ECHS1

Enoyl Coenzyme A hydratase, short chain, 1, mitochondrial, also known as ECHS1, is a human gene.^[5]

ECHS1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2HW5
Identifiers
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
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q26.3 Start 133,362,485 bp[1] End 133,373,354 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 F4 Start 139,685,623 bp[2] End 139,696,389 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver kidney tubule parotid gland human kidney mucosa of transverse colon jejunal mucosa renal medulla glomerulus apex of heart metanephric glomerulus Top expressed in brown adipose tissue right ventricle right kidney left lobe of liver myocardium of ventricle digastric muscle interventricular septum cardiac muscles adrenal gland white adipose tissue More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding catalytic activity lyase activity enoyl-CoA hydratase activity Cellular component mitochondrial matrix mitochondrion Biological process metabolism fatty acid metabolic process lipid metabolism fatty acid beta-oxidation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1892 93747 Ensembl ENSG00000127884 ENSMUSG00000025465 UniProt P30084 Q8BH95 RefSeq (mRNA) NM_004092 NM_053119 RefSeq (protein) NP_004083 NP_444349 Location (UCSC) Chr 10: 133.36 – 133.37 Mb Chr 7: 139.69 – 139.7 Mb PubMed search [3] [4]
Wikidata
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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]