ECHS1
Protein-coding gene in humans
From Wikipedia, the free encyclopedia
Enoyl Coenzyme A hydratase, short chain, 1, mitochondrial, also known as ECHS1, is a human gene.[5]
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| Aliases | ECHS1, SCEH, ECHS1D, enoyl-CoA hydratase, short chain, 1, mitochondrial, enoyl-CoA hydratase, short chain 1, mECH, mECH1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 602292; MGI: 2136460; HomoloGene: 3018; GeneCards: ECHS1; OMA:ECHS1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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The protein encoded by this gene functions in the second step of the mitochondrial fatty acid beta-oxidation pathway. It catalyzes the hydration of 2-trans-enoyl-coenzyme A (CoA) intermediates to L-3-hydroxyacyl-CoAs. The gene product is a member of the hydratase/isomerase superfamily. It localizes to the mitochondrial matrix. Transcript variants utilizing alternative transcription initiation sites have been described in the literature.[5]
Structure
The ECHS1 gene is approximately 11 kb in length, and is composed of eight exons, with exons I and VIII containing the 5'- and 3'-untranslated regions, respectively. There are two major transcription start sites, located 62 and 63 bp upstream of the translation codon, were mapped by primer extension analysis. The 5'-flanking region of the ECHS1 gene is GC-rich and contains several copies of the SP1 binding motive but no typical TATA or CAAT boxes are apparent. Alu repeat elements have been identified within the region -1052/-770 relative to the cap site and in intron 7.[6] The precursor polypeptide contains 290 amino acid residues, with an N-terminal mitochondrial targeting domain (1-27,28,29) leading to a ragged mature N-terminus. The mRNA has a 5'-untranslated sequence of 21 bp and a 3'-untranslated sequence of 391 bp.[7]
Function
Enoyl-CoA hydratase (ECH) catalyzes the second step in beta-oxidation pathway of fatty acid metabolism. The enzyme is involved in the formation of a β-hydroxyacyl-CoA thioester. The two catalytic glutamic acid residues are believed to act in concert to activate a water molecule, while Gly-141 is proposed to be involved in substrate activation. There are two potent inhibitors of ECHS, which irreversibly inactivate the enzyme via covalent adduct formation.[8]
Clinical significance
Enoyl-CoA hydratase short chain has been confirmed to interact with STAT3, such that ECHS1 specifically represses STAT3 activity by inhibiting STAT3 phosphorylation.[9] STAT3 can act as both an oncogene and a tumor suppressor. ECHS1 itself has shown to occur in many cancers, particularly in hepatocellular carcinoma (HCC) development;[10] both exogenous and endogenous forms of ECHS1 bind to HBs and induce apoptosis as a result. This means that ECHS1 may be used in the future as a therapy for patients with HBV-related hepatitis or HCC.[11]