MECR

MECR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ZSY, 2VCY
Identifiers
Aliases	MECR , CGI-63, FASN2B, NRBF1, mitochondrial trans-2-enoyl-CoA reductase, ETR1, DYTOABG
External IDs	OMIM: 608205; MGI: 1349441; HomoloGene: 5362; GeneCards: MECR; OMA:MECR - orthologs
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1p35.3 Start 29,192,657 bp [1] End 29,230,942 bp [1]
Gene location (Mouse) Chr. Chromosome 4 (mouse) [2] Band 4|4 D2.3 Start 131,570,781 bp [2] End 131,595,097 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart muscle of thigh gastrocnemius muscle prefrontal cortex anterior cingulate cortex left ventricle right frontal lobe right auricle of heart C1 segment right adrenal gland Top expressed in brown adipose tissue neural layer of retina right kidney lens proximal tubule lip lumbar spinal ganglion primary oocyte epithelium of stomach left colon More reference expression data BioGPS More reference expression data
Gene ontology Molecular function oxidoreductase activity trans-2-enoyl-CoA reductase (NADPH) activity Cellular component cytoplasm mitochondrion nucleus mitochondrial matrix Biological process fatty acid biosynthetic process lipid metabolism fatty acid metabolic process fatty acid beta-oxidation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 51102 26922 Ensembl ENSG00000116353 ENSMUSG00000028910 UniProt Q9BV79 Q9DCS3 RefSeq (mRNA) NM_001024732 NM_016011 NM_001349711 NM_001349712 NM_001349713 NM_001349714 NM_001349715 NM_001349716 NM_001349717 NM_025297 RefSeq (protein) NP_001019903 NP_057095 NP_001336640 NP_001336641 NP_001336642 NP_001336643 NP_001336644 NP_001336645 NP_001336646 NP_079573 Location (UCSC) Chr 1: 29.19 – 29.23 Mb Chr 4: 131.57 – 131.6 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Trans-2-enoyl-CoA reductase, mitochondrial is an enzyme that in humans is encoded by the MECR gene. ^{[5] [6] [7]}

Structure

The MECR gene is located on the 1st chromosome, with its specific location being 1p35.3. ^[7] The gene contains 15 exons. ^[7] MECR encodes a 21.2 kDa protein that is composed of 189 amino acids; 10 peptides have been observed through mass spectrometry data. ^{[8] [9]}

Function

The mtFAS pathway with MECR catalyzing the final reduction step.

The protein encoded by MECR is an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis (mtFAS). ^[10] MECR reduces trans-2-enoyl-ACP to acyl-ACP using NADPH as a reducing agent. The resulting saturated acyl-ACP can then re-enter the mtFAS cycle for further chain elongation. ^[11] The reaction can be summarized by the following equation:

trans-2-enoyl-ACP + NADPH + H⁺ → Acyl-ACP + NADP⁺

The mtFAS pathway is essential for producing octanoyl-ACP that is used to synthesize lipoic acid, which is essential for aerobic metabolism.

A Purkinje cell specific knock out of the Mecr gene in mice leads to neurodegeneration. ^[12]

Clinical significance

Genetic mutations to MECR have been suggested to cause MEPAN Syndrome, a neurometabolic disorder in humans that involves disruptions in the pathway involved in mitochondrial fatty acid synthesis (mtFAS). MEPAN patients were found to harbor recessive mutations in MECR, and typically present with childhood-onset dystonia, optic atrophy, and basal ganglia signal abnormalities on MRI. ^[13]

See also

• ACSF3
• Combined malonic and methylmalonic aciduria (CMAMMA)

References

1. GRCh38: Ensembl release 89: ENSG00000116353 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028910 – 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. Masuda N, Yasumo H, Furusawa T, et al. (October 1998). "Nuclear receptor binding factor-1 (NRBF-1), a protein interacting with a wide spectrum of nuclear hormone receptors". Gene. 221 (2): 225–33. doi:10.1016/S0378-1119(98)00461-2. PMID   9795230.
6. Miinalainen IJ, Chen ZJ, Torkko JM, et al. (May 2003). "Characterization of 2-enoyl thioester reductase from mammals. An ortholog of YBR026p/MRF1'p of the yeast mitochondrial fatty acid synthesis type II". The Journal of Biological Chemistry. 278 (22): 20154–61. doi: 10.1074/jbc.M302851200 . PMID   12654921.
7. "Entrez Gene: MECR mitochondrial trans-2-enoyl-CoA reductase".
8. ]Zong NC, Li H, Li H, et al. (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC   4076475 . PMID   23965338.
9. "Mitochondrial trans-2-enoyl-CoA reductase". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).^{[ permanent dead link ]}
10. Nowinski SM, Van Vranken JG, Dove KK, et al. (October 2018). "Impact of Mitochondrial Fatty Acid Synthesis on Mitochondrial Biogenesis". Current Biology. 28 (20): R1212 –R1219. Bibcode:2018CBio...28R1212N. doi:10.1016/j.cub.2018.08.022. PMC   6258005 . PMID   30352195.
11. Nowinski SM, Solmonson A, Rusin SF, et al. (2020-08-17). "Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria". eLife. 9. doi: 10.7554/eLife.58041 . ISSN   2050-084X. PMC   7470841 . PMID   32804083.
12. Nair RR, Koivisto H, Jokivarsi K, et al. (November 2018). "Impaired Mitochondrial Fatty Acid Synthesis Leads to Neurodegeneration in Mice". The Journal of Neuroscience. 38 (45): 9781–9800. doi:10.1523/JNEUROSCI.3514-17.2018. PMC   6595986 . PMID   30266742.
13. Heimer G, Kerätär JM, Riley LG, et al. (December 2016). "MECR Mutations Cause Childhood-Onset Dystonia and Optic Atrophy, a Mitochondrial Fatty Acid Synthesis Disorder". American Journal of Human Genetics. 99 (6): 1229–1244. doi:10.1016/j.ajhg.2016.09.021. PMC   5142118 . PMID   27817865.

Further reading

• Torkko JM, Koivuranta KT, Miinalainen IJ, et al. (September 2001). "Candida tropicalis Etr1p and Saccharomyces cerevisiae Ybr026p (Mrf1'p), 2-enoyl thioester reductases essential for mitochondrial respiratory competence". Molecular and Cellular Biology. 21 (18): 6243–53. doi:10.1128/MCB.21.18.6243-6253.2001. PMC   87346 . PMID   11509667.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.
• Lai CH, Chou CY, Ch'ang LY, et al. (May 2000). "Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics". Genome Research. 10 (5): 703–13. doi:10.1101/gr.10.5.703. PMC   310876 . PMID   10810093.