ECHP_HUMAN
ID ECHP_HUMAN Reviewed; 723 AA.
AC Q08426; A8K6Y3; B4DWG3; D3DNU0; Q58EZ5;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 3.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Peroxisomal bifunctional enzyme {ECO:0000305};
DE Short=PBE;
DE Short=PBFE;
DE AltName: Full=L-bifunctional protein {ECO:0000303|PubMed:15060085};
DE Short=LBP {ECO:0000303|PubMed:15060085};
DE AltName: Full=Multifunctional enzyme 1;
DE Short=MFE1;
DE Includes:
DE RecName: Full=Enoyl-CoA hydratase/3,2-trans-enoyl-CoA isomerase;
DE EC=4.2.1.17 {ECO:0000269|PubMed:15060085};
DE EC=5.3.3.8;
DE Includes:
DE RecName: Full=3-hydroxyacyl-CoA dehydrogenase;
DE EC=1.1.1.35 {ECO:0000269|PubMed:15060085};
GN Name=EHHADH {ECO:0000312|HGNC:HGNC:3247}; Synonyms=ECHD;
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), TISSUE SPECIFICITY, AND VARIANTS
RP GLY-40; ARG-41; ILE-75; GLY-325; THR-598 AND PRO-606.
RC TISSUE=Liver;
RX PubMed=8188243; DOI=10.1006/geno.1994.1013;
RA Hoefler G., Forstner M., McGuinness M.C., Hulla W., Hiden M., Krisper P.,
RA Kenner L., Ried T., Lengauer C., Zechner R., Moser H.W., Chen G.L.;
RT "cDNA cloning of the human peroxisomal enoyl-CoA hydratase: 3-hydroxyacyl-
RT CoA dehydrogenase bifunctional enzyme and localization to chromosome
RT 3q26.3-3q28: a free left Alu Arm is inserted in the 3' noncoding region.";
RL Genomics 19:60-67(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RA Cherkaoui-Malki M., Surapureddi S., Yeldandi A.V., Rao S.M., Zhu Y.,
RA Reddy J.K.;
RT "Structural organization of gene for human peroxisomal enoyl-CoA
RT hydratase/L-3-hydroxyacyl-CoA dehydrogenase: L-bifunctional enzyme (L-
RT PBE).";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP THR-274.
RC TISSUE=Placenta, and Synovium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 502-723 (ISOFORMS 1/2), AND VARIANTS THR-598
RP AND PRO-606.
RC TISSUE=Liver;
RX PubMed=1651711; DOI=10.1016/0006-291x(91)91003-u;
RA Chen G.L., Balfe A., Erwa W., Hoefler G., Gaertner J., Aikawa J.,
RA Chen W.W.;
RT "Import of human bifunctional enzyme into peroxisomes of human hepatoma
RT cells in vitro.";
RL Biochem. Biophys. Res. Commun. 178:1084-1091(1991).
RN [9]
RP ASSOCIATION WITH PERIXOSOMAL DISORDERS.
RX PubMed=3469675; DOI=10.1073/pnas.84.5.1425;
RA Chen W.W., Watkins P.A., Osumi T., Hashimoto T., Moser H.W.;
RT "Peroxisomal beta-oxidation enzyme proteins in adrenoleukodystrophy:
RT distinction between X-linked adrenoleukodystrophy and neonatal
RT adrenoleukodystrophy.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:1425-1428(1987).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15060085; DOI=10.1194/jlr.m300512-jlr200;
RA Ferdinandusse S., Denis S., Van Roermund C.W., Wanders R.J., Dacremont G.;
RT "Identification of the peroxisomal beta-oxidation enzymes involved in the
RT degradation of long-chain dicarboxylic acids.";
RL J. Lipid Res. 45:1104-1111(2004).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-584, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP ACETYLATION AT LYS-165; LYS-171; LYS-346 AND LYS-584, ACTIVITY REGULATION,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF LYS-165; LYS-171;
RP LYS-346 AND LYS-584.
RX PubMed=20167786; DOI=10.1126/science.1179689;
RA Zhao S., Xu W., Jiang W., Yu W., Lin Y., Zhang T., Yao J., Zhou L.,
RA Zeng Y., Li H., Li Y., Shi J., An W., Hancock S.M., He F., Qin L., Chin J.,
RA Yang P., Chen X., Lei Q., Xiong Y., Guan K.L.;
RT "Regulation of cellular metabolism by protein lysine acetylation.";
RL Science 327:1000-1004(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-718, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-548, 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 [16]
RP VARIANT FRTS3 LYS-3, CHARACTERIZATION OF VARIANT FRTS3 LYS-3, AND TISSUE
RP SPECIFICITY.
RX PubMed=24401050; DOI=10.1056/nejmoa1307581;
RA Klootwijk E.D., Reichold M., Helip-Wooley A., Tolaymat A., Broeker C.,
RA Robinette S.L., Reinders J., Peindl D., Renner K., Eberhart K., Assmann N.,
RA Oefner P.J., Dettmer K., Sterner C., Schroeder J., Zorger N., Witzgall R.,
RA Reinhold S.W., Stanescu H.C., Bockenhauer D., Jaureguiberry G.,
RA Courtneidge H., Hall A.M., Wijeyesekera A.D., Holmes E., Nicholson J.K.,
RA O'Brien K., Bernardini I., Krasnewich D.M., Arcos-Burgos M., Izumi Y.,
RA Nonoguchi H., Jia Y., Reddy J.K., Ilyas M., Unwin R.J., Gahl W.A.,
RA Warth R., Kleta R.;
RT "Mistargeting of peroxisomal EHHADH and inherited renal Fanconi's
RT syndrome.";
RL N. Engl. J. Med. 370:129-138(2014).
CC -!- FUNCTION: Peroxisomal trifunctional enzyme possessing 2-enoyl-CoA
CC hydratase, 3-hydroxyacyl-CoA dehydrogenase, and delta 3, delta 2-enoyl-
CC CoA isomerase activities. Catalyzes two of the four reactions of the
CC long chain fatty acids peroxisomal beta-oxidation pathway (By
CC similarity). Can also use branched-chain fatty acids such as 2-methyl-
CC 2E-butenoyl-CoA as a substrate, which is hydrated into (2S,3S)-3-
CC hydroxy-2-methylbutanoyl-CoA (By similarity). Optimal isomerase for 2,5
CC double bonds into 3,5 form isomerization in a range of enoyl-CoA
CC species (Probable). Also able to isomerize both 3-cis and 3-trans
CC double bonds into the 2-trans form in a range of enoyl-CoA species (By
CC similarity). With HSD17B4, catalyzes the hydration of trans-2-enoyl-CoA
CC and the dehydrogenation of 3-hydroxyacyl-CoA, but with opposite chiral
CC specificity (PubMed:15060085). Regulates the amount of medium-chain
CC dicarboxylic fatty acids which are essential regulators of all fatty
CC acid oxidation pathways (By similarity). Also involved in the
CC degradation of long-chain dicarboxylic acids through peroxisomal beta-
CC oxidation (PubMed:15060085). {ECO:0000250|UniProtKB:P07896,
CC ECO:0000250|UniProtKB:Q9DBM2, ECO:0000269|PubMed:15060085,
CC ECO:0000305|PubMed:15060085}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3S)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O;
CC Xref=Rhea:RHEA:16105, ChEBI:CHEBI:15377, ChEBI:CHEBI:57318,
CC ChEBI:CHEBI:58856; EC=4.2.1.17;
CC Evidence={ECO:0000269|PubMed:15060085};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16106;
CC Evidence={ECO:0000305|PubMed:15060085};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 4-saturated-(3S)-3-hydroxyacyl-CoA = a (3E)-enoyl-CoA + H2O;
CC Xref=Rhea:RHEA:20724, ChEBI:CHEBI:15377, ChEBI:CHEBI:58521,
CC ChEBI:CHEBI:137480; EC=4.2.1.17;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20725;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3Z)-enoyl-CoA = a 4-saturated (2E)-enoyl-CoA;
CC Xref=Rhea:RHEA:45900, ChEBI:CHEBI:85097, ChEBI:CHEBI:85489;
CC EC=5.3.3.8; Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45901;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3E)-enoyl-CoA = a 4-saturated (2E)-enoyl-CoA;
CC Xref=Rhea:RHEA:45228, ChEBI:CHEBI:58521, ChEBI:CHEBI:85097;
CC EC=5.3.3.8; Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45229;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:22432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57318,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726; EC=1.1.1.35;
CC Evidence={ECO:0000269|PubMed:15060085};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22433;
CC Evidence={ECO:0000305|PubMed:15060085};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2S,3S)-3-hydroxy-2-methylbutanoyl-CoA = (2E)-2-methylbut-2-
CC enoyl-CoA + H2O; Xref=Rhea:RHEA:31119, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57312, ChEBI:CHEBI:57337;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31121;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA
CC + H(+) + NADH; Xref=Rhea:RHEA:31159, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:62613; Evidence={ECO:0000269|PubMed:15060085};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31160;
CC Evidence={ECO:0000269|PubMed:15060085};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanoyl-CoA = (2E)-hexadecenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:31163, ChEBI:CHEBI:15377, ChEBI:CHEBI:61526,
CC ChEBI:CHEBI:62613; Evidence={ECO:0000269|PubMed:15060085};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31165;
CC Evidence={ECO:0000269|PubMed:15060085};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-hexadecenedioyl-CoA + H2O = (3S)-hydroxyhexadecanedioyl-
CC CoA; Xref=Rhea:RHEA:40259, ChEBI:CHEBI:15377, ChEBI:CHEBI:77075,
CC ChEBI:CHEBI:77080; Evidence={ECO:0000269|PubMed:15060085};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40260;
CC Evidence={ECO:0000269|PubMed:15060085};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanedioyl-CoA + NAD(+) = 3-
CC oxohexadecanedioyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:40267,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:77080, ChEBI:CHEBI:77081;
CC Evidence={ECO:0000269|PubMed:15060085};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40268;
CC Evidence={ECO:0000269|PubMed:15060085};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E,5Z)-tetradecadienoyl-CoA = (2E,5Z)-tetradecadienoyl-CoA;
CC Xref=Rhea:RHEA:47464, ChEBI:CHEBI:71586, ChEBI:CHEBI:87701;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:47466;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E,5Z)-octadienoyl-CoA = (2E,5Z)-octadienoyl-CoA;
CC Xref=Rhea:RHEA:49932, ChEBI:CHEBI:85108, ChEBI:CHEBI:131990;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:49934;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxydecanoyl-CoA + NAD(+) = 3-oxodecanoyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:31187, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:62548, ChEBI:CHEBI:62616;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31188;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E)-decenoyl-CoA = (2E)-decenoyl-CoA; Xref=Rhea:RHEA:45752,
CC ChEBI:CHEBI:61406, ChEBI:CHEBI:84793;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45753;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3Z)-hexenoyl-CoA = (2E)-hexenoyl-CoA; Xref=Rhea:RHEA:45748,
CC ChEBI:CHEBI:62077, ChEBI:CHEBI:85415;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45749;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3E)-hexenoyl-CoA = (2E)-hexenoyl-CoA; Xref=Rhea:RHEA:45736,
CC ChEBI:CHEBI:62077, ChEBI:CHEBI:84790;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45737;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxydecanoyl-CoA = (2E)-decenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:31191, ChEBI:CHEBI:15377, ChEBI:CHEBI:61406,
CC ChEBI:CHEBI:62616; Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31193;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexanoyl-CoA = (2E)-hexenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:30547, ChEBI:CHEBI:15377, ChEBI:CHEBI:62075,
CC ChEBI:CHEBI:62077; Evidence={ECO:0000250|UniProtKB:P07896};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30549;
CC Evidence={ECO:0000250|UniProtKB:P07896};
CC -!- ACTIVITY REGULATION: Enzyme activity enhanced by acetylation.
CC {ECO:0000269|PubMed:20167786}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.3 uM for (3S)-hydroxyhexadecanedioyl-CoA
CC {ECO:0000269|PubMed:15060085};
CC KM=10 uM for (3S)-hydroxyhexadecanoyl-CoA
CC {ECO:0000269|PubMed:15060085};
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:15060085}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P07896}.
CC -!- INTERACTION:
CC Q08426; Q5JTZ9: AARS2; NbExp=3; IntAct=EBI-2339219, EBI-308736;
CC Q08426; P60709: ACTB; NbExp=4; IntAct=EBI-2339219, EBI-353944;
CC Q08426; P63261: ACTG1; NbExp=4; IntAct=EBI-2339219, EBI-351292;
CC Q08426; P78563-4: ADARB1; NbExp=3; IntAct=EBI-2339219, EBI-12002366;
CC Q08426; Q8N2N9-4: ANKRD36B; NbExp=3; IntAct=EBI-2339219, EBI-12170453;
CC Q08426; Q5T9G4-2: ARMC12; NbExp=3; IntAct=EBI-2339219, EBI-23667468;
CC Q08426; Q9UH62: ARMCX3; NbExp=3; IntAct=EBI-2339219, EBI-717832;
CC Q08426; O14503: BHLHE40; NbExp=3; IntAct=EBI-2339219, EBI-711810;
CC Q08426; Q8N9W6-4: BOLL; NbExp=3; IntAct=EBI-2339219, EBI-11983447;
CC Q08426; Q9BV19: C1orf50; NbExp=3; IntAct=EBI-2339219, EBI-2874661;
CC Q08426; P20807-4: CAPN3; NbExp=3; IntAct=EBI-2339219, EBI-11532021;
CC Q08426; P35520: CBS; NbExp=4; IntAct=EBI-2339219, EBI-740135;
CC Q08426; Q68D86: CCDC102B; NbExp=4; IntAct=EBI-2339219, EBI-10171570;
CC Q08426; Q8IYE1: CCDC13; NbExp=3; IntAct=EBI-2339219, EBI-10961312;
CC Q08426; Q86X02: CDR2L; NbExp=3; IntAct=EBI-2339219, EBI-11063830;
CC Q08426; Q9Y592-2: CEP83; NbExp=3; IntAct=EBI-2339219, EBI-11123098;
CC Q08426; Q9Y281: CFL2; NbExp=3; IntAct=EBI-2339219, EBI-351218;
CC Q08426; Q8N5K1: CISD2; NbExp=3; IntAct=EBI-2339219, EBI-1045797;
CC Q08426; P56856: CLDN18; NbExp=3; IntAct=EBI-2339219, EBI-16354902;
CC Q08426; O00501: CLDN5; NbExp=3; IntAct=EBI-2339219, EBI-18400628;
CC Q08426; P49760: CLK2; NbExp=3; IntAct=EBI-2339219, EBI-750020;
CC Q08426; Q9NX76: CMTM6; NbExp=3; IntAct=EBI-2339219, EBI-1054315;
CC Q08426; O75208: COQ9; NbExp=3; IntAct=EBI-2339219, EBI-724524;
CC Q08426; P49447: CYB561; NbExp=3; IntAct=EBI-2339219, EBI-8646596;
CC Q08426; Q8NBI2: CYB561A3; NbExp=3; IntAct=EBI-2339219, EBI-10269179;
CC Q08426; Q96Q80: DERL3; NbExp=3; IntAct=EBI-2339219, EBI-12831318;
CC Q08426; P17661: DES; NbExp=6; IntAct=EBI-2339219, EBI-1055572;
CC Q08426; Q9NR28: DIABLO; NbExp=3; IntAct=EBI-2339219, EBI-517508;
CC Q08426; Q15125: EBP; NbExp=3; IntAct=EBI-2339219, EBI-3915253;
CC Q08426; P54849: EMP1; NbExp=3; IntAct=EBI-2339219, EBI-4319440;
CC Q08426; Q969X5: ERGIC1; NbExp=3; IntAct=EBI-2339219, EBI-781527;
CC Q08426; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-2339219, EBI-781551;
CC Q08426; P60508: ERVFRD-1; NbExp=3; IntAct=EBI-2339219, EBI-17973325;
CC Q08426; Q92915-2: FGF14; NbExp=3; IntAct=EBI-2339219, EBI-12836320;
CC Q08426; Q8IVP5: FUNDC1; NbExp=4; IntAct=EBI-2339219, EBI-3059266;
CC Q08426; O95995: GAS8; NbExp=3; IntAct=EBI-2339219, EBI-1052570;
CC Q08426; Q96IK5: GMCL1; NbExp=3; IntAct=EBI-2339219, EBI-2548508;
CC Q08426; Q4V328: GRIPAP1; NbExp=3; IntAct=EBI-2339219, EBI-717919;
CC Q08426; Q8IV36: HID1; NbExp=3; IntAct=EBI-2339219, EBI-743438;
CC Q08426; O00291: HIP1; NbExp=3; IntAct=EBI-2339219, EBI-473886;
CC Q08426; Q9NP66: HMG20A; NbExp=3; IntAct=EBI-2339219, EBI-740641;
CC Q08426; Q8NBQ5: HSD17B11; NbExp=3; IntAct=EBI-2339219, EBI-1052304;
CC Q08426; Q9BUP3-3: HTATIP2; NbExp=3; IntAct=EBI-2339219, EBI-12937691;
CC Q08426; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-2339219, EBI-747204;
CC Q08426; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-2339219, EBI-10266796;
CC Q08426; Q8NC69: KCTD6; NbExp=5; IntAct=EBI-2339219, EBI-2511344;
CC Q08426; Q7L273: KCTD9; NbExp=4; IntAct=EBI-2339219, EBI-4397613;
CC Q08426; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-2339219, EBI-10172290;
CC Q08426; Q9BYQ6: KRTAP4-11; NbExp=3; IntAct=EBI-2339219, EBI-10302392;
CC Q08426; P80188: LCN2; NbExp=3; IntAct=EBI-2339219, EBI-11911016;
CC Q08426; O95214: LEPROTL1; NbExp=5; IntAct=EBI-2339219, EBI-750776;
CC Q08426; P36941: LTBR; NbExp=3; IntAct=EBI-2339219, EBI-3509981;
CC Q08426; Q6UWN5: LYPD5; NbExp=3; IntAct=EBI-2339219, EBI-17200970;
CC Q08426; Q9NQ48: LZTFL1; NbExp=3; IntAct=EBI-2339219, EBI-2824799;
CC Q08426; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-2339219, EBI-741037;
CC Q08426; Q8N8X9: MAB21L3; NbExp=3; IntAct=EBI-2339219, EBI-10268010;
CC Q08426; O15344: MID1; NbExp=8; IntAct=EBI-2339219, EBI-2340316;
CC Q08426; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-2339219, EBI-11522433;
CC Q08426; Q96RE7: NACC1; NbExp=3; IntAct=EBI-2339219, EBI-7950997;
CC Q08426; Q7Z6G3-2: NECAB2; NbExp=3; IntAct=EBI-2339219, EBI-10172876;
CC Q08426; P35372-10: OPRM1; NbExp=3; IntAct=EBI-2339219, EBI-12807478;
CC Q08426; Q9P0S3: ORMDL1; NbExp=3; IntAct=EBI-2339219, EBI-1054848;
CC Q08426; Q8TEZ7: PAQR8; NbExp=3; IntAct=EBI-2339219, EBI-12847818;
CC Q08426; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-2339219, EBI-79165;
CC Q08426; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-2339219, EBI-302345;
CC Q08426; Q96PV4: PNMA5; NbExp=3; IntAct=EBI-2339219, EBI-10171633;
CC Q08426; Q9BZL4: PPP1R12C; NbExp=3; IntAct=EBI-2339219, EBI-721802;
CC Q08426; O75569: PRKRA; NbExp=3; IntAct=EBI-2339219, EBI-713955;
CC Q08426; O14744: PRMT5; NbExp=3; IntAct=EBI-2339219, EBI-351098;
CC Q08426; Q1KLZ0: PS1TP5BP1; NbExp=3; IntAct=EBI-2339219, EBI-9978131;
CC Q08426; O43586: PSTPIP1; NbExp=3; IntAct=EBI-2339219, EBI-1050964;
CC Q08426; O14684: PTGES; NbExp=3; IntAct=EBI-2339219, EBI-11161398;
CC Q08426; Q96HR9-2: REEP6; NbExp=3; IntAct=EBI-2339219, EBI-14065960;
CC Q08426; Q04864-2: REL; NbExp=3; IntAct=EBI-2339219, EBI-10829018;
CC Q08426; P78317: RNF4; NbExp=3; IntAct=EBI-2339219, EBI-2340927;
CC Q08426; Q9NS64: RPRM; NbExp=3; IntAct=EBI-2339219, EBI-1052363;
CC Q08426; Q96GQ5: RUSF1; NbExp=3; IntAct=EBI-2339219, EBI-8636004;
CC Q08426; Q6ZMJ2-2: SCARA5; NbExp=3; IntAct=EBI-2339219, EBI-12823227;
CC Q08426; Q8N3Y7: SDR16C5; NbExp=3; IntAct=EBI-2339219, EBI-3923480;
CC Q08426; Q8WV19: SFT2D1; NbExp=3; IntAct=EBI-2339219, EBI-2854842;
CC Q08426; Q16585: SGCB; NbExp=3; IntAct=EBI-2339219, EBI-5663627;
CC Q08426; Q15849: SLC14A2; NbExp=3; IntAct=EBI-2339219, EBI-1573290;
CC Q08426; Q9NP94: SLC39A2; NbExp=3; IntAct=EBI-2339219, EBI-12898013;
CC Q08426; Q71RC9: SMIM5; NbExp=3; IntAct=EBI-2339219, EBI-12334905;
CC Q08426; Q16637: SMN2; NbExp=3; IntAct=EBI-2339219, EBI-395421;
CC Q08426; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-2339219, EBI-17280858;
CC Q08426; O43805: SSNA1; NbExp=4; IntAct=EBI-2339219, EBI-2515299;
CC Q08426; Q9Y2D8: SSX2IP; NbExp=3; IntAct=EBI-2339219, EBI-2212028;
CC Q08426; O43759-2: SYNGR1; NbExp=3; IntAct=EBI-2339219, EBI-12187159;
CC Q08426; O43761: SYNGR3; NbExp=3; IntAct=EBI-2339219, EBI-11321949;
CC Q08426; Q9BTD3: TMEM121; NbExp=3; IntAct=EBI-2339219, EBI-12155101;
CC Q08426; Q86X19: TMEM17; NbExp=3; IntAct=EBI-2339219, EBI-11343485;
CC Q08426; Q53FP2: TMEM35A; NbExp=3; IntAct=EBI-2339219, EBI-11722971;
CC Q08426; Q15025: TNIP1; NbExp=4; IntAct=EBI-2339219, EBI-357849;
CC Q08426; P29144: TPP2; NbExp=5; IntAct=EBI-2339219, EBI-1044672;
CC Q08426; Q13077: TRAF1; NbExp=3; IntAct=EBI-2339219, EBI-359224;
CC Q08426; Q12933: TRAF2; NbExp=3; IntAct=EBI-2339219, EBI-355744;
CC Q08426; P19474: TRIM21; NbExp=3; IntAct=EBI-2339219, EBI-81290;
CC Q08426; P36406: TRIM23; NbExp=3; IntAct=EBI-2339219, EBI-740098;
CC Q08426; P14373: TRIM27; NbExp=6; IntAct=EBI-2339219, EBI-719493;
CC Q08426; Q8WV44: TRIM41; NbExp=7; IntAct=EBI-2339219, EBI-725997;
CC Q08426; Q9C035-3: TRIM5; NbExp=3; IntAct=EBI-2339219, EBI-12840050;
CC Q08426; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-2339219, EBI-2130429;
CC Q08426; Q969Q1: TRIM63; NbExp=3; IntAct=EBI-2339219, EBI-5661333;
CC Q08426; Q04323-2: UBXN1; NbExp=3; IntAct=EBI-2339219, EBI-11530712;
CC Q08426; Q08AM6: VAC14; NbExp=3; IntAct=EBI-2339219, EBI-2107455;
CC Q08426; Q96DT7-3: ZBTB10; NbExp=3; IntAct=EBI-2339219, EBI-12017160;
CC Q08426; Q9HCK0: ZBTB26; NbExp=5; IntAct=EBI-2339219, EBI-3918996;
CC Q08426; Q96BR9: ZBTB8A; NbExp=3; IntAct=EBI-2339219, EBI-742740;
CC Q08426; Q96C00: ZBTB9; NbExp=6; IntAct=EBI-2339219, EBI-395708;
CC Q08426; Q9NP64: ZCCHC17; NbExp=3; IntAct=EBI-2339219, EBI-746345;
CC Q08426; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-2339219, EBI-527853;
CC Q08426; P0DTC9: N; Xeno; NbExp=4; IntAct=EBI-2339219, EBI-25475856;
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q08426-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q08426-2; Sequence=VSP_042811;
CC -!- TISSUE SPECIFICITY: Liver and kidney. Strongly expressed in the
CC terminal segments of the proximal tubule. Lower amounts seen in the
CC brain. {ECO:0000269|PubMed:24401050, ECO:0000269|PubMed:8188243}.
CC -!- PTM: Acetylated, leading to enhanced enzyme activity. Acetylation is
CC enhanced by up to 80% after treatment either with trichostin A (TSA) or
CC with nicotinamide (NAM) with highest increase on Lys-346. Acetylation
CC and enzyme activity increased by about 1.5% on addition of fatty acids.
CC {ECO:0000269|PubMed:20167786}.
CC -!- DISEASE: Fanconi renotubular syndrome 3 (FRTS3) [MIM:615605]: A form of
CC Fanconi renotubular syndrome, a disease due to a generalized
CC dysfunction of the proximal kidney tubule resulting in decreased solute
CC and water reabsorption. Patients have polydipsia and polyuria with
CC phosphaturia, glycosuria and aminoaciduria. They may develop
CC hypophosphatemic rickets or osteomalacia, acidosis and a tendency
CC toward dehydration. Some eventually develop renal insufficiency. FRTS3
CC inheritance is autosomal dominant. {ECO:0000269|PubMed:24401050}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: Absent in patients suffering with peroxisomal disorders
CC such as Zellweger syndrome, neonatal adrenoleukodystrophy and infantile
CC Refsum disease.
CC -!- SIMILARITY: In the N-terminal section; belongs to the enoyl-CoA
CC hydratase/isomerase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the 3-hydroxyacyl-CoA
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; L07077; AAA53289.1; -; mRNA.
DR EMBL; AJ427345; CAD22483.1; -; Genomic_DNA.
DR EMBL; AJ427346; CAD22483.1; JOINED; Genomic_DNA.
DR EMBL; AJ427347; CAD22483.1; JOINED; Genomic_DNA.
DR EMBL; AJ427348; CAD22483.1; JOINED; Genomic_DNA.
DR EMBL; AJ427349; CAD22483.1; JOINED; Genomic_DNA.
DR EMBL; AJ427350; CAD22483.1; JOINED; Genomic_DNA.
DR EMBL; AJ427351; CAD22483.1; JOINED; Genomic_DNA.
DR EMBL; AK291798; BAF84487.1; -; mRNA.
DR EMBL; AK223460; BAD97180.1; -; mRNA.
DR EMBL; AK301521; BAG63025.1; -; mRNA.
DR EMBL; AC007934; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC128680; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78229.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78230.1; -; Genomic_DNA.
DR EMBL; BC038948; AAH38948.1; -; mRNA.
DR EMBL; BC110460; AAI10461.1; -; mRNA.
DR EMBL; S50245; AAB19482.1; -; mRNA.
DR CCDS; CCDS33901.1; -. [Q08426-1]
DR CCDS; CCDS54694.1; -. [Q08426-2]
DR PIR; A49613; A49613.
DR RefSeq; NP_001159887.1; NM_001166415.1. [Q08426-2]
DR RefSeq; NP_001957.2; NM_001966.3. [Q08426-1]
DR RefSeq; XP_011510819.1; XM_011512517.1.
DR AlphaFoldDB; Q08426; -.
DR SMR; Q08426; -.
DR BioGRID; 108282; 152.
DR IntAct; Q08426; 122.
DR STRING; 9606.ENSP00000231887; -.
DR DrugBank; DB00157; NADH.
DR SwissLipids; SLP:000000543; -.
DR iPTMnet; Q08426; -.
DR PhosphoSitePlus; Q08426; -.
DR BioMuta; EHHADH; -.
DR DMDM; 223590229; -.
DR EPD; Q08426; -.
DR jPOST; Q08426; -.
DR MassIVE; Q08426; -.
DR MaxQB; Q08426; -.
DR PaxDb; Q08426; -.
DR PeptideAtlas; Q08426; -.
DR PRIDE; Q08426; -.
DR ProteomicsDB; 58608; -. [Q08426-1]
DR ProteomicsDB; 58609; -. [Q08426-2]
DR Antibodypedia; 33832; 342 antibodies from 30 providers.
DR DNASU; 1962; -.
DR Ensembl; ENST00000231887.8; ENSP00000231887.3; ENSG00000113790.11. [Q08426-1]
DR Ensembl; ENST00000456310.5; ENSP00000387746.1; ENSG00000113790.11. [Q08426-2]
DR GeneID; 1962; -.
DR KEGG; hsa:1962; -.
DR MANE-Select; ENST00000231887.8; ENSP00000231887.3; NM_001966.4; NP_001957.2.
DR UCSC; uc003fpf.3; human. [Q08426-1]
DR CTD; 1962; -.
DR DisGeNET; 1962; -.
DR GeneCards; EHHADH; -.
DR HGNC; HGNC:3247; EHHADH.
DR HPA; ENSG00000113790; Group enriched (kidney, liver).
DR MalaCards; EHHADH; -.
DR MIM; 607037; gene.
DR MIM; 615605; phenotype.
DR neXtProt; NX_Q08426; -.
DR OpenTargets; ENSG00000113790; -.
DR Orphanet; 300; Bifunctional enzyme deficiency.
DR Orphanet; 3337; Primary Fanconi renotubular syndrome.
DR PharmGKB; PA27682; -.
DR VEuPathDB; HostDB:ENSG00000113790; -.
DR eggNOG; KOG1683; Eukaryota.
DR GeneTree; ENSGT00940000157516; -.
DR HOGENOM; CLU_009834_16_3_1; -.
DR InParanoid; Q08426; -.
DR OMA; TGAGWPF; -.
DR OrthoDB; 219667at2759; -.
DR PhylomeDB; Q08426; -.
DR TreeFam; TF316708; -.
DR BioCyc; MetaCyc:HS03720-MON; -.
DR PathwayCommons; Q08426; -.
DR Reactome; R-HSA-390247; Beta-oxidation of very long chain fatty acids.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR SABIO-RK; Q08426; -.
DR SignaLink; Q08426; -.
DR UniPathway; UPA00659; -.
DR BioGRID-ORCS; 1962; 10 hits in 1082 CRISPR screens.
DR ChiTaRS; EHHADH; human.
DR GenomeRNAi; 1962; -.
DR Pharos; Q08426; Tbio.
DR PRO; PR:Q08426; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q08426; protein.
DR Bgee; ENSG00000113790; Expressed in right lobe of liver and 160 other tissues.
DR ExpressionAtlas; Q08426; baseline and differential.
DR Genevisible; Q08426; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0004165; F:delta(3)-delta(2)-enoyl-CoA isomerase activity; ISS:UniProtKB.
DR GO; GO:0004300; F:enoyl-CoA hydratase activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0016863; F:intramolecular oxidoreductase activity, transposing C=C bonds; ISS:UniProtKB.
DR GO; GO:0016509; F:long-chain-3-hydroxyacyl-CoA dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0016508; F:long-chain-enoyl-CoA hydratase activity; TAS:Reactome.
DR GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:UniProtKB.
DR GO; GO:0033540; P:fatty acid beta-oxidation using acyl-CoA oxidase; TAS:Reactome.
DR InterPro; IPR006180; 3-OHacyl-CoA_DH_CS.
DR InterPro; IPR006176; 3-OHacyl-CoA_DH_NAD-bd.
DR InterPro; IPR006108; 3HC_DH_C.
DR InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR018376; Enoyl-CoA_hyd/isom_CS.
DR InterPro; IPR001753; Enoyl-CoA_hydra/iso.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00725; 3HCDH; 2.
DR Pfam; PF02737; 3HCDH_N; 1.
DR Pfam; PF00378; ECH_1; 1.
DR SUPFAM; SSF48179; SSF48179; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52096; SSF52096; 1.
DR PROSITE; PS00067; 3HCDH; 1.
DR PROSITE; PS00166; ENOYL_COA_HYDRATASE; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Disease variant; Fatty acid metabolism;
KW Isomerase; Lipid metabolism; Lyase; Multifunctional enzyme; NAD;
KW Oxidoreductase; Peroxisome; Phosphoprotein; Reference proteome.
FT CHAIN 1..723
FT /note="Peroxisomal bifunctional enzyme"
FT /id="PRO_0000109247"
FT REGION 1..282
FT /note="Enoyl-CoA hydratase / isomerase"
FT REGION 283..572
FT /note="3-hydroxyacyl-CoA dehydrogenase"
FT MOTIF 721..723
FT /note="Microbody targeting signal"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 104
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT SITE 124
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250"
FT MOD_RES 38
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 165
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20167786"
FT MOD_RES 165
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 171
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:20167786"
FT MOD_RES 219
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 219
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 250
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 280
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 290
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 346
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:20167786"
FT MOD_RES 350
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 464
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 532
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 548
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 577
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 584
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:20167786,
FT ECO:0007744|PubMed:19608861"
FT MOD_RES 584
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 591
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 591
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 710
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 710
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT MOD_RES 718
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 722
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBM2"
FT VAR_SEQ 1..96
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042811"
FT VARIANT 3
FT /note="E -> K (in FRTS3; the mutant is mistargeted to
FT mitochondria; results in impaired mitochondrial oxidative
FT phosphorylation and defects in the transport of fluids
FT across the epithelium of renal proximal tubular cells;
FT dbSNP:rs398124646)"
FT /evidence="ECO:0000269|PubMed:24401050"
FT /id="VAR_070949"
FT VARIANT 40
FT /note="V -> G (in dbSNP:rs1062551)"
FT /evidence="ECO:0000269|PubMed:8188243"
FT /id="VAR_054329"
FT VARIANT 41
FT /note="I -> R (in dbSNP:rs1062552)"
FT /evidence="ECO:0000269|PubMed:8188243"
FT /id="VAR_054330"
FT VARIANT 75
FT /note="T -> I (in dbSNP:rs1062553)"
FT /evidence="ECO:0000269|PubMed:8188243"
FT /id="VAR_047132"
FT VARIANT 274
FT /note="A -> T (in dbSNP:rs2302819)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_047133"
FT VARIANT 325
FT /note="A -> G (in dbSNP:rs1062555)"
FT /evidence="ECO:0000269|PubMed:8188243"
FT /id="VAR_054331"
FT VARIANT 598
FT /note="K -> T (in dbSNP:rs1042437)"
FT /evidence="ECO:0000269|PubMed:1651711,
FT ECO:0000269|PubMed:8188243"
FT /id="VAR_054332"
FT VARIANT 606
FT /note="T -> P (in dbSNP:rs1042438)"
FT /evidence="ECO:0000269|PubMed:1651711,
FT ECO:0000269|PubMed:8188243"
FT /id="VAR_047134"
FT VARIANT 685
FT /note="Q -> K (in dbSNP:rs11919970)"
FT /id="VAR_047135"
FT VARIANT 715
FT /note="L -> S (in dbSNP:rs11927618)"
FT /id="VAR_047136"
FT MUTAGEN 165
FT /note="K->Q: Greatly reduced acetylation and insensitive to
FT treatment with TSA and NAM; when associated with Q-171; Q-
FT 346 and Q-584."
FT /evidence="ECO:0000269|PubMed:20167786"
FT MUTAGEN 171
FT /note="K->Q: Greatly reduced acetylation and insensitive to
FT treatment with TSA and NAM; when associated with Q-165; Q-
FT 346 and Q-584."
FT /evidence="ECO:0000269|PubMed:20167786"
FT MUTAGEN 346
FT /note="K->Q: Greatly reduced acetylation and insensitive to
FT treatment with TSA and NAM; when associated with Q-165; Q-
FT 171 and Q-584."
FT /evidence="ECO:0000269|PubMed:20167786"
FT MUTAGEN 584
FT /note="K->Q: Greatly reduced acetylation and insensitive to
FT treatment with TSA and NAM; when associated with Q-165; Q-
FT 171 and Q-346."
FT /evidence="ECO:0000269|PubMed:20167786"
FT CONFLICT 117
FT /note="E -> D (in Ref. 1; AAA53289)"
FT /evidence="ECO:0000305"
FT CONFLICT 656..657
FT /note="WP -> CA (in Ref. 1; AAA53289 and 7; AAB19482)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 723 AA; 79495 MW; FC3B44B030A7BCBD CRC64;
MAEYTRLHNA LALIRLRNPP VNAISTTLLR DIKEGLQKAV IDHTIKAIVI CGAEGKFSAG
ADIRGFSAPR TFGLTLGHVV DEIQRNEKPV VAAIQGMAFG GGLELALGCH YRIAHAEAQV
GLPEVTLGLL PGARGTQLLP RLTGVPAALD LITSGRRILA DEALKLGILD KVVNSDPVEE
AIRFAQRVSD QPLESRRLCN KPIQSLPNMD SIFSEALLKM RRQHPGCLAQ EACVRAVQAA
VQYPYEVGIK KEEELFLYLL QSGQARALQY AFFAERKANK WSTPSGASWK TASARPVSSV
GVVGLGTMGR GIVISFARAR IPVIAVDSDK NQLATANKMI TSVLEKEASK MQQSGHPWSG
PKPRLTSSVK ELGGVDLVIE AVFEEMSLKK QVFAELSAVC KPEAFLCTNT SALDVDEIAS
STDRPHLVIG THFFSPAHVM KLLEVIPSQY SSPTTIATVM NLSKKIKKIG VVVGNCFGFV
GNRMLNPYYN QAYFLLEEGS KPEEVDQVLE EFGFKMGPFR VSDLAGLDVG WKSRKGQGLT
GPTLLPGTPA RKRGNRRYCP IPDVLCELGR FGQKTGKGWY QYDKPLGRIH KPDPWLSKFL
SRYRKTHHIE PRTISQDEIL ERCLYSLINE AFRILGEGIA ASPEHIDVVY LHGYGWPRHK
GGPMFYASTV GLPTVLEKLQ KYYRQNPDIP QLEPSDYLKK LASQGNPPLK EWQSLAGSPS
SKL
