ID ECHA_HUMAN Reviewed; 763 AA. AC P40939; B2R7L4; B4DYP2; Q16679; Q53T69; Q53TA2; Q96GT7; Q9UQC5; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 03-APR-2002, sequence version 2. DT 04-NOV-2026, entry version 256. DE RecName: Full=Trifunctional enzyme subunit alpha, mitochondrial; DE AltName: Full=78 kDa gastrin-binding protein; DE AltName: Full=Monolysocardiolipin acyltransferase {ECO:0000305|PubMed:23152787}; DE Short=MLCL AT {ECO:0000305}; DE EC=2.3.1.- {ECO:0000269|PubMed:23152787}; DE AltName: Full=TP-alpha; DE Includes: DE RecName: Full=Long-chain enoyl-CoA hydratase; DE Short=LCEH; DE EC=4.2.1.17 {ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828, ECO:0000269|PubMed:8163672, ECO:0000269|PubMed:8651282}; DE Includes: DE RecName: Full=Long chain 3-hydroxyacyl-CoA dehydrogenase; DE Short=LCHAD; DE EC=1.1.1.211 {ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828, ECO:0000269|PubMed:8163672, ECO:0000269|PubMed:8651282}; DE Flags: Precursor; GN Name=HADHA; Synonyms=HADH; 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), FUNCTION, CATALYTIC ACTIVITY, AND RP PATHWAY. RX PubMed=8135828; DOI=10.1006/bbrc.1994.1302; RA Kamijo T., Aoyama T., Komiyama A., Hashimoto T.; RT "Structural analysis of cDNAs for subunits of human mitochondrial fatty RT acid beta-oxidation trifunctional protein."; RL Biochem. Biophys. Res. Commun. 199:818-825(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=7918661; DOI=10.1016/0167-4781(94)90091-4; RA Zhang Q.X., Baldwin G.S.; RT "Structures of the human cDNA and gene encoding the 78 kDa gastrin-binding RT protein and of a related pseudogene."; RL Biochim. Biophys. Acta 1219:567-575(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Amygdala, and Testis; 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 GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22. RX PubMed=10075708; DOI=10.1074/jbc.274.12.8077; RA Orii K.E., Orii K.O., Souri M., Orii T., Kondo N., Hashimoto T., Aoyama T.; RT "Genes for the human mitochondrial trifunctional protein alpha- and beta- RT subunits are divergently transcribed from a common promoter region."; RL J. Biol. Chem. 274:8077-8084(1999). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=1550553; DOI=10.1016/0006-291x(92)90501-b; RA Carpenter K., Pollitt R.J., Middleton B.; RT "Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a RT multifunctional membrane-bound beta-oxidation enzyme of mitochondria."; RL Biochem. Biophys. Res. Commun. 183:443-448(1992). RN [9] RP CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=8163672; DOI=10.1172/jci117158; RA Kamijo T., Wanders R.J., Saudubray J.-M., Aoyama T., Komiyama A., RA Hashimoto T.; RT "Mitochondrial trifunctional protein deficiency. Catalytic heterogeneity of RT the mutant enzyme in two patients."; RL J. Clin. Invest. 93:1740-1747(1994). RN [10] RP CATALYTIC ACTIVITY. RX PubMed=8651282; RA Ushikubo S., Aoyama T., Kamijo T., Wanders R.J.A., Rinaldo P., Vockley J., RA Hashimoto T.; RT "Molecular characterization of mitochondrial trifunctional protein RT deficiency: formation of the enzyme complex is important for stabilization RT of both alpha- and beta-subunits."; RL Am. J. Hum. Genet. 58:979-988(1996). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-295; LYS-303; LYS-406; LYS-505; RP LYS-540 AND LYS-644, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 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 [13] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND INDUCTION. RX PubMed=23152787; DOI=10.1371/journal.pone.0048628; RA Taylor W.A., Mejia E.M., Mitchell R.W., Choy P.C., Sparagna G.C., RA Hatch G.M.; RT "Human trifunctional protein alpha links cardiolipin remodeling to beta- RT oxidation."; RL PLoS ONE 7:E48628-E48628(2012). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-756, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and 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-395, 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [17] RP REVIEW ON THE PHYSIOLOGICAL ROLE OF THE MITOCHONDRIAL FATTY ACID RP BETA-OXIDATION, FUNCTION, AND CAUTION. RX PubMed=26474213; DOI=10.1146/annurev-physiol-021115-105045; RA Houten S.M., Violante S., Ventura F.V., Wanders R.J.; RT "The Biochemistry and Physiology of Mitochondrial Fatty Acid beta-Oxidation RT and Its Genetic Disorders."; RL Annu. Rev. Physiol. 78:23-44(2016). RN [18] RP STRUCTURE BY ELECTRON MICROSCOPY, FUNCTION, SUBUNIT, AND SUBCELLULAR RP LOCATION. RX PubMed=29915090; DOI=10.1073/pnas.1801252115; RA Liang K., Li N., Wang X., Dai J., Liu P., Wang C., Chen X.W., Gao N., RA Xiao J.; RT "Cryo-EM structure of human mitochondrial trifunctional protein."; RL Proc. Natl. Acad. Sci. U.S.A. 115:7039-7044(2018). RN [19] RP X-RAY CRYSTALLOGRAPHY, FUNCTION, SUBUNIT, AND ACTIVE SITE. RX PubMed=30850536; DOI=10.1073/pnas.1816317116; RA Xia C., Fu Z., Battaile K.P., Kim J.P.; RT "Crystal structure of human mitochondrial trifunctional protein, a fatty RT acid beta-oxidation metabolon."; RL Proc. Natl. Acad. Sci. U.S.A. 116:6069-6074(2019). RN [20] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=38372965; DOI=10.1096/fj.202302163r; RA Schwantje M., Mosegaard S., Knottnerus S.J.G., van Klinken J.B., RA Wanders R.J., van Lenthe H., Hermans J., Ijlst L., Denis S.W., RA Jaspers Y.R.J., Fuchs S.A., Houtkooper R.H., Ferdinandusse S., Vaz F.M.; RT "Tracer-based lipidomics enables the discovery of disease-specific RT candidate biomarkers in mitochondrial beta-oxidation disorders."; RL FASEB J. 38:e23478-e23478(2024). RN [21] RP VARIANT LCHAD DEFICIENCY GLN-510. RX PubMed=7811722; DOI=10.1016/0005-2760(94)90064-7; RA Ijlst L., Wanders R.J.A., Ushikubo S., Kamijo T., Hashimoto T.; RT "Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: RT identification of the major disease-causing mutation in the alpha-subunit RT of the mitochondrial trifunctional protein."; RL Biochim. Biophys. Acta 1215:347-350(1994). RN [22] RP VARIANT AFLP GLN-510. RX PubMed=7846063; DOI=10.1073/pnas.92.3.841; RA Sims H.F., Brackett J.C., Powell C.K., Treem W.R., Hale D.E., Bennett M.J., RA Gibson B., Shapiro S., Strauss A.W.; RT "The molecular basis of pediatric long chain 3-hydroxyacyl-CoA RT dehydrogenase deficiency associated with maternal acute fatty liver of RT pregnancy."; RL Proc. Natl. Acad. Sci. U.S.A. 92:841-845(1995). RN [23] RP CHARACTERIZATION OF VARIANT LCHAD DEFICIENCY GLN-510. RX PubMed=8770876; DOI=10.1172/jci118863; RA Ijlst L., Ruiter J.P.N., Hoovers J.M.N., Jakobs M.E., Wanders R.J.A.; RT "Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA RT dehydrogenase deficiency. Characterization and expression of the mutant RT protein, mutation analysis on genomic DNA and chromosomal localization of RT the mitochondrial trifunctional protein alpha subunit gene."; RL J. Clin. Invest. 98:1028-1033(1996). RN [24] RP VARIANTS LCHAD DEFICIENCY PRO-342 AND GLN-510. RX PubMed=9266371; DOI=10.1023/a:1005310903004; RA Ijlst L., Oostheim W., Ruiter J.P.N., Wanders R.J.A.; RT "Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: RT identification of two new mutations."; RL J. Inherit. Metab. Dis. 20:420-422(1997). RN [25] RP VARIANTS MTPD1 ASP-282 AND ASN-305. RX PubMed=9739053; DOI=10.1172/jci2091; RA Ibdah J.A., Tein I., Dionisi-Vici C., Bennett M.J., Ijlst L., Gibson B., RA Wanders R.J.A., Strauss A.W.; RT "Mild trifunctional protein deficiency is associated with progressive RT neuropathy and myopathy and suggests a novel genotype-phenotype RT correlation."; RL J. Clin. Invest. 102:1193-1199(1998). RN [26] RP CHARACTERIZATION OF VARIANT LCHAD DEFICIENCY GLN-510, AND FUNCTION. RX PubMed=31604922; DOI=10.1038/s41467-019-12482-1; RA Miklas J.W., Clark E., Levy S., Detraux D., Leonard A., Beussman K., RA Showalter M.R., Smith A.T., Hofsteen P., Yang X., Macadangdang J., RA Manninen T., Raftery D., Madan A., Suomalainen A., Kim D.H., Murry C.E., RA Fiehn O., Sniadecki N.J., Wang Y., Ruohola-Baker H.; RT "TFPa/HADHA is required for fatty acid beta-oxidation and cardiolipin re- RT modeling in human cardiomyocytes."; RL Nat. Commun. 10:4671-4671(2019). RN [27] RP ERRATUM OF PUBMED:31604922. RX PubMed=32385292; DOI=10.1038/s41467-020-16186-9; RA Miklas J.W., Clark E., Levy S., Detraux D., Leonard A., Beussman K., RA Showalter M.R., Smith A.T., Hofsteen P., Yang X., Macadangdang J., RA Manninen T., Raftery D., Madan A., Suomalainen A., Kim D.H., Murry C.E., RA Fiehn O., Sniadecki N.J., Wang Y., Ruohola-Baker H.; RL Nat. Commun. 11:2387-2387(2020). CC -!- FUNCTION: Mitochondrial trifunctional enzyme catalyzes the last three CC of the four reactions of the mitochondrial beta-oxidation pathway CC (PubMed:1550553, PubMed:29915090, PubMed:30850536, PubMed:8135828, CC PubMed:31604922). The mitochondrial beta-oxidation pathway is the major CC energy-producing process in tissues and is performed through cycles of CC four consecutive reactions (PubMed:29915090). Each beta-oxidation cycle CC shortens the fatty acyl-CoA by two carbons, yielding one acetyl-CoA CC (for the citric acid cycle), one FADH(2), and one NADH (which donate CC electrons to the respiratory chain for ATP production) CC (PubMed:29915090). These cycles repeat until the chain is fully CC degraded to acetyl-CoA units (PubMed:29915090). Among the enzymes CC involved in this pathway, the trifunctional protein--responsible for CC the hydration, dehydrogenation, and thiolysis steps, shows specificity CC for long-chain fatty acids, such as those from dietary and stored fats CC (PubMed:30850536, PubMed:31604922). Mitochondrial trifunctional enzyme CC is a heterotetrameric complex composed of two proteins, the CC trifunctional enzyme subunit alpha/HADHA described here carries the CC 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase CC activities while the trifunctional enzyme subunit beta/HADHB bears the CC 3-ketoacyl-CoA thiolase activity (Probable) (PubMed:29915090, CC PubMed:30850536, PubMed:8135828). These activities have been CC experimentally confirmed on a few substrates derived from beta- CC oxidation of long-chain saturated fatty acids such as palmitate CC (hexadecanoate) and laurate (dodecanoate) (PubMed:1550553, CC PubMed:8135828, PubMed:8163672, PubMed:8651282). In addition, based on CC its established catalytic mechanism, and combined genetic interaction CC or mutant phenotype evidence, it is predicted to act also on other CC substrates, including long-chain unsaturated fatty acids such as oleate CC (9Z-octadecenoate), linoleate (9Z,12Z-octadecadienoate), linolenate CC (9Z,12Z,15Z-octadecatrienoate), and others (Probable) CC (PubMed:26474213). Independently of subunit beta, HADHA also exhibits a CC cardiolipin acyltransferase activity that participates in cardiolipin CC remodeling; cardiolipin is a major mitochondrial membrane phospholipid CC (PubMed:23152787, PubMed:31604922). HADHA may act downstream of CC Tafazzin/TAZ, that remodels monolysocardiolipin (MLCL) to a cardiolipin CC intermediate, and then HADHA may continue to remodel this species into CC mature tetralinoleoyl-cardiolipin (PubMed:31604922). Has also been CC proposed to act directly on MLCL; capable of acylating MLCL using CC different acyl-CoA substrates, with highest activity for oleoyl-CoA CC (PubMed:23152787). {ECO:0000269|PubMed:1550553, CC ECO:0000269|PubMed:23152787, ECO:0000269|PubMed:29915090, CC ECO:0000269|PubMed:30850536, ECO:0000269|PubMed:31604922, CC ECO:0000269|PubMed:8135828, ECO:0000269|PubMed:8163672, CC ECO:0000269|PubMed:8651282, ECO:0000303|PubMed:26474213, CC ECO:0000303|PubMed:29915090, ECO:0000303|PubMed:30850536, CC ECO:0000305|PubMed:38372965}. 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; Evidence={ECO:0000269|PubMed:1550553, CC ECO:0000269|PubMed:8135828}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16107; CC Evidence={ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a long-chain (3S)-3-hydroxy fatty acyl-CoA + NAD(+) = a long- CC chain 3-oxo-fatty acyl-CoA + NADH + H(+); Xref=Rhea:RHEA:52656, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:136757, ChEBI:CHEBI:136758; EC=1.1.1.211; CC Evidence={ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828, CC ECO:0000269|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52657; CC Evidence={ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1'-[1,2-diacyl-sn-glycero-3-phospho],3'-[1-acyl-sn-glycero-3- CC phospho]-glycerol + an acyl-CoA = a cardiolipin + CoA; CC Xref=Rhea:RHEA:35839, ChEBI:CHEBI:57287, ChEBI:CHEBI:58342, CC ChEBI:CHEBI:62237, ChEBI:CHEBI:64743; CC Evidence={ECO:0000269|PubMed:23152787}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35840; CC Evidence={ECO:0000269|PubMed:23152787}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxyeicosanoyl-CoA = (2E)-eicosenoyl-CoA + H2O; CC Xref=Rhea:RHEA:78591, ChEBI:CHEBI:15377, ChEBI:CHEBI:74691, CC ChEBI:CHEBI:87562; Evidence={ECO:0000305|PubMed:1550553, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:78593; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:8135828, CC ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxyoctadecanoyl-CoA = (2E)-octadecenoyl-CoA + H2O; CC Xref=Rhea:RHEA:78603, ChEBI:CHEBI:15377, ChEBI:CHEBI:71412, CC ChEBI:CHEBI:87561; Evidence={ECO:0000305|PubMed:1550553, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:78605; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:8135828, CC ECO:0000305|PubMed:8163672}; 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:8135828, CC ECO:0000269|PubMed:8163672, ECO:0000269|PubMed:8651282}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31165; CC Evidence={ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxytetradecanoyl-CoA = (2E)-tetradecenoyl-CoA + H2O; CC Xref=Rhea:RHEA:31171, ChEBI:CHEBI:15377, ChEBI:CHEBI:61405, CC ChEBI:CHEBI:62614; Evidence={ECO:0000305|PubMed:1550553, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31173; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:8135828, CC ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-3-hydroxydodecanoyl-CoA = (2E)-dodecenoyl-CoA + H2O; CC Xref=Rhea:RHEA:31075, ChEBI:CHEBI:15377, ChEBI:CHEBI:57330, CC ChEBI:CHEBI:62558; Evidence={ECO:0000269|PubMed:8163672}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31077; CC Evidence={ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828}; 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:0000305|PubMed:1550553, CC ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31193; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxyoctanoyl-CoA = (2E)-octenoyl-CoA + H2O; CC Xref=Rhea:RHEA:31199, ChEBI:CHEBI:15377, ChEBI:CHEBI:62242, CC ChEBI:CHEBI:62617; Evidence={ECO:0000269|PubMed:1550553, CC ECO:0000269|PubMed:8163672}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31201; CC Evidence={ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828}; 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:0000305|PubMed:1550553, CC ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:30549; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,11Z)-eicosadienoyl-CoA + H2O = (3S)-hydroxy-(11Z)- CC eicosenoyl-CoA; Xref=Rhea:RHEA:83067, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:76388, ChEBI:CHEBI:232717; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83068; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,9Z)-octadecadienoyl-CoA + H2O = (3S)-hydroxy-(9Z- CC octadecenoyl)-CoA; Xref=Rhea:RHEA:47424, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:77553, ChEBI:CHEBI:87687; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47425; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,7Z)-hexadecadienoyl-CoA + H2O = (3S)-hydroxy-(7Z- CC hexadecenoyl)-CoA; Xref=Rhea:RHEA:47436, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:87717, ChEBI:CHEBI:87718; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47437; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,5Z)-tetradecadienoyl-CoA + H2O = (3S)-hydroxy-(5Z- CC tetradecenoyl)-CoA; Xref=Rhea:RHEA:47452, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:87701, ChEBI:CHEBI:87705; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47453; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,11Z)-octadecadienoyl-CoA + H2O = (3S)-hydroxy-(11Z)- CC octadecenoyl-CoA; Xref=Rhea:RHEA:83027, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:76558, ChEBI:CHEBI:232532; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83028; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,9Z)-hexadecadienoyl-CoA + H2O = (3S)-hydroxy-(9Z- CC hexadecenoyl)-CoA; Xref=Rhea:RHEA:82923, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:77549, ChEBI:CHEBI:232641; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:82924; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,7Z)-tetradecadienoyl-CoA + H2O = (3S)-hydroxy-(7Z)- CC tetradecenoyl-CoA; Xref=Rhea:RHEA:82995, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:231719, ChEBI:CHEBI:232680; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:82996; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,5Z)-dodecadienoyl-CoA + H2O = (3S)-hydroxy-(5Z)- CC dodecenoyl-CoA; Xref=Rhea:RHEA:82959, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:232684, ChEBI:CHEBI:232686; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:82960; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,6Z)-hexadecadienoyl-CoA + H2O = (3S)-hydroxy-(6Z)- CC hexadecenoyl-CoA; Xref=Rhea:RHEA:83147, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:232761, ChEBI:CHEBI:232762; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83148; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,6Z)-octadecadienoyl-CoA + H2O = (3S)-hydroxy-(6Z)- CC octadecenoyl-CoA; Xref=Rhea:RHEA:83211, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:232772, ChEBI:CHEBI:232773; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83212; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,9Z)-eicosadienoyl-CoA + H2O = (3S)-hydroxy-(9Z)- CC eicosenoyl-CoA; Xref=Rhea:RHEA:83359, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:232892, ChEBI:CHEBI:232893; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83360; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,7Z)-octadecadienoyl-CoA + H2O = (3S)-hydroxy-(7Z)- CC octadecenoyl-CoA; Xref=Rhea:RHEA:83375, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:232899, ChEBI:CHEBI:232900; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83376; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,5Z)-hexadecadienoyl-CoA + H2O = (3S)-hydroxy-(5Z)- CC hexadecenoyl-CoA; Xref=Rhea:RHEA:83391, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:232910, ChEBI:CHEBI:232911; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83392; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(9Z,12Z)-octadecadienoyl-CoA = (2E,9Z,12Z)- CC octadecatrienoyl-CoA + H2O; Xref=Rhea:RHEA:84395, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:77558, ChEBI:CHEBI:233824; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:84397; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(7Z,10Z)-hexadecadienoyl-CoA = (2E,7Z,10Z)- CC hexadecatrienoyl-CoA + H2O; Xref=Rhea:RHEA:84399, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:233785, ChEBI:CHEBI:233826; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:84401; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,8Z)-tetradecadienoyl-CoA + H2O = (3S)-hydroxy-(8Z)- CC tetradecenoyl-CoA; Xref=Rhea:RHEA:84403, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:233831, ChEBI:CHEBI:233832; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84404; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,6Z)-dodecadienoyl-CoA + H2O = (3S)-hydroxy-(6Z)- CC dodecenoyl-CoA; Xref=Rhea:RHEA:84407, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:233835, ChEBI:CHEBI:233836; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84408; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,9Z,12Z,15Z)-octadecatetraenoyl-CoA + H2O = (3S)-hydroxy- CC (9Z,12Z,15Z)-octadecatrienoyl-CoA; Xref=Rhea:RHEA:84627, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:233840, ChEBI:CHEBI:233841; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84628; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,7Z,10Z,13Z)-hexadecatetraenoyl-CoA + H2O = (3S)-hydroxy- CC (7Z,10Z,13Z)-hexadecatrienoyl-CoA; Xref=Rhea:RHEA:84631, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:233792, ChEBI:CHEBI:233843; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84632; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,8Z,11Z)-tetradecatrienoyl-CoA + H2O = (3S)-hydroxy- CC (8Z,11Z)-tetradecadienoyl-CoA; Xref=Rhea:RHEA:84655, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:233801, ChEBI:CHEBI:233844; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84656; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,6Z,9Z)-dodecatrienoyl-CoA + H2O = (3S)-hydroxy-(6Z,9Z)- CC dodecadienoyl-CoA; Xref=Rhea:RHEA:84659, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:233847, ChEBI:CHEBI:233848; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84660; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,7Z)-decadienoyl-CoA + H2O = (3S)-hydroxy-(7Z)-decenoyl- CC CoA; Xref=Rhea:RHEA:84663, ChEBI:CHEBI:15377, ChEBI:CHEBI:233853, CC ChEBI:CHEBI:233854; Evidence={ECO:0000305|PubMed:1550553, CC ECO:0000305|PubMed:38372965, ECO:0000305|PubMed:8135828, CC ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84664; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,6Z,9Z,12Z)-octadecatetraenoyl-CoA + H2O = (3S)-hydroxy- CC (6Z,9Z,12Z)-octadecatrienoyl-CoA; Xref=Rhea:RHEA:84667, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:233778, ChEBI:CHEBI:233839; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84668; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2E,6Z,9Z,12Z,15Z)-octadecapentaenoyl-CoA + H2O = (3S)- CC hydroxy-(6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA; Xref=Rhea:RHEA:85127, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:233740, ChEBI:CHEBI:234230; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:85128; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8135828, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxyeicosanoyl-CoA + NAD(+) = 3-oxoeicosanoyl-CoA + CC NADH + H(+); Xref=Rhea:RHEA:78731, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:65115, CC ChEBI:CHEBI:87562; Evidence={ECO:0000305|PubMed:8163672, CC ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78732; CC Evidence={ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxyoctadecanoyl-CoA + NAD(+) = 3-oxooctadecanoyl-CoA CC + NADH + H(+); Xref=Rhea:RHEA:78739, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:71407, CC ChEBI:CHEBI:87561; Evidence={ECO:0000305|PubMed:8163672, CC ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78740; CC Evidence={ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA CC + NADH + H(+); 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:8135828, CC ECO:0000269|PubMed:8163672, ECO:0000269|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31160; CC Evidence={ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxytetradecanoyl-CoA + NAD(+) = 3-oxotetradecanoyl- CC CoA + NADH + H(+); Xref=Rhea:RHEA:31167, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62543, CC ChEBI:CHEBI:62614; Evidence={ECO:0000305|PubMed:8163672, CC ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31168; CC Evidence={ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-3-hydroxydodecanoyl-CoA + NAD(+) = 3-oxododecanoyl-CoA + CC NADH + H(+); Xref=Rhea:RHEA:31179, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62558, CC ChEBI:CHEBI:62615; Evidence={ECO:0000269|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31180; CC Evidence={ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxydecanoyl-CoA + NAD(+) = 3-oxodecanoyl-CoA + NADH + CC H(+); Xref=Rhea:RHEA:31187, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:62548, ChEBI:CHEBI:62616; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31188; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxyoctanoyl-CoA + NAD(+) = 3-oxooctanoyl-CoA + NADH + CC H(+); Xref=Rhea:RHEA:31195, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:62617, ChEBI:CHEBI:62619; CC Evidence={ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31196; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxyhexanoyl-CoA + NAD(+) = 3-oxohexanoyl-CoA + NADH + CC H(+); Xref=Rhea:RHEA:31143, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:62075, ChEBI:CHEBI:62418; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:8163672}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31144; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:8163672}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(11Z)-eicosenoyl-CoA + NAD(+) = 3-oxo-(11Z)- CC eicosenoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:83079, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:74011, ChEBI:CHEBI:232717; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83080; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(9Z-octadecenoyl)-CoA + NAD(+) = 3-oxo-(9Z- CC octadecenoyl)-CoA + NADH + H(+); Xref=Rhea:RHEA:47428, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:87687, ChEBI:CHEBI:87695; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47429; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(7Z-hexadecenoyl)-CoA + NAD(+) = 3-oxo-(7Z- CC hexadecenoyl)-CoA + NADH + H(+); Xref=Rhea:RHEA:47440, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:87718, ChEBI:CHEBI:87719; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47441; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(5Z-tetradecenoyl)-CoA + NAD(+) = 3-oxo-(5Z- CC tetradecenoyl)-CoA + NADH + H(+); Xref=Rhea:RHEA:47456, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:87705, ChEBI:CHEBI:87707; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47457; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(11Z)-octadecenoyl-CoA + NAD(+) = 3-oxo-(11Z)- CC octadecenoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:83031, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:76555, ChEBI:CHEBI:232532; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83032; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(9Z-hexadecenoyl)-CoA + NAD(+) = 3-oxo-(9Z- CC hexadecenoyl)-CoA + NADH + H(+); Xref=Rhea:RHEA:82931, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:232641, ChEBI:CHEBI:232642; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:82932; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(7Z)-tetradecenoyl-CoA + NAD(+) = 3-oxo-(7Z)- CC tetradecenoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:82999, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:231719, ChEBI:CHEBI:232679; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83000; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(5Z)-dodecenoyl-CoA + NAD(+) = 3-oxo-(5Z)- CC dodecenoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:83003, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:232686, ChEBI:CHEBI:232696; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83004; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(6Z)-hexadecenoyl-CoA + NAD(+) = 3-oxo-(6Z)- CC hexadecenoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:83139, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:232762, ChEBI:CHEBI:232763; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83140; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(6Z)-octadecenoyl-CoA + NAD(+) = 3-oxo-(6Z)- CC octadecenoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:83215, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:232773, ChEBI:CHEBI:232774; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83216; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(9Z)-eicosenoyl-CoA + NAD(+) = 3-oxo-(9Z)- CC eicosenoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:83363, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:232893, ChEBI:CHEBI:232898; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83364; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(7Z)-octadecenoyl-CoA + NAD(+) = 3-oxo-(7Z)- CC octadecenoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:83379, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:232900, ChEBI:CHEBI:232901; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83380; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(5Z)-hexadecenoyl-CoA + NAD(+) = 3-oxo-(5Z)- CC hexadecenoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:83395, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:232911, ChEBI:CHEBI:232912; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:83396; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(9Z,12Z)-octadecadienoyl-CoA + NAD(+) = 3-oxo- CC (9Z,12Z)-octadecadienoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:84427, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:74013, ChEBI:CHEBI:233824; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84428; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(7Z,10Z)-hexadecadienoyl-CoA + NAD(+) = 3-oxo- CC (7Z,10Z)-hexadecadienoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:84411, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:233788, ChEBI:CHEBI:233826; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84412; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(8Z)-tetradecenoyl-CoA + NAD(+) = 3-oxo-(8Z)- CC tetradecenoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:84415, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:233832, ChEBI:CHEBI:233833; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84416; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(6Z)-dodecenoyl-CoA + NAD(+) = 3-oxo-(6Z)- CC dodecenoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:84419, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:233836, ChEBI:CHEBI:233837; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84420; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(9Z,12Z,15Z)-octadecatrienoyl-CoA + NAD(+) = 3- CC oxo-(9Z,12Z,15Z)-octadecatrienoyl-CoA + NADH + H(+); CC Xref=Rhea:RHEA:84671, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:233841, ChEBI:CHEBI:233842; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84672; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(7Z,10Z,13Z)-hexadecatrienoyl-CoA + NAD(+) = 3- CC oxo-(7Z,10Z,13Z)-hexadecatrienoyl-CoA + NADH + H(+); CC Xref=Rhea:RHEA:84675, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:233794, ChEBI:CHEBI:233843; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84676; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(8Z,11Z)-tetradecadienoyl-CoA + NAD(+) = 3-oxo- CC (8Z,11Z)-tetradecadienoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:84679, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:233803, ChEBI:CHEBI:233844; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84680; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(6Z,9Z)-dodecadienoyl-CoA + NAD(+) = 3-oxo- CC (6Z,9Z)-dodecadienoyl-CoA + NADH + H(+); Xref=Rhea:RHEA:84683, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, CC ChEBI:CHEBI:233848, ChEBI:CHEBI:233849; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84684; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(7Z)-decenoyl-CoA + NAD(+) = 3-oxo-(7Z)-decenoyl- CC CoA + NADH + H(+); Xref=Rhea:RHEA:84687, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:233854, CC ChEBI:CHEBI:233855; Evidence={ECO:0000305|PubMed:1550553, CC ECO:0000305|PubMed:38372965, ECO:0000305|PubMed:8163672, CC ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84688; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(6Z,9Z,12Z)-octadecatrienoyl-CoA + NAD(+) = 3- CC oxo-(6Z,9Z,12Z)-octadecatrienoyl-CoA + NADH + H(+); CC Xref=Rhea:RHEA:84691, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:233780, ChEBI:CHEBI:233839; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:84692; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(3S)-hydroxy-(6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA + NAD(+) = CC 3-oxo-(6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA + NADH + H(+); CC Xref=Rhea:RHEA:85131, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:57945, ChEBI:CHEBI:233746, ChEBI:CHEBI:234230; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:85132; CC Evidence={ECO:0000305|PubMed:1550553, ECO:0000305|PubMed:38372965, CC ECO:0000305|PubMed:8163672, ECO:0000305|PubMed:8651282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'- CC [1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + CC hexadecanoyl-CoA = 1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3- CC phospho]-3'-[1-(9Z,12Z-octadecadienoyl)-2-hexadecanoyl-sn-glycero-3- CC phospho]-glycerol + CoA; Xref=Rhea:RHEA:43680, ChEBI:CHEBI:57287, CC ChEBI:CHEBI:57379, ChEBI:CHEBI:83580, ChEBI:CHEBI:83583; CC Evidence={ECO:0000269|PubMed:23152787}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43681; CC Evidence={ECO:0000269|PubMed:23152787}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'- CC [1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + (9Z)- CC octadecenoyl-CoA = 1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3- CC phospho]-3'-[1-(9Z,12Z-octadecadienoyl)-2-(9Z-octadecenoyl)-sn- CC glycero-3-phospho]-glycerol + CoA; Xref=Rhea:RHEA:43676, CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57387, ChEBI:CHEBI:83580, CC ChEBI:CHEBI:83582; Evidence={ECO:0000269|PubMed:23152787}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43677; CC Evidence={ECO:0000269|PubMed:23152787}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1'-[1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-3'- CC [1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho]-glycerol + CC (9Z,12Z)-octadecadienoyl-CoA = 1',3'-bis-[1,2-di-(9Z,12Z- CC octadecadienoyl)-sn-glycero-3-phospho]-glycerol + CoA; CC Xref=Rhea:RHEA:43672, ChEBI:CHEBI:57287, ChEBI:CHEBI:57383, CC ChEBI:CHEBI:83580, ChEBI:CHEBI:83581; CC Evidence={ECO:0000269|PubMed:23152787}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43673; CC Evidence={ECO:0000269|PubMed:23152787}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=18.1 uM for (9Z,12Z)-octadecadienoyl-CoA CC {ECO:0000269|PubMed:23152787}; CC KM=51.8 uM for (9Z)-octadecenoyl-CoA {ECO:0000269|PubMed:23152787}; CC KM=50.4 uM for hexadecanoyl-CoA {ECO:0000269|PubMed:23152787}; CC Vmax=6.6 umol/min/mg enzyme for the monolysocardiolipin CC acyltransferase activity with (9Z,12Z)-octadecadienoyl-CoA as CC substrate {ECO:0000269|PubMed:23152787}; CC Vmax=716 pmol/min/mg enzyme for the monolysocardiolipin CC acyltransferase activity with (9Z)-octadecenoyl-CoA as substrate CC {ECO:0000269|PubMed:23152787}; CC Vmax=795 pmol/min/mg enzyme for the monolysocardiolipin CC acyltransferase activity with hexadecanoyl-CoA as substrate CC {ECO:0000269|PubMed:23152787}; CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation. CC {ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828}. CC -!- SUBUNIT: Heterotetramer of 2 alpha/HADHA and 2 beta/HADHB subunits; CC forms the mitochondrial trifunctional enzyme (PubMed:29915090, CC PubMed:30850536). Also purified as higher order heterooligomers CC including a 4 alpha/HADHA and 4 beta/HADHB heterooligomer which CC physiological significance remains unclear (PubMed:29915090, CC PubMed:8163672). The mitochondrial trifunctional enzyme interacts with CC MTLN (By similarity). {ECO:0000250|UniProtKB:Q8BMS1, CC ECO:0000269|PubMed:29915090, ECO:0000269|PubMed:30850536, CC ECO:0000269|PubMed:8163672}. CC -!- INTERACTION: CC P40939; O95166: GABARAP; NbExp=5; IntAct=EBI-356720, EBI-712001; CC P40939; Q9H0R8: GABARAPL1; NbExp=4; IntAct=EBI-356720, EBI-746969; CC P40939; P60520: GABARAPL2; NbExp=4; IntAct=EBI-356720, EBI-720116; CC P40939; P55084: HADHB; NbExp=11; IntAct=EBI-356720, EBI-356635; CC P40939; P42858: HTT; NbExp=3; IntAct=EBI-356720, EBI-466029; CC P40939; Q9GZQ8: MAP1LC3B; NbExp=4; IntAct=EBI-356720, EBI-373144; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:29915090}. CC Mitochondrion inner membrane {ECO:0000269|PubMed:29915090}. CC Note=Protein stability and association with mitochondrion inner CC membrane do not require HADHB. {ECO:0000269|PubMed:29915090}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P40939-1; Sequence=Displayed; CC Name=2; CC IsoId=P40939-2; Sequence=VSP_059010, VSP_059011; CC -!- INDUCTION: Up-regulated by thyroid hormone (at protein level). CC {ECO:0000269|PubMed:23152787}. CC -!- DISEASE: Mitochondrial trifunctional protein deficiency 1 (MTPD1) CC [MIM:609015]: An autosomal recessive metabolic disorder of long-chain CC fatty acid oxidation, biochemically characterized by loss of all enzyme CC activities of the mitochondrial trifunctional protein complex. The CC disease phenotype ranges from a fatal form characterized by early-onset CC cardiomyopathy, cardiac failure and early death to less severe, late- CC onset forms with myopathy, recurrent rhabdomyolysis, and sensorimotor CC axonal neuropathy as key features. {ECO:0000269|PubMed:9739053}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Long-chain 3-hydroxyl-CoA dehydrogenase deficiency (LCHAD CC deficiency) [MIM:609016]: The clinical features are very similar to TFP CC deficiency. Biochemically, LCHAD deficiency is characterized by reduced CC long-chain 3-hydroxyl-CoA dehydrogenase activity, while the other CC enzyme activities of the TFP complex are normal or only slightly CC reduced. {ECO:0000269|PubMed:7811722, ECO:0000269|PubMed:9266371}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Maternal acute fatty liver of pregnancy (AFLP) [MIM:609016]: CC Severe maternal illness occurring during pregnancies with affected CC fetuses. This disease is associated with LCHAD deficiency and CC characterized by sudden unexplained infant death or hypoglycemia and CC abnormal liver enzymes (Reye-like syndrome). CC {ECO:0000269|PubMed:7846063}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: In the N-terminal section; belongs to the enoyl-CoA CC hydratase/isomerase family. {ECO:0000305}. CC -!- SIMILARITY: In the central section; belongs to the 3-hydroxyacyl-CoA CC dehydrogenase family. {ECO:0000305}. CC -!- CAUTION: The experimental data for the mitochondrial beta-oxidation of CC unsaturated fatty acids are scarce and some reactions in this entry are CC inferred from combined genetic interaction or mutant phenotype evidence CC and direct experimental evidence in parent reaction. CC {ECO:0000303|PubMed:26474213, ECO:0000305|PubMed:1550553, CC ECO:0000305|PubMed:8163672}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG63804.1; Type=Miscellaneous discrepancy; Note=Wrong choice of frame.; Evidence={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; D16480; BAA03941.1; -; mRNA. DR EMBL; U04627; AAA56664.1; -; mRNA. DR EMBL; AK302532; BAG63804.1; ALT_SEQ; mRNA. DR EMBL; AK313027; BAG35861.1; -; mRNA. DR EMBL; AC010896; AAY14643.1; -; Genomic_DNA. DR EMBL; AC011742; AAX93141.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00703.1; -; Genomic_DNA. DR EMBL; BC009235; AAH09235.1; -; mRNA. DR EMBL; AB020811; BAA76735.1; -; Genomic_DNA. DR CCDS; CCDS1721.1; -. [P40939-1] DR PIR; JC2108; JC2108. DR RefSeq; NP_000173.2; NM_000182.5. [P40939-1] DR PDB; 5ZQZ; EM; 4.20 A; A/C=1-763. DR PDB; 5ZRV; EM; 7.70 A; A/C/E/G=1-763. DR PDB; 6DV2; X-ray; 3.60 A; G/H/I/J/K/L=37-763. DR AlphaFoldDB; P40939; -. DR EMDB; EMD-6940; -. DR EMDB; EMD-6944; -. DR SMR; P40939; -. DR BioGRID; 109280; 581. DR ComplexPortal; CPX-6245; Mitochondrial trifunctional enzyme complex. DR CORUM; P40939; -. DR FunCoup; P40939; 1300. DR IntAct; P40939; 251. DR NDEx; IQUERY-CP-HADHA; 5 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000370023; -. DR BindingDB; P40939; -. DR ChEMBL; CHEMBL4295759; -. DR DrugBank; DB00157; NADH. DR SwissLipids; SLP:000000247; -. DR GlyCosmos; P40939; 5 sites, 4 glycans. DR GlyGen; P40939; 5 sites, 2 N-linked glycans (2 sites), 2 O-linked glycans (2 sites). DR iPTMnet; P40939; -. DR MetOSite; P40939; -. DR PhosphoSitePlus; P40939; -. DR SwissPalm; P40939; -. DR BioMuta; HADHA; -. DR DMDM; 20141376; -. DR REPRODUCTION-2DPAGE; IPI00031522; -. DR CPTAC; CPTAC-214; -. DR CPTAC; CPTAC-215; -. DR jPOST; P40939; -. DR MassIVE; P40939; -. DR PaxDb; 9606-ENSP00000370023; -. DR PeptideAtlas; P40939; -. DR PRIDE; P40939; -. DR ProteomicsDB; 5539; -. DR ProteomicsDB; 55392; -. [P40939-1] DR Pumba; P40939; -. DR Antibodypedia; 3074; 272 antibodies from 36 providers. DR DNASU; 3030; -. DR Ensembl; ENST00000380649.8; ENSP00000370023.3; ENSG00000084754.13. [P40939-1] DR Ensembl; ENST00000646483.1; ENSP00000496185.1; ENSG00000084754.13. [P40939-2] DR Ensembl; ENST00000942141.1; ENSP00000612200.1; ENSG00000084754.13. [P40939-1] DR GeneID; 3030; -. DR KEGG; hsa:3030; -. DR MANE-Select; ENST00000380649.8; ENSP00000370023.3; NM_000182.5; NP_000173.2. DR UCSC; uc002rgy.3; human. [P40939-1] DR AGR; HGNC:4801; -. DR ClinPGx; PA29175; -. DR CTD; 3030; -. DR DisGeNET; 3030; -. DR GeneCards; HADHA; -. DR GeneReviews; HADHA; -. DR HGNC; HGNC:4801; HADHA. DR HPA; ENSG00000084754; Tissue enhanced (skeletal). DR MalaCards; HADHA; -. DR MIM; 600890; gene. DR MIM; 609015; phenotype. DR MIM; 609016; phenotype. DR OpenTargets; ENSG00000084754; -. DR Orphanet; 243367; Acute fatty liver of pregnancy. DR Orphanet; 5; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency. DR Orphanet; 746; Mitochondrial trifunctional protein deficiency. DR VEuPathDB; HostDB:ENSG00000084754; -. DR eggNOG; KOG1683; Eukaryota. DR GeneTree; ENSGT00940000154677; -. DR HOGENOM; CLU_009834_16_1_1; -. DR InParanoid; P40939; -. DR OMA; AACHHAQ; -. DR OrthoDB; 10004768at2759; -. DR PAN-GO; P40939; 4 GO annotations based on evolutionary models. DR PhylomeDB; P40939; -. DR BioCyc; MetaCyc:HS01481-MONOMER; -. DR BRENDA; 1.1.1.211; 2681. DR PathwayCommons; P40939; -. DR Reactome; R-HSA-1482798; Acyl chain remodeling of CL. DR Reactome; R-HSA-77285; Beta oxidation of myristoyl-CoA to lauroyl-CoA. DR Reactome; R-HSA-77288; mitochondrial fatty acid beta-oxidation of unsaturated fatty acids. DR Reactome; R-HSA-77305; Beta oxidation of palmitoyl-CoA to myristoyl-CoA. DR Reactome; R-HSA-77310; Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA. DR Reactome; R-HSA-77346; Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA. DR Reactome; R-HSA-77348; Beta oxidation of octanoyl-CoA to hexanoyl-CoA. DR Reactome; R-HSA-77350; Beta oxidation of hexanoyl-CoA to butanoyl-CoA. DR SABIO-RK; P40939; -. DR SignaLink; P40939; -. DR SIGNOR; P40939; -. DR UniPathway; UPA00659; -. DR Agora; ENSG00000084754; -. DR BioGRID-ORCS; 3030; 18 hits in 1162 CRISPR screens. DR CD-CODE; 232F8A39; P-body. DR CD-CODE; DEE660B4; Stress granule. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; HADHA; human. DR GenomeRNAi; 3030; -. DR Pharos; P40939; Tbio. DR PRO; PR:P40939; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P40939; protein. DR Bgee; ENSG00000084754; Expressed in jejunal mucosa and 211 other cell types or tissues. DR ExpressionAtlas; P40939; baseline and differential. DR GO; GO:0016507; C:mitochondrial fatty acid beta-oxidation multienzyme complex; IPI:ComplexPortal. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0003857; F:(3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity; TAS:ProtInc. DR GO; GO:0018812; F:3-hydroxyacyl-CoA dehydratase activity; EXP:UniProtKB. DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; TAS:ProtInc. DR GO; GO:0004300; F:enoyl-CoA hydratase activity; EXP:UniProtKB. DR GO; GO:0016509; F:long-chain (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity; EXP:UniProtKB. DR GO; GO:0052816; F:long-chain fatty acyl-CoA hydrolase activity; IDA:UniProt. DR GO; GO:0070403; F:NAD+ binding; IEA:InterPro. DR GO; GO:0035965; P:cardiolipin acyl-chain remodeling; IDA:UniProtKB. DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:ComplexPortal. DR CDD; cd06558; crotonase-like; 1. DR DisProt; DP03726; -. DR FunFam; 3.90.226.10:FF:000011; Fatty acid oxidation complex subunit alpha; 1. DR FunFam; 3.40.50.720:FF:000009; Fatty oxidation complex, alpha subunit; 1. DR FunFam; 1.10.1040.50:FF:000002; Trifunctional enzyme subunit alpha, mitochondrial; 1. DR Gene3D; 1.10.1040.50; -; 1. DR Gene3D; 3.90.226.10; 2-enoyl-CoA Hydratase, Chain A, domain 1; 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; IPR012803; Fa_ox_alpha_mit. DR InterPro; IPR050136; FA_oxidation_alpha_subunit. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR NCBIfam; TIGR02441; fa_ox_alpha_mit; 1. DR PANTHER; PTHR43612; TRIFUNCTIONAL ENZYME SUBUNIT ALPHA; 1. DR PANTHER; PTHR43612:SF7; TRIFUNCTIONAL ENZYME SUBUNIT ALPHA, MITOCHONDRIAL; 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. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Disease variant; KW Fatty acid metabolism; Lipid metabolism; Lyase; Membrane; Methylation; KW Mitochondrion; Mitochondrion inner membrane; Multifunctional enzyme; NAD; KW Oxidoreductase; Phosphoprotein; Proteomics identification; KW Reference proteome; Transferase; Transit peptide. FT TRANSIT 1..36 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 37..763 FT /note="Trifunctional enzyme subunit alpha, mitochondrial" FT /id="PRO_0000007403" FT ACT_SITE 510 FT /note="For hydroxyacyl-coenzyme A dehydrogenase activity" FT /evidence="ECO:0000269|PubMed:8770876" FT SITE 151 FT /note="Important for long-chain enoyl-CoA hydratase FT activity" FT /evidence="ECO:0000305|PubMed:30850536" FT SITE 173 FT /note="Important for long-chain enoyl-CoA hydratase FT activity" FT /evidence="ECO:0000305|PubMed:30850536" FT SITE 498 FT /note="Important for hydroxyacyl-coenzyme A dehydrogenase FT activity" FT /evidence="ECO:0000305|PubMed:30850536" FT MOD_RES 46 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 46 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 60 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 60 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 129 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 166 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 166 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 213 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 214 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 214 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 230 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 249 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 249 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 289 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 295 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 303 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 303 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 316 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 326 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 326 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 334 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 334 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 350 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 350 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 353 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 395 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 399 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 406 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 406 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 411 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 411 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 415 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 419 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64428" FT MOD_RES 440 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 460 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 460 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 505 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 505 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 519 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 519 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 540 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 569 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 569 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 634 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 644 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 644 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 646 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 650 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64428" FT MOD_RES 664 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 664 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 728 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 728 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 735 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 756 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 759 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT MOD_RES 759 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8BMS1" FT VAR_SEQ 61..82 FT /note="VNTLSKELHSEFSEVMNEIWAS -> HVSRLQDPSRSNTAITRSTENS (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_059010" FT VAR_SEQ 83..763 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_059011" FT VARIANT 282 FT /note="V -> D (in MTPD1; mild phenotype with slowly FT progressive myopathy and sensorimotor polyneuropathy; FT dbSNP:rs137852773)" FT /evidence="ECO:0000269|PubMed:9739053" FT /id="VAR_021125" FT VARIANT 305 FT /note="I -> N (in MTPD1; mild phenotype with slowly FT progressive myopathy and sensorimotor polyneuropathy; FT dbSNP:rs137852774)" FT /evidence="ECO:0000269|PubMed:9739053" FT /id="VAR_021126" FT VARIANT 342 FT /note="L -> P (in LCHAD deficiency; dbSNP:rs137852772)" FT /evidence="ECO:0000269|PubMed:9266371" FT /id="VAR_021127" FT VARIANT 358 FT /note="Q -> K (in dbSNP:rs2229420)" FT /id="VAR_048908" FT VARIANT 510 FT /note="E -> Q (in AFLP and LCHAD deficiency; loss of FT long-chain-3-hydroxyacyl-CoA dehydrogenase activity; FT abnormal cardiolipin remodeling with reduced formation of FT mature tetralinoleoyl-cardiolipin; sarcomere dissolution; FT loss of mitochondrial potential gradient; FT dbSNP:rs137852769)" FT /evidence="ECO:0000269|PubMed:7811722, FT ECO:0000269|PubMed:7846063, ECO:0000269|PubMed:8770876, FT ECO:0000269|PubMed:9266371" FT /id="VAR_002273" FT CONFLICT 146 FT /note="L -> V (in Ref. 1; BAA03941)" FT /evidence="ECO:0000305" FT CONFLICT 152 FT /note="V -> L (in Ref. 2; AAA56664)" FT /evidence="ECO:0000305" FT CONFLICT 171 FT /note="T -> A (in Ref. 2; AAA56664)" FT /evidence="ECO:0000305" FT CONFLICT 178 FT /note="A -> I (in Ref. 2; AAA56664)" FT /evidence="ECO:0000305" FT CONFLICT 197..198 FT /note="AL -> VF (in Ref. 2; AAA56664)" FT /evidence="ECO:0000305" FT CONFLICT 206 FT /note="S -> N (in Ref. 2; AAA56664)" FT /evidence="ECO:0000305" FT CONFLICT 211 FT /note="R -> S (in Ref. 2; AAA56664)" FT /evidence="ECO:0000305" FT CONFLICT 576 FT /note="T -> P (in Ref. 2; AAA56664)" FT /evidence="ECO:0000305" FT CONFLICT 694 FT /note="L -> S (in Ref. 1; BAA03941)" FT /evidence="ECO:0000305" SQ SEQUENCE 763 AA; 83000 MW; 247FF7B4E48FB484 CRC64; MVACRAIGIL SRFSAFRILR SRGYICRNFT GSSALLTRTH INYGVKGDVA VVRINSPNSK VNTLSKELHS EFSEVMNEIW ASDQIRSAVL ISSKPGCFIA GADINMLAAC KTLQEVTQLS QEAQRIVEKL EKSTKPIVAA INGSCLGGGL EVAISCQYRI ATKDRKTVLG TPEVLLGALP GAGGTQRLPK MVGVPAALDM MLTGRSIRAD RAKKMGLVDQ LVEPLGPGLK PPEERTIEYL EEVAITFAKG LADKKISPKR DKGLVEKLTA YAMTIPFVRQ QVYKKVEEKV RKQTKGLYPA PLKIIDVVKT GIEQGSDAGY LCESQKFGEL VMTKESKALM GLYHGQVLCK KNKFGAPQKD VKHLAILGAG LMGAGIAQVS VDKGLKTILK DATLTALDRG QQQVFKGLND KVKKKALTSF ERDSIFSNLT GQLDYQGFEK ADMVIEAVFE DLSLKHRVLK EVEAVIPDHC IFASNTSALP ISEIAAVSKR PEKVIGMHYF SPVDKMQLLE IITTEKTSKD TSASAVAVGL KQGKVIIVVK DGPGFYTTRC LAPMMSEVIR ILQEGVDPKK LDSLTTSFGF PVGAATLVDE VGVDVAKHVA EDLGKVFGER FGGGNPELLT QMVSKGFLGR KSGKGFYIYQ EGVKRKDLNS DMDSILASLK LPPKSEVSSD EDIQFRLVTR FVNEAVMCLQ EGILATPAEG DIGAVFGLGF PPCLGGPFRF VDLYGAQKIV DRLKKYEAAY GKQFTPCQLL ADHANSPNKK FYQ //