ECHS1

Last updated
ECHS1
Protein ECHS1 PDB 1dub.png
Available structures
PDB Ortholog search: PDBe RCSB
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
Orthologs
SpeciesHumanMouse
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
View/Edit Human View/Edit Mouse

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

Contents

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 hypatocellular 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]

Related Research Articles

<span class="mw-page-title-main">Enoyl CoA isomerase</span> Type of enzyme

Enoyl-CoA-(∆) isomerase (EC 5.3.3.8, also known as dodecenoyl-CoA- isomerase, 3,2-trans-enoyl-CoA isomerase, ∆3 ,∆2 -enoyl-CoA isomerase, or acetylene-allene isomerase, is an enzyme that catalyzes the conversion of cis- or trans-double bonds of coenzyme A bound fatty acids at gamma-carbon to trans double bonds at beta-carbon as below:

In biochemistry and metabolism, beta oxidation (also β-oxidation) is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA. Acetyl-CoA enters the citric acid cycle, generating NADH and FADH2, which are electron carriers used in the electron transport chain. It is named as such because the beta carbon of the fatty acid chain undergoes oxidation and is converted to a carbonyl group to start the cycle all over again. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes.

<span class="mw-page-title-main">ACADM</span> Mammalian protein found in Homo sapiens

ACADM is a gene that provides instructions for making an enzyme called acyl-coenzyme A dehydrogenase that is important for breaking down (degrading) a certain group of fats called medium-chain fatty acids.

<span class="mw-page-title-main">Mitochondrial trifunctional protein</span> Inner mitochondrial membrane protein

Mitochondrial trifunctional protein (MTP) is a protein attached to the inner mitochondrial membrane which catalyzes three out of the four steps in beta oxidation. MTP is a hetero-octamer composed of four alpha and four beta subunits:

<span class="mw-page-title-main">HADHA</span> Protein-coding gene in the species Homo sapiens

Trifunctional enzyme subunit alpha, mitochondrial also known as hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, 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.

<span class="mw-page-title-main">HADHB</span> Protein-coding gene in the species Homo sapiens

Trifunctional enzyme subunit beta, mitochondrial (TP-beta) also known as 3-ketoacyl-CoA thiolase, acetyl-CoA acyltransferase, or beta-ketothiolase is an enzyme that in humans is encoded by the HADHB gene.

<span class="mw-page-title-main">2,4 Dienoyl-CoA reductase</span> Class of enzymes

2,4 Dienoyl-CoA reductase also known as DECR1 is an enzyme which in humans is encoded by the DECR1 gene which resides on chromosome 8. This enzyme catalyzes the following reactions

The crotonase family comprises mechanistically diverse proteins that share a conserved trimeric quaternary structure, the core of which consists of 4 turns of a (beta/beta/alpha)n superhelix.

<span class="mw-page-title-main">Methylglutaconyl-CoA hydratase</span> Protein-coding gene in the species Homo sapiens

3-Methylglutaconyl-CoA hydratase, also known as MG-CoA hydratase and AUH, is an enzyme encoded by the AUH gene on chromosome 19. It is a member of the enoyl-CoA hydratase/isomerase superfamily, but it is the only member of that family that is able to bind to RNA. Not only does it bind to RNA, AUH has also been observed to be involved in the metabolic enzymatic activity, making it a dual-role protein. Mutations of this gene have been found to cause a disease called 3-Methylglutaconic Acuduria Type 1.

<span class="mw-page-title-main">HSD17B4</span> Protein-coding gene in the species Homo sapiens

D-bifunctional protein (DBP), also known as peroxisomal multifunctional enzyme type 2 (MFP-2), as well as 17β-hydroxysteroid dehydrogenase type IV is a protein that in humans is encoded by the HSD17B4 gene. It's an alcohol oxidoreductase, specifically 17β-Hydroxysteroid dehydrogenase. It is involved in fatty acid β-oxidation and steroid metabolism.

<span class="mw-page-title-main">ACOX1</span> Protein-coding gene in the species Homo sapiens

Peroxisomal acyl-coenzyme A oxidase 1 is an enzyme that in humans is encoded by the ACOX1 gene.

<span class="mw-page-title-main">NDUFA5</span> Protein-coding gene in the species Homo sapiens

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 is an enzyme that in humans is encoded by the NDUFA5 gene. The NDUFA5 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.

<span class="mw-page-title-main">ACOT7</span> Protein-coding gene in the species Homo sapiens

Cytosolic acyl coenzyme A thioester hydrolase is an enzyme that in humans is encoded by the ACOT7 gene.

<span class="mw-page-title-main">GLYAT</span> Protein-coding gene in the species Homo sapiens

Glycine-N-acyltransferase, also known as GLYAT, is an enzyme which in humans is encoded by the GLYAT gene.

<span class="mw-page-title-main">ACOT11</span> Protein-coding gene in the species Homo sapiens

Acyl-coenzyme A thioesterase 11 also known as StAR-related lipid transfer protein 14 (STARD14) is an enzyme that in humans is encoded by the ACOT11 gene. This gene encodes a protein with acyl-CoA thioesterase activity towards medium (C12) and long-chain (C18) fatty acyl-CoA substrates which relies on its StAR-related lipid transfer domain. Expression of a similar murine protein in brown adipose tissue is induced by cold exposure and repressed by warmth. Expression of the mouse protein has been associated with obesity, with higher expression found in obesity-resistant mice compared with obesity-prone mice. Alternative splicing results in two transcript variants encoding different isoforms.

<span class="mw-page-title-main">MECR</span> Protein-coding gene in the species Homo sapiens

Trans-2-enoyl-CoA reductase, mitochondrial is an enzyme that in humans is encoded by the MECR gene.

<span class="mw-page-title-main">ECH1</span> Protein-coding gene in the species Homo sapiens

Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial is an enzyme that in humans is encoded by the ECH1 gene.

<span class="mw-page-title-main">PECR</span> Protein-coding gene in the species Homo sapiens

Peroxisomal trans-2-enoyl-CoA reductase is an enzyme that in humans is encoded by the PECR gene.

<span class="mw-page-title-main">Hydroxyacyl-Coenzyme A dehydrogenase</span> Protein-coding gene in the species Homo sapiens

Hydroxyacyl-Coenzyme A dehydrogenase (HADH) is an enzyme which in humans is encoded by the HADH gene.

<span class="mw-page-title-main">Acyl-CoA thioesterase 9</span> Protein-coding gene in humans

Acyl-CoA thioesterase 9 is a protein that is encoded by the human ACOT9 gene. It is a member of the acyl-CoA thioesterase superfamily, which is a group of enzymes that hydrolyze Coenzyme A esters. There is no known function, however it has been shown to act as a long-chain thioesterase at low concentrations, and a short-chain thioesterase at high concentrations.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000127884 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025465 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Gene: ECHS1 enoyl Coenzyme A hydratase, short chain, 1, mitochondrial".
  6. ↑ Janssen, U; Davis, E. M.; Le Beau, M. M.; Stoffel, W (1997). "Human mitochondrial enoyl-CoA hydratase gene (ECHS1): Structural organization and assignment to chromosome 10q26.2-q26.3". Genomics. 40 (3): 470–5. doi:10.1006/geno.1996.4597. PMID   9073515.
  7. ↑ Kanazawa, M; Ohtake, A; Abe, H; Yamamoto, S; Satoh, Y; Takayanagi, M; Niimi, H; Mori, M; Hashimoto, T (1993). "Molecular cloning and sequence analysis of the cDNA for human mitochondrial short-chain enoyl-CoA hydratase". Enzyme & Protein. 47 (1): 9–13. doi:10.1159/000468650 (inactive 2024-06-08). PMID   8012501.{{cite journal}}: CS1 maint: DOI inactive as of June 2024 (link)
  8. ↑ Agnihotri, G; Liu, H. W. (2003). "Enoyl-CoA hydratase. Reaction, mechanism, and inhibition". Bioorganic & Medicinal Chemistry. 11 (1): 9–20. doi:10.1016/s0968-0896(02)00333-4. PMID   12467702.
  9. ↑ Chang, Y; Wang, S. X.; Wang, Y. B.; Zhou, J; Li, W. H.; Wang, N; Fang, D. F.; Li, H. Y.; Li, A. L.; Zhang, X. M.; Zhang, W. N. (2013). "ECHS1 interacts with STAT3 and negatively regulates STAT3 signaling". FEBS Letters. 587 (6): 607–13. Bibcode:2013FEBSL.587..607C. doi:10.1016/j.febslet.2013.02.005. PMID   23416296. S2CID   23233213.
  10. ↑ Zhu, X. S.; Dai, Y. C.; Chen, Z. X.; Xie, J. P.; Zeng, W; Lin, Y. Y.; Tan, Q. H. (2013). "Knockdown of ECHS1 protein expression inhibits hepatocellular carcinoma cell proliferation via suppression of Akt activity". Critical Reviews in Eukaryotic Gene Expression. 23 (3): 275–82. doi:10.1615/critreveukaryotgeneexpr.2013007531. PMID   23879543.
  11. ↑ Xiao, C. X.; Yang, X. N.; Huang, Q. W.; Zhang, Y. Q.; Lin, B. Y.; Liu, J. J.; Liu, Y. P.; Jazag, A; Guleng, B; Ren, J. L. (2013). "ECHS1 acts as a novel HBs Ag-binding protein enhancing apoptosis through the mitochondrial pathway in HepG2 cells". Cancer Letters. 330 (1): 67–73. doi:10.1016/j.canlet.2012.11.030. PMID   23178449.

Further reading

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