ENO1
Available structures PDB Ortholog search:PDBeRCSB List of PDB id codes 2PSN,3B97
Identifiers
Aliases	ENO1, ENO1L1, MPB1, NNE, PPH, HEL-S-17, enolase 1
External IDs	OMIM:172430;MGI:95393;HomoloGene:134343;GeneCards:ENO1;OMA:ENO1 - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p36.23 Start 8,861,000bp[1] End 8,879,190bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4 E2|4 81.24 cM Start 150,321,178bp[2] End 150,333,336bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone nucleus accumbens right frontal lobe Achilles tendon renal medulla putamen mucosa of esophagus smooth muscle tissue embryo ascending aorta Top expressed in layer of retina neural layer of retina neural tube tail of embryo lens granulocyte Mesencephalon right kidney epiblast ventricular zone More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding metal ion binding protein binding lyase activity GTPase binding magnesium ion binding RNA binding cadherin binding DNA-binding transcription repressor activity, RNA polymerase II-specific phosphopyruvate hydratase activity protein homodimerization activity RNA polymerase II transcription regulatory region sequence-specific DNA binding Cellular component cytoplasm M band membrane extracellular exosome nucleus extracellular space phosphopyruvate hydratase complex cytosol plasma membrane cell surface cell cortex region Biological process gluconeogenesis regulation of transcription, DNA-templated glycolytic process response to virus transcription, DNA-templated negative regulation of cell growth negative regulation of transcription, DNA-templated negative regulation of transcription by RNA polymerase II positive regulation of plasminogen activation positive regulation of muscle contraction canonical glycolysis negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway positive regulation of ATP biosynthetic process Sources:Amigo /QuickGO
Orthologs Species Human Mouse Entrez 2023 13806 Ensembl ENSG00000074800 ENSMUSG00000063524 UniProt P06733 P17182 RefSeq (mRNA) NM_001201483 NM_001428 NM_001353346 NM_023119 NM_001379127 NM_001379128 RefSeq (protein) NP_001188412 NP_001419 NP_001340275 NP_001366056 NP_001366057 NP_075608 NP_001020559 Location (UCSC) Chr 1: 8.86 – 8.88 Mb Chr 4: 150.32 – 150.33 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Enolase 1 (ENO1), more commonly known asalpha-enolase, is aglycolyticenzyme expressed in most tissues, one of theisozymes ofenolase. Each isoenzyme is ahomodimer composed of 2 alpha, 2 gamma, or 2 betasubunits, and functions as a glycolytic enzyme. Alpha-enolase, in addition, functions as a structurallens protein (tau-crystallin) in themonomeric form.Alternative splicing of this gene results in a shorter isoform that has been shown to bind to thec-myc promoter and function as atumor suppressor. Severalpseudogenes have been identified, including one on the long arm of chromosome 1. Alpha-enolase has also been identified as anautoantigen inHashimoto encephalopathy.^[5]

ENO1 is one of three enolase isoforms, the other two beingENO2 (ENO-γ) andENO3 (ENO-β).^[6] Each isoform is aprotein subunit that canhetero- orhomodimerize to form αα, αβ, αγ, ββ, and γγ dimers.^[7] TheENO1 gene spans 18kb and lacks aTATA box while possessing multipletranscription start sites.^[8] Ahypoxia-responsive element can be found in theENO1promoter and allows the enzyme to function in aerobicglycolysis and contribute to theWarburg effect intumor cells.^[9]

The mRNA transcript of theENO1 gene can be alternatively translated into acytoplasmic protein, with amolecular weight of 48kDa, or anuclear protein, with a molecular weight of a 37 kDa.^[9][10] The nuclear form was previously identified as Myc-binding protein-1 (MBP1), which downregulates the protein level of thec-mycprotooncogene.^[10] Astart codon at codon 97 ofENO1 and aKozak consensus sequence were found preceding the3' region ofENO1 encoding the MBP1 protein. In addition, theN-terminal region of the MBP1 protein it critical to DNA binding and, thus, its inhibitory function.^[10]

As an enolase, ENO1 is a glycolytic enzyme the catalyzes the conversion of2-phosphoglycerate tophosphoenolpyruvate.^[6][9][11] This isozyme is ubiquitously expressed in adult human tissues, includingliver,brain,kidney, andspleen.^[6] Within cells, ENO1 predominantlylocalizes to thecytoplasm, though an alternatively translated form is localized to thenucleus.^[6][9] Its nuclear form, also known as MBP1, functions solely as atumor suppressor by binding and inhibiting thec-myc protooncogene promoter, and lacks the glycolytic enzyme activity of the cytoplasmic form.^[10] ENO1 also plays a role in other functions, including a cell surface receptor forplasminogen onpathogens, such asstreptococci, and activated immune cells, leading to systemic infection or tissue invasion; anoxidative stress protein inendothelial cells; a lenscrystalline; aheat shock protein; and a binding partner ofcytoskeletal andchromatin structures to aid intranscription.^{[9][10][11][12][13]}

ENO1 overexpression has been associated with multiple tumors, includingglioma,neuroendocrine tumors,neuroblastoma,pancreatic cancer,prostate cancer,cholangiocarcinoma,thyroid carcinoma,lung cancer,hepatocellular carcinoma, andbreast cancer.^{[6][9][13][14]} In many of these tumors, ENO1 promoted cell proliferation by regulating thePI3K/AKT signaling pathway and inducedtumorigenesis by activating plasminogen.^[6][9] Moreover, ENO1 is expressed on the tumor cell surface during pathological conditions such asinflammation,autoimmunity, andmalignancy. Its role as a plasminogen receptor leads toextracellular matrix degradation and cancer invasion.^[9][13][14] Due to its surface expression, targeting surface ENO1 enables selective targeting of tumor cells while leaving the ENO1 inside normal cells functional.^[9] Moreover, in tumors such asnon-Hodgkin lymphomas (NHLs) and breast cancer, inhibition of ENO1 expression decreased tolerance tohypoxia while increasing sensitivity toradiation therapy, thus indicating that ENO1 may have aidedchemoresistance.^[6][11] Considering these factors, ENO1 holds great potential to serve as an effective therapeutic target for treating many types of tumors in patients.^[6][11][13]

ENO1 is located on the 1p36 tumor suppressor locus nearMIR34A which is homozygously deleted inGlioblastoma,Hepatocellular carcinoma andCholangiocarcinoma.^[15][16] The co-deletion of ENO1 is a passenger event with the resultant tumor cells being entirely dependent onENO2 for the execution ofglycolysis.^[17][18] Tumor cells with such deletions are exceptionally sensitive towards ablation of ENO2.^[17][18] Inhibition of ENO2 in ENO1-homozygously deleted cancer cells constitutes an example ofsynthetic lethality treatment for cancer.

ENO1 has been detected inserum drawn from children diagnosed withjuvenile idiopathic arthritis.^[19]

Alpha-enolase has been identified as anautoantigen inHashimoto's encephalopathy.^[20] Single studies have also identified it as an autoantigen associated with severeasthma^[21] and a putative target antigen of anti-endothelial cell antibody inBehçet's disease.^[22] Reduced expression of the enzyme has been found in thecorneal epithelium of people suffering fromkeratoconus.^[23][24]

CagA protein was found to activate ENO1 expression through activating theSrc andMEK/ERKpathways as a mechanism for H.pylori-mediated gastric diseases.^[14]

Enolase deficiency is a rare inborn error of metabolism disease, leads tohemolytic anemia in affected homozygous carriers of loss of function mutations in ENO1.^[25] As with other glycolysis enzyme deficiency diseases, the condition is aggravated by redox-cycling agents such asnitrofurantoin.

Click on genes, proteins and metabolites below to link to respective articles.^{[§ 1]}

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|alt=Glycolysis and Gluconeogenesisedit]]

Glycolysis and Gluconeogenesisedit

1. ^The interactive pathway map can be edited at WikiPathways:"GlycolysisGluconeogenesis_WP534".

Alpha-enolase has been shown tointeract withTRAPPC2.^[26]

• Enolase
• ENO2
• ENO3

• Alpha-Enolase Linked to Severe Asthma -medscape news report, 25 aug 2006.
• HumanENO1 genome location andENO1 gene details page in theUCSC Genome Browser.

This article incorporates text from theUnited States National Library of Medicine, which is in thepublic domain.

• Genes on human chromosome 1
• Enzymes
• Glycolysis

• Articles with short description
• Short description is different from Wikidata
• Use dmy dates from October 2020
• Wikipedia articles incorporating text from the United States National Library of Medicine