ENO1
Available structures PDB Ortholog search: PDBe RCSB 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
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p36.23 Start 8,861,000 bp[1] End 8,879,250 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4 E2|4 81.24 cM Start 150,236,721 bp[2] End 150,248,879 bp[2]
RNA expression pattern 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 • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • phosphopyruvate hydratase activity • protein homodimerization activity • RNA polymerase II regulatory region sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding Cellular component • cytoplasm • M band • membrane • extracellular exosome • cell 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 from RNA polymerase II promoter • 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
RefSeq (protein)	NP_001188412 NP_001419 NP_001340275	NP_075608
Location (UCSC)	Chr 1: 8.86 – 8.88 Mb	Chr 4: 150.24 – 150.25 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Enolase 1 (ENO1), more commonly known as alpha-enolase, is a glycolytic enzyme expressed in most tissues, one of the isozymes of enolase. Each isoenzyme is a homodimer composed of 2 alpha, 2 gamma, or 2 beta subunits, and functions as a glycolytic enzyme. Alpha-enolase, in addition, functions as a structural lens protein (tau-crystallin) in the monomeric form. Alternative splicing of this gene results in a shorter isoform that has been shown to bind to the c-myc promoter and function as a tumor suppressor. Several pseudogenes have been identified, including one on the long arm of chromosome 1. Alpha-enolase has also been identified as an autoantigen in Hashimoto encephalopathy.^[5]

Structure[edit]

ENO1 is one of three enolase isoforms, the other two being ENO2 (ENO-γ) and ENO3 (ENO-β).^[6] Each isoform is a protein subunit that can hetero- or homodimerize to form αα, αβ, αγ, ββ, and γγ dimers.^[7] The ENO1 gene spans 18 kb and lacks a TATA box while possessing multiple transcription start sites.^[8] A hypoxia-responsive element can be found in the ENO1 promoter and allows the enzyme to function in aerobic glycolysis and contribute to the Warburg effect in tumor cells.^[9]

Relationship to Myc-binding protein-1[edit]

The mRNA transcript of the ENO1 gene can be alternatively translated into a cytoplasmic protein, with a molecular weight of 48 kDa, or a nuclear 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 the c-myc protooncogene.^[10][11] A start codon at codon 97 of ENO1 and a Kozak consensus sequence were found preceding the 3' region of ENO1 encoding the MBP1 protein. In addition, the N-terminal region of the MBP1 protein it critical to DNA binding and, thus, its inhibitory function.^[10]

Function[edit]

As an enolase, ENO1 is a glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate.^[6][9][12] This isozyme is ubiquitously expressed in adult human tissues, including liver, brain, kidney, and spleen.^[6] Within cells, ENO1 predominantly localizes to the cytoplasm, though an alternatively translated form is localizes to the nucleus.^[6][9] Its nuclear form, also known as MBP1, functions solely as a tumor suppressor by binding and inhibiting the c-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 for plasminogen on pathogens, such as streptococci, and activated immune cells, leading to systemic infection or tissue invasion; an oxidative stress protein in endothelial cells; a lens crystalline; a heat shock protein; and a binding partner of cytoskeletal and chromatin structures to aid in transcription.^{[9][10][12][13][14]}

Clinical significance[edit]

Cancer[edit]

ENO1 overexpression has been associated with multiple tumors, including glioma, neuroendocrine tumors, neuroblastoma, pancreatic cancer, prostate cancer, cholangiocarcinoma, thyroid carcinoma, lung cancer, hepatocellular carcinoma, and breast cancer.^{[6][9][14][15]} In many of these tumors, ENO1 promoted cell proliferation by regulating the PI3K/AKT signaling pathway and induced tumorigenesis by activating plasminogen.^[6][9] Moreover, ENO1 is expressed on the tumor cell surface during pathological conditions such as inflammation, autoimmunity, and malignancy. Its role as a plasminogen receptor leads to extracellular matrix degradation and cancer invasion.^[9][14][15] 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 as Non-Hodgkin's Lymphomas (NHLs) and breast cancer, inhibition of ENO1 expression decreased tolerance to hypoxia while increasing sensitivity to radiation therapy, thus indicating that ENO1 may have aided chemoresistance.^[6][12] Considering these factors, ENO1 holds great potential to serve as an effective therapeutic target for treating many types of tumors in patients.^[6][12][14]

ENO1 is located on the 1p36 tumor suppressor locus near MIR34A which is homozygously deleted in Glioblastoma, Hepatocellular carcinoma and Cholangiocarcinoma.^[16][17][18] The co-deletion of ENO1 is a passenger event with the resultant tumor cells being entirely dependent on ENO2 for the execution of glycolysis.^[19][20] Tumor cells with such deletions are exceptionally sensitive towards ablation of ENO2.^[19][20] Inhibition of ENO2 in ENO1-homozygously deleted cancer cells constitutes an example of synthetic lethality treatment for cancer.

Autoimmune disease[edit]

ENO1 has been detected in serum drawn from children diagnosed with juvenile idiopathic arthritis.^[21]

Alpha-enolase has been identified as an autoantigen in Hashimoto's encephalopathy.^[22] Single studies have also identified it as an autoantigen associated with severe asthma^[23] and a putative target antigen of anti-endothelial cell antibody in Behçet's disease.^[24] Reduced expression of the enzyme has been found in the corneal epithelium of people suffering from keratoconus.^[25][26]

Gastrointestinal disease[edit]

CagA protein was found to activate ENO1 expression through activating the Src and MEK/ERK pathways as a mechanism for H. pylori-mediated gastric diseases.^[15]

Hemolytic anemia[edit]

Enolase deficiency is a rare inborn error of metabolism disease, leads to hemolytic anemia in affected homozygous carriers of loss of function mutations in ENO1.^[27] As with other glycolysis enzyme deficiency diseases, the condition is aggravated by redox-cycling agents such as nitrofurantoin.

Interactive pathway map[edit]

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

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|{{{bSize}}}px|alt=Glycolysis and Gluconeogenesis edit]]

Glycolysis and Gluconeogenesis edit

1. 
   ^ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"""""""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
   

Interactions[edit]

Alpha-enolase has been shown to interact with TRAPPC2.^[28]

See also[edit]

• Enolase


• ENO2


• ENO3

External links[edit]

• 
  Alpha-Enolase Linked to Severe Asthma - medscape news report, 25 aug 2006.


• Human ENO1 genome location and ENO1 gene details page in the UCSC Genome Browser.

References[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.