Enolase 3 (ENO3), more commonly known as beta-enolase (ENO-β), is anenzyme that in humans is encoded by theENO3gene.
This gene encodes one of the threeenolaseisoenzymes found in mammals. This isoenzyme is found inskeletal muscle cells in the adult where it may play a role in muscle development and regeneration. A switch fromalpha enolase to beta enolase occurs in muscle tissue during development in rodents. Mutations in this gene have been associated withglycogen storage disease.Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jul 2010][5]
ENO3 is one of three enolase isoforms, the other two beingENO1 (ENO-α) andENO2 (ENO-γ).[6][7] Each isoform is aprotein subunit that can formhetero- orhomodimers of the following combinations: αα, αβ, αγ, ββ, and γγ.[8][9][10]
TheENO3 gene spans 6kb and contains 12exons, though the first exon is anuntranslated region and, thus, non-coding. This first intron, along with the5'-flanking region, contains aconsensus sequence for muscle-specific regulatory factors that includes a CC(A + T-rich)6GG box, a M-CAT-box CAATCCT, and two myocyte-specific enhancer-binding factor 1 boxes.[7][10] Upstream of the first exon lies aTATA-like box andCpG-rich region, which contains recognition motifs for binding transcriptional regulatory factors such asSp1, activator protein 1 and 2, CCAAT box transcription factor/nuclear factor I, andcyclic AMP.[7] Unlike the other enolase genes, which possess multiple transcription initiation sites,ENO3 possesses a single initiation site located 26bp downstream of the TATA-like box.[10]
This gene encodes a 433-residue dimeric protein.[7] Due to its comparatively small length and highly conservedintron/exon organization among the three enolase isoforms, ENO3 is suggested to have been the last to diverge from a common ancestral gene.[10]
As an enolase, ENO3 is a glycolytic enzyme that catalyzes the reversible conversion of2-phosphoglycerate tophosphoenolpyruvate.[7][8] This particular isoform is predominantly expressed in adultstriated muscle, including skeletal andcardiac muscle.[6][7][10] During fetal muscle development, there is a transcriptional switch from expressing ENO1 to ENO3 influenced by muscleinnervation andMyo D1.[7][10] ENO3 is expressed at higher levels in fast-twitch fibers than in slow-twitch fibers.[10]
ENO3 has been associated with energy metabolism in cancer cells.TFG-TEC, anoncoprotein, activates ENO3 expression by altering thechromatin structure of the ENO3 promoter and increasing theacetylation ofhistone H3.[8]
Muscle β-enolase deficiency (glycogen storage disease type XIII) is a rare inherited metabolicmyopathy caused by a defect in the enzyme'sactive site, thus disrupting its glycolytic activity. Though this deficiency is characterized as anautosomal recessive condition, bothheterozygous andhomozygous mutations were identified in theENO3 gene. The heterozygous mutations were linked to milder symptoms while the homozygous mutations tended to produce more severe symptoms, includingrhabdomyolysis. Advances ingenetic testing, such asexome sequencing and specific gene panels, can provide greater access to diagnoses for muscle β-enolase deficiency and other rare disorders.[9]
^abZhu X, Miao X, Wu Y, Li C, Guo Y, Liu Y, Chen Y, Lu X, Wang Y, He S (Jul 2015). "ENO1 promotes tumor proliferation and cell adhesion mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphomas".Experimental Cell Research.335 (2):216–23.doi:10.1016/j.yexcr.2015.05.020.PMID26024773.
^abcdKim AY, Lim B, Choi J, Kim J (Aug 2015). "The TFG-TEC oncoprotein induces transcriptional activation of the human β-enolase gene via chromatin modification of the promoter region".Molecular Carcinogenesis.55 (10):1411–1423.doi:10.1002/mc.22384.PMID26310886.S2CID25167240.
^abMusumeci O, Brady S, Rodolico C, Ciranni A, Montagnese F, Aguennouz M, Kirk R, Allen E, Godfrey R, Romeo S, Murphy E, Rahman S, Quinlivan R, Toscano A (Dec 2014). "Recurrent rhabdomyolysis due to muscle β-enolase deficiency: very rare or underestimated?".Journal of Neurology.261 (12):2424–8.doi:10.1007/s00415-014-7512-7.PMID25267339.S2CID20446106.
Comi GP, Fortunato F, Lucchiari S, Bordoni A, Prelle A, Jann S, Keller A, Ciscato P, Galbiati S, Chiveri L, Torrente Y, Scarlato G, Bresolin N (Aug 2001). "Beta-enolase deficiency, a new metabolic myopathy of distal glycolysis".Annals of Neurology.50 (2):202–7.doi:10.1002/ana.1095.PMID11506403.S2CID21913565.
Li TB, Liu XH, Feng S, Hu Y, Yang WX, Han Y, Wang YG, Gong LM (Jun 2004). "Characterization of MR-1, a novel myofibrillogenesis regulator in human muscle".Acta Biochimica et Biophysica Sinica.36 (6):412–8.doi:10.1093/abbs/36.6.412.PMID15188056.
