939};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + 3-methylhexadecanoyl-CoA + O2 = 2-hydroxy-3-
CC methylhexadecanoyl-CoA + CO2 + succinate; Xref=Rhea:RHEA:44000,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:58784, ChEBI:CHEBI:83969;
CC Evidence={ECO:0000269|PubMed:10744784, ECO:0000269|PubMed:12923223};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44001;
CC Evidence={ECO:0000305|PubMed:10744784, ECO:0000305|PubMed:12923223};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + hexadecanoyl-CoA + O2 = 2-
CC hydroxyhexadecanoyl-CoA + CO2 + succinate; Xref=Rhea:RHEA:54596,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:57379, ChEBI:CHEBI:74115;
CC Evidence={ECO:0000269|PubMed:12031666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54597;
CC Evidence={ECO:0000305|PubMed:12031666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + O2 + octanoyl-CoA = 2-hydroxyoctanoyl-CoA +
CC CO2 + succinate; Xref=Rhea:RHEA:54600, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:57386, ChEBI:CHEBI:138290;
CC Evidence={ECO:0000269|PubMed:12031666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54601;
CC Evidence={ECO:0000305|PubMed:12031666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + decanoyl-CoA + O2 = 2-hydroxydecanoyl-CoA +
CC CO2 + succinate; Xref=Rhea:RHEA:54604, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:61430, ChEBI:CHEBI:138292;
CC Evidence={ECO:0000269|PubMed:12031666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54605;
CC Evidence={ECO:0000305|PubMed:12031666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + 3-methylbutanoyl-CoA + O2 = 2-hydroxy-3-
CC methylbutanoyl-CoA + CO2 + succinate; Xref=Rhea:RHEA:54612,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:57345, ChEBI:CHEBI:138296;
CC Evidence={ECO:0000269|PubMed:12031666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54613;
CC Evidence={ECO:0000305|PubMed:12031666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + heptadecanoyl-CoA + O2 = 2-
CC hydroxyheptadecanoyl-CoA + CO2 + succinate; Xref=Rhea:RHEA:54616,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:74307, ChEBI:CHEBI:138297;
CC Evidence={ECO:0000269|PubMed:12031666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54617;
CC Evidence={ECO:0000305|PubMed:12031666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + eicosanoyl-CoA + O2 = 2-hydroxyeicosanoyl-CoA
CC + CO2 + succinate; Xref=Rhea:RHEA:54620, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:57380, ChEBI:CHEBI:138298;
CC Evidence={ECO:0000269|PubMed:12031666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54621;
CC Evidence={ECO:0000305|PubMed:12031666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + O2 + octadecanoyl-CoA = 2-
CC hydroxyoctadecanoyl-CoA + CO2 + succinate; Xref=Rhea:RHEA:54624,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:57394, ChEBI:CHEBI:74116;
CC Evidence={ECO:0000269|PubMed:12031666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54625;
CC Evidence={ECO:0000305|PubMed:12031666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + dodecanoyl-CoA + O2 = 2-hydroxydodecanoyl-CoA
CC + CO2 + succinate; Xref=Rhea:RHEA:54628, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:57375, ChEBI:CHEBI:138299;
CC Evidence={ECO:0000269|PubMed:12031666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54629;
CC Evidence={ECO:0000305|PubMed:12031666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + O2 + tetradecanoyl-CoA = 2-
CC hydroxytetradecanoyl-CoA + CO2 + succinate; Xref=Rhea:RHEA:54632,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:57385, ChEBI:CHEBI:138300;
CC Evidence={ECO:0000269|PubMed:12031666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54633;
CC Evidence={ECO:0000305|PubMed:12031666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + hexanoyl-CoA + O2 = 2-hydroxyhexanoyl-CoA +
CC CO2 + succinate; Xref=Rhea:RHEA:55172, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:62620, ChEBI:CHEBI:138630;
CC Evidence={ECO:0000269|PubMed:12031666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55173;
CC Evidence={ECO:0000305|PubMed:12031666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + butanoyl-CoA + O2 = 2-hydroxybutanoyl-CoA +
CC CO2 + succinate; Xref=Rhea:RHEA:55176, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:57371, ChEBI:CHEBI:138628;
CC Evidence={ECO:0000269|PubMed:12031666};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55177;
CC Evidence={ECO:0000305|PubMed:12031666};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + 3-methylnonanoyl-CoA + O2 = 2-hydroxy-3-
CC methylnonanoyl-CoA + CO2 + succinate; Xref=Rhea:RHEA:55180,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:138633, ChEBI:CHEBI:138634;
CC Evidence={ECO:0000269|PubMed:12923223};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55181;
CC Evidence={ECO:0000305|PubMed:12923223};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + 3-methylundecanoyl-CoA + O2 = 2-hydroxy-3-
CC methylundecanoyl-CoA + CO2 + succinate; Xref=Rhea:RHEA:55184,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:84183, ChEBI:CHEBI:138632;
CC Evidence={ECO:0000269|PubMed:12923223};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55185;
CC Evidence={ECO:0000305|PubMed:12923223};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + 3-methyldodecanoyl-CoA + O2 = 2-hydroxy-3-
CC methyldodecanoyl-CoA + CO2 + succinate; Xref=Rhea:RHEA:55192,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:138636, ChEBI:CHEBI:138637;
CC Evidence={ECO:0000269|PubMed:12923223};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55193;
CC Evidence={ECO:0000305|PubMed:12923223};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:10744784, ECO:0000269|PubMed:16186124,
CC ECO:0000269|PubMed:9326939};
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
CC Evidence={ECO:0000269|PubMed:10744784, ECO:0000269|PubMed:16186124};
CC -!- COFACTOR:
CC Name=ATP; Xref=ChEBI:CHEBI:30616;
CC Evidence={ECO:0000269|PubMed:10744784};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10744784};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=40.8 uM for 3-methylhexadecanoyl-CoA
CC {ECO:0000269|PubMed:12923223};
CC KM=29.5 uM for phytanoyl-CoA (in presence of SCP2)
CC {ECO:0000269|PubMed:12031666};
CC KM=29.1 uM for hexadecanoyl-CoA (in presence of SCP2)
CC {ECO:0000269|PubMed:12031666};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC -!- SUBUNIT: Interacts with FKBP52 (PubMed:10051602). Interacts with
CC PHYHIP. {ECO:0000269|PubMed:10051602, ECO:0000269|PubMed:10686344}.
CC -!- INTERACTION:
CC O14832; Q6PCB6: ABHD17C; NbExp=3; IntAct=EBI-721853, EBI-22011868;
CC O14832; Q96FT7-4: ASIC4; NbExp=3; IntAct=EBI-721853, EBI-9089489;
CC O14832; Q8N865: C7orf31; NbExp=3; IntAct=EBI-721853, EBI-10174456;
CC O14832; Q9UJX2: CDC23; NbExp=3; IntAct=EBI-721853, EBI-396137;
CC O14832; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-721853, EBI-350590;
CC O14832; Q8IUI8: CRLF3; NbExp=3; IntAct=EBI-721853, EBI-2872414;
CC O14832; Q3B7T1: EDRF1; NbExp=3; IntAct=EBI-721853, EBI-2870947;
CC O14832; P29323-3: EPHB2; NbExp=3; IntAct=EBI-721853, EBI-25838727;
CC O14832; Q8IZU0: FAM9B; NbExp=7; IntAct=EBI-721853, EBI-10175124;
CC O14832; A5PKX9: INADL; NbExp=3; IntAct=EBI-721853, EBI-12035052;
CC O14832; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-721853, EBI-714379;
CC O14832; Q9UPM6: LHX6; NbExp=3; IntAct=EBI-721853, EBI-10258746;
CC O14832; P43364: MAGEA11; NbExp=4; IntAct=EBI-721853, EBI-739552;
CC O14832; Q9UDY8-2: MALT1; NbExp=3; IntAct=EBI-721853, EBI-12056869;
CC O14832; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-721853, EBI-25830200;
CC O14832; O75925: PIAS1; NbExp=3; IntAct=EBI-721853, EBI-629434;
CC O14832; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-721853, EBI-25829984;
CC O14832; O00463: TRAF5; NbExp=3; IntAct=EBI-721853, EBI-523498;
CC O14832; Q86UV6-2: TRIM74; NbExp=3; IntAct=EBI-721853, EBI-10259086;
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000269|PubMed:9326939}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O14832-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14832-2; Sequence=VSP_046289;
CC -!- TISSUE SPECIFICITY: Expressed in liver, kidney, and T-cells, but not in
CC spleen, brain, heart, lung and skeletal muscle.
CC -!- DISEASE: Refsum disease (RD) [MIM:266500]: A rare autosomal recessive
CC peroxisomal disorder characterized by the accumulation of the branched-
CC chain fatty acid, phytanic acid, in blood and tissues. Cardinal
CC clinical features are retinitis pigmentosa, peripheral neuropathy,
CC cerebellar ataxia, and elevated protein levels in the cerebrospinal
CC fluid (CSF). Half of all patients exhibit generalized, mild to moderate
CC ichthyosis resembling ichthyosis vulgaris. Less constant features are
CC nerve deafness, anosmia, skeletal abnormalities, cataracts and cardiac
CC impairment. {ECO:0000269|PubMed:10709665, ECO:0000269|PubMed:10767344,
CC ECO:0000269|PubMed:14974078, ECO:0000269|PubMed:9326939,
CC ECO:0000269|PubMed:9326940}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PhyH family. {ECO:0000305}.
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DR EMBL; AF023462; AAB81834.1; -; mRNA.
DR EMBL; AF112977; AAD20602.1; -; mRNA.
DR EMBL; AF242386; AAF74123.1; -; Genomic_DNA.
DR EMBL; AF242379; AAF74123.1; JOINED; Genomic_DNA.
DR EMBL; AF242380; AAF74123.1; JOINED; Genomic_DNA.
DR EMBL; AF242381; AAF74123.1; JOINED; Genomic_DNA.
DR EMBL; AF242382; AAF74123.1; JOINED; Genomic_DNA.
DR EMBL; AF242383; AAF74123.1; JOINED; Genomic_DNA.
DR EMBL; AF242384; AAF74123.1; JOINED; Genomic_DNA.
DR EMBL; AF242385; AAF74123.1; JOINED; Genomic_DNA.
DR EMBL; AL138764; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC029512; AAH29512.1; -; mRNA.
DR CCDS; CCDS41489.1; -. [O14832-2]
DR CCDS; CCDS7097.1; -. [O14832-1]
DR RefSeq; NP_001032626.1; NM_001037537.1. [O14832-2]
DR RefSeq; NP_001310009.1; NM_001323080.1. [O14832-2]
DR RefSeq; NP_006205.1; NM_006214.3. [O14832-1]
DR PDB; 2A1X; X-ray; 2.50 A; A=31-338.
DR PDBsum; 2A1X; -.
DR AlphaFoldDB; O14832; -.
DR SMR; O14832; -.
DR BioGRID; 111282; 23.
DR IntAct; O14832; 22.
DR STRING; 9606.ENSP00000263038; -.
DR DrugBank; DB00025; Antihemophilic factor, human recombinant.
DR DrugBank; DB00126; Ascorbic acid.
DR DrugBank; DB13998; Lonoctocog alfa.
DR DrugBank; DB13999; Moroctocog alfa.
DR SwissLipids; SLP:000001017; -.
DR iPTMnet; O14832; -.
DR PhosphoSitePlus; O14832; -.
DR SwissPalm; O14832; -.
DR BioMuta; PHYH; -.
DR EPD; O14832; -.
DR jPOST; O14832; -.
DR MassIVE; O14832; -.
DR MaxQB; O14832; -.
DR PaxDb; O14832; -.
DR PeptideAtlas; O14832; -.
DR PRIDE; O14832; -.
DR ProteomicsDB; 2048; -.
DR ProteomicsDB; 48268; -. [O14832-1]
DR ABCD; O14832; 1 sequenced antibody.
DR Antibodypedia; 1999; 461 antibodies from 33 providers.
DR DNASU; 5264; -.
DR Ensembl; ENST00000263038.9; ENSP00000263038.4; ENSG00000107537.14. [O14832-1]
DR Ensembl; ENST00000396913.6; ENSP00000380121.2; ENSG00000107537.14. [O14832-2]
DR GeneID; 5264; -.
DR KEGG; hsa:5264; -.
DR MANE-Select; ENST00000263038.9; ENSP00000263038.4; NM_006214.4; NP_006205.1.
DR UCSC; uc001ime.4; human. [O14832-1]
DR CTD; 5264; -.
DR DisGeNET; 5264; -.
DR GeneCards; PHYH; -.
DR GeneReviews; PHYH; -.
DR HGNC; HGNC:8940; PHYH.
DR HPA; ENSG00000107537; Tissue enhanced (liver, skeletal muscle, tongue).
DR MalaCards; PHYH; -.
DR MIM; 266500; phenotype.
DR MIM; 602026; gene.
DR neXtProt; NX_O14832; -.
DR OpenTargets; ENSG00000107537; -.
DR Orphanet; 773; Refsum disease.
DR PharmGKB; PA33280; -.
DR VEuPathDB; HostDB:ENSG00000107537; -.
DR eggNOG; KOG3290; Eukaryota.
DR GeneTree; ENSGT00390000001775; -.
DR HOGENOM; CLU_060877_0_0_1; -.
DR InParanoid; O14832; -.
DR OMA; NRTEGFR; -.
DR OrthoDB; 623398at2759; -.
DR PhylomeDB; O14832; -.
DR TreeFam; TF313667; -.
DR BioCyc; MetaCyc:HS03003-MON; -.
DR BRENDA; 1.14.11.18; 2681.
DR PathwayCommons; O14832; -.
DR Reactome; R-HSA-389599; Alpha-oxidation of phytanate.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR Reactome; R-HSA-9033500; TYSND1 cleaves peroxisomal proteins.
DR SignaLink; O14832; -.
DR UniPathway; UPA00199; -.
DR BioGRID-ORCS; 5264; 13 hits in 1081 CRISPR screens.
DR ChiTaRS; PHYH; human.
DR EvolutionaryTrace; O14832; -.
DR GenomeRNAi; 5264; -.
DR Pharos; O14832; Tbio.
DR PRO; PR:O14832; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; O14832; protein.
DR Bgee; ENSG00000107537; Expressed in vastus lateralis and 203 other tissues.
DR ExpressionAtlas; O14832; baseline and differential.
DR Genevisible; O14832; HS.
DR GO; GO:0097731; C:9+0 non-motile cilium; IDA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0031406; F:carboxylic acid binding; IDA:CAFA.
DR GO; GO:0008198; F:ferrous iron binding; IDA:UniProtKB.
DR GO; GO:0031418; F:L-ascorbic acid binding; IDA:UniProtKB.
DR GO; GO:0048244; F:phytanoyl-CoA dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0019606; P:2-oxobutyrate catabolic process; IEA:Ensembl.
DR GO; GO:0006103; P:2-oxoglutarate metabolic process; IDA:CAFA.
DR GO; GO:0001561; P:fatty acid alpha-oxidation; IDA:UniProtKB.
DR GO; GO:0006720; P:isoprenoid metabolic process; IDA:UniProtKB.
DR GO; GO:0097089; P:methyl-branched fatty acid metabolic process; IDA:UniProtKB.
DR DisProt; DP00327; -.
DR InterPro; IPR008775; Phytyl_CoA_dOase.
DR Pfam; PF05721; PhyH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cataract; Deafness; Dioxygenase;
KW Disease variant; Ichthyosis; Iron; Metal-binding; Oxidoreductase;
KW Peroxisome; Peroxisome biogenesis disorder; Phosphoprotein;
KW Reference proteome; Retinitis pigmentosa; Transit peptide; Vitamin C.
FT TRANSIT 1..30
FT /note="Peroxisome"
FT /evidence="ECO:0000250|UniProtKB:P57093"
FT CHAIN 31..338
FT /note="Phytanoyl-CoA dioxygenase, peroxisomal"
FT /id="PRO_0000024053"
FT BINDING 120
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:16186124"
FT BINDING 157
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:16186124"
FT BINDING 175..177
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:16186124"
FT BINDING 175
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:16186124"
FT BINDING 177
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:16186124"
FT BINDING 193
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:16186124"
FT BINDING 264
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:16186124"
FT BINDING 266
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:16186124"
FT BINDING 275
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:16186124"
FT MOD_RES 59
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35386"
FT MOD_RES 108
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35386"
FT MOD_RES 231
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35386"
FT MOD_RES 252
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:O35386"
FT MOD_RES 317
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..100
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_046289"
FT VARIANT 29
FT /note="P -> S (in dbSNP:rs28938169)"
FT /evidence="ECO:0000269|PubMed:10767344"
FT /id="VAR_017482"
FT VARIANT 83
FT /note="N -> Y (in RD)"
FT /id="VAR_018619"
FT VARIANT 173
FT /note="P -> S (in RD)"
FT /evidence="ECO:0000269|PubMed:10767344"
FT /id="VAR_017483"
FT VARIANT 175
FT /note="H -> R (in RD)"
FT /id="VAR_018631"
FT VARIANT 176
FT /note="Q -> K (in RD; dbSNP:rs28939672)"
FT /evidence="ECO:0000269|PubMed:10767344"
FT /id="VAR_017484"
FT VARIANT 177
FT /note="D -> G (in RD; total loss of activity;
FT dbSNP:rs770262329)"
FT /evidence="ECO:0000269|PubMed:10767344"
FT /id="VAR_017485"
FT VARIANT 192
FT /note="A -> AA (in RD)"
FT /evidence="ECO:0000269|PubMed:10767344"
FT /id="VAR_012980"
FT VARIANT 193
FT /note="W -> R (in RD)"
FT /evidence="ECO:0000269|PubMed:10767344"
FT /id="VAR_017486"
FT VARIANT 197
FT /note="E -> Q (in RD)"
FT /evidence="ECO:0000269|PubMed:10767344"
FT /id="VAR_017487"
FT VARIANT 199
FT /note="I -> F (in RD)"
FT /evidence="ECO:0000269|PubMed:10767344"
FT /id="VAR_017488"
FT VARIANT 204
FT /note="G -> S (in RD; total loss of activity;
FT dbSNP:rs104894173)"
FT /evidence="ECO:0000269|PubMed:10709665,
FT ECO:0000269|PubMed:10767344"
FT /id="VAR_017489"
FT VARIANT 215
FT /note="G -> S (in dbSNP:rs7901902)"
FT /id="VAR_050528"
FT VARIANT 220
FT /note="H -> Y (in RD; dbSNP:rs767216891)"
FT /evidence="ECO:0000269|PubMed:10767344"
FT /id="VAR_017490"
FT VARIANT 245
FT /note="R -> Q (in dbSNP:rs62619919)"
FT /evidence="ECO:0000269|PubMed:10767344,
FT ECO:0000269|PubMed:27535533"
FT /id="VAR_017491"
FT VARIANT 257
FT /note="F -> S (in RD; dbSNP:rs1211564430)"
FT /evidence="ECO:0000269|PubMed:10767344"
FT /id="VAR_017492"
FT VARIANT 269
FT /note="N -> H (in RD; dbSNP:rs104894179)"
FT /evidence="ECO:0000269|PubMed:10767344,
FT ECO:0000269|PubMed:9326940"
FT /id="VAR_005525"
FT VARIANT 275
FT /note="R -> Q (in RD; total loss of activity;
FT dbSNP:rs104894174)"
FT /evidence="ECO:0000269|PubMed:10767344"
FT /id="VAR_017493"
FT VARIANT 275
FT /note="R -> W (in RD; total loss of activity;
FT dbSNP:rs104894178)"
FT /evidence="ECO:0000269|PubMed:10767344,
FT ECO:0000269|PubMed:9326939"
FT /id="VAR_005526"
FT HELIX 57..64
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 65..69
FT /evidence="ECO:0007829|PDB:2A1X"
FT HELIX 75..89
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:2A1X"
FT HELIX 128..135
FT /evidence="ECO:0007829|PDB:2A1X"
FT HELIX 137..147
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 149..161
FT /evidence="ECO:0007829|PDB:2A1X"
FT HELIX 177..180
FT /evidence="ECO:0007829|PDB:2A1X"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 189..197
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:2A1X"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 255..258
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 264..266
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 275..284
FT /evidence="ECO:0007829|PDB:2A1X"
FT HELIX 296..301
FT /evidence="ECO:0007829|PDB:2A1X"
FT HELIX 320..327
FT /evidence="ECO:0007829|PDB:2A1X"
FT STRAND 329..333
FT /evidence="ECO:0007829|PDB:2A1X"
SQ SEQUENCE 338 AA; 38538 MW; FBF9639E7C79A6B0 CRC64;
MEQLRAAARL QIVLGHLGRP SAGAVVAHPT SGTISSASFH PQQFQYTLDN NVLTLEQRKF
YEENGFLVIK NLVPDADIQR FRNEFEKICR KEVKPLGLTV MRDVTISKSE YAPSEKMITK
VQDFQEDKEL FRYCTLPEIL KYVECFTGPN IMAMHTMLIN KPPDSGKKTS RHPLHQDLHY
FPFRPSDLIV CAWTAMEHIS RNNGCLVVLP GTHKGSLKPH DYPKWEGGVN KMFHGIQDYE
ENKARVHLVM EKGDTVFFHP LLIHGSGQNK TQGFRKAISC HFASADCHYI DVKGTSQENI
EKEVVGIAHK FFGAENSVNL KDIWMFRARL VKGERTNL
