HADHA
| HADHA | |||
|---|---|---|---|
Gene ontology | |||
| Molecular function |
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| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 2: 26.19 – 26.24 Mb | Chr 5: 30.32 – 30.36 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Trifunctional enzyme subunit alpha, mitochondrial also known as hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit is a protein that in humans is encoded by the HADHA gene. Mutations in HADHA have been associated with trifunctional protein deficiency or long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency.[5]
Structure
HADHA is an 82.9 kDa protein composed of 763 amino acids.[6][7]
The
Function
This gene encodes the alpha subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial
Clinical significance
Mutations in this gene result in trifunctional protein deficiency or long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency.[5]
The most common form of the mutation is G1528C, in which the guanine at the 1528th position is changed to a cytosine. The gene mutation creates a protein deficiency that is associated with impaired oxidation of long-chain fatty acids that can lead to sudden infant death.[10] Clinical manifestations of this deficiency can include myopathy, cardiomyopathy, episodes of coma, and hypoglycemia.[11] Long-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency is associated with some pregnancy-specific disorders, including preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), hyperemesis gravidarum,[12][13] acute fatty liver of pregnancy,[14] and maternal floor infarct of the placenta.[12][13]
From a clinical perspective, HADHA might also be a useful marker to predict resistance to certain types of chemotherapy in patients with lung cancer.[15]
Interactions
HADHA has been shown to have 142 binary
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000084754 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025745 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d "Entrez Gene: Hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit".
- PMID 23965338.
- ^ "hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 2016-03-05. Retrieved 2015-03-18.
- PMID 1550553.
- ISBN 978-0-470-23396-2.
- PMID 8770876.
- PMID 2284166.
- ^ PMID 12118083.
- ^ S2CID 38407420.
- PMID 11001809.
- PMID 22471497.
- ^ "142 binary interactions found for search term HADHA". IntAct Molecular Interaction Database. EMBL-EBI. Retrieved 2018-08-25.
Further reading
- Rakheja D, Bennett MJ, Rogers BB (Jul 2002). "Long-chain L-3-hydroxyacyl-coenzyme a dehydrogenase deficiency: a molecular and biochemical review". Laboratory Investigation. 82 (7): 815–24. PMID 12118083.
- Isaacs JD, Sims HF, Powell CK, Bennett MJ, Hale DE, Treem WR, Strauss AW (Sep 1996). "Maternal acute fatty liver of pregnancy associated with fetal trifunctional protein deficiency: molecular characterization of a novel maternal mutant allele". Pediatric Research. 40 (3): 393–8. PMID 8865274.
- Gillingham MB, Matern D, Harding CO (Oct 2009). "Effect of feeding, exercise and genotype on plasma 3-hydroxyacylcarnitines in children with lchad deficiency". Topics in Clinical Nutrition. 24 (4): 359–365. PMID 20589231.
- Milewska M, McRedmond J, Byrne PC (Nov 2009). "Identification of novel spartin-interactors shows spartin is a multifunctional protein". Journal of Neurochemistry. 111 (4): 1022–30. S2CID 205621232.
- Weekes J, Morrison K, Mullen A, Wait R, Barton P, Dunn MJ (Feb 2003). "Hyperubiquitination of proteins in dilated cardiomyopathy". Proteomics. 3 (2): 208–16. S2CID 19874662.
- Bogenhagen DF, Rousseau D, Burke S (Feb 2008). "The layered structure of human mitochondrial DNA nucleoids". Journal of Biological Chemistry. 283 (6): 3665–75. PMID 18063578.
- Zhang QX, Baldwin GS (Oct 1994). "Structures of the human cDNA and gene encoding the 78 kDa gastrin-binding protein and of a related pseudogene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1219 (2): 567–75. PMID 7918661.
- IJlst L, Oostheim W, Ruiter JP, Wanders RJ (Jul 1997). "Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of two new mutations". Journal of Inherited Metabolic Disease. 20 (3): 420–2. S2CID 23046057.
- Yagi M, Lee T, Awano H, Tsuji M, Tajima G, Kobayashi H, Hasegawa Y, Yamaguchi S, Takeshima Y, Matsuo M (Dec 2011). "A patient with mitochondrial trifunctional protein deficiency due to the mutations in the HADHB gene showed recurrent myalgia since early childhood and was diagnosed in adolescence". Molecular Genetics and Metabolism. 104 (4): 556–9. PMID 22000755.
External links
- PDBe-KB provides an overview of all the structure information available in the PDB for Human Trifunctional enzyme subunit alpha, mitochondrial (HADHA)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
