ID ECHB_HUMAN Reviewed; 474 AA. AC P55084; B2RB16; B4E2W0; O14969; Q53TA6; Q96C77; Q9H3F5; Q9T2V8; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 17-JUN-2020, entry version 202. DE RecName: Full=Trifunctional enzyme subunit beta, mitochondrial; DE AltName: Full=TP-beta; DE Includes: DE RecName: Full=3-ketoacyl-CoA thiolase; DE EC=2.3.1.155 {ECO:0000269|PubMed:7958339, ECO:0000269|PubMed:8135828, ECO:0000269|PubMed:8163672, ECO:0000269|PubMed:8651282}; DE EC=2.3.1.16 {ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:7958339, ECO:0000269|PubMed:8135828, ECO:0000269|PubMed:8163672, ECO:0000269|PubMed:8651282}; DE AltName: Full=Acetyl-CoA acyltransferase; DE AltName: Full=Beta-ketothiolase; DE Flags: Precursor; GN Name=HADHB; ORFNames=MSTP029; 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 [GENOMIC DNA], AND VARIANT MTPD LYS-444. RC TISSUE=Blood; RX PubMed=9259266; DOI=10.1093/hmg/6.8.1215; RA Orii K.E., Aoyama T., Wakui K., Fukushima Y., Miyajima H., Yamaguchi S., RA Orii T., Kondo N., Hashimoto T.; RT "Genomic and mutational analysis of the mitochondrial trifunctional protein RT beta-subunit (HADHB) gene in patients with trifunctional protein RT deficiency."; RL Hum. Mol. Genet. 6:1215-1224(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Heart; RA Liu B., Liu Y.Q., Wang X.Y., Zhao B., Sheng H., Zhao X.W., Liu S., Xu Y.Y., RA Ye J., Song L., Gao Y., Zhang C.L., Zhang J., Wei Y.J., Cao H.Q., Zhao Y., RA Liu L.S., Ding J.F., Gao R.L., Wu Q.Y., Qiang B.Q., Yuan J.G., Liew C.C., RA Zhao M.S., Hui R.T.; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Stomach, and Tongue; 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 [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-209. RC TISSUE=Colon, Hypothalamus, Skeletal muscle, and Urinary bladder; 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 PROTEIN SEQUENCE OF 34-52. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [8] RP PROTEIN SEQUENCE OF 48-63, AND CATALYTIC ACTIVITY. RC TISSUE=Liver; RX PubMed=7958339; DOI=10.1042/bst0220427; RA Middleton B.; RT "The mitochondrial long-chain trifunctional enzyme: 2-enoyl-CoA hydratase, RT 3-hydroxyacyl-CoA dehydrogenase and 3-oxoacyl-CoA thiolase."; RL Biochem. Soc. Trans. 22:427-431(1994). RN [9] RP PROTEIN SEQUENCE OF 62-72 AND 96-111. RC TISSUE=Adipocyte; RX PubMed=15242332; DOI=10.1042/bj20040647; RA Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.; RT "Vectorial proteomics reveal targeting, phosphorylation and specific RT fragmentation of polymerase I and transcript release factor (PTRF) at the RT surface of caveolae in human adipocytes."; RL Biochem. J. 383:237-248(2004). RN [10] RP CATALYTIC ACTIVITY. 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 [11] 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 [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-72 AND LYS-188, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND INTERACTION RP WITH RSAD2. RX PubMed=21527675; DOI=10.1126/science.1202007; RA Seo J.Y., Yaneva R., Hinson E.R., Cresswell P.; RT "Human cytomegalovirus directly induces the antiviral protein viperin to RT enhance infectivity."; RL Science 332:1093-1097(2011). RN [15] RP IDENTIFICATION BY 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 CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER ARG-33, AND 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, RP SUBCELLULAR LOCATION, AND TOPOLOGY. 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 34-474, 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 VARIANTS MTPD HIS-61; HIS-247 AND GLY-263, AND 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 [20] RP VARIANTS MTPD ASP-59; CYS-61; HIS-61; GLY-117; PRO-121; PRO-133; GLY-242; RP HIS-247; 259-GLY--PRO-270 DEL; GLY-263; ASP-280; ARG-294; LEU-294; SER-301 RP AND LYS-444. RX PubMed=12754706; DOI=10.1002/humu.10211; RA Spiekerkoetter U., Sun B., Khuchua Z., Bennett M.J., Strauss A.W.; RT "Molecular and phenotypic heterogeneity in mitochondrial trifunctional RT protein deficiency due to beta-subunit mutations."; RL Hum. Mutat. 21:598-607(2003). RN [21] RP VARIANT [LARGE SCALE ANALYSIS] VAL-119. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Mitochondrial trifunctional enzyme catalyzes the last three CC of the four reactions of the mitochondrial beta-oxidation pathway CC (PubMed:8135828, PubMed:29915090, PubMed:30850536). The mitochondrial CC beta-oxidation pathway is the major energy-producing process in tissues CC and is performed through four consecutive reactions breaking down fatty CC acids into acetyl-CoA (PubMed:29915090). Among the enzymes involved in CC this pathway, the trifunctional enzyme exhibits specificity for long- CC chain fatty acids (PubMed:30850536). Mitochondrial trifunctional enzyme CC is a heterotetrameric complex composed of two proteins, the CC trifunctional enzyme subunit alpha/HADHA carries the 2,3-enoyl-CoA CC hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities, while the CC trifunctional enzyme subunit beta/HADHB described here bears the 3- CC ketoacyl-CoA thiolase activity (PubMed:8135828, PubMed:29915090, CC PubMed:30850536). {ECO:0000269|PubMed:29915090, CC ECO:0000269|PubMed:30850536, ECO:0000269|PubMed:8135828, CC ECO:0000303|PubMed:29915090, ECO:0000303|PubMed:30850536}. CC -!- CATALYTIC ACTIVITY: CC Reaction=acetyl-CoA + an acyl-CoA = a 3-oxoacyl-CoA + CoA; CC Xref=Rhea:RHEA:21564, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, CC ChEBI:CHEBI:58342, ChEBI:CHEBI:90726; EC=2.3.1.16; CC Evidence={ECO:0000269|PubMed:7958339, ECO:0000269|PubMed:8135828, CC ECO:0000269|PubMed:8163672, ECO:0000269|PubMed:8651282}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21566; CC Evidence={ECO:0000269|PubMed:8135828}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acetyl-CoA + butanoyl-CoA = 3-oxohexanoyl-CoA + CoA; CC Xref=Rhea:RHEA:31111, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, CC ChEBI:CHEBI:57371, ChEBI:CHEBI:62418; CC Evidence={ECO:0000269|PubMed:1550553}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31113; CC Evidence={ECO:0000269|PubMed:8135828}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acetyl-CoA + hexanoyl-CoA = 3-oxooctanoyl-CoA + CoA; CC Xref=Rhea:RHEA:31203, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, CC ChEBI:CHEBI:62619, ChEBI:CHEBI:62620; CC Evidence={ECO:0000269|PubMed:8163672}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31205; CC Evidence={ECO:0000269|PubMed:8135828}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acetyl-CoA + octanoyl-CoA = 3-oxodecanoyl-CoA + CoA; CC Xref=Rhea:RHEA:31087, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, CC ChEBI:CHEBI:57386, ChEBI:CHEBI:62548; CC Evidence={ECO:0000269|PubMed:1550553}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31089; CC Evidence={ECO:0000269|PubMed:8135828}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acetyl-CoA + decanoyl-CoA = 3-oxododecanoyl-CoA + CoA; CC Xref=Rhea:RHEA:31183, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, CC ChEBI:CHEBI:61430, ChEBI:CHEBI:62615; CC Evidence={ECO:0000269|PubMed:8163672}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31185; CC Evidence={ECO:0000269|PubMed:8135828}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acetyl-CoA + dodecanoyl-CoA = 3-oxotetradecanoyl-CoA + CoA; CC Xref=Rhea:RHEA:31091, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, CC ChEBI:CHEBI:57375, ChEBI:CHEBI:62543; CC Evidence={ECO:0000269|PubMed:1550553}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:31093; CC Evidence={ECO:0000269|PubMed:8135828}; CC -!- CATALYTIC ACTIVITY: CC Reaction=acetyl-CoA + tetradecanoyl-CoA = 3-oxohexadecanoyl-CoA + CoA; CC Xref=Rhea:RHEA:18161, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, CC ChEBI:CHEBI:57349, ChEBI:CHEBI:57385; EC=2.3.1.155; CC Evidence={ECO:0000269|PubMed:1550553, ECO:0000269|PubMed:7958339, CC ECO:0000269|PubMed:8135828, ECO:0000269|PubMed:8163672, CC ECO:0000269|PubMed:8651282}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18163; CC Evidence={ECO:0000269|PubMed:8135828}; CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation. CC {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). Interacts with RSAD2/viperin (PubMed:21527675). CC {ECO:0000269|PubMed:21527675, ECO:0000269|PubMed:29915090, CC ECO:0000269|PubMed:30850536, ECO:0000269|PubMed:8163672}. CC -!- INTERACTION: CC P55084; Q9H0R8: GABARAPL1; NbExp=4; IntAct=EBI-356635, EBI-746969; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:21527675}. CC Mitochondrion inner membrane {ECO:0000269|PubMed:21527675}. CC Mitochondrion outer membrane {ECO:0000269|PubMed:21527675}. Endoplasmic CC reticulum {ECO:0000269|PubMed:21527675}. Note=Protein stability and CC association with membranes require HADHA. CC {ECO:0000269|PubMed:29915090}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P55084-1; Sequence=Displayed; CC Name=2; CC IsoId=P55084-2; Sequence=VSP_054426; 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:12754706, ECO:0000269|PubMed:8651282, CC ECO:0000269|PubMed:9259266}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Thiolase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA22061.1; Type=Erroneous gene model prediction; 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; D16481; BAA03942.1; -; mRNA. DR EMBL; D86850; BAA22061.1; ALT_SEQ; Genomic_DNA. DR EMBL; AF113209; AAG39280.1; -; mRNA. DR EMBL; AK304455; BAG65272.1; -; mRNA. DR EMBL; AK314455; BAG37063.1; -; mRNA. DR EMBL; AC010896; AAY14644.1; -; Genomic_DNA. DR EMBL; BC014572; AAH14572.1; -; mRNA. DR EMBL; BC017564; AAH17564.1; -; mRNA. DR EMBL; BC030824; AAH30824.1; -; mRNA. DR EMBL; BC066963; AAH66963.1; -; mRNA. DR CCDS; CCDS1722.1; -. [P55084-1] DR CCDS; CCDS62872.1; -. [P55084-2] DR PIR; JC2109; JC2109. DR RefSeq; NP_000174.1; NM_000183.2. [P55084-1] DR RefSeq; NP_001268441.1; NM_001281512.1. DR RefSeq; NP_001268442.1; NM_001281513.1. [P55084-2] DR RefSeq; XP_011531105.1; XM_011532803.1. [P55084-1] DR PDB; 5ZQZ; EM; 4.20 A; B/D=1-474. DR PDB; 5ZRV; EM; 7.70 A; B/D/F/H=1-474. DR PDB; 6DV2; X-ray; 3.60 A; A/B/C/D/E/F=34-474. DR PDBsum; 5ZQZ; -. DR PDBsum; 5ZRV; -. DR PDBsum; 6DV2; -. DR SMR; P55084; -. DR BioGRID; 109282; 266. DR CORUM; P55084; -. DR IntAct; P55084; 96. DR MINT; P55084; -. DR STRING; 9606.ENSP00000325136; -. DR MoonProt; P55084; -. DR iPTMnet; P55084; -. DR MetOSite; P55084; -. DR PhosphoSitePlus; P55084; -. DR SwissPalm; P55084; -. DR BioMuta; HADHB; -. DR DMDM; 116241345; -. DR UCD-2DPAGE; P55084; -. DR EPD; P55084; -. DR jPOST; P55084; -. DR MassIVE; P55084; -. DR MaxQB; P55084; -. DR PaxDb; P55084; -. DR PeptideAtlas; P55084; -. DR PRIDE; P55084; -. DR ProteomicsDB; 56786; -. [P55084-1] DR ProteomicsDB; 5856; -. DR Antibodypedia; 27848; 230 antibodies. DR DNASU; 3032; -. DR Ensembl; ENST00000317799; ENSP00000325136; ENSG00000138029. [P55084-1] DR Ensembl; ENST00000545822; ENSP00000442665; ENSG00000138029. [P55084-2] DR GeneID; 3032; -. DR KEGG; hsa:3032; -. DR UCSC; uc002rgz.4; human. [P55084-1] DR CTD; 3032; -. DR DisGeNET; 3032; -. DR EuPathDB; HostDB:ENSG00000138029.13; -. DR GeneCards; HADHB; -. DR HGNC; HGNC:4803; HADHB. DR HPA; ENSG00000138029; Tissue enhanced (heart muscle, skeletal muscle). DR MalaCards; HADHB; -. DR MIM; 143450; gene. DR MIM; 609015; phenotype. DR neXtProt; NX_P55084; -. DR OpenTargets; ENSG00000138029; -. DR Orphanet; 746; Mitochondrial trifunctional protein deficiency. DR PharmGKB; PA29177; -. DR eggNOG; KOG1392; Eukaryota. DR eggNOG; COG0183; LUCA. DR GeneTree; ENSGT00950000182771; -. DR InParanoid; P55084; -. DR KO; K07509; -. DR OMA; MTAFPEP; -. DR OrthoDB; 1129049at2759; -. DR PhylomeDB; P55084; -. DR TreeFam; TF315243; -. DR BioCyc; MetaCyc:HS06436-MONOMER; -. 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 UniPathway; UPA00659; -. DR BioGRID-ORCS; 3032; 1 hit in 786 CRISPR screens. DR ChiTaRS; HADHB; human. DR GeneWiki; HADHB; -. DR GenomeRNAi; 3032; -. DR Pharos; P55084; Tbio. DR PRO; PR:P55084; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P55084; protein. DR Bgee; ENSG00000138029; Expressed in heart right ventricle and 236 other tissues. DR ExpressionAtlas; P55084; baseline and differential. DR Genevisible; P55084; HS. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005740; C:mitochondrial envelope; TAS:ProtInc. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL. DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; TAS:ProtInc. DR GO; GO:0003988; F:acetyl-CoA C-acyltransferase activity; IBA:GO_Central. DR GO; GO:0050633; F:acetyl-CoA C-myristoyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0004300; F:enoyl-CoA hydratase activity; TAS:ProtInc. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0035965; P:cardiolipin acyl-chain remodeling; TAS:Reactome. DR GO; GO:0006635; P:fatty acid beta-oxidation; IBA:GO_Central. DR CDD; cd00751; thiolase; 1. DR Gene3D; 3.40.47.10; -; 1. DR InterPro; IPR002155; Thiolase. DR InterPro; IPR016039; Thiolase-like. DR InterPro; IPR020615; Thiolase_acyl_enz_int_AS. DR InterPro; IPR020610; Thiolase_AS. DR InterPro; IPR020617; Thiolase_C. DR InterPro; IPR020613; Thiolase_CS. DR InterPro; IPR020616; Thiolase_N. DR Pfam; PF02803; Thiolase_C; 1. DR Pfam; PF00108; Thiolase_N; 1. DR SUPFAM; SSF53901; SSF53901; 2. DR TIGRFAMs; TIGR01930; AcCoA-C-Actrans; 1. DR PROSITE; PS00098; THIOLASE_1; 1. DR PROSITE; PS00737; THIOLASE_2; 1. DR PROSITE; PS00099; THIOLASE_3; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Acyltransferase; Alternative splicing; KW Direct protein sequencing; Disease mutation; Endoplasmic reticulum; KW Fatty acid metabolism; Lipid metabolism; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Mitochondrion outer membrane; Polymorphism; KW Reference proteome; Transferase; Transit peptide. FT TRANSIT 1..33 FT /note="Mitochondrion" FT /evidence="ECO:0000244|PubMed:25944712, FT ECO:0000269|PubMed:12665801" FT CHAIN 34..474 FT /note="Trifunctional enzyme subunit beta, mitochondrial" FT /id="PRO_0000034080" FT INTRAMEM 173..220 FT /evidence="ECO:0000305|PubMed:29915090" FT ACT_SITE 138 FT /note="Acyl-thioester intermediate" FT /evidence="ECO:0000305|PubMed:30850536" FT ACT_SITE 458 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000305|PubMed:30850536" FT SITE 428 FT /note="Increases nucleophilicity of active site Cys" FT /evidence="ECO:0000305|PubMed:30850536" FT MOD_RES 72 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000244|PubMed:19608861" FT MOD_RES 72 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q99JY0" FT MOD_RES 188 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000244|PubMed:19608861" FT MOD_RES 188 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q99JY0" FT MOD_RES 190 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99JY0" FT MOD_RES 272 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99JY0" FT MOD_RES 291 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99JY0" FT MOD_RES 293 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q99JY0" FT MOD_RES 293 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q99JY0" FT MOD_RES 298 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99JY0" FT MOD_RES 332 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q99JY0" FT MOD_RES 332 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q99JY0" FT MOD_RES 348 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99JY0" FT MOD_RES 361 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99JY0" FT VAR_SEQ 1..36 FT /note="MTILTYPFKNLPTASKWALRFSIRPLSCSSQLRAAP -> MTLVSGWLLYGW FT II (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054426" FT VARIANT 59 FT /note="G -> D (in MTPD)" FT /evidence="ECO:0000269|PubMed:12754706" FT /id="VAR_021128" FT VARIANT 61 FT /note="R -> C (in MTPD; dbSNP:rs780351691)" FT /evidence="ECO:0000269|PubMed:12754706" FT /id="VAR_021129" FT VARIANT 61 FT /note="R -> H (in MTPD; dbSNP:rs121913132)" FT /evidence="ECO:0000269|PubMed:12754706, FT ECO:0000269|PubMed:8651282" FT /id="VAR_007493" FT VARIANT 117 FT /note="R -> G (in MTPD)" FT /evidence="ECO:0000269|PubMed:12754706" FT /id="VAR_021130" FT VARIANT 119 FT /note="A -> V (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035705" FT VARIANT 121 FT /note="L -> P (in MTPD; dbSNP:rs773127211)" FT /evidence="ECO:0000269|PubMed:12754706" FT /id="VAR_021131" FT VARIANT 133 FT /note="T -> P (in MTPD; dbSNP:rs371159065)" FT /evidence="ECO:0000269|PubMed:12754706" FT /id="VAR_021132" FT VARIANT 209 FT /note="P -> S (in dbSNP:rs17851200)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_028231" FT VARIANT 242 FT /note="D -> G (in MTPD; dbSNP:rs1166120479)" FT /evidence="ECO:0000269|PubMed:12754706" FT /id="VAR_021133" FT VARIANT 247 FT /note="R -> H (in MTPD; dbSNP:rs121913133)" FT /evidence="ECO:0000269|PubMed:12754706, FT ECO:0000269|PubMed:8651282" FT /id="VAR_007494" FT VARIANT 259..270 FT /note="Missing (in MTPD)" FT /evidence="ECO:0000269|PubMed:12754706" FT /id="VAR_021134" FT VARIANT 263 FT /note="D -> G (in MTPD; dbSNP:rs121913131)" FT /evidence="ECO:0000269|PubMed:12754706, FT ECO:0000269|PubMed:8651282" FT /id="VAR_007495" FT VARIANT 277 FT /note="K -> R (in dbSNP:rs57969630)" FT /id="VAR_061897" FT VARIANT 280 FT /note="G -> D (in MTPD; dbSNP:rs751772298)" FT /evidence="ECO:0000269|PubMed:12754706" FT /id="VAR_021135" FT VARIANT 294 FT /note="P -> L (in MTPD)" FT /evidence="ECO:0000269|PubMed:12754706" FT /id="VAR_021136" FT VARIANT 294 FT /note="P -> R (in MTPD)" FT /evidence="ECO:0000269|PubMed:12754706" FT /id="VAR_021137" FT VARIANT 301 FT /note="G -> S (in MTPD; dbSNP:rs891954464)" FT /evidence="ECO:0000269|PubMed:12754706" FT /id="VAR_021138" FT VARIANT 444 FT /note="R -> K (in MTPD; dbSNP:rs121913134)" FT /evidence="ECO:0000269|PubMed:12754706, FT ECO:0000269|PubMed:9259266" FT /id="VAR_017409" FT CONFLICT 1 FT /note="M -> MT (in Ref. 3; AAG39280 and 6; AAH14572/ FT AAH17564/AAH30824/AAH66963)" FT /evidence="ECO:0000305" SQ SEQUENCE 474 AA; 51294 MW; A7B41C37BEC1E6AD CRC64; MTILTYPFKN LPTASKWALR FSIRPLSCSS QLRAAPAVQT KTKKTLAKPN IRNVVVVDGV RTPFLLSGTS YKDLMPHDLA RAALTGLLHR TSVPKEVVDY IIFGTVIQEV KTSNVAREAA LGAGFSDKTP AHTVTMACIS ANQAMTTGVG LIASGQCDVI VAGGVELMSD VPIRHSRKMR KLMLDLNKAK SMGQRLSLIS KFRFNFLAPE LPAVSEFSTS ETMGHSADRL AAAFAVSRLE QDEYALRSHS LAKKAQDEGL LSDVVPFKVP GKDTVTKDNG IRPSSLEQMA KLKPAFIKPY GTVTAANSSF LTDGASAMLI MAEEKALAMG YKPKAYLRDF MYVSQDPKDQ LLLGPTYATP KVLEKAGLTM NDIDAFEFHE AFSGQILANF KAMDSDWFAE NYMGRKTKVG LPPLEKFNNW GGSLSLGHPF GATGCRLVMA AANRLRKEGG QYGLVAACAA GGQGHAMIVE AYPK //