P55084 (ECHB_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 119.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Trifunctional enzyme subunit beta, mitochondrial Alternative name(s): TP-beta Including the following 1 domains:
| ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 474 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)
| Catalytic activity | Acyl-CoA + acetyl-CoA = CoA + 3-oxoacyl-CoA. Ref.8 |
| Pathway | |
| Subunit structure | Octamer of 4 alpha (HADHA) and 4 beta (HADHB) subunits. Ref.10 |
| Subcellular location | |
| Involvement in disease | Defects in HADHB are a cause of trifunctional protein deficiency (TFP deficiency) [MIM:609015]. The clinical manifestations are very variable and include hypoglycemia, cardiomyopathy and sudden death. Phenotypes with mainly hepatic and neuromyopathic involvement can also be distinguished. Biochemically, TFP deficiency is defined by the loss of all three enzyme activities of the TFP complex. |
| Sequence similarities | Belongs to the thiolase family. |
| Sequence caution | The sequence BAA22061.1 differs from that shown. Reason: Erroneous gene model prediction. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Fatty acid metabolism Lipid metabolism |
| Cellular component | Mitochondrion |
| Coding sequence diversity | Polymorphism |
| Disease | Disease mutation |
| Domain | Transit peptide |
| Molecular function | Acyltransferase Transferase |
| PTM | Acetylation |
| Technical term | Complete proteome Direct protein sequencing Reference proteome |
| Gene Ontology (GO) | |
| Biological process | fatty acid beta-oxidation Traceable author statement. Source: Reactome |
| Cellular component | mitochondrial nucleoid Inferred from direct assay. Source: BHF-UCL |
| Molecular function | 3-hydroxyacyl-CoA dehydrogenase activity Traceable author statement. Source: ProtInc acetyl-CoA C-acyltransferase activityTraceable author statement. Source: ProtInc enoyl-CoA hydratase activityTraceable author statement. Source: ProtInc protein bindingInferred from physical interaction. Source: IntAct |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| GABARAPL1 | Q9H0R8 | 4 | EBI-356635,EBI-746969 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Transit peptide | 1 – 33 | 33 | Mitochondrion Ref.7 | ||||||
| Chain | 34 – 474 | 441 | Trifunctional enzyme subunit beta, mitochondrial | PRO_0000034080 | |||||
Sites | |||||||||
| Active site | 138 | 1 | Acyl-thioester intermediate By similarity | ||||||
| Active site | 428 | 1 | Proton acceptor By similarity | ||||||
| Active site | 458 | 1 | Proton acceptor By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 72 | 1 | N6-acetyllysine Ref.11 | ||||||
| Modified residue | 188 | 1 | N6-acetyllysine Ref.11 | ||||||
| Modified residue | 201 | 1 | N6-acetyllysine By similarity | ||||||
| Modified residue | 348 | 1 | N6-acetyllysine By similarity | ||||||
Natural variations | |||||||||
| Natural variant | 59 | 1 | G → D in TFP deficiency. Ref.14 | VAR_021128 | |||||
| Natural variant | 61 | 1 | R → C in TFP deficiency. Ref.14 | VAR_021129 | |||||
| Natural variant | 61 | 1 | R → H in TFP deficiency. Ref.13 Ref.14 | VAR_007493 | |||||
| Natural variant | 117 | 1 | R → G in TFP deficiency. Ref.14 | VAR_021130 | |||||
| Natural variant | 119 | 1 | A → V in a breast cancer sample; somatic mutation. Ref.15 | VAR_035705 | |||||
| Natural variant | 121 | 1 | L → P in TFP deficiency. Ref.14 | VAR_021131 | |||||
| Natural variant | 133 | 1 | T → P in TFP deficiency. Ref.14 | VAR_021132 | |||||
| Natural variant | 209 | 1 | P → S. Ref.6 Corresponds to variant rs17851200 [ dbSNP | Ensembl ]. | VAR_028231 | |||||
| Natural variant | 242 | 1 | D → G in TFP deficiency. Ref.14 | VAR_021133 | |||||
| Natural variant | 247 | 1 | R → H in TFP deficiency. Ref.13 Ref.14 | VAR_007494 | |||||
| Natural variant | 259 – 270 | 12 | Missing in TFP deficiency. | VAR_021134 | |||||
| Natural variant | 263 | 1 | D → G in TFP deficiency. Ref.13 Ref.14 | VAR_007495 | |||||
| Natural variant | 277 | 1 | K → R. Corresponds to variant rs57969630 [ dbSNP | Ensembl ]. | VAR_061897 | |||||
| Natural variant | 280 | 1 | G → D in TFP deficiency. Ref.14 | VAR_021135 | |||||
| Natural variant | 294 | 1 | P → L in TFP deficiency. Ref.14 | VAR_021136 | |||||
| Natural variant | 294 | 1 | P → R in TFP deficiency. Ref.14 | VAR_021137 | |||||
| Natural variant | 301 | 1 | G → S in TFP deficiency. Ref.14 | VAR_021138 | |||||
| Natural variant | 444 | 1 | R → K in TFP deficiency. Ref.2 Ref.14 | VAR_017409 | |||||
Experimental info | |||||||||
| Sequence conflict | 1 | 1 | M → MT in AAG39280. Ref.3 | ||||||
| Sequence conflict | 1 | 1 | M → MT in AAH14572. Ref.6 | ||||||
| Sequence conflict | 1 | 1 | M → MT in AAH17564. Ref.6 | ||||||
| Sequence conflict | 1 | 1 | M → MT in AAH30824. Ref.6 | ||||||
| Sequence conflict | 1 | 1 | M → MT in AAH66963. Ref.6 | ||||||
Sequences
| ||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "Structural analysis of cDNAs for subunits of human mitochondrial fatty acid beta-oxidation trifunctional protein." Kamijo T., Aoyama T., Komiyama A., Hashimoto T. Biochem. Biophys. Res. Commun. 199:818-825(1994) [PubMed: 8135828] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [2] | "Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency." Orii K.E., Aoyama T., Wakui K., Fukushima Y., Miyajima H., Yamaguchi S., Orii T., Kondo N., Hashimoto T. Hum. Mol. Genet. 6:1215-1224(1997) [PubMed: 9259266] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT TFP DEFICIENCY LYS-444. Tissue: Blood. |
| [3] | Liu B., Liu Y.Q., Wang X.Y., Zhao B., Sheng H., Zhao X.W., Liu S., Xu Y.Y., Ye J., Song L., Gao Y., Zhang C.L., Zhang J., Wei Y.J., Cao H.Q., Zhao Y., Liu L.S., Ding J.F. Hui R.T.Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart. |
| [4] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Tongue. |
| [5] | "Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. Wilson R.K.Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | "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], VARIANT SER-209. Tissue: Colon, Hypothalamus, Skeletal muscle and Urinary bladder. |
| [7] | "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 34-52. Tissue: Platelet. |
| [8] | "The mitochondrial long-chain trifunctional enzyme: 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase and 3-oxoacyl-CoA thiolase." Middleton B. Biochem. Soc. Trans. 22:427-431(1994) [PubMed: 7958339] [Abstract] Cited for: PROTEIN SEQUENCE OF 48-63, CATALYTIC ACTIVITY. Tissue: Liver. |
| [9] | "Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes." Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V. Biochem. J. 383:237-248(2004) [PubMed: 15242332] [Abstract] Cited for: PROTEIN SEQUENCE OF 62-72 AND 96-111. Tissue: Adipocyte. |
| [10] | "Mitochondrial trifunctional protein deficiency. Catalytic heterogeneity of the mutant enzyme in two patients." Kamijo T., Wanders R.J., Saudubray J.-M., Aoyama T., Komiyama A., Hashimoto T. J. Clin. Invest. 93:1740-1747(1994) [PubMed: 8163672] [Abstract] Cited for: SUBUNIT. |
| [11] | "Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-72 AND LYS-188, MASS SPECTROMETRY. |
| [12] | "Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. |
| [13] | "Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits." Ushikubo S., Aoyama T., Kamijo T., Wanders R.J.A., Rinaldo P., Vockley J., Hashimoto T. Am. J. Hum. Genet. 58:979-988(1996) [PubMed: 8651282] [Abstract] Cited for: VARIANTS TFP DEFICIENCY HIS-61; HIS-247 AND GLY-263. |
| [14] | "Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations." Spiekerkoetter U., Sun B., Khuchua Z., Bennett M.J., Strauss A.W. Hum. Mutat. 21:598-607(2003) [PubMed: 12754706] [Abstract] Cited for: VARIANTS TFP DEFICIENCY ASP-59; CYS-61; HIS-61; GLY-117; PRO-121; PRO-133; GLY-242; HIS-247; 259-GLY--PRO-270 DEL; GLY-263; ASP-280; ARG-294; LEU-294; SER-301 AND LYS-444. |
| [15] | "The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-119. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | D16481 mRNA. Translation: BAA03942.1. D86850 Genomic DNA. Translation: BAA22061.1. Sequence problems. AF113209 mRNA. Translation: AAG39280.1. AK314455 mRNA. Translation: BAG37063.1. AC010896 Genomic DNA. Translation: AAY14644.1. BC014572 mRNA. Translation: AAH14572.1. BC017564 mRNA. Translation: AAH17564.1. BC030824 mRNA. Translation: AAH30824.1. BC066963 mRNA. Translation: AAH66963.1. |
| IPI | IPI00022793. |
| PIR | JC2109. |
| RefSeq | NP_000174.1. NM_000183.2. |
| UniGene | Hs.515848. |
3D structure databases | |
| ProteinModelPortal | P55084. |
| SMR | P55084. Positions 53-472. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P55084. 19 interactions. |
| MINT | MINT-1154861. |
| STRING | P55084. |
PTM databases | |
| PhosphoSite | P55084. |
Polymorphism databases | |
| DMDM | 116241345. |
2D gel databases | |
| UCD-2DPAGE | P55084. |
Proteomic databases | |
| PRIDE | P55084. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000317799; ENSP00000325136; ENSG00000138029. |
| GeneID | 3032. |
| KEGG | hsa:3032. |
| UCSC | uc002rgz.1. human. |
Organism-specific databases | |
| CTD | 3032. |
| GeneCards | GC02P026466. |
| H-InvDB | HIX0001894. |
| HGNC | HGNC:4803. HADHB. |
| HPA | HPA037539. |
| MIM | 143450. gene. 609015. phenotype. |
| neXtProt | NX_P55084. |
| Orphanet | 746. Mitochondrial trifunctional protein deficiency. |
| PharmGKB | PA29177. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG08749. |
| HOVERGEN | HBG104782. |
| InParanoid | P55084. |
| OMA | QILANFK. |
| PhylomeDB | P55084. |
Enzyme and pathway databases | |
| Reactome | REACT_22258. Metabolism of lipids and lipoproteins. |
Gene expression databases | |
| ArrayExpress | P55084. |
| Bgee | P55084. |
| CleanEx | HS_HADHB. |
| Genevestigator | P55084. |
| GermOnline | ENSG00000138029. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR002155. Thiolase. IPR016039. Thiolase-like. IPR016038. Thiolase-like_subgr. IPR020615. Thiolase_acyl_enz_int_AS. IPR020610. Thiolase_AS. IPR020617. Thiolase_C. IPR020613. Thiolase_CS. IPR020616. Thiolase_N. [Graphical view] |
| Gene3D | G3DSA:3.40.47.10. Thiolase-like_subgr. 4 hits. |
| KO | K07509. |
| PANTHER | PTHR18919. Thiolase. 1 hit. |
| Pfam | PF02803. Thiolase_C. 1 hit. PF00108. Thiolase_N. 1 hit. [Graphical view] |
| SUPFAM | SSF53901. Thiolase-like. 2 hits. |
| TIGRFAMs | TIGR01930. AcCoA-C-Actrans. 1 hit. |
| PROSITE | PS00098. THIOLASE_1. 1 hit. PS00737. THIOLASE_2. 1 hit. PS00099. THIOLASE_3. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 12002. |
| SOURCE | Search... |
Entry information
| Entry name | ECHB_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P55084 Secondary accession number(s): B2RB16 Q9T2V8 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| SIMILARITY comments Index of protein domains and families |

Clusters with