Reviewed, UniProtKB/Swiss-Prot Q8BMS1 (ECHA_MOUSE)

Names and origin

Protein names

Recommended name:
    Trifunctional enzyme subunit alpha, mitochondrial
Alternative name(s):
    TP-alpha
Including the following 2 domains:
    1- Recommended name:
            Long-chain enoyl-CoA hydratase
              EC=4.2.1.17
    2- Recommended name:
            Long chain 3-hydroxyacyl-CoA dehydrogenase
              EC=1.1.1.211

Gene names

Name:

Hadha

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	763 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Bifunctional subunit.
Catalytic activity	(3S)-3-hydroxyacyl-CoA = trans-2(or 3)-enoyl-CoA + H2O. (S)-3-hydroxyacyl-CoA + NAD+ = 3-oxoacyl-CoA + NADH.
Pathway	Lipid metabolism; fatty acid beta-oxidation.
Subunit structure	Octamer of 4 alpha (HADHA) and 4 beta (HADHB) subunits By similarity.
Subcellular location	Mitochondrion matrix By similarity.
Post-translational modification	Acetylation of Lys-569 and Lys-728 is observed in liver mitochondria from fasted mice but not from fed mice.
Sequence similarities	In the N-terminal section; belongs to the enoyl-CoA hydratase/isomerase family. In the central section; belongs to the 3-hydroxyacyl-CoA dehydrogenase family.

Ontologies

Keywords
Biological process	Fatty acid metabolism Lipid metabolism
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	NAD
Molecular function	Lyase Oxidoreductase
PTM	Acetylation
Technical term	Multifunctional enzyme
Gene Ontology (GO)
Biological process	fatty acid beta-oxidation Inferred from mutant phenotype. Source: MGI oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	fatty acid beta-oxidation multienzyme complex Inferred from electronic annotation. Source: InterPro mitochondrial inner membrane Inferred from direct assay. Source: MGI
Molecular function	3-hydroxyacyl-CoA dehydrogenase activity Inferred from electronic annotation. Source: InterPro enoyl-CoA hydratase activity Traceable author statement. Source: MGI long-chain-3-hydroxyacyl-CoA dehydrogenase activity Inferred from direct assay. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 36	36	Mitochondrion Potential
	Chain	37 – 763	727	Trifunctional enzyme subunit alpha, mitochondrial		PRO_0000322639
Sites
	Active site	151	1	By similarity
	Active site	173	1	Proton donor By similarity
Amino acid modifications
	Modified residue	569	1	N6-acetyllysine Ref.3
	Modified residue	728	1	N6-acetyllysine Ref.3
Experimental info
	Sequence conflict	459	1	L → S in AAH37009. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8BMS1-1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 73D203795D5C1141	FASTA	763	82,670
	10 20 30 40 50 60 MVASRAIGSL SRFSAFRILR SRGCICRSFT TSSALLTRTH INYGVKGDVA VIRINSPNSK 70 80 90 100 110 120 VNTLNKEVQS EFIEVMNEIW ANDQIRSAVL ISSKPGCFVA GADINMLSSC TTPQEATRIS 130 140 150 160 170 180 QEGQRMFEKL EKSPKPVVAA ISGSCLGGGL ELAIACQYRI ATKDRKTVLG VPEVLLGILP 190 200 210 220 230 240 GAGGTQRLPK MVGVPAAFDM MLTGRNIRAD RAKKMGLVDQ LVEPLGPGIK SPEERTIEYL 250 260 270 280 290 300 EEVAVNFAKG LADRKVSAKQ SKGLVEKLTT YAMTVPFVRQ QVYKTVEEKV KKQTKGLYPA 310 320 330 340 350 360 PLKIIDAVKA GLEQGSDAGY LAESQKFGEL ALTKESKALM GLYNGQVLCK KNKFGAPQKN 370 380 390 400 410 420 VQQLAILGAG LMGAGIAQVS VDKGLKTLLK DTTVTGLGRG QQQVFKGLND KVKKKALTSF 430 440 450 460 470 480 ERDSIFSNLI GQLDYKGFEK ADMVIEAVFE DLGVKHKVLK EVESVTPEHC IFASNTSALP 490 500 510 520 530 540 INQIAAVSKR PEKVIGMHYF SPVDKMQLLE IITTDKTSKD TTASAVAVGL RQGKVIIVVK 550 560 570 580 590 600 DGPGFYTTRC LAPMMSEVMR ILQEGVDPKK LDALTTGFGF PVGAATLADE VGVDVAQHVA 610 620 630 640 650 660 EDLGKAFGER FGGGSVELLK QMVSKGFLGR KSGKGFYIYQ EGSKNKSLNS EMDNILANLR 670 680 690 700 710 720 LPAKPEVSSD EDVQYRVITR FVNEAVLCLQ EGILATPAEG DIGAVFGLGF PPCLGGPFRF 730 740 750 760 VDLYGAQKVV DRLRKYESAY GTQFTPCQLL LDHANNSSKK FYQ

References

[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Skin.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Eye, Liver and Olfactory epithelium.
[3]	"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey." Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y. Mol. Cell 23:607-618(2006) [PubMed: 16916647] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-569 AND LYS-728, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AK029017 mRNA. Translation: BAC26245.1. AK170683 mRNA. Translation: BAE41956.1. BC037009 mRNA. Translation: AAH37009.1. BC046978 mRNA. Translation: AAH46978.1. BC058569 mRNA. Translation: AAH58569.1.
IPI	IPI00223092.
RefSeq	NP_849209.1.
UniGene	Mm.200497
3D structure databases
HSSP	HSSP built from PDB template 2DUB based on UniProtKB P14604.
ModBase	Search...
PTM databases
PhosphoSite	Q8BMS1.
Proteomic databases
PRIDE	Q8BMS1.
Genome annotation databases
Ensembl	ENSMUSG00000025745. Mus musculus. [Contig view]
GeneID	97212.
KEGG	mmu:97212.
NMPDR	fig|10090.3.peg.11342.
Organism-specific databases
MGI	MGI:2135593. Hadha.
Phylogenomic databases
HOVERGEN	Q8BMS1.
OMA	Q8BMS1. AYAMTIP.
Enzyme and pathway databases
BRENDA	1.1.1.211. 244. 4.2.1.17. 244.
Gene expression databases
Bgee	Q8BMS1.
Family and domain databases
InterPro	IPR006180. 3-OHacyl-CoA_DH_CS. IPR006176. 3-OHacyl-CoA_DH_NAD-bd. IPR006108. 3HC_DH_C. IPR001753. Crotonase_core. IPR013328. DH_multihelical. IPR018376. Enoyl-CoA_hyd/isom_CS. IPR012803. Fa_ox_alpha_mit. IPR016040. NAD(P)-bd_dom. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit. G3DSA:1.10.1040.10. Opine_DH. 1 hit.
Pfam	PF00725. 3HCDH. 1 hit. PF02737. 3HCDH_N. 1 hit. PF00378. ECH. 1 hit. [Graphical view]
TIGRFAMs	TIGR02441. fa_ox_alpha_mit. 1 hit.
PROSITE	PS00067. 3HCDH. 1 hit. PS00166. ENOYL_COA_HYDRATASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	352627.
SOURCE	Search...

Entry information

Entry name

ECHA_MOUSE

Accession

Primary (citable) accession number: Q8BMS1
Secondary accession number(s): Q5U5Y5

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	March 1, 2003
Last modified:	June 16, 2009
This is version 66 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)