Alpha-enolase

Enolase 1, (alpha)
Rendering based on PDB 2PSN.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2PSN, 3B97
Identifiers
Symbols	ENO1 ; ENO1L1; MPB1; NNE; PPH
External IDs	OMIM: 172430 MGI: 95393 HomoloGene: 134343 ChEMBL: 3298 GeneCards: ENO1 Gene
EC number	4.2.1.11
Gene ontology Molecular function • magnesium ion binding • DNA binding • transcription factor activity, sequence-specific DNA binding • transcription corepressor activity • phosphopyruvate hydratase activity • protein binding • poly(A) RNA binding • GTPase binding Cellular component • phosphopyruvate hydratase complex • extracellular space • nucleus • cytoplasm • cytosol • plasma membrane • membrane • M band • extracellular exosome Biological process • negative regulation of transcription from RNA polymerase II promoter • carbohydrate metabolic process • glucose metabolic process • gluconeogenesis • transcription, DNA-templated • response to virus • negative regulation of cell growth • small molecule metabolic process • negative regulation of transcription, DNA-templated • canonical glycolysis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2023	13806
Ensembl	ENSG00000074800	ENSMUSG00000059040
UniProt	P06733	P17182
RefSeq (mRNA)	NM_001201483	NM_023119
RefSeq (protein)	NP_001188412	NP_075608
Location (UCSC)	Chr 1: 8.86 – 8.88 Mb	Chr 18: 48.05 – 48.05 Mb
PubMed search	[1]	[2]

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.

Structure

ENO1 is one of three enolase isoforms, the other two being ENO2 (ENO-γ) and ENO3 (ENO-β). Each isoform is a protein subunit that can hetero- or homodimerize to form αα, αβ, αγ, ββ, and γγ dimers. The ENO1 gene spans 18 kb and lacks a TATA box while possessing multiple transcription start sites. 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.

Relationship to Myc-binding protein-1

The mRNA transcript of the ENO1 gene can be alternatively spliced into a cytoplasmic protein, with a molecular weight of 48 kDa, or a nuclear protein, with a molecular weight of a 37 kDa. The nuclear form was previously identified as Myc-binding protein-1 (MBP1), which downregulates the activity of the c-myc protooncogene. 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.

Function

As an enolase, ENO1 is a glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. This isozyme is ubiquitously expressed in adult human tissues, including liver, brain, kidney, and spleen. Within cells, ENO1 predominantly localizes to the cytoplasm, though an alternatively spliced form is localizes to the nucleus. 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. 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.

Clinical significance

Cancer

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. In many of these tumors, ENO1 promoted cell proliferation by regulating the PI3K/AKT signaling pathway and induced tumorigenesis by activating plasminogen. 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. Due to its surface expression, targeting surface ENO1 enables selective targeting of tumor cells while leaving the ENO1 inside normal cells functional. 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. Considering these factors, ENO1 holds great potential to serve as an effective therapeutic target for treating many types of tumors in patients.

Autoimmune disease

ENO1 has been detected in serum drawn from children diagnosed with juvenile idiopathic arthritis.

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

Gastrointestinal disease

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.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.

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

File:WP534.png

Glycolysis and Gluconeogenesis edit

Interactions

Alpha-enolase has been shown to interact with TRAPPC2.

See also

• Enolase
• ENO2
• ENO3

External links

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

References

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