ECHA_HUMAN
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 03-AUG-2022, entry version 236.
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 EC=2.3.1.- {ECO:0000269|PubMed:23152787};
DE AltName: Full=TP-alpha;
DE Includes:
DE RecName: Full=Long-chain enoyl-CoA hydratase;
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 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 STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS), FUNCTION, SUBUNIT, AND
RP SUBCELLULAR 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 [18]
RP X-RAY CRYSTALLOGRAPHY (3.60 ANGSTROMS) OF 37-763, FUNCTION, SUBUNIT, AND
RP 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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
RP VARIANTS MTPD 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).
CC -!- FUNCTION: Mitochondrial trifunctional enzyme catalyzes the last three
CC of the four reactions of the mitochondrial beta-oxidation pathway
CC (PubMed:8135828, PubMed:1550553, PubMed:29915090, PubMed:30850536). The
CC mitochondrial beta-oxidation pathway is the major energy-producing
CC process in tissues and is performed through four consecutive reactions
CC breaking down fatty acids into acetyl-CoA (PubMed:29915090). Among the
CC enzymes involved in this pathway, the trifunctional enzyme exhibits
CC specificity for long-chain fatty acids (PubMed:30850536). Mitochondrial
CC trifunctional enzyme is a heterotetrameric complex composed of two
CC proteins, the trifunctional enzyme subunit alpha/HADHA described here
CC carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA
CC dehydrogenase activities while the trifunctional enzyme subunit
CC beta/HADHB bears the 3-ketoacyl-CoA thiolase activity (PubMed:8135828,
CC PubMed:29915090, PubMed:30850536). Independently of the subunit beta,
CC the trifunctional enzyme subunit alpha/HADHA also has a
CC monolysocardiolipin acyltransferase activity (PubMed:23152787). It
CC acylates monolysocardiolipin into cardiolipin, a major mitochondrial
CC membrane phospholipid which plays a key role in apoptosis and supports
CC mitochondrial respiratory chain complexes in the generation of ATP
CC (PubMed:23152787). Allows the acylation of monolysocardiolipin with
CC different acyl-CoA substrates including oleoyl-CoA for which it
CC displays the highest activity (PubMed:23152787).
CC {ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:23152787,
CC ECO:0000269|PubMed:29915090, ECO:0000269|PubMed:30850536,
CC ECO:0000269|PubMed:8135828, ECO:0000303|PubMed:29915090,
CC ECO:0000303|PubMed:30850536}.
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 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:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20726;
CC Evidence={ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828};
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)-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)-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=a long-chain (3S)-3-hydroxy fatty acyl-CoA + NAD(+) = a long-
CC chain 3-oxo-fatty acyl-CoA + H(+) + NADH; 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=(3S)-hydroxyoctanoyl-CoA + NAD(+) = 3-oxooctanoyl-CoA + H(+) +
CC NADH; 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:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828};
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:0000303|PubMed:1550553};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31188;
CC Evidence={ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-3-hydroxydodecanoyl-CoA + NAD(+) = 3-oxododecanoyl-CoA +
CC H(+) + NADH; 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:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxytetradecanoyl-CoA + NAD(+) = 3-oxotetradecanoyl-
CC CoA + H(+) + NADH; Xref=Rhea:RHEA:31167, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62543,
CC ChEBI:CHEBI:62614; Evidence={ECO:0000303|PubMed:1550553};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31168;
CC Evidence={ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA
CC + H(+) + NADH; Xref=Rhea:RHEA:31159, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:62613; Evidence={ECO:0000269|PubMed:8135828,
CC ECO:0000269|PubMed:8163672, ECO:0000269|PubMed:8651282};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31160;
CC Evidence={ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:8135828};
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=(9Z)-octadecenoyl-CoA + 1'-[1,2-di-(9Z,12Z-octadecadienoyl)-
CC sn-glycero-3-phospho]-3'-[1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phospho]-glycerol = 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=(9Z,12Z)-octadecadienoyl-CoA + 1'-[1,2-di-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phospho]-3'-[1-(9Z,12Z-
CC octadecadienoyl)-sn-glycero-3-phospho]-glycerol = 1',3'-bis-[1,2-di-
CC (9Z,12Z-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:8163672,
CC PubMed:29915090). 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=7; 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 (MTPD)
CC [MIM:609015]: A disease biochemically characterized by loss of all
CC enzyme activities of the mitochondrial trifunctional protein complex.
CC Variable clinical manifestations include hypoglycemia, cardiomyopathy,
CC delayed psychomotor development, sensorimotor axonopathy, generalized
CC weakness, hepatic dysfunction, respiratory failure. Sudden infant death
CC may occur. Most patients die from heart failure.
CC {ECO:0000269|PubMed:9739053}. Note=The disease is caused by variants
CC affecting the gene represented 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 -!- SEQUENCE CAUTION:
CC Sequence=BAG63804.1; Type=Miscellaneous discrepancy; Note=Wrong choice of frame.; Evidence={ECO:0000305};
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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_000182.4. [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 PDBsum; 5ZQZ; -.
DR PDBsum; 5ZRV; -.
DR PDBsum; 6DV2; -.
DR AlphaFoldDB; P40939; -.
DR SMR; P40939; -.
DR BioGRID; 109280; 417.
DR ComplexPortal; CPX-6245; Mitochondrial trifunctional enzyme complex.
DR CORUM; P40939; -.
DR IntAct; P40939; 140.
DR MINT; P40939; -.
DR STRING; 9606.ENSP00000370023; -.
DR ChEMBL; CHEMBL4295759; -.
DR DrugBank; DB00157; NADH.
DR SwissLipids; SLP:000000247; -.
DR GlyGen; P40939; 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 UCD-2DPAGE; P40939; -.
DR CPTAC; CPTAC-214; -.
DR CPTAC; CPTAC-215; -.
DR EPD; P40939; -.
DR jPOST; P40939; -.
DR MassIVE; P40939; -.
DR MaxQB; P40939; -.
DR PaxDb; P40939; -.
DR PeptideAtlas; P40939; -.
DR PRIDE; P40939; -.
DR ProteomicsDB; 5539; -.
DR ProteomicsDB; 55392; -. [P40939-1]
DR Antibodypedia; 3074; 222 antibodies from 32 providers.
DR DNASU; 3030; -.
DR Ensembl; ENST00000380649.8; ENSP00000370023.3; ENSG00000084754.12. [P40939-1]
DR Ensembl; ENST00000646483.1; ENSP00000496185.1; ENSG00000084754.12. [P40939-2]
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 CTD; 3030; -.
DR DisGeNET; 3030; -.
DR GeneCards; 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 neXtProt; NX_P40939; -.
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 PharmGKB; PA29175; -.
DR VEuPathDB; HostDB:ENSG00000084754; -.
DR eggNOG; KOG1683; Eukaryota.
DR GeneTree; ENSGT00940000154677; -.
DR HOGENOM; CLU_009834_16_1_1; -.
DR InParanoid; P40939; -.
DR OMA; PFRYMDT; -.
DR PhylomeDB; P40939; -.
DR TreeFam; TF352288; -.
DR BioCyc; MetaCyc:HS01481-MON; -.
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 UniPathway; UPA00659; -.
DR BioGRID-ORCS; 3030; 14 hits in 1082 CRISPR screens.
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 209 other tissues.
DR ExpressionAtlas; P40939; baseline and differential.
DR Genevisible; P40939; HS.
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:3-hydroxyacyl-CoA dehydrogenase activity; TAS:ProtInc.
DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; TAS:ProtInc.
DR GO; GO:0004300; F:enoyl-CoA hydratase activity; IBA:GO_Central.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IEA:Ensembl.
DR GO; GO:0016509; F:long-chain-3-hydroxyacyl-CoA dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0016508; F:long-chain-enoyl-CoA hydratase activity; IEA:Ensembl.
DR GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0035965; P:cardiolipin acyl-chain remodeling; IDA:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:ComplexPortal.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
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; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00725; 3HCDH; 2.
DR Pfam; PF02737; 3HCDH_N; 1.
DR Pfam; PF00378; ECH_1; 1.
DR SUPFAM; SSF48179; SSF48179; 2.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52096; SSF52096; 1.
DR TIGRFAMs; TIGR02441; fa_ox_alpha_mit; 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; Reference proteome; Transferase;
KW 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 MTPD; 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 MTPD; 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 long-
FT chain-3-hydroxyacyl-CoA dehydrogenase activity;
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
