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 27-MAR-2024, entry version 218. 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-36513937; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 153. DR IntAct; Q08426; 122. DR STRING; 9606.ENSP00000231887; -. DR DrugBank; DB00157; NADH. DR SwissLipids; SLP:000000543; -. DR iPTMnet; Q08426; -. DR PhosphoSitePlus; Q08426; -. DR SwissPalm; Q08426; -. DR BioMuta; EHHADH; -. DR DMDM; 223590229; -. DR EPD; Q08426; -. DR jPOST; Q08426; -. DR MassIVE; Q08426; -. DR MaxQB; Q08426; -. DR PaxDb; 9606-ENSP00000231887; -. DR PeptideAtlas; Q08426; -. DR ProteomicsDB; 58608; -. [Q08426-1] DR ProteomicsDB; 58609; -. [Q08426-2] DR Pumba; Q08426; -. DR Antibodypedia; 33832; 376 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 AGR; HGNC:3247; -. 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; YNGAAMG; -. DR OrthoDB; 622692at2759; -. DR PhylomeDB; Q08426; -. DR TreeFam; TF316708; -. DR BioCyc; MetaCyc:HS03720-MONOMER; -. 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; 13 hits in 1164 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 161 other cell types or tissues. DR ExpressionAtlas; Q08426; baseline and differential. 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:0018812; F:3-hydroxyacyl-CoA dehydratase activity; TAS:Reactome. 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: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 CDD; cd06558; crotonase-like; 1. DR Gene3D; 1.10.1040.50; -; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. 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 PANTHER; PTHR23309; 3-HYDROXYACYL-COA DEHYROGENASE; 1. DR PANTHER; PTHR23309:SF9; PEROXISOMAL BIFUNCTIONAL ENZYME; 1. DR Pfam; PF00725; 3HCDH; 2. DR Pfam; PF02737; 3HCDH_N; 1. DR Pfam; PF00378; ECH_1; 1. DR SUPFAM; SSF48179; 6-phosphogluconate dehydrogenase C-terminal domain-like; 2. DR SUPFAM; SSF52096; ClpP/crotonase; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR PROSITE; PS00067; 3HCDH; 1. DR PROSITE; PS00166; ENOYL_COA_HYDRATASE; 1. DR Genevisible; Q08426; HS. 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; FT Q-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; FT Q-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; FT Q-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; FT Q-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 //