ID   ECHP_MOUSE              Reviewed;         718 AA.
AC   Q9DBM2; Q91W49;
DT   24-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 4.
DT   27-MAR-2024, entry version 184.
DE   RecName: Full=Peroxisomal bifunctional enzyme {ECO:0000305};
DE            Short=PBE;
DE            Short=PBFE;
DE   AltName: Full=L-peroxisomal bifunctional enzyme {ECO:0000303|PubMed:24075987};
DE            Short=L-PBE {ECO:0000303|PubMed:24075987};
DE   AltName: Full=Multifunctional enzyme 1;
DE            Short=MFE1;
DE   AltName: Full=Multifunctional protein 1 {ECO:0000303|PubMed:17442273};
DE            Short=MFP-1 {ECO:0000303|PubMed:17442273};
DE   Includes:
DE     RecName: Full=Enoyl-CoA hydratase/3,2-trans-enoyl-CoA isomerase;
DE              EC=4.2.1.17 {ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
DE              EC=5.3.3.8;
DE   Includes:
DE     RecName: Full=3-hydroxyacyl-CoA dehydrogenase;
DE              EC=1.1.1.35 {ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
GN   Name=Ehhadh {ECO:0000312|MGI:MGI:1277964};
GN   Synonyms=L-pbe {ECO:0000303|PubMed:24075987};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Liver;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Kidney;
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   [4]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=17442273; DOI=10.1016/j.bbrc.2007.03.198;
RA   Dirkx R., Meyhi E., Asselberghs S., Reddy J., Baes M., Van Veldhoven P.P.;
RT   "Beta-oxidation in hepatocyte cultures from mice with peroxisomal gene
RT   knockouts.";
RL   Biochem. Biophys. Res. Commun. 357:718-723(2007).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-543, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, and Pancreas;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=24075987; DOI=10.1016/j.celrep.2013.08.032;
RA   Ding J., Loizides-Mangold U., Rando G., Zoete V., Michielin O., Reddy J.K.,
RA   Wahli W., Riezman H., Thorens B.;
RT   "The peroxisomal enzyme L-PBE is required to prevent the dietary toxicity
RT   of medium-chain fatty acids.";
RL   Cell Rep. 5:248-258(2013).
RN   [7]
RP   SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-38; LYS-163; LYS-172; LYS-181;
RP   LYS-189; LYS-217; LYS-240; LYS-252; LYS-274; LYS-278; LYS-288; LYS-329;
RP   LYS-527; LYS-572; LYS-579; LYS-586; LYS-705 AND LYS-717, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
RN   [8]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-172; LYS-189; LYS-217; LYS-248;
RP   LYS-274; LYS-344; LYS-348; LYS-355; LYS-459; LYS-579; LYS-586 AND LYS-705,
RP   AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA   Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA   Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT   "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT   identifies substrates of SIRT3 in metabolic pathways.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
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
CC       (PubMed:17442273, PubMed:24075987). Can also use branched-chain fatty
CC       acids such as 2-methyl-2E-butenoyl-CoA as a substrate, which is
CC       hydrated into (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA (By similarity).
CC       Optimal isomerase for 2,5 double bonds into 3,5 form isomerization in a
CC       range of enoyl-CoA species. Also able to isomerize both 3-cis and 3-
CC       trans double bonds into the 2-trans form in a range of enoyl-CoA
CC       species (By similarity). With HSD17B4, catalyzes the hydration of
CC       trans-2-enoyl-CoA and the dehydrogenation of 3-hydroxyacyl-CoA, but
CC       with opposite chiral specificity (Probable). Regulates the amount of
CC       medium-chain dicarboxylic fatty acids which are essential regulators of
CC       all fatty acid oxidation pathways (PubMed:24075987). Also involved in
CC       the degradation of long-chain dicarboxylic acids through peroxisomal
CC       beta-oxidation (By similarity). {ECO:0000250|UniProtKB:P07896,
CC       ECO:0000250|UniProtKB:Q08426, ECO:0000269|PubMed:17442273,
CC       ECO:0000269|PubMed:24075987, ECO:0000305|PubMed:24075987}.
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:17442273, ECO:0000269|PubMed:24075987};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16107;
CC         Evidence={ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
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:17442273, ECO:0000269|PubMed:24075987};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22433;
CC         Evidence={ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
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=(2E)-dodecenedioyl-CoA + H2O = (3S)-hydroxydodecanedioyl-CoA;
CC         Xref=Rhea:RHEA:39075, ChEBI:CHEBI:15377, ChEBI:CHEBI:76340,
CC         ChEBI:CHEBI:76342; Evidence={ECO:0000269|PubMed:24075987};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39076;
CC         Evidence={ECO:0000269|PubMed:24075987};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(3S)-hydroxydodecanedioyl-CoA + NAD(+) = 3-oxododecanedioyl-
CC         CoA + H(+) + NADH; Xref=Rhea:RHEA:39079, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:76342,
CC         ChEBI:CHEBI:76346; Evidence={ECO:0000269|PubMed:24075987};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39080;
CC         Evidence={ECO:0000269|PubMed:24075987};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2E)-octenedioyl-CoA + H2O = (3S)-hydroxyoctanedioyl-CoA;
CC         Xref=Rhea:RHEA:22532, ChEBI:CHEBI:15377, ChEBI:CHEBI:76330,
CC         ChEBI:CHEBI:76333; Evidence={ECO:0000269|PubMed:17442273,
CC         ECO:0000269|PubMed:24075987};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22533;
CC         Evidence={ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(3S)-hydroxyoctanedioyl-CoA + NAD(+) = 3-oxooctanedioyl-CoA +
CC         H(+) + NADH; Xref=Rhea:RHEA:22848, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:76333,
CC         ChEBI:CHEBI:76335; Evidence={ECO:0000269|PubMed:17442273,
CC         ECO:0000269|PubMed:24075987};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22849;
CC         Evidence={ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2E)-decenedioyl-CoA + H2O = (3S)-hydroxydecanedioyl-CoA;
CC         Xref=Rhea:RHEA:39091, ChEBI:CHEBI:15377, ChEBI:CHEBI:76347,
CC         ChEBI:CHEBI:76348; Evidence={ECO:0000269|PubMed:24075987};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39092;
CC         Evidence={ECO:0000269|PubMed:24075987};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(3S)-hydroxydecanedioyl-CoA + NAD(+) = 3-oxodecanedioyl-CoA +
CC         H(+) + NADH; Xref=Rhea:RHEA:39095, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:76348,
CC         ChEBI:CHEBI:76349; Evidence={ECO:0000269|PubMed:24075987};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39096;
CC         Evidence={ECO:0000269|PubMed:24075987};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2E)-tetradecenedioyl-CoA + H2O = (3S)-
CC         hydroxytetradecanedioyl-CoA; Xref=Rhea:RHEA:40207, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:77038, ChEBI:CHEBI:77039;
CC         Evidence={ECO:0000269|PubMed:17442273};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40208;
CC         Evidence={ECO:0000269|PubMed:17442273};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(3S)-hydroxytetradecanedioyl-CoA + NAD(+) = 3-
CC         oxotetradecanedioyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:40211,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC         ChEBI:CHEBI:77038, ChEBI:CHEBI:77041;
CC         Evidence={ECO:0000269|PubMed:17442273};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40212;
CC         Evidence={ECO:0000269|PubMed:17442273};
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   -!- 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:0000250|UniProtKB:Q08426};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31160;
CC         Evidence={ECO:0000250|UniProtKB:Q08426};
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:0000250|UniProtKB:Q08426};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31165;
CC         Evidence={ECO:0000250|UniProtKB:Q08426};
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:0000250|UniProtKB:Q08426};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40260;
CC         Evidence={ECO:0000250|UniProtKB:Q08426};
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:0000250|UniProtKB:Q08426};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40268;
CC         Evidence={ECO:0000250|UniProtKB:Q08426};
CC   -!- ACTIVITY REGULATION: Enzyme activity enhanced by acetylation.
CC       {ECO:0000250|UniProtKB:Q08426}.
CC   -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC       {ECO:0000269|PubMed:17442273, ECO:0000269|PubMed:24075987}.
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P07896}.
CC   -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000305|PubMed:24075987}.
CC   -!- PTM: Acetylated, leading to enhanced enzyme activity. Acetylation is
CC       enhanced by up to 80% after treatment either with trichostin A (TCA) or
CC       with nicotinamide (NAM) with highest increase on Lys-344. Acetylation
CC       and enzyme activity increased by about 1.5% on addition of fatty acids
CC       (By similarity). {ECO:0000250|UniProtKB:Q08426}.
CC   -!- DISRUPTION PHENOTYPE: Mutant mice fed a normal chow are phenotypically
CC       indistinguishable from wild-types. Mutant mice fed coconut oil rapidly
CC       lose weight and most of them die within 3 weeks. They overaccumulate
CC       dicarboxylic fatty acids, which activate all fatty acid oxidation
CC       pathways and lead to liver inflammation, fibrosis, and death.
CC       {ECO:0000269|PubMed:24075987}.
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; AK004867; BAB23628.1; -; mRNA.
DR   EMBL; BC016899; AAH16899.1; -; mRNA.
DR   EMBL; CH466521; EDK97607.1; -; Genomic_DNA.
DR   CCDS; CCDS28063.1; -.
DR   RefSeq; NP_076226.2; NM_023737.3.
DR   AlphaFoldDB; Q9DBM2; -.
DR   SMR; Q9DBM2; -.
DR   BioGRID; 216525; 16.
DR   IntAct; Q9DBM2; 1.
DR   MINT; Q9DBM2; -.
DR   STRING; 10090.ENSMUSP00000023559; -.
DR   SwissLipids; SLP:000000402; -.
DR   SwissLipids; SLP:000000491; -.
DR   GlyGen; Q9DBM2; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9DBM2; -.
DR   PhosphoSitePlus; Q9DBM2; -.
DR   SwissPalm; Q9DBM2; -.
DR   EPD; Q9DBM2; -.
DR   jPOST; Q9DBM2; -.
DR   MaxQB; Q9DBM2; -.
DR   PaxDb; 10090-ENSMUSP00000023559; -.
DR   PeptideAtlas; Q9DBM2; -.
DR   ProteomicsDB; 277754; -.
DR   Antibodypedia; 33832; 376 antibodies from 30 providers.
DR   DNASU; 74147; -.
DR   Ensembl; ENSMUST00000023559.7; ENSMUSP00000023559.6; ENSMUSG00000022853.8.
DR   GeneID; 74147; -.
DR   KEGG; mmu:74147; -.
DR   UCSC; uc007yrm.2; mouse.
DR   AGR; MGI:1277964; -.
DR   CTD; 1962; -.
DR   MGI; MGI:1277964; Ehhadh.
DR   VEuPathDB; HostDB:ENSMUSG00000022853; -.
DR   eggNOG; KOG1683; Eukaryota.
DR   GeneTree; ENSGT00940000157516; -.
DR   HOGENOM; CLU_009834_16_3_1; -.
DR   InParanoid; Q9DBM2; -.
DR   OMA; YNGAAMG; -.
DR   OrthoDB; 622692at2759; -.
DR   PhylomeDB; Q9DBM2; -.
DR   TreeFam; TF316708; -.
DR   Reactome; R-MMU-390247; Beta-oxidation of very long chain fatty acids.
DR   Reactome; R-MMU-9033241; Peroxisomal protein import.
DR   UniPathway; UPA00659; -.
DR   BioGRID-ORCS; 74147; 3 hits in 79 CRISPR screens.
DR   PRO; PR:Q9DBM2; -.
DR   Proteomes; UP000000589; Chromosome 16.
DR   RNAct; Q9DBM2; Protein.
DR   Bgee; ENSMUSG00000022853; Expressed in right kidney and 196 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR   GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; ISS: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; ISS:UniProtKB.
DR   GO; GO:0019899; F:enzyme binding; ISO:MGI.
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; ISS:UniProtKB.
DR   GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
DR   GO; GO:0006637; P:acyl-CoA metabolic process; TAS:MGI.
DR   GO; GO:0006635; P:fatty acid beta-oxidation; IMP:MGI.
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; Q9DBM2; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Fatty acid metabolism; Isomerase; Lipid metabolism; Lyase;
KW   Multifunctional enzyme; NAD; Oxidoreductase; Peroxisome; Phosphoprotein;
KW   Reference proteome.
FT   CHAIN           1..718
FT                   /note="Peroxisomal bifunctional enzyme"
FT                   /id="PRO_0000109248"
FT   REGION          1..280
FT                   /note="Enoyl-CoA hydratase / isomerase"
FT   REGION          281..567
FT                   /note="3-hydroxyacyl-CoA dehydrogenase"
FT   MOTIF           716..718
FT                   /note="Microbody targeting signal"
FT                   /evidence="ECO:0000250"
FT   BINDING         99
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   SITE            102
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250"
FT   SITE            122
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         38
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         163
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q08426"
FT   MOD_RES         163
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         172
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         172
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         181
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         189
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         189
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         217
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         217
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         240
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         248
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         252
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         274
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         274
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         278
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         288
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         329
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         344
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         348
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         355
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         459
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         527
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         543
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         572
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         579
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         579
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         586
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         586
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         705
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         705
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         717
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   CONFLICT        499
FT                   /note="D -> G (in Ref. 1; BAB23628)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   718 AA;  78301 MW;  A405717EC7A3EBD9 CRC64;
     MAEYLRLPHS LAMIRLCNPP VNAISPTVIT EVRNGLQKAS LDHTVRAIVI CGANDNFCAG
     ADIHGFKSPT GLTLGSLVDE IQRYQKPVVA AIQGVALGGG LELALGCHYR IANAKARVGF
     PEVMLGILPG ARGTQLLPRV VGVPVALDLI TSGRHISTDE ALKLGILDVV VKSDPVEEAI
     KFAQTVIGKP IEPRRILNKP VPSLPNMDSV FAEAIAKVRK QYPGRLAPET CVRSVQASVK
     HPYEVAIKEE AKLFMYLRGS GQARALQYAF FAEKSANKWS TPSGASWKTA SAQPVSSVGV
     LGLGTMGRGI AISFARVGIP VVAVESDPKQ LDTAKKIITS TLEKEASKSG QASAKPNLRF
     SSSTKELSSV DLVIEAVFED MNLKKKVFAE LSALCKPGAF LCTNTSALDV DDIASSTDRP
     QLVIGTHFFS PAHIMRLLEV IPSRYSSPTT IATVMSLSKR IGKIGVVVGN CYGFVGNRML
     APYYNQGYFL IEEGSKPEDV DGVLEEFGFR MGPFRVSDLA GLDVGWKVRK GQGLTGPSLP
     PGTPTRKRGN TRYSPIADML CEAGRFGQKT GKGWYQYDKP LGRIHKPDPW LSEFLSQYRE
     THHIKQRSIS KEEILERCLY SLINEAFRIL EEGMAASPEH IDVIYLHGYG WPRHVGGPMY
     YAASVGLPTV LEKLQKYYRQ NPDIPQLEPS DYLRRLVAQG SPPLKEWQSL AGPHSSKL
//