ECHA_MOUSE
ID ECHA_MOUSE Reviewed; 763 AA.
AC Q8BMS1; Q3TCY3; Q5U5Y5; Q8QZU4;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Trifunctional enzyme subunit alpha, mitochondrial;
DE AltName: Full=Monolysocardiolipin acyltransferase {ECO:0000250|UniProtKB:P40939};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:P40939};
DE AltName: Full=TP-alpha;
DE Includes:
DE RecName: Full=Long-chain enoyl-CoA hydratase;
DE EC=4.2.1.17 {ECO:0000250|UniProtKB:P40939};
DE Includes:
DE RecName: Full=Long chain 3-hydroxyacyl-CoA dehydrogenase;
DE EC=1.1.1.211 {ECO:0000250|UniProtKB:P40939};
DE Flags: Precursor;
GN Name=Hadha;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Eye, Liver, and Olfactory epithelium;
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 [3]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-129, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=16916647; DOI=10.1016/j.molcel.2006.06.026;
RA Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y.,
RA Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y.;
RT "Substrate and functional diversity of lysine acetylation revealed by a
RT proteomics survey.";
RL Mol. Cell 23:607-618(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231; SER-316; THR-395 AND
RP SER-647, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-60 AND LYS-406, SUCCINYLATION
RP [LARGE SCALE ANALYSIS] AT LYS-46; LYS-60; LYS-166; LYS-213; LYS-214;
RP LYS-230; LYS-249; LYS-303; LYS-326; LYS-334; LYS-350; LYS-406; LYS-411;
RP LYS-415; LYS-436; LYS-440; LYS-460; LYS-505; LYS-519; LYS-569; LYS-620;
RP LYS-634; LYS-644; LYS-646; LYS-664; LYS-728 AND LYS-759, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast, and Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-46; LYS-60; LYS-129; LYS-166;
RP LYS-214; LYS-249; LYS-289; LYS-303; LYS-326; LYS-334; LYS-350; LYS-353;
RP LYS-406; LYS-411; LYS-436; LYS-460; LYS-505; LYS-519; LYS-540; LYS-569;
RP LYS-644; LYS-664; LYS-728; LYS-735 AND LYS-759, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [7]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-399, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [8]
RP INTERACTION WITH MTLN, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=29949755; DOI=10.1016/j.celrep.2018.05.058;
RA Makarewich C.A., Baskin K.K., Munir A.Z., Bezprozvannaya S., Sharma G.,
RA Khemtong C., Shah A.M., McAnally J.R., Malloy C.R., Szweda L.I.,
RA Bassel-Duby R., Olson E.N.;
RT "MOXI Is a Mitochondrial Micropeptide That Enhances Fatty Acid beta-
RT Oxidation.";
RL Cell Rep. 23:3701-3709(2018).
CC -!- FUNCTION: Mitochondrial trifunctional enzyme catalyzes the last three
CC of the four reactions of the mitochondrial beta-oxidation pathway. 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. Among the enzymes involved
CC in this pathway, the trifunctional enzyme exhibits specificity for
CC long-chain fatty acids. Mitochondrial trifunctional enzyme is a
CC heterotetrameric complex composed of two proteins, the trifunctional
CC enzyme subunit alpha/HADHA described here carries the 2,3-enoyl-CoA
CC hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the
CC trifunctional enzyme subunit beta/HADHB bears the 3-ketoacyl-CoA
CC thiolase activity. Independently of the subunit beta, the trifunctional
CC enzyme subunit alpha/HADHA also has a monolysocardiolipin
CC acyltransferase activity. It acylates monolysocardiolipin into
CC cardiolipin, a major mitochondrial membrane phospholipid which plays a
CC key role in apoptosis and supports mitochondrial respiratory chain
CC complexes in the generation of ATP. Allows the acylation of
CC monolysocardiolipin with different acyl-CoA substrates including
CC oleoyl-CoA for which it displays the highest activity.
CC {ECO:0000250|UniProtKB:P40939}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3S)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O;
CC Xref=Rhea:RHEA:16105, ChEBI:CHEBI:15377, ChEBI:CHEBI:57318,
CC ChEBI:CHEBI:58856; EC=4.2.1.17;
CC Evidence={ECO:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16107;
CC Evidence={ECO:0000250|UniProtKB:P40939};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 4-saturated-(3S)-3-hydroxyacyl-CoA = a (3E)-enoyl-CoA + H2O;
CC Xref=Rhea:RHEA:20724, ChEBI:CHEBI:15377, ChEBI:CHEBI:58521,
CC ChEBI:CHEBI:137480; EC=4.2.1.17;
CC Evidence={ECO:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20726;
CC Evidence={ECO:0000250|UniProtKB:P40939};
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:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31201;
CC Evidence={ECO:0000250|UniProtKB:P40939};
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:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31077;
CC Evidence={ECO:0000250|UniProtKB:P40939};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanoyl-CoA = (2E)-hexadecenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:31163, ChEBI:CHEBI:15377, ChEBI:CHEBI:61526,
CC ChEBI:CHEBI:62613; Evidence={ECO:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31165;
CC Evidence={ECO:0000250|UniProtKB:P40939};
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:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52657;
CC Evidence={ECO:0000250|UniProtKB:P40939};
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:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31196;
CC Evidence={ECO:0000250|UniProtKB:P40939};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxydecanoyl-CoA + NAD(+) = 3-oxodecanoyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:31187, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:62548, ChEBI:CHEBI:62616;
CC Evidence={ECO:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31188;
CC Evidence={ECO:0000250|UniProtKB:P40939};
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:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31180;
CC Evidence={ECO:0000250|UniProtKB:P40939};
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:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31168;
CC Evidence={ECO:0000250|UniProtKB:P40939};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3S)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA
CC + H(+) + NADH; Xref=Rhea:RHEA:31159, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:62613; Evidence={ECO:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31160;
CC Evidence={ECO:0000250|UniProtKB:P40939};
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:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43681;
CC Evidence={ECO:0000250|UniProtKB:P40939};
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:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43677;
CC Evidence={ECO:0000250|UniProtKB:P40939};
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:0000250|UniProtKB:P40939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43673;
CC Evidence={ECO:0000250|UniProtKB:P40939};
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC {ECO:0000250|UniProtKB:P40939}.
CC -!- SUBUNIT: Heterotetramer of 2 alpha/HADHA and 2 beta/HADHB subunits;
CC forms the mitochondrial trifunctional enzyme (By similarity). Also
CC purified as higher order heterooligomers including a 4 alpha/HADHA and
CC 4 beta/HADHB heterooligomer which physiological significance remains
CC unclear (By similarity). The mitochondrial trifunctional enzyme
CC interacts with MTLN (PubMed:29949755). {ECO:0000250|UniProtKB:P40939,
CC ECO:0000269|PubMed:29949755}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P40939}.
CC Mitochondrion inner membrane {ECO:0000250|UniProtKB:P40939}.
CC Note=Protein stability and association with mitochondrion inner
CC membrane do not require HADHB. {ECO:0000250|UniProtKB:P40939}.
CC -!- PTM: Acetylation of Lys-569 and Lys-728 is observed in liver
CC mitochondria from fasted mice but not from fed mice.
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}.
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DR EMBL; AK029017; BAC26245.1; -; mRNA.
DR EMBL; AK170478; BAE41822.1; -; mRNA.
DR EMBL; AK170683; BAE41956.1; -; mRNA.
DR EMBL; BC027156; AAH27156.1; -; mRNA.
DR EMBL; BC037009; AAH37009.1; -; mRNA.
DR EMBL; BC046978; AAH46978.1; -; mRNA.
DR EMBL; BC058569; AAH58569.1; -; mRNA.
DR CCDS; CCDS19155.1; -.
DR RefSeq; NP_849209.1; NM_178878.2.
DR AlphaFoldDB; Q8BMS1; -.
DR SMR; Q8BMS1; -.
DR BioGRID; 220648; 38.
DR IntAct; Q8BMS1; 8.
DR MINT; Q8BMS1; -.
DR STRING; 10090.ENSMUSP00000120976; -.
DR iPTMnet; Q8BMS1; -.
DR PhosphoSitePlus; Q8BMS1; -.
DR SwissPalm; Q8BMS1; -.
DR REPRODUCTION-2DPAGE; IPI00223092; -.
DR EPD; Q8BMS1; -.
DR jPOST; Q8BMS1; -.
DR MaxQB; Q8BMS1; -.
DR PaxDb; Q8BMS1; -.
DR PeptideAtlas; Q8BMS1; -.
DR PRIDE; Q8BMS1; -.
DR ProteomicsDB; 277753; -.
DR Antibodypedia; 3074; 222 antibodies from 32 providers.
DR DNASU; 97212; -.
DR Ensembl; ENSMUST00000156859; ENSMUSP00000120976; ENSMUSG00000025745.
DR GeneID; 97212; -.
DR KEGG; mmu:97212; -.
DR UCSC; uc008wvc.1; mouse.
DR CTD; 3030; -.
DR MGI; MGI:2135593; Hadha.
DR VEuPathDB; HostDB:ENSMUSG00000025745; -.
DR eggNOG; KOG1683; Eukaryota.
DR GeneTree; ENSGT00940000154677; -.
DR HOGENOM; CLU_009834_16_1_1; -.
DR InParanoid; Q8BMS1; -.
DR OMA; PFRYMDT; -.
DR OrthoDB; 219667at2759; -.
DR PhylomeDB; Q8BMS1; -.
DR TreeFam; TF352288; -.
DR Reactome; R-MMU-1482798; Acyl chain remodeling of CL.
DR Reactome; R-MMU-77285; Beta oxidation of myristoyl-CoA to lauroyl-CoA.
DR Reactome; R-MMU-77305; Beta oxidation of palmitoyl-CoA to myristoyl-CoA.
DR Reactome; R-MMU-77310; Beta oxidation of lauroyl-CoA to decanoyl-CoA-CoA.
DR Reactome; R-MMU-77346; Beta oxidation of decanoyl-CoA to octanoyl-CoA-CoA.
DR Reactome; R-MMU-77348; Beta oxidation of octanoyl-CoA to hexanoyl-CoA.
DR Reactome; R-MMU-77350; Beta oxidation of hexanoyl-CoA to butanoyl-CoA.
DR UniPathway; UPA00659; -.
DR BioGRID-ORCS; 97212; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Hadha; mouse.
DR PRO; PR:Q8BMS1; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8BMS1; protein.
DR Bgee; ENSMUSG00000025745; Expressed in myocardium of ventricle and 247 other tissues.
DR Genevisible; Q8BMS1; MM.
DR GO; GO:0016507; C:mitochondrial fatty acid beta-oxidation multienzyme complex; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0042645; C:mitochondrial nucleoid; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; ISO:MGI.
DR GO; GO:0003988; F:acetyl-CoA C-acyltransferase activity; ISO:MGI.
DR GO; GO:0004300; F:enoyl-CoA hydratase activity; ISO:MGI.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; ISO:MGI.
DR GO; GO:0016509; F:long-chain-3-hydroxyacyl-CoA dehydrogenase activity; IDA:MGI.
DR GO; GO:0016508; F:long-chain-enoyl-CoA hydratase activity; ISO:MGI.
DR GO; GO:0051287; F:NAD binding; ISO:MGI.
DR GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0035965; P:cardiolipin acyl-chain remodeling; ISS:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IMP:MGI.
DR GO; GO:0032868; P:response to insulin; IMP:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
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 Acetylation; Fatty acid metabolism; Lipid metabolism; Lyase; Membrane;
KW Methylation; Mitochondrion; Mitochondrion inner membrane;
KW Multifunctional enzyme; NAD; Oxidoreductase; Phosphoprotein;
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_0000322639"
FT ACT_SITE 510
FT /note="For hydroxyacyl-coenzyme A dehydrogenase activity"
FT /evidence="ECO:0000250|UniProtKB:P40939"
FT SITE 151
FT /note="Important for long-chain enoyl-CoA hydratase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:P40939"
FT SITE 173
FT /note="Important for long-chain enoyl-CoA hydratase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:P40939"
FT SITE 498
FT /note="Important for hydroxyacyl-coenzyme A dehydrogenase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:P40939"
FT MOD_RES 46
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 46
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 60
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753,
FT ECO:0007744|PubMed:23806337"
FT MOD_RES 60
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 129
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:16916647,
FT ECO:0007744|PubMed:23576753"
FT MOD_RES 166
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 166
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 213
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 214
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 214
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 230
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 249
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 249
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 289
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 295
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P40939"
FT MOD_RES 303
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 303
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 316
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 326
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 326
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 334
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 334
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 350
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 350
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 353
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 395
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 399
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 406
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753,
FT ECO:0007744|PubMed:23806337"
FT MOD_RES 406
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 411
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 411
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 415
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64428"
FT MOD_RES 436
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 436
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 440
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 460
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 460
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 505
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 505
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 519
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 519
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 540
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 569
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 569
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 620
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 634
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 644
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 644
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 646
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 647
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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:0007744|PubMed:23576753"
FT MOD_RES 664
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 728
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 728
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 735
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 759
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 759
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 196
FT /note="A -> D (in Ref. 1; BAE41822)"
FT /evidence="ECO:0000305"
FT CONFLICT 459
FT /note="L -> S (in Ref. 2; AAH37009)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 763 AA; 82670 MW; 73D203795D5C1141 CRC64;
MVASRAIGSL SRFSAFRILR SRGCICRSFT TSSALLTRTH INYGVKGDVA VIRINSPNSK
VNTLNKEVQS EFIEVMNEIW ANDQIRSAVL ISSKPGCFVA GADINMLSSC TTPQEATRIS
QEGQRMFEKL EKSPKPVVAA ISGSCLGGGL ELAIACQYRI ATKDRKTVLG VPEVLLGILP
GAGGTQRLPK MVGVPAAFDM MLTGRNIRAD RAKKMGLVDQ LVEPLGPGIK SPEERTIEYL
EEVAVNFAKG LADRKVSAKQ SKGLVEKLTT YAMTVPFVRQ QVYKTVEEKV KKQTKGLYPA
PLKIIDAVKA GLEQGSDAGY LAESQKFGEL ALTKESKALM GLYNGQVLCK KNKFGAPQKN
VQQLAILGAG LMGAGIAQVS VDKGLKTLLK DTTVTGLGRG QQQVFKGLND KVKKKALTSF
ERDSIFSNLI GQLDYKGFEK ADMVIEAVFE DLGVKHKVLK EVESVTPEHC IFASNTSALP
INQIAAVSKR PEKVIGMHYF SPVDKMQLLE IITTDKTSKD TTASAVAVGL RQGKVIIVVK
DGPGFYTTRC LAPMMSEVMR ILQEGVDPKK LDALTTGFGF PVGAATLADE VGVDVAQHVA
EDLGKAFGER FGGGSVELLK QMVSKGFLGR KSGKGFYIYQ EGSKNKSLNS EMDNILANLR
LPAKPEVSSD EDVQYRVITR FVNEAVLCLQ EGILATPAEG DIGAVFGLGF PPCLGGPFRF
VDLYGAQKVV DRLRKYESAY GTQFTPCQLL LDHANNSSKK FYQ
